Background and Objectives. Leptadenia hastata is a liana from the family of Asclepiadaceae used in tropical Africa to treat diabetes mellitus. In this study, we investigated its hepatoprotective mechanisms on acetaminophen- (APAP-) induced toxicity through in vivo and in silico approaches. Materials and Methods. Various aqueous extracts were prepared from this plant and preadministered per os to albino mice 3 h before APAP administration, once daily for one week. Animals from the normal group were given only distilled water while those from negative control received only APAP 250 mg/kg. After treatment, mice were sacrificed, the liver was collected for histopathology analysis, and different biochemical markers (alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNFα)) were measured. The content of the active extract was analyzed by HPLC/UV. Molecular docking was conducted using iGEMDOCK software, and the drug-likeness and pharmacokinetic profiles were evaluated using Swiss ADME. Results. APAP administration significantly increased (p<0.001) ALT in liver homogenates when compared to normal controls whereas the stem decoction at 250 mg/kg significantly (p<0.001) reduced this activity to a normal value comparable to silymarin 50 mg/kg which is better than leaf and root extracts. Moreover, the stem decoction also significantly reduced the MDA levels (p<0.05) and increased those of GSH, SOD, and CAT (p<0.001) at doses of 250 and 500 mg/kg compared to the negative control. A significant (p<0.001) decrease of TNFα levels and leukocyte infiltration was observed following treatment with this extract. The HPLC/UV analysis of the decoction revealed the presence of dihydroxycoumarin, quinine, and scopoletin with the following retention times: 2.6, 5.1, and 7.01 min, respectively. In silico studies showed that quinine and dihydroxycoumarin had great potentials to be orally administered drugs and possessed strong binding affinities with TNFα, TNF receptor, cyclooxygenase-2, iNOS, cytochrome P450 2E1, and GSH reductase. Conclusion. Based on these results, L. hastata could be considered a source of promising hepatoprotective compounds with antioxidant and anti-inflammatory properties.
Tectona grandis (T. grandis) is a medicinal plant widely used in Cameroon to treat typhoid fever and several other diseases. Despite its heavy use for medical purposes, no study has yet been conducted to assess its potentially toxic effects. This study aimed at evaluating the acute and subchronic toxicological profile of Tectona grandis leaf extract in rats. The acute toxicity study revealed neither behavioral disturbances nor death in rats. The lethal dose (DL50) of this extract is greater than 5000 mg/kg body weight. The subchronic toxicity study showed no significant change in weight gain in rats at test doses throughout the treatment period. However, there was a significant decrease in alanine transaminase activity and serum protein levels at all doses. Alkaline phosphatase activity decreased at doses of 30, 90, and 270 mg/kg and increased at the dose of 810 mg/kg body weight. Serum and urinary urea levels increased simultaneously at doses of 270 and 810 mg/kg body weight. Repeated administration of the extract also increased total cholesterol, high-density lipoprotein levels in both sexes were compared to respective controls, and the ratio of high- to low-density lipoprotein was found to be greater than 1 in all animals. However, at the dose of 810 mg/kg, necrosis was observed on the kidney sections and vascular congestion on the liver sections of animals. Aqueous extract of T. grandis did not lead to any adverse effects in rats after acute and subchronic treatment at 30 and 90 mg/kg doses. This extract can, therefore, be used for the formulation of typhoid fever phytomedicine at the therapeutic dose of 30 mg/kg, but before this, chronic and mutagenic toxicity evaluations must be carried out.
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