Posted on Leave a comment

Internet Archive experiences outages after DDoS attacks, data breach – SiliconANGLE News

UPDATED 17:12 EST / OCTOBER 10 2024
by Maria Deutscher
The Internet Archive today experienced a distributed denial-of-service attack that took two of its services offline.
The malicious traffic surge is the latest in a series of cybersecurity incidents to have hit the nonprofit over the past few days. It previously experienced at least one other DDoS attack and, more notably, a data breach that compromised 31 million user records. It’s unclear whether the cyberattacks were carried out by the same hacker.
The Internet Archive operates the Wayback Machine, a popular free archive of the web. Since launching in the mid-1990s, it has saved more than 800 billion webpages with about 100 petabytes of data. The nonprofit also stores digital copies of other media including books and software code.
The first of the recent cyberattacks against the Internet Archive came to light at the end of September. A hacker sent Troy Hunt, the operator of the cybersecurity service Have I Been Pwned, a dataset stolen from the nonprofit. A few days later, Hunt analyzed the file and determined that it contains more than 31 million records belonging to Internet Archive users.
The dataset included usernames, email addresses, timestamps indicating when the affected users changed their passwords, and the passwords themselves. The Internet Archive scrambled the passwords with a hashing system, which means they are unlikely to pose a cybersecurity risk. Hashing is a data processing method that turns login credentials into a seemingly random string of characters.
The Internet Archive used a particularly secure hashing algorithm called Bcrypt. The algorithm is designed in such a way that scrambling passwords consumes a significant amount of processing power. Thanks to that architecture, deciphering a hash to obtain the original password also requires prohibitively large amounts of infrastructure, which makes bypassing Bcrypt impractical for hackers.
The password hashes and other stolen records were sent to Hunt in a 6.4-gigabyte SQL file. After reviewing the contents of the dataset, he notified the Internet Archive and uploaded the file to Have I Been Pwned. That service allows consumers to check if their data has been compromised in a cyberattack.
Internet Archive users learned that it was breached on Wednesday, when a hacker compromised the nonprofit’s website and displayed a message announcing a cyberattack had taken place. The message was followed by a DDoS attack a few hours later. A second DDoS attack took place this morning.
Internet Archive founder Brewster Kahle wrote on X that the hacker message displayed on Wednesday was created using a vulnerable JavaScript library. In response, the nonprofit has disabled that library. Kahle added that Internet Archive staffers are “scrubbing systems” and upgrading the organization’s cybersecurity systems.
The DDoS attack that followed the hacker’s message affected the availability of not only the Wayback Machine but also the nonprofit’s Open Library book archive. In an update published this morning, Kahle stated that the Internet Archive is “being cautious and prioritizing keeping data safe at the expense of service availability.”
THANK YOU
Russia’s finance minister reveals bitcoin is being used to conduct foreign trade
US allocates $3B to ‘rip and replace’ Chinese technology at smaller telcos
Iran votes to lift bans on WhatsApp, Google Play and other foreign-owned apps
Marriott and Starwood ordered to implement security overhaul in FTC settlement
Apple asks to participate in Google’s upcoming antitrust trial
North Korean hackers linked to hack of 4,500 bitcoins from Japanese crypto exchange
Russia’s finance minister reveals bitcoin is being used to conduct foreign trade
BLOCKCHAIN – BY MIKE WHEATLEY . 16 HOURS AGO
US allocates $3B to ‘rip and replace’ Chinese technology at smaller telcos
SECURITY – BY DUNCAN RILEY . 17 HOURS AGO
Iran votes to lift bans on WhatsApp, Google Play and other foreign-owned apps
POLICY – BY MIKE WHEATLEY . 2 DAYS AGO
Marriott and Starwood ordered to implement security overhaul in FTC settlement
SECURITY – BY DUNCAN RILEY . 2 DAYS AGO
Apple asks to participate in Google’s upcoming antitrust trial
APPS – BY MARIA DEUTSCHER . 2 DAYS AGO
North Korean hackers linked to hack of 4,500 bitcoins from Japanese crypto exchange
SECURITY – BY DUNCAN RILEY . 2 DAYS AGO
Forgot Password?
Like Free Content? Subscribe to follow.

source

Posted on Leave a comment

WishGarden Herbs Fast-Acting Legendary Herbal Tincture Blends Add Plant Power to Dry January Mocktails that Boost Happiness, Ease Stress and Enhance Connection – PR Newswire

Searching for your content…
In-Language News
Contact Us
888-776-0942
from 8 AM – 10 PM ET
Dec 30, 2024, 10:00 ET
Share this article
Swapping Herbs for Alcohol Makes Mocktails More Fun and Enhances Benefits for the Sober Curious
LOUISVILLE, Colo., Dec. 30, 2024 /PRNewswire/ — WishGarden Herbs, the number one selling fast-acting liquid herbal blends brand, is reminding the sober curious that mocktails can deliver feel-good benefits with the help of plant-powered herbal tinctures. Whether it’s Dry January or an ordinary Friday night, 25 percent of Americans over 21 are interested in living a sober lifestyle, and data shows that sober curious individuals are driving a mocktail trend, according to opinion research firm Civic Science.

“Gen Z and millennials are discovering the power of medicinal plants to help you feel better fast. One of the easiest ways to start incorporating herbs into your wellness routine is to add specific herbal blends into a mocktail,” said Erin Stokes, Naturopathic Doctor and Medical Director at WishGarden. “Our herbal tinctures can level up mocktails to do everything from providing a sense of calm to elevating your mood, so that replacing that nightly glass of wine doesn’t have to feel boring.” 
Making Mocktail Moments
Perfect for parties, friendly gatherings or nights in, WishGarden’s new Mocktail Kit contains all the essentials to mix up creative, flavorful drinks that bring a natural boost to every sip. Tasty mocktail recipes featuring herbal blends can transform any drink into something functional that promotes happiness, relaxation and enhances social connection. Even better – with WishGarden’s herbal blends you can enjoy the night and still feel great in the morning!
WishGarden’s Mocktail Kit includes four of the brand’s best-selling blends that are perfect mocktail add-ins:
Stir Up Sustainability
Feel even better about your wellness mocktail knowing it’s from a company that is focused on so much more than herbal remedies – WishGarden’s mission encompasses a more sustainable future. The rapid growth of herbal teas, essential oils and supplements is putting plant species at risk due to over-harvesting and unsustainable growing practices. As a result, it’s become critical to prioritize sourcing plants from regenerative organic farms, forest farmers who grow and harvest sustainably, and ethical wildcrafters. For 45 years, WishGarden’s approach has begun with intentional sourcing of sustainably grown medicinal plants and all partnerships are traced through a rigorous Vendor Verification Program that evaluates every single ingredient. For more on WishGarden’s approach to sourcing, visit the company blog
WishGarden’s Mocktail Kit can be purchased online and each featured blend is available individually online and in stores nationwide. To learn more visit WishGardenHerbs.com.
About WishGarden Herbs
Woman-owned and family-run since 1979, WishGarden Herbs is the number one selling liquid herbal blends brand in the U.S. For 45 years, we have used extensive scientific research and drawn upon thousands of years of traditional use to craft dynamic herbal tinctures that speak the body’s language, ensuring fast and effective absorption without additives, fillers, sugars, or gums. WishGarden uses only the highest-quality, organic and sustainably sourced herbs from domestic organic regenerative farms, forest farmers, and ethical wildcrafters. Our hand-in-hand partnerships, traced through a rigorous Vendor Verification Program, reflect a deep commitment to ecological and community well-being, propelled forward by founder Catherine Hunziker’s pioneering work in championing Herbal Regenerative Agriculture in the US. We’re not just about herbs; we’re about a healthier, more sustainable future. Learn more on WishGardenHerbs.com and join their community @wishgardenherbs.
SOURCE WishGarden Herbs
WishGarden Herbs, the number one selling liquid herbal supplement brand in the U.S., has launched a marketing campaign called "Meet the Moment™". The …
WishGarden Herbs, the #1 best-selling liquid herbal blends brand in the US, has expanded its leadership team with three strategic hires that share…
Retail
Beverages
Health Care & Hospitals
New Products & Services
Do not sell or share my personal information:

source

Posted on Leave a comment

| Black PR Wire, Inc. – Black PR Wire

(Black PR Wire) Wilmington, Delaware – On the heels of President Joe Biden’s recent pardoning of his son and commutation of several sentences from federal death row, 21 Members of Congress have formally appealed to President Biden in a letter to exonerate Marcus Garvey for “mail fraud in a case that was marred by prosecutorial and governmental misconduct.” 
Along with notable legal scholars, business and community leaders nationwide, the Center for Global Africa (CGA) led by Professor Ezrah Aharone, Founder & Chair, Center for Global Africa, USA and the Marcus Garvey Institute for Human Development (MGIHD) led by Dr. Julius Garvey the surviving son of Marcus Garvey will host a press conference to amplify Delaware voices who are calling on President Joe Biden to take action. 
This empowering event takes place on Thursday, January 2, 2025 from 3 – 4 PM (EST), Peter Spencer Plaza @ The Garvey Flag, located at 800 N. French Street in Wilmington, Delaware.  
 
The Center for Global Africa recently released The Garvey Legacy Film Trailer www.legacymovementfilm.com to support the exoneration movement and mobilize Delaware’s black leadership to align with national and international networks that are advocating for reparative justice for Marcus Garvey.  On November 19th, Dr. Julius Garvey released Justice 4 Garvey, a collection of informative essays and personal narratives about the senior Garvey’s life and work, demonstrating his essential influence on current social justice movements. 
WHAT:                 
Press Conference/Media & Community Event to Elevate the Request for President Biden to exonerate the Black Civil Rights Leader, Marcus Garvey.
WHEN:                
Thursday, January 2, 2025 | 3 – 4 PM (EST)
WHERE:               
Peter Spencer Plaza @ The Garvey Flag, 800 N. French Street, Wilmington, Delaware
CONTACT:          
Alicia Clark | (302) 540-0954 | aclark@centerforglobalafrica.com                         
Bernadette Morris | (877) BLACKPR | newsroom@blackprwire.com
HBCU project
bprw side
partner businesswire
Sonshine Communications
Subscribe for Thrivin'

source

Posted on Leave a comment

Religion Focus of New Eiteljorg Efforts Funded by $2.5M Lilly Endowment Inc. Grant – Native News Online

Thanks to a $2.5 million grant the museum received from Lilly Endowment Inc., expressions of religion and spirituality among Native peoples and within the American West will be the focus of major projects at the Eiteljorg Museum of American Indians and Western Art.
Lilly Endowment made the grant through its Religion and Cultural Institutions Initiative. With the support, the museum will:

Enjoying Native News Coverage?
NNO Logo Make A Donation Here

“The Eiteljorg Museum will continue to engage our audiences in the exploration of religious and cultural expressions in the American West and among the Indigenous Peoples of North America, developing a better understanding of this complex subject,” Eiteljorg President and CEO Kathryn Haigh said. “We are grateful to Lilly Endowment Inc. for generously supporting this effort that will make an impact for years to come.” 
In 2019, Lilly Endowment launched the Religion and Cultural Institutions Initiative. Its aim is to support museums and other cultural organizations as they strengthen their capacity to provide fair, accurate and balanced portrayals of the role religion has played and continues to play in the United States and around the world.
Can we take a minute to talk about tribal sovereignty?
Sovereignty isn’t just a concept – it’s the foundation of Native nations’ right to govern, protect our lands, and preserve our cultures. Every story we publish strengthens tribal sovereignty.
Unlike mainstream media, we center Indigenous voices and report directly from Native communities. When we cover land rights, water protection, or tribal governance, we’re not just sharing news – we’re documenting our living history and defending our future.
Our journalism is powered by readers, not shareholders. If you believe in the importance of Native-led media in protecting tribal sovereignty, consider supporting our work today. 
Right now, your support goes twice as far. Thanks to a generous $35,000 matching fund, every dollar you give during December 2024 will be doubled to protect sovereignty and amplify Native voices.
No paywalls. No corporate owners. Just independent, Indigenous journalism.

source

Posted on Leave a comment

Powerball winning numbers for December 30 drawing: Jackpot rises to $163 million – USA TODAY

The final Powerball drawing of 2024 sees an estimated $163 million jackpot up for grabs after no one won the prize Saturday.
The game has seen nine winners this year, the largest of which came in April when three players in Oregon − including a cancer survivor − split a $1.3 billion jackpot. The most recent win came earlier this month when a ticket sold in New York had the winning numbers for a $256 million jackpot.
The first drawing of 2025 will occur on New Year’s Day. The holiday was lucky last New Year’s Day, with a Michigan lottery club winning an $842 million jackpot to start the year.
The last Powerball draw of 2024 happened shortly after 11 p.m. ET and we have the results below.
The winning numbers for the Powerball drawing on Dec. 30, 2024, are: 9, 19, 33, 38, 39 Powerball: 1
Holiday deals: Shop this season’s top products and sales curated by our editors.
Powerplay: 3X
Winning lottery numbers are sponsored by Jackpocket, the official digital lottery courier of the USA TODAY network.
Check back Tuesday to see if anyone won in the final Powerball drawing of the year.
To find the full list of previous Powerball winners, click the link to the lottery’s website.
In order to purchase a $2 Powerball ticket, you’ll have to visit your local convenience store, gas station or grocery store − and in a handful of states, you can purchase tickets online.
To play, you will need to pick six numbers in total to mark on your ticket. Five numbers will be white balls ranging from numbers 1 to 69. The Powerball is red and one number which is between 1 and 26.
If you want to increase your chances of winning, you can add a “Power Play” for $1 which increases the winnings for all non-jackpot prizes. This addition can multiply winnings by 2X3X, 4X5X, or 10X.
Players can also ask a cashier for a “Quick Pick” where a cashier will give you computer-generated numbers on a printed Powerball ticket.
Drawings are held on Monday, Wednesday and Saturday nights. If there’s no jackpot winner, the cash prize will increase by millions.
Tickets can be purchased in person at gas stations, convenience stores and grocery stores. Some airport terminals may also sell lottery tickets.
You can also order tickets online through Jackpocket, the official digital lottery courier of the USA TODAY Network, in these U.S. states and territories: Arizona, Arkansas, Colorado, Idaho, Maine, Massachusetts, Minnesota, Montana, Nebraska, New Hampshire, New Jersey, New Mexico, New York, Ohio, Oregon, Puerto Rico, Texas, Washington D.C. and West Virginia. The Jackpocket app allows you to pick your lottery game and numbers, place your order, see your ticket and collect your winnings all using your phone or home computer.
Jackpocket is the official digital lottery courier of the USA TODAY Network. Gannett may earn revenue for audience referrals to Jackpocket services. Must be 18+, 21+ in AZ and 19+ in NE. Not affiliated with any State Lottery. Gambling Problem? Call 1-877-8-HOPE-NY or text HOPENY (467369) (NY); 1-800-327-5050(MA); 1-877-MYLIMIT (OR); 1-800-981-0023 (PR); 1-800-GAMBLER (all others). Visit jackpocket.com/tos for full terms.

source

Posted on Leave a comment

A comprehensive metabolome profiling of Terminalia chebula Terminalia bellerica , and Phyllanthus emblica to explore the medicinal potential of Triphala – Nature.com

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.
Advertisement
Scientific Reports volume 14, Article number: 31635 (2024)
Metrics details
Triphala is a traditional Ayurvedic herbal formulation composed of three fruits: amla (Phyllanthus emblica), bibhitaki (Terminalia bellerica), and haritaki (Terminalia chebula). Triphala is a potent Ayurvedic remedy that promotes digestion, detoxification, and overall wellness, while also providing antioxidant benefits through its trio of nutrient-rich fruits. In order to elucidate the individual contributions of the three ingredients of Triphala from molecular perspective, the individual ingredients were used for the untargeted LCMS/MS analysis. Fresh fruits (PE, TC, and TB) were collected, processed into coarse powders, and sequentially extracted {hexane, chloroform, and ethyl acetate}. LCMS/MS data analysis was performed on the resultant metabolites, with bioinformatics tools employed for pathway enrichment, target prediction, and classification of identified compounds. Additionally, polyphenols were identified as key compounds with potential health benefits. LCMS analysis of the individual extracts identified a total of 10227 features, resulting in 2515 annotated metabolites, with PE contributing the highest number at 1286. Comparative analysis revealed 408 non-redundant metabolites, with 74.2% being unique to individual fruits, underscoring the complementary phytochemical profiles. Pathway enrichment analysis highlighted dominant phenylpropanoid biosynthesis pathways across all extracts, while a comprehensive polyphenol classification identified 71 polyphenols, with significant interactions predicted between polyphenols and gut microbiota. Additionally, five common polyphenols showed potential human targets related to antioxidant activity. These findings provide a deeper understanding of the phytochemical diversity and potential health benefits of Triphala, supporting its traditional use in promoting health.
There is a growing understanding that phytochemical diversity in our food, beyond the macronutrients and micronutrients in the food we eat, is a cornerstone for good health1,2. Carlson (2010) estimates that there are more than 25000 bioactive food constituents3. These belong to three major phytochemical groups: the terpenoids, the alkaloids, and the phenylpropanoids and allied phenolic compounds. Terpenoids are derived from the five-carbon precursor isopentenyl diphosphate (IPP). Alkaloids are phytochemicals which contain one or more nitrogen atoms and are biosynthesized principally from amino acids. The phenolic compounds are formed by way of either the shikimic acid pathway or the mevalonate/acetate pathway. Within the body, the phytochemicals in food are pleiotropic and have multiple effects on areas such as cellular physiology, inflammation, insulin sensitization, stress response, cell signaling and epigenetic changes4,5,6,7. More recently, the mediation of gut in the effect of phytonutrients has been hypothesized. Well studied examples of such gut mediated transformation of phenolics into actives include the conversion of ellagic acid to Urolithin A8 and diadzein to equol9. Due to their ability to address multiple mechanisms simultaneously, it has been proposed that phytonutrients may be especially helpful in chronic diseases. For example, polyphenols have been suggested to be a potential nutraceutical intervention in type 2 diabetes10,11, where there are several dysfunctional processes related to glucose and lipid metabolism that impact several body systems. A phytochemically-rich diet could be an important pillar of preventive health strategies.
Polyherbal whole food supplements and nutraceuticals are rich in phytochemicals and can add phytonutrient diversity to our diet. Ayurveda has a number of polyherbal formulations that are recommended as food supplements and tonics. One of the popular formulations is ‘Triphala’ which is the Sanskrit word for ‘three fruits’. This food supplement combines dried and powdered fruits of the plants Terminalia chebula (TC), Terminalia bellerica (TB) and Phyllanthus emblica (PE) in equal proportions12. A typical daily consumption is 3 g a day of the dry powder, taken as is, or as a soup in water, or with other ingredients such as honey or ghee13. All the three fruits are highly astringent in their in-mouth experience accompanied with sourness and bitterness and hints of sweetness and pungency, indicating presence of phytochemicals with different functional groups.
There are many health benefits associated with daily consumption of Triphala in Ayurvedic literature. It is considered a longevity tonic—one that can make a person live to be a centenarian14. It is used for treatment of ulcers and wounds15, chronic fever, obesity, heart diseases and diabetes16. Triphala is said to help cleansing the mucus of the digestive villi, making for a more effective digestive process and support the elimination process. Individually, PE is a fruit that has been suggested to support intestinal repair, TB has been suggested to pull the old mucus off the wall and TC has been suggested to strengthen the intestinal muscles to contract more efficiently when the bowels need to move17,18.
The wide popularity of this polyherbal formulation amongst Indians and their diaspora, and its many benefits mentioned in Ayurveda, has led to scientific interest in it. Over the last two decades many research studies have focused on the bioactivity of the three fruits individually and of the mixed formulation. This includes evaluating their extracts in assays pertaining to cancer19, diabetes20,21,22,23,24, inflammation inhibition and immunomodulatory activity25,26,27,28, gastrointestinal disorders29,30,31, hepatoprotective activity32,33, antibacterial activity34, antiplasmodial activity and cardioprotective activity35. Extracts of PE have been studied for skin lightening, treatment of gonorrhea, prevention of greying of hair36, treatment of diabetes, hysteria, jaundice, eczema, piles, diarrhea, menorrhagia, scurvy, and increases red blood counts37,38,39,40,41,42. TB has been studied for treatment of cough, asthma, anorexia, vomiting, arthritis, fever, epilepsy, splenomegaly, piles, diarrhea, leprosy, brain tonic and laxative38,43,44,45,46.
The broad sensory and biological activity of the three ingredients suggests a large phytochemical diversity. Previous research has primarily focused on either the targeted identification of specific bioactive compounds or the overall profile of the Triphala formulation, without investigating how the individual ingredients contribute to its therapeutic effects. More recently, untargeted approaches using LCMS have been used to understand the overall phytochemical profile47 and identified more than 1500 compounds. However, a question that is left unanswered is the contribution of each of the three ingredients and the reason why they need to be combined as a single mix. Our study addresses this gap by performing a detailed untargeted metabolome analysis of the individual powders from the three fruits that comprise the Ayurvedic formulation Triphala—Terminalia chebula (TC), Terminalia bellerica (TB), and Phyllanthus emblica (PE)—using LCMS, and then comparing the metabolome profiles of the three fruits, allowing us to explore how their combined properties may work synergistically in the formulation. Additionally, we characterize the polyphenols in each fruit, predict their human targets, and assess their bioavailability, providing new insights into the molecular mechanisms underlying Triphala’s therapeutic potential.
This is the first study to profile each ingredient separately using a consistent analytical approach. This enables assessment of the distinct contributions of each fruit and an understanding of their complementary roles in the formulation. A key novelty of our study is the identification of complementary and supplementary phytochemical profiles, which helps explain the rationale behind the traditional combination of these three ingredients.
Fresh PE fruits were collected from ICAR-Indian Institute of Horticultural Research (IIHR), Bengaluru, India. Fresh TC and TB fruits were collected from the medicinal plant garden of The University of Trans-Disciplinary Health Sciences and Technology (TDU), Bengaluru, India. The PE, TC & TB fruits were cut, deseeded and crushed and oven dried at 50 °C. The dried fruits were separately ground into a coarse powder. The coarse powders were stored in separate air tight containers for subsequent extraction.
Each of the three dried powders was extracted sequentially with three solvents, used in increasing order of polarity, in a Soxhlet apparatus following the methods of Singh et al. (2019)48. The three solvents used were hexane (boiling point- 68.7 °C and polarity ~ 0.1), chloroform (BP- 61.2 °C and polarity ~ 4.1) and ethyl acetate (BP- 77.1 °C and polarity ~ 4.4). Briefly, 10 g of dried powder was taken in the thimble of the Soxhlet apparatus and 100 ml of solvent was taken in the flask giving a dried powder to solvent ratio of 1:10 (w/v). The extraction was carried out till a colourless solvent was obtained and the number of cycles noted.
The solvent extracts obtained were centrifuged at 10000 rpm for 10 min and the supernatants collected. Each supernatant was evaporated separately to dryness at 30 to 40 °C and stored at -80 °C till further processing. Just before LCMS/MS, the dried samples were taken out of the freezer and brought to room temperature. The three dried solvent extracts of each fruit were then combined and suspended in 1 ml of 100% methanol and used for LCMS/MS analysis. All the solvents for the present study were from Merck and of HPLC grade.
LCMS/MS was carried out on a QTRAP 6500 mass spectrometer (SCIEX, Framingham, MA, USA) interfaced with a 1290 Infinity HPLC system (Agilent Technologies). The samples were injected using a programmed auto sampler onto Poroshell 120 EC-C18 analytical column (2.1 mm × 100mm, 2.7µ) (Agilent Technologies, USA). Ultra performance liquid chromatography (UPLC; Waters ACQUITY UPLC system) Reverse phase, analytical column, HSS T3 C18 (100 × 2.1 mm i.d., 1.8-µm particle size; Waters) Q-Exactive Orbitrap-focus mass analyzer (Thermo Finnigan) PC machine with Windows operating system LCMS was used for the present analysis49. The Waters ACQUITY UPLC (Waters) coupled to a Q-Exactive Orbitrap-focus system (Thermo Finnigan) via an electrospray ionization (ESI) interface. Samples were run in both positive and negative ionization modes to provide the broadest coverage of the metabolome. Elution buffer A was prepared with a 0.1% solution (v/v) of ULC/MS grade formic acid (for liquid chromatography; Biosolve) and ultrapure water. Elution buffer B was prepared with a 0.1% solution (v/v) of ULC/MS grade formic acid (for liquid chromatography; Biosolve) and ultrapure acetonitrile (ULC/MS grade; Biosolve, cat. no. 01204102). The mobile phases used for the analysis included 0.1% formic acid in water (Solvent A) and 0.1% formic acid in 90% acetonitrile (Solvent B). The system was equilibrated by injecting 3–5 blank samples (methanol) and the samples were injected in a randomized manner. Each sample was analyzed in positive ionization mode, immediately followed by the same sample analyzed in negative ionization mode.
The metabolites were eluted using the following gradient: 2% B for 1 min, 2–30% B for 9 min, 30–60% B for 1 min, 60–95% B for 2 min, 95% B for 4 min, 95–2% B for 12 s and 2% B for 3 min. The total run time was set to 20 min and the flow rate was set to 0.300 ml/min and the injection volume was set to 10 µl. Data were acquired in both positive and negative scan modes using the information dependent acquisition (IDA) method in the Enhanced MS (EMS) to Enhanced Product Ion (EPI) scan mode. The Analyst software (version 1.6.2, Sciex) was used for the acquisition of data. The ESI source parameters of QTRAP 6500 included Ion Source Gas 1 (GS1) as 40 psi, Ion Source Gas 2 (GS2) as 40 psi, Curtain gas (CUR) as 35 psi, source temperature 350 °C and Collisionally activated dissociation (CAD) gas at high. The ion spray voltage was set to 350 V and the declustering potential was set to 100 V in the negative as well as positive scan modes. The instrument was set to acquire m/z range 50–1000 Da. Data was searched against NIST spectral library 2017 using SCIEX OS 3.0 software.
The putatively identified metabolites were further filtered based on their library hit score. Metabolites with library hit score > 70 were considered for further analysis50,51,52,53. For the metabolites with library hit score > 70, the PubChem IDs were retrieved from PubChem using PubChem API. Corresponding SMILES were retrieved from PubChem Identifier Exchange Service (https://pubchem.ncbi.nlm.nih.gov/docs/identifier-exchange-service).
Pathway analysis of the identified metabolites was conducted using Metaboanalyst 5.054. The analysis utilized the Arabidopsis thaliana pathway library. For over-representation analysis, the hypergeometric test was employed, and pathway topology analysis was performed using relative-betweenness centrality. Venn diagrams were constructed using Calculate and draw custom Venn diagrams, an online tool (https://bioinformatics.psb.ugent.be/webtools/Venn/).
The protein targets were predicted separately for exclusive metabolites of TC, PE and TB using the “Find my Compound’s Targets” tool (http://bindingdb.org/bind/chemsearch/marvin/FMCT.jsp) in BindingDB55. For the prediction of targets, a similarity criterion of 0.85 was employed. The metabolite-human target network was constructed using an open source software platform Cytoscape.
The identified metabolites from all three plants were classified into super class, class and subclasses using ClassyFire56 a web based metabolite classification tool. Further metabolites from each plant have been classified into polyphenols using Phenol-Explorer 3.657. The ADME (Absorption, distribution, metabolism, and excretion) properties of polyphenols were predicted using SwissADME. The polyphenols between TC, PE and TB were compared and common polyphenols were used to predict potential human targets using SwissTargetPrediction58. The pathway enrichment of predicted human targets were performed using ShinyGO 0.8059. The overall workflow of the study is given in Supplement-1.
This study investigated the individual contributions of the three components of Triphala—TC, TB and PE to elucidate the rationale behind their traditional formulation. Previous research by Subbannayya et al. (2018)47 did a global metabolite profiling of the extract of the mix of TC, PE and TB, using LCMS/MS, and identified 1897 putatively annotated metabolites. Since the profiling was done on an extract of the mix, the contribution of each fruit could not be done. As the goal of our study was to study the unique contribution of each fruit to the phytochemical profile of the Triphala mix, PE, TC and TB were extracted separately and profiling of the phytochemicals was done by LCMS/MS using electrospray ionization. The electrospray ionization technique produces positive and negative ions at high voltage by solvent evaporation, giving a broad coverage of the metabolome. By identifying complementary and supplementary sets of metabolites, we aimed to provide a molecular perspective on the synergistic benefits that justify the combined use of these three fruits in Triphala.
The LCMS/MS analysis identified a total of 10227 ions/features identified from PE, TC, and TB extracts. The features were searched against the National Institute of Standards and Technology (NIST) spectral library to identify the metabolites. This annotation resulted in a total of 2515 metabolites with TC having 975, PE having 1286 and TB having 254 metabolites. Further annotated metabolites were filtered using a library hit score of 70 as a cut-off. This yielded 787 metabolites, with TC having 295, PE having 396 and TB having 96 (Table 1). The positive ion mode released more ions in all the three extracts with 184 in PE, 141 in TC and 54 in TB. The negative ion mode identified 91 in PE of which 46 were new, 71 in TB, of which 64 were new, and 24 in TB of which 20 were new. 15 metabolites were identified by both + ve and -ve mode in PE, 7 in TC and 4 in TB (Fig. 1).
Comparison of metabolites from Triphala sample. (A) Common and unique metabolites among PE, TC and TB; (B) Common and unique metabolites at different electrospray ionization (ESI + ve and –ve mode).
Further, the metabolites with library hit score > 70 were used for comparing the unique contribution of TC, PE and TB. A total of 408 non-redundant metabolites (Fig. 1) were identified. The highest number of metabolites, 260, was identified in PE extract. 205 metabolites were identified in TC extract and 74 in TB extract. The list of all metabolites is given in Supplement 2.
Eighteen metabolites were common to all the three fruit extracts. PE and TC shared an additional 72 metabolites, PE and TB 7 metabolites, while TC and TB shared an additional 16 metabolites beyond the 18 shared by all three. Thus, 74.2% of the metabolites are uniquely contributed by one fruit and only 4.4% are shared by all three fruits (Table 2). This underscores a high level of complementarity between the phytochemical profiles of these fruits. The unique and overlapping metabolites of TC, PE, and TB suggest a synergistic interaction where the combined phytochemical profiles enhance the overall therapeutic efficacy of Triphala. For instance, the complementary action of polyphenols from TC and flavonoids from PE can provide a broad spectrum of antioxidant and anti-inflammatory effects, which are more potent when combined than when used individually. This synergism is likely due to the multiple molecular targets and pathways modulated by the diverse set of metabolites.
The extraction methods extracted both polar metabolites associated with metabolomics and some less polar compounds typically associated with lipidomics. To analyse further, the phytochemicals were classified into two big classes: the lipid metabolome and the non-lipid metabolome. They were further classified into super class, class and subclasses using ClassyFire56. Subsequently, the metabolites were further classified into primary (carbohydrates, lipids, amino acids, etc.) and secondary metabolites through manual inspection using class and subclasses identified through ClassyFire. 184 metabolites could be anotated using ClassyFire in the TC extract, 229 in the PE extract, and 65 in TB extract. Of these, the primary metabolites in TC and PE were 64 each, and TB had 25. TC had 120 secondary metabolites, PE 165, and TB 40. Furthermore, the functional group diversity within these secondary metabolites was highlighted, with TC exhibiting 11 superclasses and 27 classes, PE with 8 superclasses and 36 classes, and TB with 7 superclasses and 15 classes. Notably, TC and PE displayed a broader range of both superclass and class in secondary metabolites compared to TB. The diverse functional groups, including flavonoids, phenolic acids, and terpenoids, are associated with various health benefits. Flavonoids such as quercetin and kaempferol possess anti-inflammatory, anti-carcinogenic, and cardioprotective properties. Phenolic acids like gallic acid and ellagic acid exhibit strong antioxidant activities, reducing the risk of chronic diseases by neutralizing free radicals. Terpenoids, which were also present though to a smaller extent, may be contributing to the anti-microbial and anti-inflammatory effects of Triphala, supporting its traditional use in promoting gastrointestinal health and overall well-being.
In PE, the predominant non-lipidome metabolites belong to the phenylpropanoids and polyketides superclass, with flavonoids being the most abundant class. Additionally, benzenoids, including benzene and substituted derivatives were also identified in PE. TC had a significant presence of benzene derivatives. Phenols, prenol lipids, and steroids were also notable components. Flavonoids, carboxylic acids, and cinnamic acids were present in appreciable amounts as well. In TB, the chemical composition was less diverse, with a notable presence of benzene derivatives, and organooxygen compounds. Phenols and carboxylic acids were also present but to a lesser extent compared to the other extracts (Fig. 2). As mentioned above, the extraction method also extracted a number of lipids and lipid-like molecules. Fatty acyls and prenol lipids were noteworthy in PE. TC and TB also had notable fatty acyls. The presence of flavonoids, phenols, and fatty acyls, known for their health-promoting properties, aligns with the holistic therapeutic value attributed to Triphala in traditional medicine12.
Classification of metabolites into class and subclass level from TC, PE and TB.
The secondary metabolites from three fruits were used for pathway enrichment analysis which revealed the dominance of phenylpropanoid and related biosynthetic pathways. Flavonoid, flavone & flavonol biosynthesis appearedin all three. These pathways lead to the secondary metabolites in classes of benzenoids, phenylpropanoid and polyketides. More specifically, in TC, the most significantly enriched pathways included phenylpropanoid biosynthesis, and flavone & flavonol biosynthesis, PE exhibited a pronounced emphasis on flavonoid biosynthesis, flavone and flavonol biosynthesis, and phenylpropanoid biosynthesis. TB had fewer pathways enriched than TC and PE but notably included the pathway for phenylpropanoid biosynthesis (Fig. 3). The pathways leading to the other major secondary metabolite groups such as alkaloids and terpenoids did not appear prominently in this analysis. The presence of the phenylpropanoid biosynthesis pathway in all three components of Triphala underscored its significance, as phenylpropanoids play an essential role in plant defense and exhibit notable antioxidant properties with potential health benefits. Additionally, the flavonoid biosynthesis pathway was specifically observed in PE and TC, indicating a rich flavonoid content within their metabolite profiles. Flavonoids are recognized for their anti-inflammatory, antioxidant, and anticancer activities, further enhancing the therapeutic potential of Triphala. The phenylpropanoid pathways are crucial for synthesizing various phenolic compounds known for their potent antioxidant and anti-inflammatory properties. These pathways generate metabolites that can scavenge free radicals, thereby protecting cells from oxidative damage.
Top 10 enriched pathways of metabolites identified from Triphala plants. Bubble size represents the number of metabolites identified from each pathway.
The untargeted metabolome study of Triphala churna (powder) by Subbannayya et al., 2018, had reported the metabolites chebulinic acid, methyl gallate, vanillic acid, ( +) catechin, epicatechin and intermediates of quercetin, cinnamic acid, kaempferol, luteolin, quinic acid, caffeic acid and coumaric acid. These phytochemicals have also been reported in previous HPLC and LCMS studies on PE60,61,62 and Terminalia species TC and TB60,63. All these metabolites were identified in our analysis as well. The full list of metabolites of Triphala curated from literature and its comparison with the metabolites identified in this study is given in Supplement-3.
To take the analysis further, we compared the top 20 metabolites, based on their signal strengths, in the three plant samples: TC, PE and TB (Table 3). Polyphenols figured in the top 20 list in all the three. TC had gallic acid and ethyl gallate in its top 20, PE had ellagic acid, quercetin, kaempferol, t-cinnamic acid, and quercitrin. TB had ethyl gallate. These molecules are known to be astringent with sour and bitter notes and may contribute significantly to the overall sensory profile of the three. Additionally, these molecules are also known for their antioxidant properties64 and may contribute to keeping the gut environment free of reactive oxygen species.
Besides polyphenols there were other functional groups dominant in the LCMS/MS scans of the three extracts. TC had a notable abundance of fatty acids and glycerol derivatives, including prominent metabolites such as phytanic acid and 1-stearoyl-rac-glycerol. This suggests a potential emphasis on lipid-related pathways or biosynthesis. The metabolome profile of PE showcased a rich assortment of compounds, ranging from essential acids like DL-malic acid to flavonoids such as quercetin and kaempferol, and rejuvenating agents like loganin. This indicated a broad spectrum of biochemical pathways active within PE. . PE has been regarded as a good source of ascorbic acid65 and its identification in the top 20 metabolite list supported this. The metabolic profile of TB revealed presence of fatty acid derivatives such as pristanic acid and methyl hexadecanoate to specialized molecules such as the benzyl hexadecyl dimethyl ammonium cation and 17-phenyltrinorprostaglandin E2.
Overall, these distinct metabolic fingerprints contributed to the nuanced understanding of the individual plant’s roles within the Triphala formulation, paving the way for deeper investigations into their health-promoting properties and synergistic effects.
The dominance of polyphenols was apparent from the list of phytochemicals identified in the three fruits and the pathway enrichment exercise. Polyphenols are recognized as a class of molecules that are generally astringent in taste66 and have antioxidant property67. This is in line with the Ayurveda pharmacology wherein the three fruits PE, TC, and TB are classified as ‘Kashaya’ (Sanskrit word for astringent) group of medicinal and food ingredients in Ayurveda literature68,69,70. Equally, modern literature finds the antioxidant activity of these three fruits interesting and there are a number of published articles documenting this for the individual fruit extracts71,72,73,74 as well as for the mix75. We therefore studied the phenolic components of PE, TC and TB in greater detail. The polyphenols were classified using the Phenol-Explorer database57. Total 71 metabolites were classified as polyphenols from all three plants (28 from TC, 36 from PE and 7 from TB). The list of all polyphenols along with their classification is given in Supplement-4.
PE had the most phytochemicals in the flavonoid class, specifically flavanones and flavonols, TC was rich in phenolic acid class, with notable metabolites including hydroxybenzoic acids and hydroxybenzaldehydes. TB’s polyphenols included hydroxybenzoic acids and hydroxycinnamaldehyde, amongst others. Notably, lignans and stilbenes maintained minimal levels across all three fruit extracts (Fig. 4). TC exhibited ten unique polyphenols, while TB had one unique polyphenol, and PE had 17 unique polyphenols (Fig. 5). Pyrogallol, gallic acid, ferulaldehyde, gallic acid ethyl ester (ethyl gallate) and sinapaldehyde were found in all three.
Polyphenol classification of Triphala metabolites (TC, PE and TB).
Comparison of polyphenols from Triphala ingredients (TC, PE and TB). (A) Venn diagram showing the common and unique metabolites between TC, PE and TB; (B) Network depicting the Triphala plants and and corresponding containing polyphenols.
In general, polyphenols have poor absorption in the small intestine76,77. This suggests that a significant proportion of dietary polyphenols are expected to reach the colon where they may interact with the gut microbiome78,79,80,81.
The association between polyphenols identified in TC, PE & TB and gut microbes was investigated using GMMAD2 (Gut Microbial Metabolite Association with Disease; http://guolab.whu.edu.cn/GMMAD2). This platform provides comprehensive information on metabolite-related interactions between gut microbes and human diseases. We downloaded the interactions between microbes and metabolites and extracted the polyphenol-microbe interactions based on the PubChem IDs of Triphala polyphenols.
In total, 439 gut bacterial species (corresponding to 174 bacterial genera) demonstrated interactions with 19 polyphenols. Among the bacterial genera, Escherichia showed the highest number of interactions with polyphenols (8), followed by Eubacterium (6), Enterococcus (6), Bifidobacterium (6), Clostridium (5), Bacteroides (5), and others (Supplement 5; Fig. 1). These findings were in accordance with the Ma and Chen (2020)82. The interactions observed in our study between gut bacterial species and Triphala polyphenols further elucidated the significant impact of dietary polyphenols on microbial dynamics. These interactions suggest a significant role of polyphenols in modulating the gut microbiota composition. Polyphenols such as catechol and 3,4-dihydroxybenzoic acid, which interact with multiple bacterial genera, can enhance gut health by promoting the growth of beneficial bacteria and inhibiting pathogenic species. This modulation can lead to improved gut barrier function and reduced inflammation, thereby contributing to overall metabolic regulation and health benefits8,82.
Regarding polyphenols, phenol exhibited the highest number of interactions, with 133 bacterial genera, followed by catechol (61), 3,4-dihydroxybenzoic acid (39), 4-hydroxybenzaldehyde (21), and others (Supplement-5; Fig. 2). The complete list of bacterial genera and their associated polyphenols is provided in the supplementary material (Supplement-6).
Further, the ADME characteristics of the 47 classified polyphenols were examined. These characteristics encompassed physicochemical properties, lipophilicity, water solubility, pharmacokinetics, adherence to drug-like criteria, and relevance to medicinal chemistry. Oral bioavailability for potential active compounds was assessed using both Lipinski’s Rule of Five83 and Veber’s Rule84. The molecular weight of the polyphenols ranged from 94.11 (phenol with the least number of heavy atoms—7) to 610.56 g/mol (neohesperidin with maximum number of heavy atoms—43). Phenol was identified only in TC whereas neohesperidin was identified in both TC and PE (Supplement-7).
Out of 47 polyphenols, 33 polyphenols showed high GI (Gastrointestinal) absorption, 17 showed BBB (Blood Brain Barrier) permeant, 14 polyphenols identified as PGP (P-glycoprotein) substrate. The BBB potential was previously reported from amla extract for ischemia injury in rats85. The Log Kp (skin permeation) values for 47 metabolites ranged from − 10.54 to − 5.69 cm/s, with more negative values indicating lower skin permeation potential and less negative values suggesting higher permeation potential. With respect to water solubility, one polyphenol was predicted as moderately soluble, and 36 polyphenols predicted as water soluble. Ten polyphenols were predicted as highly soluble ( syringaldehyde, gallic acid, syringic acid, pyrogallol, caffeic acid, dihydro-p-coumaric acid, protocatechuic acid, catechol, 4-hydroxybenzaldehyde, and phenol).
In terms of drug-likeliness properties, 36 polyphenols exhibited adherence to Lipinski’s rule of five with no violations, while three polyphenols had a single violation, six polyphenols had two violations, and two polyphenols showed three violations. Additionally, with respect to Veber’s rule, 35 polyphenols demonstrated full compliance, while 12 polyphenols exhibited a single violation (Supplement-7).
A deeper assessment on oral bioavailability was done for five polyphenols that were found to be common to all the three fruit extracts (TC, PE, and TB), using the bioavailability radar device. The bioavailability radar device considered key parameters, including lipophilicity, size, polarity, solubility, flexibility, and saturation, to gauge the affinity of the drug and potential absorption. Among the five polyphenols, pyrogallol, gallic acid, ferulaldehyde, ethyl gallate, and sinapaldehyde, the saturation values for all except ethyl gallate suggested that they fell outside the desired range for optimal bioavailability. Saturation is a crucial factor influencing the absorption and effectiveness of orally administered drugs. On the positive side, all five polyphenols demonstrated favourable values for other bioavailability parameters such as lipophilicity, size, polarity, solubility, and flexibility. Despite the saturation challenge, these polyphenols possessed characteristics that could contribute to some absorption and utilization within the body (Supplement-5; Fig. 3).
The above results revealed insights into the potential mechanisms of absorption and distribution within the body, and the sites of action for the polyphenols. Firstly, the observation that the majority of these polyphenols exhibited minimal skin transport suggested limited permeability through the skin barrier. Furthermore, the high-water solubility predicted for most of the polyphenols suggested that they were likely to dissolve readily in aqueous environments. Surprisingly, a significant proportion of these polyphenols showed high gastrointestinal (GI) absorption potential, suggesting there may be some absorption through the small intestine80. Moreover, the identification of polyphenols capable of crossing the blood–brain barrier (BBB) further underscored their potential systemic effects86. This is supported by previous rat model studies demonstrating the presence of polyphenols in the brain following administration85.
Triphala has been reported to exhibit the capability to effectively neutralize various reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radicals through scavenging activity. Takauji et al., (2016) showed the eliminated reactive oxygen species (ROS) in HeLa cells using Triphala formulation87. Umapathi et al., (2019) assessed the effects of Triphala churna (powder) on the free radical scavenging activities such as hydrogen peroxide, nitric oxide (NO) radical, and superoxide anion radical scavenging activities in vitro88,89 and studied the free radical scavenging property of Triphala using phenyl) -(2,4,6-trinitrophenyl) iminoazanium (DPPH) scavenging of ferric ion, O2-, NO, H2O2 models88. Triphala has also been reported to have a regulatory impact on signaling pathways associated with oxidative stress. Specifically, it was shown to influence transcription factors like Nrf2, thereby promoting the expression of genes responsible for antioxidant production90. Since a few of the polyphenol molecules may have some absorption into the serum, they could potentially play a role in these activities. To understand the molecular basis of above reported results in literature, a network pharmacology approach was undertaken and metabolites were used to predict the human targets related to antioxidant activity. From this study, the Nrf2 transcription factor was one of the targets identified from metabolites of TC, PE and TB. Observations also revealed the identification of targets associated with antioxidant activity, including enzymes like glutathione reductase and glutathione transferase (Fig. 6). The antioxidants present in TC, PE and TB can stimulate the endogenous production of crucial enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase. These enzymes, in turn, contribute to reinforcing the body’s ability to counteract oxidative stress and maintain cellular health12. The multifaceted antioxidant properties of molecules found in TC, PE and TB could potentially be responsible for protecting cells and promoting the overall well-being promise of Triphala.
Human target predicted from metabolites of TC, PE and TB.
The five polyphenols which were common between all three plants were used to predict the potential human targets using SwissTarget prediction. Total 48 targets (probability > 0.1) were identified for 5 polyphenols common in TC, PE and TB (Fig. 7). Carbonic anhydrase I (CA I) and carbonic anhydrase II (CA II) enzymes were identified as potential targets for all four polyphenols analysed. Chandran et al. (2015) conducted a network pharmacology analysis of Triphala, utilizing reported metabolites and identifying human targets associated with these compounds. The study highlighted common metabolites such as ellagic acid, quercetin, chebulanin, methyl gallate, among others, across the three fruits, and reported their associated human targets and diseases. Interestingly, the authors also identified carbonic anhydrase as one of the targets for Triphala metabolites, which aligns with the findings of our study91.
Polyphenols (TC, PE and TB)—human target network.
Triphala may contribute to the overall antioxidant defense within the body. In the context of the target prediction analysis for the five polyphenols, it was observed that ferulaldehyde specifically targets Nrf2. This interaction implied that ferulaldehyde, one of the polyphenols, may play a role in activating Nrf2, consequently enhancing the expression of antioxidant response elements (ARE) and contributing to the overall cellular antioxidant defense90,92.
Carbonic anhydrase I (CA I) and carbonic anhydrase II (CA II) are two crucial isoforms within the carbonic anhydrase enzyme family. These enzymes, which are zinc metalloenzymes, play vital roles in various physiological processes, including the regulation of acid–base balance, carbon dioxide transport, and maintenance of cellular pH93,94. Both CA I and CA II are integral members of the broader carbonic anhydrase family, responsible for catalysing the interconversion of carbon dioxide and water to bicarbonate and protons94. Their activities are essential for preserving physiological pH, regulating ion transport, and facilitating diverse metabolic processes throughout the body. The intricate roles of CA I and CA II underscore their significance in maintaining homeostasis and supporting fundamental cellular functions.
These human targets were classified into different classes. Among these, lyase was the most prevalent, with 27 potential targets, suggesting a frequent association between polyphenols and targets classified under this category, while kinase and transferase were associated with four and three potential targets, respectively. Unspecified enzymes were identified as potential targets in six cases. Other target types such as secreted protein, family A G protein-coupled receptor, membrane receptor, nuclear receptor, other ion channel, oxidoreductase, and unclassified protein each represented one potential target in the dataset (Supplement-5; Fig. 4). This distribution provided insights into the diversity of target classifications linked to the polyphenols, highlighting the potential multifaceted roles of these compounds across various biological processes and molecular pathways.
Pathway analysis of human targets associated with five common polyphenols in TC, PE, and TB revealed potential effects on various cellular functions. These polyphenols demonstrated enrichment in pathways related to cellular structural integrity, such as Adherens junction and proximal tubule bicarbonate reclamation, suggesting an impact on cellular transport processes.
Furthermore, these polyphenols showed enrichment in pathways linked to metabolic regulation, exemplified by central carbon metabolism in cancer. This mirrors traditional use of Triphala as a digestive aid and metabolism regulator12, indicating a potential role in influencing cellular metabolic processes for overall health promotion. Additionally, there was significant enrichment in pathways related to nitrogen metabolism, EGFR tyrosine kinase inhibitor resistance, HIF-1 signaling pathway, and Endocrine resistance, suggesting a broader impact on cellular signaling and nitrogen-related processes (Supplement-5; Fig. 5).
The findings of this study lay a robust foundation for future research and development of Triphala-based herbal supplements by providing a comprehensive framework for the profiling of its constituent ingredients. This enhances the understanding of their synergistic interactions and facilitates targeted therapeutic applications, while also aiding in the standardization and quality control of Triphala formulations. Additionally, it supports the integration of traditional herbal medicine with modern pharmacotherapy, offering insights from ADME analysis and network pharmacology. These insights elucidate the pharmacokinetics and potential molecular targets of the bioactive compounds present in Triphala, thereby informing the rational design of supplements with optimized bioavailability and therapeutic efficacy. Furthermore, the study clarifies the rationale for combining the distinct botanicals of Triphala, highlighting their collective therapeutic potential and underscoring the need for continued investigation into the pharmacokinetic properties and molecular interactions of its constituents.
In this study we have done the metabolomeanalysis of the individual powders of the three fruits that comprise the popular Ayurveda formulation calledTriphala by untargeted profiling using LCMS/MS. The study elucidates the individual contributions of the three ingredients of Triphala and provides an understanding of the reason for combining them into a single formulation. By identifying the complementary and the supplementary molecule sets we are able to state why the three fruits have been combined in a formulation from a molecular perspective. Our results show that of the three main groups of secondary metabolites (alkaloids, phenolics & isoprenoids), the phytoprofile of the three fruits is dominated by phenolic acids. Therefore, we have characterized the polyphenols from all the three fruits and also identified potential human targets from the polyphenols as well as predicted the bioavailability of the identified polyphenols. This is the first holistic study of metabolome of Triphala (three species separately) with special reference to the contribution of polyphenols for therapeutic purposes. The study provides strong evidence for the complementary and synergistic roles of TC, TB, and PE in Triphala. Each ingredient contributes unique and valuable phytochemicals that, when combined, enhance the overall medicinal potential of Triphala. This comprehensive profiling supports the traditional use of Triphala in Ayurveda for promoting health.
The ADME analysis on the polyphenols in these botanicals reveals that most are water soluble and have at least some potential to be absorbed into the bloodstream in the small intestine. This suggests three points of action & absorption—bioactivity in the gut (such as antioxidant activity to keep the colon environment reactive oxygen species free), transformation by gut bacteria to forms that have better absorbability in the colon (such as urolithin A from ellagic acid), and direct absorption into bloodstream through small intestine. Together, the wide-spectrum polyphenols resulting from the blend of the three fruits and the three points of action & absorption, explain the multiple benefits associated with this polyherbal whole food supplement. The insights will also be useful in standardizing processing and products.
The raw data used during the current study available from the corresponding author on reasonable request.
Grusak, M. A. Genomics-assisted plant improvement to benefit human nutrition and health. Trends Plant Sci. 4, 164–166 (1999).
Article  CAS  PubMed  Google Scholar 
Minich, D. M. A review of the science of colorful, plant-based food and practical strategies for “eating the rainbow”. J. Nutr. Metab. 2019, 1–19 (2019).
Article  Google Scholar 
Carlsen, M. H. et al. The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr. J. 9 (2010).
Banudevi, S., Swaminathan, S. & Maheswari, K. U. Pleiotropic role of dietary phytochemicals in cancer: Emerging perspectives for combinational therapy. Nutr. Cancer 67, 1021–1048 (2015).
Article  CAS  PubMed  Google Scholar 
Minich, D. M. & Bland, J. S. Dietary management of the metabolic syndrome beyond macronutrients. Nutr. Rev. 66(8), 429–444 (2008).
Article  PubMed  Google Scholar 
Remely, M. et al. Therapeutic perspectives of epigenetically active nutrients. Br. J. Pharmacol. 172, 2756–2768 (2015).
Article  CAS  PubMed  Google Scholar 
Sundin, T. & Hentosh, P. InTERTesting association between telomerase, mTOR and phytochemicals. Expert Rev. Mol. Med. 14, e8 (2012).
Article  CAS  PubMed  Google Scholar 
Kikuchi, H., Harata, K., Madhyastha, H. & Kuribayashi, F. Ellagic acid and its fermentative derivative urolithin A show reverse effects on the gp91-phox gene expression, resulting in opposite alterations in all-trans retinoic acid-induced superoxide generating activity of U937 cells. Biochem. Biophys. Rep. 25, 100891 (2021).
CAS  PubMed  PubMed Central  Google Scholar 
Mayo, B., Vázquez, L. & Flórez, A. B. Equol: A bacterial metabolite from the daidzein isoflavone and its presumed beneficial health effects. Nutrients 11, 2231 (2019).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Bahadoran, Z., Mirmiran, P. & Azizi, F. Dietary polyphenols as potential nutraceuticals in management of diabetes: A review. J. Diabetes Metab. Disord. 12, 43 (2013).
Article  PubMed  PubMed Central  Google Scholar 
Sun, C. et al. Dietary polyphenols as antidiabetic agents: Advances and opportunities. Food Front. 1, 18–44 (2020).
Article  Google Scholar 
Peterson, C. T., Denniston, K. & Chopra, D. Therapeutic uses oftriphalain ayurvedic medicine. J. Altern. Complement. Med. 23, 607–614 (2017).
Article  PubMed  PubMed Central  Google Scholar 
Momin, M., Amin, A. F. & Pundarikakshudu, K. Development and evaluation of triphala formulations. Indian J. Pharm. Sci 66, 427–432 (2004).
CAS  Google Scholar 
Agniveśa, C., Śarm, R. M. & Dash, B. Agniveaś’s Caraka sahita: Text with English Translation & Critical Exposition Based on Cakrapi Datta’s yurveda dpik. Chowkhamba Sanskrit Series Office (1976).
Bhishagratna, K. An English Translation of the Sushruta Samhita, Based on Original Sanskrit Text, with a Full and Comprehensive Introd. in Additional Texts, Different Readings, Notes, Comparative Views, Index, Glossary And Plates (Varanasi, India, 1963).
Vagbhata. Ashtanga Hridayam with Commentaries of Arunadatta and of Hemadri Edited by Bhisagacharya Harisastri Paradkara Vaidya, Chaukhambha Orientalia. (2005).
Alwadhi, A. Triphala: A wonder drug of Ayurveda. Int. J. Health Sci. Res. 11, 314–316 (2021).
Article  Google Scholar 
Singh Shridevi Gothe Nadana, G. Smriti Chawala Pharmacological potential and phytochemical evaluation of Emblica officinalis—A wonder herb in Ayurveda. in Chemistry, Biological Activities and Therapeutic Applications of Medicinal Plants in Ayurvedaby (eds. Amalraj, A. & Kuttappan, S.) vol. 10 (Karthik Varma Royal Society of Chemistry, Cambridge, CB40WF, UK).
Vadde, R., Radhakrishnan, S., Reddivari, L. & Vanamala, J. K. P. Triphala extract suppresses proliferation and induces apoptosis in human colon cancer stem cells via suppressing c-Myc/cyclin D1 and elevation of Bax/Bcl-2 ratio. Biomed Res. Int. 2015, 1–12 (2015).
Article  Google Scholar 
Latha, R. C. R. & Daisy, P. Therapeutic potential of octyl gallate isolated from fruits of Terminalia bellerica in streptozotocin-induced diabetic rats. Pharm. Biol. 51, 798–805 (2013).
Article  CAS  PubMed  Google Scholar 
Eltimamy, M., Elshamarka, M., Aboelsaad, M., Sayed, M. & Moawad, H. Effects of alcoholic extract of Terminalia chebula dried fruit on blood biochemical profile in diabetic rats. J. Diabetes Metab. Disord. 21, 159–170 (2022).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Kumar, G. P. S., Arulselvan, P., Kumar, D. S. & Subramanian, S. P. Anti-diabetic activity of fruits of Terminalia chebula on streptozotocin induced diabetic rats. J. Health Sci. 52, 283–291 (2006).
Article  Google Scholar 
Huang, Y.-N. et al. Anti-hyperglycemic effect of chebulagic acid from the fruits of Terminalia chebula Retz. Int. J. Mol. Sci. 13, 6320–6333 (2012).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Shyni, G. L. et al. Chebulagic acid from Terminalia chebula enhances insulin mediated glucose uptake in 3T3-L1 adipocytes via PPARγ signaling pathway. Biofactors 40, 646–657 (2014).
Article  CAS  PubMed  Google Scholar 
Shanmuganathan, S. & Angayarkanni, N. Chebulagic acid Chebulinic acid and Gallic acid, the active principles of Triphala, inhibit TNFα induced pro-angiogenic and pro-inflammatory activities in retinal capillary endothelial cells by inhibiting p38, ERK and NFkB phosphorylation. Vascul. Pharmacol. 108, 23–35 (2018).
Article  CAS  PubMed  Google Scholar 
Aher, V. & Wahi, A. Immunomodulatory activity of alcohol extract of Terminalia chebula Retz combretaceae. Trop. J. Pharm. Res. 10 (2011)
Yang, M. H., Ali, Z., Khan, I. A. & Khan, S. I. Anti-inflammatory activity of constituents isolated from Terminalia chebula. Nat. Prod. Commun. 9, 965–968 (2014).
CAS  PubMed  Google Scholar 
Ou, L. et al. Terminalia chebula Retz. aqueous extract inhibits the Helicobacter pylori-induced inflammatory response by regulating the inflammasome signaling and ER-stress pathway. J. Ethnopharmacol. 320, 117428 (2024).
Article  CAS  PubMed  Google Scholar 
Dusi, S. & Department of Pharmaceutical Chemistry, Delhi Pharmaceutical Sciences and Research University, New Delhi – 110017. Crude extract of Terminalia chebula fruit effect on Gastro intestinal disorders using different animal models. ijpbms 01, (2021).
Chatterjee, A., Chatterjee, S. & Bandyopadhyay, S. K. H. pylori-induced gastric ulcer: Pathophysiology and herbal remedy. Int. J. Biol. Med. Res. 3, 1461–1465 (2012).
Google Scholar 
Mehra, D. & Vyas, N. Role of Terminalia chebula on gastrointestinal mucosa. Res. J. Pharm. Technol. 5, 1183–1186 (2012).
Google Scholar 
Feng, X.-H. et al. In vivo hepatoprotective activity and the underlying mechanism of chebulinic acid from Terminalia chebula fruit. Phytomedicine 83, 153479 (2021).
Article  CAS  PubMed  Google Scholar 
Gupta, R. & Singh, R. Hepatoprotective activities of triphala and its constituents. Int. J. Pharma Res. Rev. 4, 34–55 (2015).
CAS  Google Scholar 
Kannan, S. R. & Hopper, W. Antibacterial activity of Terminalia chebula Retz fruit extract. Afr. J. Microbiol. Res. 3, 180–184 (2009).
Google Scholar 
Dodke, P. C. & Pansare, T. A. Ayurvedic and modern aspect of Terminalia chebula Retz. Haritaki an overview. Int. J. Ayurvedic Herbal Med. 7, 2508–2517 (2017).
Google Scholar 
Mirunalini, S. & Krishnaveni, M. Therapeutic potential of Phyllanthus emblica (amla): the ayurvedic wonder. J. Basic Clin. Physiol. Pharmacol. 21, 93–105 (2010).
Article  PubMed  Google Scholar 
Fatima, N., Usharani, P. & Muralidhar. Effects of Phyllanthus emblica extract on endothelial dysfunction and biomarkers of oxidative stress in patients with type 2 diabetes mellitus: a randomized, double-blind, controlled study. Diabetes Metab. Syndr. Obes. 275 (2013) https://doi.org/10.2147/dmso.s46341.
Barbara, G. et al. Mucosal permeability and immune activation as potential therapeutic targets of probiotics in irritable bowel syndrome. J. Clin. Gastroenterol. 46, S52–S55 (2012).
Article  PubMed  Google Scholar 
Wasilewski, A., Zielińska, M., Storr, M. & Fichna, J. Beneficial effects of probiotics, prebiotics, synbiotics, and psychobiotics in inflammatory bowel disease. Inflamm. Bowel Dis. 21, 1674–1682 (2015).
Article  PubMed  Google Scholar 
Basturk, A. et al. Efficacy of synbiotic, probiotic, and prebiotic treatments for irritable bowel syndrome in children: A randomized controlled trial. Turk. J. Gastroenterol. 27, 439–443 (2020).
Article  Google Scholar 
Kumar, N. S., Nair, A. S., Nair, A. M. & Murali, M. Pharmacological and therapeutic effects of triphala-a literature review. J. Pharmacogn. Phytochem. JPP 23, 23–27 (2016).
Google Scholar 
Gupta, H., Kumar, S., Roy, S. & Gaud, R. S. Patent protection strategies. J. Pharm. Bioallied Sci. 2, 2 (2010).
Article  PubMed  PubMed Central  Google Scholar 
Kilpatrick, L. A. et al. Mo2030 neurobiology of psychological resilience in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients. Gastroenterology 148, S-774 (2015).
Article  Google Scholar 
Grundmann, O. Complementary and alternative medicines in irritable bowel syndrome: An integrative view. World J. Gastroenterol. 20, 346 (2014).
Article  PubMed  PubMed Central  Google Scholar 
Lauche, R. et al. Efficacy and safety of Ayurvedic herbs in diarrhoea-predominant irritable bowel syndrome: A randomised controlled crossover trial. Complement. Ther. Med. 26, 171–177 (2016).
Article  PubMed  Google Scholar 
Joos, S. et al. Use of complementary and alternative medicine in Germany—A survey of patients with inflammatory bowel disease. BMC Complement. Altern. Med. 6, (2006).
Subbannayya, Y. et al. Global metabolite profiling and network pharmacology of triphala identifies neuromodulatory receptor proteins as potential targets. J. Proteins Proteomics 9, 101–114 (2018).
CAS  Google Scholar 
Singh, S., Bala, E. K. L., Singh, D. S. S. & Kumari, E. A. Effect of processing conditions on solvent extraction of Amla (Emblica officinalis) seed oil. Pharma Innov. 8, 128–131 (2019).
Article  Google Scholar 
Glauser, G., Veyrat, N., Rochat, B., Wolfender, J.-L. & Turlings, T. C. J. Ultra-high pressure liquid chromatography–mass spectrometry for plant metabolomics: A systematic comparison of high-resolution quadrupole-time-of-flight and single stage Orbitrap mass spectrometers. J. Chromatogr. A 1292, 151–159 (2013).
Article  CAS  PubMed  Google Scholar 
Silva, E. et al. Untargeted metabolomics analysis by UHPLC-MS/MS of soybean plant in a compatible response to Phakopsora pachyrhizi infection. Metabolites 11, 179 (2021).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Siddaiah, C. et al. Metabolite profiling of Alangium salviifolium bark using advanced LC/MS and GC/Q-TOFTechnology. Cells 10, 1 (2020).
Article  PubMed  PubMed Central  Google Scholar 
Shah, S. M. Z. et al. Untargeted screening of plant metabolites based on data-independent and data-dependent acquisition modes using LC-ESI-QTOF-MS: Tribulus terrestris L. as a case study. Arab. J. Chem. 16, 104978 (2023).
Article  CAS  Google Scholar 
Chen, Y., Guo, J., Xing, S., Yu, H. & Huan, T. Global-scale metabolomic profiling of human hair for simultaneous monitoring of endogenous metabolome, short- and long-term exposome. Front. Chem. 9 (2021).
Pang, Z. et al. MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 49, W388–W396 (2021).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Nicola, G., Berthold, M. R., Hedrick, M. P. & Gilson, M. K. Connecting proteins with drug-like compounds: Open source drug discovery workflows with BindingDB and KNIME. Database (Oxford) 2015, bav087 (2015).
Djoumbou Feunang, Y. et al. ClassyFire: automated chemical classification with a comprehensive, computable taxonomy. J. Cheminform. 8 (2016).
Neveu, V. et al. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford) 2010, bap024–bap024 (2010).
Daina, A., Michielin, O. & Zoete, V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 47, W357–W364 (2019).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Ge, S. X., Jung, D. & Yao, R. ShinyGO: A graphical gene-set enrichment tool for animals and plants. Bioinformatics 36, 2628–2629 (2020).
Article  CAS  PubMed  Google Scholar 
Avula, B., Wang, Y.-H., Wang, M., Shen, Y.-H. & Khan, I. Simultaneous determination and characterization of tannins and triterpene saponins from the fruits of various species of Terminalia and phyllantus emblica using a UHPLC-UV-MS method: Application to triphala. Planta Med. 79, 181–188 (2013).
Article  CAS  PubMed  Google Scholar 
Kumar, S., Singh, A. & Kumar, B. Identification and characterization of phenolics and terpenoids from ethanolic extracts of Phyllanthus species by HPLC-ESI-QTOF-MS/MS. J. Pharm. Anal. 7, 214–222 (2017).
Article  PubMed  PubMed Central  Google Scholar 
Yang, B., Kortesniemi, M., Liu, P., Karonen, M. & Salminen, J.-P. Analysis of hydrolyzable tannins and other phenolic compounds in emblic leafflower (Phyllanthus emblica L.) fruits by high performance liquid chromatography–electrospray ionization mass spectrometry. J. Agric. Food Chem. 60, 8672–8683 (2012).
Article  CAS  PubMed  Google Scholar 
Dhanani, T., Shah, S. & Kumar, S. A validated high-performance liquid chromatography method for determination of tannin-related marker constituents Gallic acid, corilagin, chebulagic acid, ellagic acid and chebulinic acid in four Terminalia species from India. J. Chromatogr. Sci. 53, 625–632 (2015).
Article  CAS  PubMed  Google Scholar 
Youssef, A. M. M., Maaty, D. A. M. & Al-Saraireh, Y. M. Phytochemical Analysis and Profiling of Antioxidants and Anticancer Compounds from Tephrosia purpurea (L.) subsp. apollinea Family Fabaceae. Molecules 28, 3939 (2023).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Majeed, M., Bhat, B., Jadhav, A. N., Srivastava, J. S. & Nagabhushanam, K. Ascorbic acid and tannins from emblica officinalis Gaertn. Fruits—A revisit. J. Agric. Food Chem. 57, 220–225 (2009).
Article  CAS  PubMed  Google Scholar 
Choi, K.-O., Lee, D. H., Park, S. J., Im, D. & Hur, Y. Y. Correlations between phenolic composition and perceived astringency of wines. Appl. Sci. (Basel) 10, 8020 (2020).
Article  CAS  Google Scholar 
Zeb, A. Concept, mechanism, and applications of phenolic antioxidants in foods. J. Food Biochem. 44 (2020).
Meher, S. K., Panda, P., Das, B., Bhuyan, G. C. & Rath, K. K. Pharmacological Profile of Terminalia chebula Retz. and Willd. (Haritaki) in Ayurveda with evidences. Res. J. Pharmacol. Pharmacodyn. 10, 115 (2018).
Article  Google Scholar 
Garg, N. & Jain, A. Therapeutic and medicinal uses of vibhitaka: A review. Asian J. Sci. Technol. 4776–4781 (2017).
Timudom, T., Chaiyasut, C., Sivamaruthi, B. S., Tiampasook, P. & Nacapunchai, D. Anti-sebum efficacy of Phyllanthus emblica L. (emblica) toner on facial skin. Appl. Sci. (Basel) 10, 8193 (2020).
Article  CAS  Google Scholar 
Na Takuathung, M., Wongnoppavich, A., Jaijoy, K., Soonthornchareonnon, N. & Sireeratawong, S. Antioxidant and antitumorigenic activities of the standardized water extract from fruit of Terminalia chebula Retz. var. chebula. Nat. Prod. Commun. 18 (2023).
Suksaeree, J., Wunnakup, T. & Monton, C. Synergistic antioxidant activity of plant compositions contained in Chatuphalathika herbal recipe: Terminalia chebula Retz. var. chebula, Terminalia arjuna Wight and Arn., Terminalia bellirica (Gaertn.) Roxb., and Phyllanthus emblica L. Adv. Tradit. Med. 22, 547–556 (2022).
Hazra, B., Sarkar, R., Biswas, S. & Mandal, N. Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis. BMC Complement. Altern. Med. 10 (2010).
Khan, A. et al. Antioxidant activity and inhibitory effect of some commonly used medicinal plants against lipid per-oxidation in mice brain. Afr. J. Tradit. Complement. Altern. Med. 11, 83 (2014).
Article  PubMed  PubMed Central  Google Scholar 
Naik, G. H. et al. In vitro antioxidant studies and free radical reactions of triphala, an ayurvedic formulation and its constituents. Phytother. Res. 19, 582–586 (2005).
Article  CAS  PubMed  Google Scholar 
Chen, L., Cao, H. & Xiao, J. Polyphenols. In Polyphenols: Properties, Recovery, and Applications 45–67 (Elsevier, 2018).
Swallah, M. S., Fu, H., Sun, H., Affoh, R. & Yu, H. The impact of polyphenol on general nutrient metabolism in the monogastric gastrointestinal tract. J. Food Qual. 2020, 1–12 (2020).
Article  Google Scholar 
Scalbert, A., Morand, C., Manach, C. & Rémésy, C. Absorption and metabolism of polyphenols in the gut and impact on health. Biomed. Pharmacother. 56, 276–282 (2002).
Article  CAS  PubMed  Google Scholar 
Ray, S. K. & Mukherjee, S. Evolving interplay between dietary polyphenols and gut Microbiota—An emerging importance in healthcare. Front. Nutr. 8 (2021).
Manach, C., Williamson, G., Morand, C., Scalbert, A. & Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 81, 230S-242S (2005).
Article  CAS  PubMed  Google Scholar 
Aura, A.-M. Microbial metabolism of dietary phenolic compounds in the colon. Phytochem. Rev. 7, 407–429 (2008).
Article  CAS  Google Scholar 
Ma, G. & Chen, Y. Polyphenol supplementation benefits human health via gut microbiota: A systematic review via meta-analysis. J. Funct. Foods 66, 103829 (2020).
Article  CAS  Google Scholar 
Lipinski, C. A. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov. Today Technol. 1, 337–341 (2004).
Article  CAS  PubMed  Google Scholar 
Veber, D. F. et al. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45, 2615–2623 (2002).
Article  CAS  PubMed  Google Scholar 
Tripathi, D., Sunita & Bhattacharya, S. Effect of Emblica Officinalis (Amla) on blood brain barrier disruption and serum cytokines level following ischemia reperfusion injury in rats. Cerebrovascu. Dis. 44 (2017).
Youdim, K. A., Shukitt-Hale, B. & Joseph, J. A. Flavonoids and the brain: interactions at the blood–brain barrier and their physiological effects on the central nervous system. Free Radic. Biol. Med. 37, 1683–1693 (2004).
Article  CAS  PubMed  Google Scholar 
Takauji, Y. et al. Triphala, a formulation of traditional Ayurvedic medicine, shows protective effect against X-radiation in HeLa cells. J. Biosci. 41, 569–575 (2016).
Article  PubMed  Google Scholar 
Umapathy, D., Bhuvaneswarri, J., Jayamathi, G., Sadhana & Preethe Jayaraman, S. Free radical scavenging potentials of Triphala: A medicinal herb used in Indian Ayurvedic system of medicine. Drug Invention Today 12, 407–411 (2019).
Babu, D., Gurumurthy, P. & Sai Cherian, K. M. Antioxidant and free radical scavenging activity of triphala determined by using different in vitro models. J. Med. Plants Res. 2898–2905 (2013).
Prasad, S. & Srivastava, S. K. Oxidative stress and cancer: Chemopreventive and therapeutic role of Triphala. Antioxidants (Basel) 9, 72 (2020).
Chandran, U., Mehendale, N., Tillu, G. & Patwardhan, B. Network pharmacology of Ayurveda formulation triphala with special reference to anti-cancer property. Comb. Chem. High Throughput Screen. 18, 846–854 (2015).
Article  CAS  PubMed  Google Scholar 
Giudice, A., Arra, C. & Turco, M. C. Review of molecular mechanisms involved in the activation of the Nrf2-ARE signaling pathway by chemopreventive agents. In Methods in Molecular Biology 37–74 (Humana Press, Totowa, NJ, 2010).
Occhipinti, R. & Boron, W. F. Role of carbonic anhydrases and inhibitors in acid–base physiology: Insights from mathematical modeling. Int. J. Mol. Sci. 20, 3841 (2019).
Article  CAS  PubMed  PubMed Central  Google Scholar 
Sharker, M. R. et al. Molecular characterization of carbonic anhydrase II (CA II) and its potential involvement in regulating shell formation in the Pacific abalone, Haliotis discus hannai. Front. Mol. Biosci. 8 (2021).
Download references
Authors acknowledge Rural India Supporting Trust (RIST) for the faculty support.
These authors contributed equally: Santhosh N. Hegde and Lavanya Devi K.
The University of Trans-Disciplinary Health Sciences and Technology (TDU), 74/2, Post Attur via Yelahanka, Jarakabande Kaval, Bengaluru, 560 064, India
Santhosh N. Hegde, Lavanya Devi K, Mahima Choudhary, Nandita Menon & Gurmeet Singh
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
GS involved in designing study, initiating and heading the project. GS and LDK involved in data generation. SNH involved in data analysis, interpretation and drafting manuscript. MC and NM involved in sample collection and solvent extraction protocols. GS and LDK were involved in editing the manuscript and providing inputs.
Correspondence to Lavanya Devi K or Gurmeet Singh.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Reprints and permissions
Hegde, S.N., K, L.D., Choudhary, M. et al. A comprehensive metabolome profiling of Terminalia chebula, Terminalia bellerica, and Phyllanthus emblica to explore the medicinal potential of Triphala. Sci Rep 14, 31635 (2024). https://doi.org/10.1038/s41598-024-80544-6
Download citation
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-024-80544-6
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative
Advertisement
Scientific Reports (Sci Rep) ISSN 2045-2322 (online)
© 2024 Springer Nature Limited
Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

source

Posted on Leave a comment

Delaware Lottery Powerball, Play 3 Day winning numbers for Dec. 30, 2024 – The News Journal

The Delaware Lottery offers several draw games for those aiming to win big. Here’s a look at Monday, Dec. 30, 2024 results for each game:
09-19-33-38-39, Powerball: 01, Power Play: 3
Check Powerball payouts and previous drawings here.
Day: 6-7-0
Night: 8-9-0
Check Play 3 payouts and previous drawings here.
Day: 3-7-9-7
Night: 6-7-8-8
Check Play 4 payouts and previous drawings here.
07-11-14-15-31-35
Check Multi-Win Lotto payouts and previous drawings here.
07-14-18-25-47, Lucky Ball: 18
Check Lucky For Life payouts and previous drawings here.
12-16-38-45-50, Star Ball: 08, ASB: 02
Check Lotto America payouts and previous drawings here.
Day: 5-6-4-6-9
Night: 1-9-6-0-8
Check Play 5 payouts and previous drawings here.
Feeling lucky? Explore the latest lottery news & results
Check previous winning numbers and payouts at Delaware Lottery.
Fortunately for First State residents, the Delaware Lottery allows winners remain anonymous. Unlike many other states that require a prize be over a certain jackpot, Delawareans can remain anonymous no matter how much, or how little, they win.
Tickets are valid for up to one year past the drawing date for drawing game prizes or within one year of the announced end of sales for Instant Games, according to delottery.com.
Missed a draw? Peek at the past week’s winning numbers.
This results page was generated automatically using information from TinBu and a template written and reviewed by a Delaware Online digital operations manager. You can send feedback using this form.

source

Posted on Leave a comment

Cleveland Mayor Justin Bibb tells Browns city will invoke 'Modell Law' in effort to keep team from leaving downtown – WKYC.com

CLEVELAND — As 2024 comes to a close, the war between the Browns and the city of Cleveland rages on.
In a letter obtained by 3News Monday, Mayor Justin Bibb told Browns owners Jimmy and Dee Haslam the city intends to invoke the so-called “Modell Law” in an effort to keep the club from leaving downtown in favor of a new domed stadium in nearby Brook Park. The letter cites the statue first passed by the Ohio General Assembly in 1996, a year after Art Modell moved the original Browns from Cleveland to Baltimore.
Bibb first announced in September that the Browns were moving ahead with plans for a Brook Park facility rather than a new or renovated one in Cleveland proper, an announcement the organization confirmed shortly thereafter. Law Director Mark Griffin told 3News that month that the city would “move forward” with using the Modell Law to stop the team from leaving, only for the team to preempt them with their own federal lawsuit seeking to have the entire law declared unconstitutional.
The entire statute from the Ohio Revised Code reads as follows:
“No owner of a professional sports team that uses a tax-supported facility for most of its home games and receives financial assistance from the state or a political subdivision thereof shall cease playing most of its home games at the facility and begin playing most of its home games elsewhere unless the owner either:
To Bibb and others sharing his position, the law applies just the same regardless if a team is merely moving one town over or to an entirely different state. As the Browns have played in the “tax-supported facility” that is Huntington Bank Field since returning to the NFL in 1999, the city believes local interests should now be afforded the opportunity to purchase the team rather than see the club move to Brook Park.
“Yet, to date, the Browns have not provided the City or others with the opportunity to purchase the team, as required by law,” Bibb wrote. “And if that opportunity were provided, the City intends to take a leadership role in assembling an ‘individual or group of individuals who reside in the area’ in purchasing the team.”
The mayor concluded his letter by giving the Haslams until Jan. 9 to respond to his demands. Should they refuse, “the City intends to take appropriate legal action.”
You can read Mayor Bibb’s entire letter to the Browns and Haslams below.
With the Browns’ lease of Huntington Bank Field along Lake Erie expiring in 2028, the Haslams announced earlier this year that they had narrowed their future stadium options down to either renovating the current facility or building a brand new one. On Aug. 1, Bibb and the city unveiled a $461 funding proposal towards a $1 billion revamp of the existing site, but the Haslams instead opted for the Brook Park option, a $3.6 billion project (when including surrounding development) that would cost taxpayers more than $1 billion.
“A solution like this will be transformative not only for Cleveland and Northeast Ohio, but also the entire state of Ohio from the resulting events, tourism, and job creation,” the Haslams said at the time. “Additionally, moving the current stadium will allow the city and region’s collective vision for the Cleveland lakefront to be optimally realized, and downtown will benefit from the major events the Brook Park dome brings to the region.”
The owners also turned down a proposal to build a new stadium on the existing site of Burke Lakefront Airport, calling it “cost prohibitive and not feasible, especially with no certainty regarding potential timing of closure of the Airport.” The Brook Park stadium would be placed on 176 acres of land near Cleveland Hopkins International Airport that the Haslams were given the option to purchase.
Cuyahoga County Executive Chris Ronayne has blasted the Brook Park proposal, vowing not to give the Browns a dime of taxpayer money unless they remain in Cleveland. State leaders like Gov. Mike DeWine have been more neutral on the issue, but following the team’s move to have the Modell Law thrown out, Attorney General Dave Yost moved to intervene on the city’s behalf, a motion that has since been granted. Bibb also copied Yost in his letter to the Haslams on Monday.
“People who live in Cleveland are part of the state of Ohio too, and they’re the folks that are intended to be protected by this (law),” Yost told 3News’ Candice Hare last week when asked about the lawsuit. “There is a lot of public interest here, and I think that we will see a lot of interesting arguments made over the coming months.”
The Modell Law has technically never been tested in court and has so far been officially invoked only once, when in 2018 the state sued Columbus Crew owner Anthony Precourt to keep him from moving the Major League Soccer club to Austin, Texas. That case ended up being dropped before trial when Precourt was awarded an Austin expansion team in exchange for agreeing to sell the Crew to an ownership group led by (ironically) the Haslams.
The city of Cleveland has yet to officially respond in court to the Browns’ lawsuit. The current deadline for them to do so is Jan. 15, although that date has already been pushed back twice.
3News’ Dave DeNatale contributed to this report
Next up in 5
Example video title will go here for this video
Next up in 5
Example video title will go here for this video

In Other News
Notifications can be turned off anytime in the browser settings.

source