Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches

Abstract

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.

Antioxidant and Anti‐Inflammatory Effects of Anacardium occidentale L. and Anacardium microcarpum D. Extracts on the Liver of IL‐10 Knockout Mice

“…Using the wild-type strain, the acetaminophen induced in experimental albino rats shows significant elevation in levels of the serum marker enzymes, aspartate transaminase and alanine transaminase, and of lipid peroxides with decreased levels of antioxidant enzymes such as superoxide dismutase and catalase, showing its high harmful potential [ 45 ]. In addition, this protocol has also been widely used for analyzing the protective and curative effects of plant extracts, especially associated with pathologies of the digestive system [ 46 , 47 ].…”

Indigenous Nigeria medicinal herbal remedies: A potential source for therapeutic against rheumatoid arthritis

“…It is rich in bioactive compounds, including quinine, scopoletin, silibinin, dihydroxycoumarin, lupeol, lutein, β-carotene, cynanforidin, and gagminin. [243][244][245] The treatment of lupeol (42 mmol/ear) on the ear of male albino mice induced with croton prevented edema by 80%. Further structural modifications on lupeol, including acetylation, palmitoylation, and hemisuccinate ester, resulted in 72%, 54%, and 90% reduction in edema.…”

Phytochemical Characterization, Functional Nutrition, and Anti-Diabetic Potentials of Leptadenia hastata (pers) Decne Leaves: In Silico and In Vitro Studies

“…Decne, a member of the Asclepiadaceae family widely distributed in Tropical Africa, is one of the herbal remedies used by traditional healers to treat DM. 11 , 24 Furthermore, several experimental studies have reported the anti-diabetic activity of L hastata . 7 , 11 , 17 Other reported pharmacological and biological potentials of different parts of L hastata include antimicrobial, antiandrogenic, anti-inflammatory, and antibacterial activities.…”

“…7 , 11 , 17 Other reported pharmacological and biological potentials of different parts of L hastata include antimicrobial, antiandrogenic, anti-inflammatory, and antibacterial activities. 24 The anti-DM activity of medicinal plants is also anchored on active pharmaceutical phytoconstituents, including phytochemicals, vitamins, and minerals. 11 This study investigated the phytochemicals, vitamins, and minerals in L hastata and employed computational techniques to discover potential HPA antagonists, drug-likeness, pharmacokinetics properties, and safety profiles of compounds identified in ethanol extract of L hastata (EELH) using gas chromatography–mass spectrophotometer (GC-MS) and gas chromatography–flame ionization detector (GC-FID).…”