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

Authors: PARVEEN, ABIDAH - University Of Mississippi; MAQBOOL, MIR TAHIR - University Of Mississippi; WANG, YAN-HONG - University Of Mississippi; ALI, ZULFIQAR - University Of Mississippi; KHAN, IKHLAS - University Of Mississippi; ASHFAQ, M. KHALID - University Of Mississippi

Submitted to: Planta Medica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/2020
Publication Date: 5/3/2020
Citation: Parveen, A., Maqbool, M., Wang, Y., Ali, Z., Khan, I.A., Ashfaq, M. 2020. Evaluation of the hepatotoxic potential of Tinospora crispa and its isolated borapetosides B, C and F in a murine model. Planta Medica. 86(07):489-495. https://doi.org/10.1055/a-1127-7503.
DOI: https://doi.org/10.1055/a-1127-7503

Interpretive Summary: Although there are several reports that endorse the medicinal significance of T. crispa, yet several preclinical and clinical reports illustrate its toxicity. Hepatotoxicity is the major reported adverse effect of T crispa. To date, five human hepatotoxicity cases have been reported including one death. Preclinical reports by other investigators showed that administration of T. crispa to rats for six months induced signs of hepatotoxicity and slight nephro-toxicity as well as behavioral toxicity. At the National Center for Natural Products Research, we attempted to isolate compounds from this plant. Furanoditerpenoids, borapetosides B, C and F were isolated from T. crispa and characterized by Nuclear Magnetic Resonance (NMR) and mass techniques. These compounds as well as the whole methanolic plant extract were then tested in mice to evaluate their hepatotoxic potential in normal mice and also in health compromised mice as natural products have been demonstrated in some studies to cause toxic effects when administered during health compromised conditions. Co-treatment of non-toxic dose of lipopolysaccharide (LPS) with xenobiotic in a rodent models has been useful in evaluating potential synergistic hepatotoxic effect. In our studies we attempted to evaluate role of T. crispa and isolated borapetosides, B, C and F on liver in mice under health compromised conditions induced by LPS. Results from our studies showed that the plasma liver enzyme alanine transaminase (ALT) remained normal. Liver histopathology showed no remarkable changes. In conclusion, no hepatotoxicity was observed in any of the methanolic extracts or pure compounds tested under the given experimental conditions.

Technical Abstract: Hepatotoxic potential of the methanolic extract of the stems of Tinospora crispa and of its furanoditerpenoid compounds, borapetosides B, C and F was investigated in normal and health compromised mice. Health compromised condition was established by a single i.p. injection of lipopolysaccharide (LPS) (6mg/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 (1gm/kg b.wt./day) or standardized combination of borapetosides B, C and F (500mg/kg b.wt.) with or without a single dose of LPS (1gm/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 alanine transaminase (ALT) levels were normal and liver histopathology unaltered. No conclusive hepatotoxicity was observed in any of the methanolic extracts or pure compounds tested under the given experimental conditions.