Download PDF
Planta Med 2020; 86(07): 489-495
DOI: 10.1055/a-1127-7503
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Evaluation of the hepatotoxic potential of Tinospora crispa and its isolated borapetosides B, C and F in a murine model

Abidah Parveen
1   Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, USA
2   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, USA
3   Department of Pharmaceutical Sciences, Abbottabad University of Science and Technology, Havelian, KPK, Pakistan
,
Mir Tahir Maqbool
2   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, USA
,
Yan-Hong Wang
2   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, USA
,
Zulfiqar Ali
2   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, USA
,
Ikhlas A. Khan
1   Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, USA
2   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, USA
,
M. Khalid Ashfaq
2   National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, USA
› Author AffiliationsSupported by: U.S. Department of Agriculture 58-6060-6-015
Supported by: U.S. Food and Drug Administration 2U01FD004246-06
Further Information

Publication History

received 08 December 2019
revised 25 February 2020

accepted 26 February 2020

Publication Date:
26 March 2020 (online)

    Permissions and Reprints

Abstract

The hepatotoxic potential of the methanolic extract of the stems of Tinospora crispa and of its furano-diterpenoid–borapetosides B, C, and F–was investigated in normal and health-compromised mice. Health-compromised condition was established by a single intraperitoneal injection of LPS (6 mg/kg). Two different sets of experiments were conducted to evaluate the hepatotoxic potential. A 21-day study where the mice were dosed with the extract of T. crispa (1 gm/kg b. wt./day) or standardized combination of borapetosides B, C and F (500 mg/kg b. wt.) with or without a single dose of LPS (1 gm/kg b. wt./day). In the acute toxicity study, mice were dosed with borapetosides B, C, and F (500 mg/kg b. wt.). Results showed that the ALT levels were normal and liver histopathology unaltered. No conclusive hepatotoxicity was observed in the methanolic extract or pure compounds tested under the given experimental conditions.

Key words

Tinospora crispa - Menispermaceae - borapetoside F - hepatotoxicity - lipopolysaccharide - alanine transaminase
 

  • References

  • 1 Björnsson ES. Drug-induced liver injury: an overview over the most critical compounds. Arch Toxicol 2015; 89: 327-334
    CrossrefPubMedGoogle Scholar
  • 2 Aithal GP, Ramsay L, Daly AK, Sonchit N, Leathart JBS, Alexander G, Kenna JG, Caldwell J, Day CP. Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity. Hepatology 2004; 39: 1430-1440
    CrossrefPubMedGoogle Scholar
  • 3 Pauli-Magnus C, Meier PJ. Hepatobiliary transporters and drug-induced cholestasis. Hepatology 2006; 44: 778-787
    CrossrefPubMedGoogle Scholar
  • 4 Smith T, Gillespie M, Eckl V, Knepper J, Morton-Reynolds C. Herbal supplement sales in US increase by 9.4 % in 2018. HerbalGram 2019; 123: 62-73
    PubMedGoogle Scholar
  • 5 Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, Reddy KR, Seeff LB, Serrano J, Sherker AH, Stolz A, Talwalkar J, Vega M, Vuppalanchi R. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology 2014; 60: 1399-1408
    CrossrefPubMedGoogle Scholar
  • 6 Zheng EX, Navarro VJ. Liver iInjury from herbal, dietary, and weight loss supplements: a review. J Clin Transl Hepatol 2015; 3: 93-98
    PubMedGoogle Scholar
  • 7 Noor H, Ashcroft SJH. Pharmacological characterisation of the antihyperglycaemic properties of Tinospora crispa extract. J Ethnopharmacol 1998; 62: 7-13
    CrossrefPubMedGoogle Scholar
  • 8 Lam SH, Ruan CT, Hsieh PH, Su MJ, Lee SS. Hypoglycemic diterpenoids from Tinospora crispa . J Nat Prod 2012; 75: 153-159
    CrossrefPubMedGoogle Scholar
  • 9 Ounjaijean S, Chachiyo S, Somsak V. Hypoglycemia induced by Plasmodium berghei infection is prevented by treatment with Tinospora crispa stem extract. Parasitol Int 2019; 68: 57-59
    CrossrefPubMedGoogle Scholar
  • 10 Nutham N, Sakulmettatham S, Klongthalay S, Chutoam P, Somsak V. Protective effects of Tinospora crispa stem extract on renal damage and hemolysis during Plasmodium berghei infection in mice. J Pathog 2015; 2015: 738608
    PubMedGoogle Scholar
  • 11 Sulaiman M, Zakaria Z, Lihan R. Antinociceptive and anti-inflammatory activities of Tinospora crispa in various animal models. J Trop Med 2008; 3: 66-69
    PubMedGoogle Scholar
  • 12 Thomas A, Rajesh EK, Kumar DS. The significance of Tinospora crispa in treatment of diabetes mellitus. Phyther Res 2016; 30: 357-366
    PubMedGoogle Scholar
  • 13 Sharif AA, Unyah NZ, Nordin N, Basir R, Wana MN, Alapid AA, Mustapha T, Majid RA. Susceptibility of Toxoplasma gondii to ethanolic extract of Tinospora crispa in vero cells. Evid Based Complement Alternat Med 2019; 2019: 2916547
    PubMedGoogle Scholar
  • 14 Chavalittumrong P, Attawish A, Chuthaputti A, Chuntapet P. Toxicological study of crude extract of Tinospora crispa . Thai J Pharm Sci 1997; 21: 199-210
    PubMedGoogle Scholar
  • 15 Kadir F, Othman F, Abdulla M, Hussan F, Hassandarvish P. Effect of Tinospora crispa on thioacetamide-induced liver cirrhosis in rats. Indian J Pharmacol 2011; 43: 64
    CrossrefPubMedGoogle Scholar
  • 16 Sangsuwan C, Udompanthurak S, Vannasaeng S, Thamlikitkul V. Randomized controlled trial of Tinospora crispa for additional therapy in patients with Type 2 diabetes mellitus. J Med Assoc Thail 2004; 87: 543-546
    PubMedGoogle Scholar
  • 17 Denis G, Gérard Y, Sahpaz S, Laporte R, Viget N, Ajana F, Riff B, Mouton Y, Bailleul F, Yazdanpanah Y. Malarial prophylaxis with medicinal plants: toxic hepatitis due to Tinospora crispa . Therapie 2007; 62: 271-272
    CrossrefPubMedGoogle Scholar
  • 18 Langrand J, Regnault H, Cachet X, Bouzidi C, Villa AF, Serfaty L, Garnier R, Michel S. Toxic hepatitis induced by a herbal medicine: Tinospora crispa . Phytomedicine 2014; 21: 1120-1123
    CrossrefPubMedGoogle Scholar
  • 19 Huang W, Tu C, Wang F, Huang S. Literature review of liver injury induced by Tinospora crispa associated with two cases of acute fulminant hepatitis. Complement Ther Med 2019; 42: 286-291
    CrossrefPubMedGoogle Scholar
  • 20 Cachet X, Langrand J, Riffault-Valois L, Bouzidi C, Colas C, Dugay A, Michel S, Boucaud-Maitre D. Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by Tinospora crispa . Sci Rep 2018; 8: 13520
    CrossrefPubMedGoogle Scholar
  • 21 Subehan. Usia T, Iwata H, Kadota S, Tezuka Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol 2006; 105: 449-455
    CrossrefPubMedGoogle Scholar
  • 22 Galanos C, Freudenberg MA, Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A 1979; 76: 5939-5943
    CrossrefPubMedGoogle Scholar
  • 23 Formal SB, Abrams GD, Schneider H, Sprinz H. Experimental shigella infections. VI. Role of the small intestine in an experimental infection in guinea pigs. J Bacteriol 1963; 85: 119-125
    CrossrefPubMedGoogle Scholar
  • 24 Abdel-Bakky MSB, Hammad MA, Walkerit LA, Ashfaq MK. Developing and characterizing a mouse model of hepatotoxicity using oral pyrrolizidine alkaloid (monocrotaline) administration, with potentiation of the liver injury by co-administration of LPS. Nat Prod Commun 2010; 5: 1457-1462
    PubMedGoogle Scholar
  • 25 Gardner CR, Heck DE, Yang CS, Thomas PE, Zhang XJ, DeGeorge GL, Laskin J, Laskin D. Role of nitric oxide in acetaminophen-induced hepatotoxicity in the rat. Hepatology 1998; 27: 748-754
    CrossrefPubMedGoogle Scholar
  • 26 Sneed RA, Grimes SD, Schultze AE, Brown AP, Ganey PE. Bacterial endotoxin enhances the hepatotoxicity of allyl alcohol. Toxicol Appl Pharmacol 1997; 144: 77-87
    CrossrefPubMedGoogle Scholar
  • 27 Hamesch K, Borkham-Kamphorst E, Strnad P, Weiskirchen R. Lipopolysaccharide-induced inflammatory liver injury in mice. Lab Anim 2015; 49: 37-46
    CrossrefPubMedGoogle Scholar
  • 28 Saleh IG, Ali Z, Abe N, Wilson FD, Hamada FM, Abd-Ellah MF, Walker LA, Khan IA, Ashfaq MK. Effect of green tea and its polyphenols on mouse liver. Fitoterapia 2013; 90: 151-159
    CrossrefPubMedGoogle Scholar
  • 29 Saleh IG, Ali Z, Hamada FM, Abd-Ellah MF, Walker LA, Khan IK, Ashfaq MK. Effect of green tea and EGCG on liver: in vivo and in vitro study. J Clinic Toxicol 2013; 3: 86
    PubMedGoogle Scholar
  • 30 Liu C, Fan H, Li Y, Xiao X. Research advances on hepatotoxicity of herbal medicines in China. Biomed Res Int 2016; 2016: 7150391
    PubMedGoogle Scholar
  • 31 Gowda S, Desai PB, Hull VV, Math AAK, Vernekar SN, Kulkarni SS. A review on laboratory liver function tests. Pan Afr Med J 2009; 22: 3
    PubMedGoogle Scholar
  • 32 Gupta R. Biomarkers in Toxicology. 2nd Edition. Academic Press; 2019: 251-257
    CrossrefGoogle Scholar
  • 33 Salazar JH. Overview of urea and creatinine. Lab Med 2014; 45: e19-e20
    CrossrefPubMedGoogle Scholar
  • 34 Wu MT, Lam KK, Lee WC, Hsu KT, Wu CH, Cheng BC, Ng HY, Chi PJ, Lee YT, Lee CT. Albuminuria, proteinuria, and urinary albumin to protein ratio in chronic kidney disease. J Clin Lab Anal 2012; 26: 82-92
    CrossrefPubMedGoogle Scholar
  • 35 Brown AC. Liver toxicity related to herbs and dietary supplements: online table of case reports. Part 2 of 5 series. Food Chem Toxicol 2017; 107: 472-501
    CrossrefPubMedGoogle Scholar
  • 36 Parveen A, Huang Y, Fantoukh O, Alhusban M, Raman V, Wang YH, Wang W, Ali Z, Khan IA. Rearranged clerodane diterpenoid from Tinospora crispa . Natural Prod Res 2019; DOI: 10.1080/14786419.2019.1633648.
    CrossrefPubMedGoogle Scholar