UHPLC/GC-TOF-MS metabolomics, MTT assay, and molecular docking studies reveal physostigmine as a new anticancer agent from the ethyl acetate and butanol fractions of Kigelia africana (Lam.) Benth. fruit extracts.

Kigelia africana plant is widely used as a herbal remedy in preventing the onset and the treatment of cancer-related infections. With the increase in the research interest of the plant, the specific chemical compound or metabolite that confers its anticancer properties has not been adequately investigated. The ethyl acetate and butanol fractions of the fruit extracts were evaluated by 2-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl-2H-tetrazolium bromide assay against four different cell lines, with the ethyl acetate fraction having inhibition concentration values of 0.53 and 0.42 µM against Hep G2 and HeLa cells, respectively. More than 235 phytoconstituents were profiled using UHPLC-TOF-MS, while more than 15 chemical compounds were identified using GC-MS from the fractions. Molecular docking studies revealed that physostigmine, fluazifop, dexamethasone, sulfisomidine, and desmethylmirtazapine could favorably bind at higher binding energies of -8.3, -8.6, -8.2, and -8.1 kcal/mol, respectively, better than camptothecin with a binding energy of -7.9 kcal/mol. The results of this study showed that physostigmine interacted well with topoisomerase IIα and had a high score of pharmacokinetic prediction using absorption, distribution, metabolism, excretion, and toxicity profiles, thereby suggesting that drug design using physostigmine as a base structure could serve as an alternative against the toxic side effects of doxorubicin and camptothecin.

Metabolome modulatory effects of Kigelia africana (Lam.) Benth. fruit extracts on oxidative stress, hyperlipidaemic biomarkers in STZ-induced diabetic rats and antidiabetic effects in 3T3 L1 adipocytes.

OBJECTIVES: The management of diabetes is considered a global problem, and a cure is yet to be discovered. This study investigated the modulatory effect of Kigelia africana fruit on oxidative stress and hyperlipidaemic biomarkers in STZ-induced diabetic rats, profiled phytoconstituents using GC-TOF-MS and evaluated antidiabetic effects on 3T3 L1 adipocytes. METHODS: Thirty male Wistar rats (120-150 g) were divided into six groups (n = 5). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) and treated with 100, 200 and 400 of hexane fraction of KA for 28 days. Immunohistochemical evaluation was carried out using avidin-biotin immunoperoxidase (ABI) method. Catalase and SOD activities as well as the levels of total protein, albumin, bilirubin, triglyceride, cholesterol, and high-density lipoprotein were measured. KEY FINDINGS: The expressions of oxidative stress and hyperlipidaemic biomarkers alongside fasting blood glucose concentrations were remarkedly decreased in KA-treated diabetic rats. Moreover, there was a significant increase in endocrine cell distribution, area covered with increase in ß-cell mass, composition and morphology of KA-treated animals. Additionally, there was constant up-regulation in 3T3 L1 adipocytes due to the presence of phytoconstituents. CONCLUSION: Kigelia africana fruit can act as a modulatory agent due to its ameliorative effects against oxidative stress.