Skip to main content

Intervention of Ayurvedic drug Tinospora cordifolia attenuates the metabolic alterations in hypertriglyceridemia: a pilot clinical trial



Hypertriglyceridemia (HG) is an independent risk factor with more prevalence than hypercholesterolemia and its attributes to cardiovascular disease (CVD) and pancreatitis. Hence, it becomes imperative to search for new triglyceride (TG) lowering agents. Tinospora cordifolia (TC) is a well-known Ayurvedic drug and a rich source of protoberberine alkaloids hence can contribute to TG lowering without side effects. Hence, to explore the therapeutic efficacy of T. cordifolia and its effects on biochemistry and metabolome in the patients of hyper-triglyceridemia, clinical trials were conducted.


Patients (n = 24) with hypertriglyceridemia were randomized into two groups to receive T. cordifolia extract (TCE) (3.0 g/per day) and metformin (850 mg/day) for 14 days having >300 mg/dl triglyceride level and cholesterol in the range of 130–230 mg/dl. Lipid profiles of blood samples were analyzed. Urine samples were subjected to HPLC-QTOF-MS to quantify oxidative damage and abnormal metabolic regulation.


Intervention with TCE reduced the triglyceride, LDL, and VLDL levels to 380.45 ± 17.44, 133.25 ± 3.18, and 31.85 ± 5.88 mg/dL and increased the HDL to 47.50 ± 9.05 mg/dL significantly (p < 0.05) in the HG patients after 14 days treatment. TCE dosage potently suppressed the inflammatory and oxidative stress marker’s i.e. levels of isoprostanes significantly (p < 0.01). Qualitative metabolomics approach i.e. PCA and PLS-DA showed significant alterations (p < 0.05) in the levels of 40 metabolites in the urine samples from different groups.


TCE administration depleted the levels of markers of HG i.e. VLDL, TG, and LDL significantly. Metabolomics studies established that the anti-HG activity of TCE was due to its antioxidative potential and modulation of the biopterin, butanoate, amino acid, and vitamin metabolism.

Clinical trials registry

India (CTRI) registration no. CTRI- 2016-08-007187.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6





Peroxisome proliferator-activated receptors


Partial least-squares-discriminant analysis






Rapid Resolution Liquid Chromatography


Electrospray Ionization Quadrupole Time of Flight Mass Spectrometry


Tinospora cordifolia Extract


Aspartate transaminase


Alanine transaminase


Retention time


  1. Upadhyay A, Kumar K, Kumar A, Mishra H. Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) -validation of the Ayurvedic pharmacology through experimental and clinical studies. Int J Ayurveda Res. 2010:112.

  2. Pathak P, Vyas M, Vyas H, Naria M. Rasayana effect of Guduchi Churna on the life span of Drosophila melanogaster. AYU (An Int Q J Res Ayurveda). 2016;37:67.

    Article  Google Scholar 

  3. Haque MA, Jantan I, Abbas Bukhari SN. Tinospora species: an overview of their modulating effects on the immune system. J Ethnopharmacol. 2017:67–85.

  4. Sannegowda KM, Venkatesha SH, Moudgil KD. Tinospora cordifolia inhibits autoimmune arthritis by regulating key immune mediators of inflammation and bone damage. Int J Immunopathol Pharmacol. 2015;28(4):521–31.

    CAS  Article  Google Scholar 

  5. Sharma B, Dabur R. Protective effects of Tinospora cordifolia on hepatic and gastrointestinal toxicity induced by chronic and moderate alcoholism. Alcohol Alcohol. 2015;51:1–10.

    Article  Google Scholar 

  6. Parveen A, Wang YH, Fantoukh O, Alhusban M, Raman V, Ali Z, et al. Development of a chemical fingerprint as a tool to distinguish closely related Tinospora species and quantitation of marker compounds. J Pharm Biomed Anal. 2020;178:112894.

    CAS  Article  Google Scholar 

  7. Bajpai V, Kumar S, Singh A, Bano N, Pathak M, Kumar N, et al. Metabolic fingerprinting of dioecious Tinospora cordifolia (Thunb) Miers stem using DART TOF MS and differential pharmacological efficacy of its male and female plants. Ind Crop Prod. 2017;101:46–53.

    CAS  Article  Google Scholar 

  8. Bhalerao BM, Vishwakarma KS, Maheshwari VL. Tinospora cordifolia (Willd.) Miers ex Hook.f. & Thoms.-plant tissue culture and comparative chemo-profiling study as a function of different supporting trees. Indian J Nat Prod Resour. 2013;4:380–6.

    CAS  Google Scholar 

  9. Tiwari M, Dwivedi UN, Kakkar P. Tinospora cordifolia extract modulates COX-2, iNOS, ICAM-1, pro-inflammatory cytokines and redox status in murine model of asthma. J Ethnopharmacol. 2014;153(2):326–37.

    CAS  Article  Google Scholar 

  10. Reddy SS, Ramatholisamma P, Karuna R, Saralakumari D. Preventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress in male Wistar rats. Food Chem Toxicol. 2009;47(9):2224–9.

    CAS  Article  Google Scholar 

  11. Singh H, Sharma AK, Gupta M, Singh AP, Kaur G. Tinospora cordifolia attenuates high fat diet-induced obesity and associated hepatic and renal dysfunctions in rats. PharmaNutrition. 2020;26:100189.

    Article  Google Scholar 

  12. Baskaran R, Priya LB, Kumar VS, Padma VV. Tinospora cordifolia extract prevents cadmium-induced oxidative stress and hepatotoxicity in experimental rats. J Ayurveda Integr Med. 2018;9(4):252–7.

    Article  Google Scholar 

  13. Kosaraju J, Chinni S, Roy PD, Kannan E, Antony AS, Kumar MS. Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced parkinsonism. Indian J Pharmacol. 2014;46(2):176–80.

    Article  Google Scholar 

  14. Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 1999;13(4):275–91.

    CAS  Article  Google Scholar 

  15. Kuchay MS, Farooqui KJ, Bano T, Khandelwal M, Gill H, Mithal A. Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: Case series and literature review. Arch Endocrinol Metab. 2017:198–201.

  16. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11–22.

    CAS  Article  Google Scholar 

  17. Chu AHY, Moy FM. Joint association of sitting time and physical activity with metabolic risk factors among middle-aged Malays in a developing country: a cross-sectional study. PLoS One. 2013;8.

  18. Hasani-Ranjbar S, Jouyandeh Z, Abdollahi M. A systematic review of anti-obesity medicinal plants – an update. J Diabetes Metab Disord. 2013.

  19. Shirolkar A, Gahlaut A, Hooda V, Dabur R. Phytochemical composition changes in untreated stem juice of Tinospora cordifolia (W) Mier during refrigerated storage. J Pharm Res. 2013;7:1–6.

    CAS  Google Scholar 

  20. Chernushevich IV, Loboda AV, Thomson BA. An introduction to quadrupole-time-of-flight mass spectrometry. J Mass Spectrom. 2001;36:849–65.

    CAS  Article  Google Scholar 

  21. Shirolkar A, Sharma B, Lata S, Dabur R. Guduchi Sawras (Tinospora cordifolia): an Ayurvedic drug treatment modulates the impaired lipid metabolism in alcoholics through dopaminergic neurotransmission and anti-oxidant defense system. Biomed Pharmacother. 2016;83:1265–77.

    Article  Google Scholar 

  22. Aoyagi K. Inhibition of arginine synthesis by urea: a mechanism for arginine deficiency in renal failure which leads to increased hydroxyl radical generation. InGuanidino Compounds in Biology and Medicine. 2003:11–5.

  23. Pacana T, Cazanave S, Verdianelli A, Patel V, Min HK, Mirshahi F, et al. Dysregulated hepatic methionine metabolism drives homocysteine elevation in diet-induced nonalcoholic fatty liver disease. PLoS One. 2015;10:e0136822.

    Article  Google Scholar 

  24. Singh R, Devi S, Gollen R. Role of free radical in atherosclerosis, diabetes and dyslipidaemia: larger-than-life. Diabetes Metab Res Rev. 2015;31(2):113–26.

    CAS  Article  Google Scholar 

  25. Radosinska J, Bacova B, Bernatova I, Navarova J, Zhukovska A, Shysh A, et al. Myocardial NOS activity and connexin-43 expression in untreated and omega-3 fatty acids-treated spontaneously hypertensive and hereditary hypertriglyceridemic rats. Mol Cell Biochem. 2011;347(1–2):163–73.

    CAS  Article  Google Scholar 

  26. Tejero J, Stuehr D. Tetrahydrobiopterin in nitric oxide synthase. IUBMB Life. 2013;65(4):358–65.

    CAS  Article  Google Scholar 

  27. Mortensen PB. Formation and degradation of dicarboxylic acids in relation to alterations in fatty acid oxidation in rats. Biochim Biophys Acta (BBA)/Lipids Lipid Metab. 1992;1124:71–9.

    CAS  Article  Google Scholar 

  28. Zhang W, He H, Wang H, Wang S, Li X, Liu Y, et al. Activation of transsulfuration pathway by salvianolic acid a treatment: a homocysteine-lowering approach with beneficial effects on redox homeostasis in high-fat diet-induced hyperlipidemic rats. Nutr Metab. 2013;10(1):1–1.

    Article  Google Scholar 

  29. Montuschi P, Barnes PJ, Roberts LJ. Isoprostanes: markers and mediators of oxidative stress. FASEB J [Internet]. 2004;18:1791–800.

    CAS  Article  Google Scholar 

  30. Milne GL, Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers. 2005:10–23.

  31. van’t Erve TJ, Kadiiska MB, London SJ, Mason RP. Classifying oxidative stress by F2-isoprostane levels across human diseases: a meta-analysis. Redox Biol. 2017;12:582–99.

    Article  Google Scholar 

  32. Bifari F, Nisoli E. Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view. Br J Pharmacol. 2017:1366–77.

  33. Neinast MD, Jang C, Hui S, Murashige DS, Chu Q, Morscher RJ, et al. Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids. Cell Metab. 2019;29:417–29.

    CAS  Article  Google Scholar 

  34. Arany Z, Neinast M. Branched chain amino acids in metabolic disease. Curr Diab Rep. 2018;18(10):76.

    Article  Google Scholar 

  35. Kametani T, Koshida H, Nagaoka T, Miyakoshi H. Hypertriglyceridemia is an independent risk factor for development of impaired fasting glucose and diabetes mellitus: a 9-year longitudinal study in Japanese. Inter Med. 2002;41:516–21.

    Article  Google Scholar 

  36. Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. The hypertriglyceridemia is associated with isolated impaired glucose tolerance in subjects without insulin resistance. Endocr Res. 2015;40:70–3.

    Article  Google Scholar 

  37. Mook-Kanamori DO, Römisch-Margl W, Kastenmüller G, Prehn C, Petersen AK, Illig T, et al. Increased amino acids levels and the risk of developing of hypertriglyceridemia in a 7-year follow-up. J Endocrinol Investig. 2014;37:369–74.

    CAS  Article  Google Scholar 

  38. Nie C, He T, Zhang W, Zhang G, Ma X. Branched chain amino acids: beyond nutrition metabolism. Int J Mol Sci. 2018;19.

  39. Newgard CB. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab. 2012:606–14.

  40. Abdoli N, Azarmi Y, Eghbal MA. Mitigation of statins-induced cytotoxicity and mitochondrial dysfunction by L-carnitine in freshly-isolated rat hepatocytes. Res Pharm Sci. 2015;10:143–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Noipha K, Ratanachaiyavong S, Purintrapiban J, Herunsalee A, Ninla-Aesong P. Effect of Tinospora crispa on glucose uptake in skeletal muscle: role of glucose transporter 1 expression and extracellular signal-regulated kinase1/2 activation. Asian Biomed. 2011;5:361–9.

    Google Scholar 

  42. El-Hattab AW, Scaglia F. Disorders of carnitine biosynthesis and transport. Mol Genet Metab. 2015:107–12.

  43. Kersten S, Stienstra R. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver. Biochimie. 2017:75–84.

Download references


Authors wish to acknowledge the CCRAS, Ministry of AYUSH, Govt of India for supporting the work.

Author information

Authors and Affiliations



AS and RD design the study and conducted the experiment. AY, RD and TK Mandal interpret the data and design the manuscript.

Corresponding author

Correspondence to Rajesh Dabur.

Ethics declarations

Ethics approval

Human Ethics Committee of the PDDYP Ayurveda College, Pune, India approved the study wide letter no. RRI/2011/HEC/2023 dated 18-02-2011.

Conflict of interest

All authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material


(DOCX 101 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shirolkar, A., Yadav, A., Mandal, T.K. et al. Intervention of Ayurvedic drug Tinospora cordifolia attenuates the metabolic alterations in hypertriglyceridemia: a pilot clinical trial. J Diabetes Metab Disord 19, 1367–1379 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Tinospora cordifolia
  • Hyperlipidemia
  • Hyper-triglyceridemia
  • Metabolomics