tribulus and Chemical-and-Drug-Induced-Liver-Injury

Fructus Tribuli (FT) has been commonly used as a traditional medicine for thousands of years. With the diverse uses of FT, more attention has been paid to its hepatorenal toxicity. However, the compounds causing the hepatorenal toxicity of FT remain undetermined. Terrestrosin D (TED), a major spirostanol saponin isolated from FT, may exert hepatorenal toxicity.. This study aimed to evaluate the potential hepatorenal toxicity of TED, and preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity.. Cytotoxicity assays, a repeated-dose 28-day in-vivo study, a toxicokinetic study, and a tissue distribution study were used to evaluate the potential hepatorenal toxicity of TED. Furthermore, network pharmacology was applied to preliminarily explore the possible mechanism of TED-induced hepatorenal toxicity.. Both the in vitro and in vivo studies showed that the spirostanol saponin TED had potential hepatorenal toxicity. Nonetheless, hepatorenal toxicity induced by oral treatment with TED at a dosage range of 5 - 15 mg/kg daily for 28 consecutive days to Sprague-Dawley (SD) rats was reversible after 14 days of TED withdrawal. The toxicokinetic study demonstrated that the systematic exposure of SD rats to TED had an accumulation phenomenon and a dose-dependent trend after a 28-day repeated-dose oral administration. The tissue distribution study revealed that TED had a targeted distribution in the liver and kidneys accompanied by a phenomenon of accumulation in SD rats. Network pharmacology combined with molecular docking methods was used to screen for the key targets (HSP90AA1, CNR1, and DRD2) and the key pathways of TED-induced hepatorenal toxicity.. The spirostanol saponin TED, a major spirostanol saponin isolated from FT, had potential hepatorenal toxicity.

Topics: Animals; Cell Line; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Kidney Diseases; Male; Molecular Docking Simulation; Network Pharmacology; Rats; Rats, Sprague-Dawley; Saponins; Tissue Distribution; Toxicity Tests; Tribulus

A new phenolic amide, tribulusimide D (4-hydroxy-N-[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propen-1-yl]-3-methoxybenzamide) (1), together with a known phenolic amide, terrestriamide ((E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-oxoethyl]-prop-2-enamide) (2) and a flavonol glycoside, quercetin-3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (3) were isolated from the H2O extract of Tribuli Fructus. Compounds 1 and 3 showed significant hepatoprotective activities, with EC50 values of 13.46 +/- 0.2 and 7.06 +/- 0.7 microM, respectively, against tacrine-induced cytotoxicity in HepG2 cells.

Topics: Carbohydrate Sequence; Cell Line; Chemical and Drug Induced Liver Injury; Fruit; Guaiacol; Imides; Molecular Sequence Data; Nootropic Agents; Plant Extracts; Protective Agents; Spectrometry, Mass, Electrospray Ionization; Tacrine; Tribulus

Herbal medications are being progressively utilized all over the world. Nevertheless, herbal remedies are not without hazards and several cases of adverse reactions have been described. Tribulus terrestris is traditionally used because of its aphrodisiac and antiurolithiatic activities with almost complete inhibition of stone formation. We report a case of T. terrestris-induced hepatotoxicity, nephrotoxicity and neurotoxicity in an Iranian male patient who used the plant's extract to prevent kidney stone formation. He presented with seizure and very high serum aminotransferases and creatinine after consuming herbal water for 2 days. Discontinuation of the herbal remedy resulted in improvement in symptoms and normalization of his liver enzymes.

Topics: Acute Kidney Injury; Adult; Chemical and Drug Induced Liver Injury; Creatinine; Humans; Male; Tribulus

FT-IR spectra of liver tissue isolated from mice, Mus musculus, have been recorded in the region of 4000 - 400 cm-1 for normal, mercury treated and recovery phase. In this study, the total protein content was found to be decreased in the liver tissues after treatment with median-lethal dose of mercuric chloride. The marked fall in the level of bio-chemical constituent in the tissue due to metal exposure indicates the rapid initiation of the breakdown of the bio-chemical constituents to meet the energy demand during toxic stress. During the recovery phase, the decreased levels of bio-chemical constituents are restored to near normal level. Methanol fractions of Tribulus terrestris fruit extract was administrated on mercury intoxicated mice for 15 days. After the administration, the mercury-intoxicated animals slowly recovered from the adverse effect of mercury poisoning with the help of plant bio-formulations. The results are discussed in detail.

Topics: Animals; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Fruit; Liver; Mercuric Chloride; Mercury Poisoning; Mice; Phytotherapy; Plant Extracts; Protective Agents; Spectrophotometry, Infrared; Tribulus