PHARMACOLOGY OF TRIPHALA WITH SPECIAL FOCUS ON THEIR CHEMICAL CONSTITUENTS
DOI:
https://doi.org/10.22159/ijap.2022.v14ti.32%20Keywords:
Triphala, Terminalia chebula, Terminalia bellerica, Phyllanthus embilica, Anticancer, Molecular mechanism, Bioactive compoundAbstract
This review is based on Ayurvedic texts and online scientific databases like PubMed, Google Scholar, Science Direct to study use of scientific research methods in ayurvedic formulation Triphala. The following keywords were used: Triphala, terminalia chebula, terminalia bellerica, Phyllanthus embilica, chemical constituents, gallic acid, chebulinic acid, and molecular docking to write this review. Studies about Triphala and their individual drugs as well as their active compounds were concentrated upon. There are many research works being conducted on Triphala and its therapeutic effect. Yet, the need to develop these works to a fully utilisable form for the medical community is not achieved. This review concludes that Triphala is a treasure that needs to be further evaluated for the betterment of health globally.
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Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016 Apr 29;21(5):559. doi: 10.3390/molecules21050559, PMID 27136524, PMCID PMC6273146.
Puranik A, Patwardhan B. Ayurveda and metabolic diseases: the whole is greater than the sum of the parts. 2012. p. 443-56. doi: 10.1016/B978-0-12-385083-6.00035-8.
Shastri PP, Sharangadhara Samhita of Sharangadhara, Sanskrit text with Adhamalla’s Dipika commentary and Kashiram’s Gudartha-Dipika commentary, Madhyamakhanda, Ch 6; 2020. p. 179.
Sharma PV. Charaka samhita part 2. Chaukambha Orientalia Varanasi. 2011;24:1.3/41-42.
Vahata SAN. Ashtavaidyan vaidyamadhom cheriya narayanan namboodiri math ashtanga hridaya samhitha with sasilekha commentary of Indu. 2nd ed. Varanasi, India: Chowkambha Krishnadas Academy; 2019. p. 513.
Belapurkar P, Goyal P, Tiwari Barua P. Immunomodulatory effects of triphala and its individual constituents: a review. Indian J Pharm Sci. 2014 Nov-Dec;76(6):467-75. PMID 25593379, PMCID PMC4293677.
Peterson CT, Pourang A, Dhaliwal S, Kohn JN, Uchitel S, Singh H. Modulatory effects of Triphala and Manjistha dietary supplementation on human gut microbiota: A double-blind, randomized, placebo-controlled pilot study. J Altern Complement Med. 2020 Nov;26(11):1015-24. doi: 10.1089/acm.2020.0148. PMID 32955913.
Wang W, Liu T, Yang L, Ma Y, Dou F, Shi L. Study on the multi-targets mechanism of triphala on cardio-cerebral vascular diseases based on network pharmacology. Biomed Pharmacother. 2019 Aug;116:108994. doi: 10.1016/j.biopha.2019.108994. PMID 31112872.
Shi Y, Sahu RP, Srivastava SK. Triphala inhibits both in vitro and in vivo xenograft growth of pancreatic tumor cells by inducing apoptosis. BMC Cancer. 2008 Oct 10;8:294. doi: 10.1186/1471-2407-8-294, PMID 18847491, PMCID PMC2576337.
Nariya M, Shukla V, Jain S, Ravishankar B. Comparison of enteroprotective efficacy of triphala formulations (Indian Herbal Drug) on methotrexate-induced small intestinal damage in rats. Phytother Res. 2009 Aug;23(8):1092-8. doi: 10.1002/ptr.2744, PMID 19170156.
Mashyal P, Bhargav H, Raghuram N. Safety and usefulness of Laghu shankha prakshalana in patients with essential hypertension: A self controlled clinical study. J Ayurveda Integr Med. 2014 Oct-Dec;5(4):227-35. doi: 10.4103/0975-9476.131724, PMID 25624697, PMCID PMC4296435.
Rudrapal M, Celik I, Khan J, Ansari MA, Alomary MN, Yadav R. Identification of bioactive molecules from Triphala (Ayurvedic herbal formulation) as potential inhibitors of SARS-CoV-2 main protease (Mpro) through computational investigations. J King Saud Univ Sci. 2022 Apr;34(3):101826. doi: 10.1016/j.jksus.2022.101826. PMID 35035181, PMCID PMC8744360.
Jagetia GC, Baliga MS, Malagi KJ, Sethukumar Kamath M. The evaluation of the radioprotective effect of Triphala (an ayurvedic rejuvenating drug) in the mice exposed to gamma-radiation. Phytomedicine. 2002 Mar;9(2):99-108. doi: 10.1078/0944-7113-00095, PMID 11995956.
Mohanasundaram S, Rangarajan N, Sampath V, Porkodi K, Pennarasi M. GC-MS and HPLC analysis of antiglycogenolytic and glycogenic compounds in kaempferol 3-O–gentiobioside containing Senna alata L. leaves in experimental rats. Translational. Metab Syndr Research. 2021;4:10-7.
Vemuri PK, Dronavalli L, Nayakudugari P, Kunta A, Challagulla R. Phytochemical analysis and biochemical characterization f terminalia chebula extracts for its medicinal use. Biomed Pharmacol J. 2019;12(3):1525-9. doi: 10.13005/bpj/1783.
Wu L, Zhang Q, Liang W, Ma Y, Niu L, Zhang L. Phytochemical analysis using UPLC-MSn combined with network pharmacology approaches to explore the biomarkers for the quality control of the anticancer tannin fraction of Phyllanthus emblica L. habitat in Nepal. Evid Based Complement Alternat Med. 2021. doi: 10.1155/2021/6623791, PMID 33833816.
Li K, Han X, Li R, Xu Z, Pan T, Liu J. Composition, antivirulence activity, and active property distribution of the fruit of terminalia chebula retz. J Food Sci. 2019 Jul;84(7):1721-9. doi: 10.1111/1750-3841.14655. PMID 31206192.
Zhang XR, Zhu HT, Wang D, Yang Z, Yang CR, Zhang YJ, Termitomenins AE. Five new lignans from Terminalia chebula var. tomentella (Kurz) C. B. Clarke Fitoterapia. 2020;143:104571. doi: 10.1016/j.fitote.2020.104571. PMID 32209392.
Kumar N, Khurana SM. Phytochemistry and medicinal potential of the Terminalia bellirica Roxb. (Bahera). Indian J Nat Prod Resour. 2018;9(2):97-107.
Makihara H, Koike Y, Ohta M, Horiguchi Babamoto E, Tsubata M, Kinoshita K. Gallic acid, the active ingredient of terminalia bellirica, enhances adipocyte differentiation and adiponectin secretion. Biol Pharm Bull. 2016;39(7):1137-43. doi: 10.1248/bpb.b16-00064. PMID 27374289.
Yang F, Yaseen A, Chen B, Li F, Wang L, Hu W. Chemical constituents from the fruits of Phyllanthus emblica L. Biochem Syst Ecol. 2020;92:104122. doi: 10.1016/j.bse.2020.104122.
Pawar V, Lahorkar P, Anantha Narayana DB. Development of a RP-HPLC method for analysis of Triphala Curna and its applicability to test variations in Triphala Curna preparations. Indian J Pharm Sci. 2009 Jul;71(4):382-6. doi: 10.4103/0250-474X.57286, PMID 20502543, PMCID PMC2865809.
Mohanasundaram S, Doss VA, Maddisetty P, Magesh R, Sivakumar K, Subathra M. Pharmacological analysis of hydroethanolic extract of Senna alata (L.) for in vitro free radical scavenging and cytotoxic activities against Hep G2 cancer cell line. Pak J Pharm Sci. 2019;32(3):931-4.
Pandurangan AK, Mohebali N, Esa NM, Looi CY, Ismail S, Saadatdoust Z. Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: possible mechanisms. Int Immunopharmacol. 2015 Oct;28(2):1034-43. doi: 10.1016/j.intimp.2015.08.019. PMID 26319951.
Li Y, Zhang L, Wang X, Wu W, Qin R. Effect of syringic acid on antioxidant biomarkers and associated inflammatory markers in mice model of asthma. Drug Dev Res. 2019 Mar;80(2):253-61. doi: 10.1002/ddr.21487. PMID 30474283.
Lin Y, Luo T, Weng A, Huang X, Yao Y, Fu Z. Gallic acid alleviates gouty arthritis by inhibiting NLRP3 inflammasome activation and pyroptosis through enhancing Nrf2 signaling. Front Immunol. 2020 Dec 7;11:580593. doi: 10.3389/fimmu.2020.580593, PMID 33365024, PMCID PMC7750458.
Variya BC, Bakrania AK, Madan P, Patel SS. Acute and 28-days repeated dose sub-acute toxicity study of gallic acid in albino mice. Regul Toxicol Pharmacol. 2019 Feb;101:71-8. doi: 10.1016/j.yrtph.2018.11.010. PMID 30465803.
Lu K, Basu S. The natural compound chebulagic acid inhibits vascular endothelial growth factor a mediated regulation of endothelial cell functions. Sci Rep. 2015 Apr 10;5:9642. doi: 10.1038/srep09642, PMID 25859636, PMCID PMC4819393.
Vasu G, Sundaram R, Muthu K. Chebulagic acid attenuates HFD/streptozotocin induced impaired glucose metabolism and insulin resistance via up regulations of PPAR γ and GLUT 4 in type 2 diabetic rats. Toxicol Mech Methods. 2022 Mar;32(3):159-70. doi: 10.1080/15376516.2021.1976333. PMID 34470562.
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. Vasc Pharmacol. 2018 Sep;108:23-35. doi: 10.1016/j.vph.2018.04.005. PMID 29678603.
Yang Y, Xiu J, Liu J, Zhang L, Li X, Xu Y. Chebulagic acid, a hydrolyzable tannin, exhibited antiviral activity in vitro and in vivo against human enterovirus 71. Int J Mol Sci. 2013 May 3;14(5):9618-27. doi: 10.3390/ijms14059618. Erratum in: Int J Mol Sci. PMID: 23644889, PMC3676802.
Mohanasundaram S, Ramirez Asis E, Quispe Talla A, Bhatt MW, Shabaz M. Experimental replacement of hops by mango in beer: production and comparison of total phenolics, flavonoids, minerals, carbohydrates, proteins and toxic substances. Int J Syst Assur Eng Manag. 2022;13(S1):132-45. doi: 10.1007/s13198-021-01308-3.
Kim J, Ahn D, Chung SJ. Chebulinic acid suppresses adipogenesis in 3T3-L1 preadipocytes by inhibiting PPP1CB activity. Int J Mol Sci. 2022 Jan 13;23(2):865. doi: 10.3390/ijms23020865, PMID 35055051, PMCID PMC8775935.
Wang M, Li Y, Hu X. Chebulinic acid derived from triphala is a promising antitumour agent in human colorectal carcinoma cell lines. BMC Complement Altern Med. 2018 Dec 27;18(1):342. doi: 10.1186/s12906-018-2412-5, PMID 30587184, PMCID PMC6307174.
Srinivasulu C, Ramgopal M, Ramanjaneyulu G, Anuradha CM, Suresh Kumar C. Syringic acid (SA)‒ a review of its occurrence, biosynthesis, pharmacological and industrial importance. Biomed Pharmacother. 2018 Dec;108:547-57. doi: 10.1016/j.biopha.2018.09.069. PMID 30243088.
Mohanasundaram S, Rangarajan N, Sampath V, Porkodi K, Dass Prakash MV, Monicka N. GC-MS identification of anti-inflammatory and anticancer metabolites in edible milky white mushroom (Calocybe indica) against human breast cancer (MCF-7) cells. Res J Pharm Technol. 2021;14(8):4300-6.
Rangarajan N, Sampath, Dass Prakash M, Mohanasundaram S. UV Spectrophotometry and FTIR analysis of phenolic compounds with antioxidant potentials in glycyrrhiza glabra and zingiber officinale. IJRPS 2021;12(1):877-83. doi: 10.26452/ijrps.v12i1.4215.
Robles H. Tannic acid. Encyclopedia of toxicology. 3rd ed. Wexler P, editor. Academic Press; 2014. p. 474-5. doi: 10.1016/B978-0-12-386454-3.00542-X.
Barium sulfate. Meyler’s side effects of drugs. 16th ed Aronson JK, editor. Elsevier, 2016. p. 827-9. doi: 10.1016/B978-0-444-53717-1.00350-4.
Chun JH, Henckel MM, Knaub LA, Hull SE, Pott GB, Walker LA. (-)-Epicatechin improves vasoreactivity and mitochondrial respiration in thermoneutral-housed wistar rat vasculature. Nutrients. 2022 Mar 5;14(5):1097. doi: 10.3390/nu14051097, PMID 35268072, PMCID PMC8912787.
Rangarajan N, Sangeetha R, Mohanasundaram S, Sampath, Porkodi K, Dass Prakash MV. Additive inhibitory effect of the peels of Citrus limon and Citrus sinensis against amylase and glucosidase activity. IJRPS 2020;11(4):6876-80. doi: 10.26452/ijrps.v11i4.3661.
Zhang M, Vervoort L, Moalin M, Mommers A, Douny C, den Hartog GJM. The chemical reactivity of (-)-epicatechin quinone mainly resides in its B-ring. Free Radic Biol Med. 2018 Aug 20;124:31-9. doi: 10.1016/j.freeradbiomed.2018.05.087. PMID 29859347.
Wang Q, Sivakumar K, Mohanasundaram S. Impacts of extrusion processing on food nutritional components. Int J Syst Assur Eng Manag. 2022;13(S1):364-74. doi: 10.1007/s13198-021-01422-2.
Chowdhury HU, Adnan MD, Oh KK, Cho DH. Decrypting molecular mechanism insight of phyllanthus emblica L. fruit in the treatment of type 2 diabetes mellitus by network pharmacology, Phytomedicine. Plus. 2021;1(4):100144. doi: 10.1016/j.phyplu.2021.100144.
Bansode TS, Salalkar BK. Strategies in the design of antidiabetic drugs from Terminalia chebula using in silico and in vitro approach. Micromedicine. 2016;4(2):60-7. doi: 10.5281/zenodo.167869.
Rajmohamed MA, Natarajan S, Palanisamy P, Abdulkader AM, Govindaraju A. Antioxidant and cholinesterase inhibitory activities of ethyl acetate extract of terminalia chebula: cell-free in vitro and in silico studies. Pharmacogn Mag. 2017;13(Suppl 3):S437-45. doi: 10.4103/pm.pm_57_17. PMID 29142396.
Fei LC, Gaurav A, Al-Nema M. In silico investigations on the probable macromolecular drug targets involved in the anti-schizophrenia activity of terminalia bellerica. Lett Org Chem. 2021;19(1):83-92. doi: 10.2174/1570178618666210315152721.
Meghana Y, Srikanth J. Ex vivo, in vitro and in silico neuroprotective activity of selected traditional medicinal plants-a reverse pharmacological approach. Int J Pharm Res. 2021.
Majumder M, Khanam T, Rahaman M, Rahimul M, Hossain TN, Chakrabarty N. Anticancer potential of isolated phytochemicals from terminalia bellerica against breast cancer: in silico molecular docking approach. World J Pharm Res. 2017 Feb 19;6(4):1763-71.
Khan SL, Siddiqui FA, Shaikh MS, Nema NV, Shaikh AA. Discovery of potential inhibitors of the receptor-binding domain (RBD) of pandemic disease-causing SARS-CoV-2 spike glycoprotein from triphala through molecular docking. Current Chinese Chemistry. 2021;2(1). doi: 10.2174/2666001601666210322121802.
Unnisa A, Khan SL, Sheikh FAH, Mahefooz S, Kazi AA, Siddiqui FA. In silico inhibitory potential of triphala constituents against cytochrome P450 2E1 for the prevention of thioacetamide-induced hepatotoxicity. J Pharm Res Int. 2021:367-75. doi: 10.9734/jpri/2021/v33i43A32499.
Abhinand CS, Athira PA, Soumya SJ, Sudhakaran PR. Multiple targets directed multiple ligands: an in silico and in vitro approach to evaluating the effect of triphala on angiogenesis. Biomolecules. 2020 Jan 23;10(2):177. doi: 10.3390/biom10020177, PMID 31979409, PMCID PMC7072423.
Chandran U, Mehendale N, Patil S, Chaguturu R, Patwardhan B. Network pharmacology. Innov Approaches Drug Discov. 2017:127-64. doi: 10.1016/B978-0-12-801814-9.00005-2, PMCID PMC7148629.
Zhao Y, Wang M, Tsering J, Li H, Li S, Li Y. An integrated study on the antitumor effect and mechanism of Triphala against gynecological cancers based on network pharmacological prediction and in vitro experimental validation. Integr Cancer Ther. 2018;17(3):894-901. doi: 10.1177/1534735418774410, PMID 29742928.
Murthy Malladi S, Sastry Yarla N, Kumar Pandey D. Enzyme inhibition activity both in vitro and in silico screening of triphala plant extracts on phospholipase A2. Int J Pharm Investig. 2021;11(2):158-64, doi: 10.5530/ijpi.2021.2.29.
Chainani SH, Siddana S, Reddy C, Manjunathappa TH, Manjunath M, Rudraswamy S. Antiplaque and antigingivitis efficacy of triphala and chlorhexidine mouthrinse among schoolchildren– a cross-over, double-blind, randomised controlled trial. Oral Health Prev Dent. 2014;12(3):209-17. doi: 10.3290/j.ohpd.a32674. PMID 25197734.
Srinagesh J, Pushpanjali K. Assessment of antibacterial efficacy of triphala against mutans streptococci: a randomised control trial. Oral Health Prev Dent. 2011;9(4):387-93. PMID 22238738.
Pradeep AR, Suke DK, Martande SS, Singh SP, Nagpal K, Naik SB. Triphala, a new herbal mouthwash for the treatment of gingivitis: a randomized controlled clinical trial. J Periodontol. 2016 Nov;87(11):1352-9. doi: 10.1902/jop.2016.130406. Epub 2016 Jul 21. PMID: 27442086.
Victor Arokia Doss VA, Prasad Maddisetty P, Mohanasundaram S. Biological active compounds with various medicinal values of Strychnos nux-vomica–a pharmacological summary. J Global Trends Pharm Sci. 2016;7(1):3044-7.
Ning W, Li S, Tsering J, Ma Y, Li H, Ma Y, Ogbuehi AC, Pan H, Li H, Hu S, Liu X, Deng Y, Zhang J, Hu X. Protective effect of riphala against oxidative stress-induced neurotoxicity. BiomMed Res Int. 2021 Apr 7;2021:6674988. doi: 10.1155/2021/6674988, PMID: 33898626, PMCID: PMC8052154.
Sahragard A, Alavi Z, Abolhassanzadeh Z, Moein M, Mohammadi Bardbori A, Omidi M, Zarshenas MM. Assessment of the cytotoxic activity of riphala: A semisolid traditional formulation on HepG2 cancer cell line. BiomMed Res Int. 2021 Aug 11;2021:6689568. doi: 10.1155/2021/6689568, PMID: 34471640, PMCID: PMC8405286.
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