In vivo toxicity, anti-hyperlipidaemic, antioxidant and anti-atherogenic activities of 'LIPO A' A traditional herbal product in rodents.

Hyperlipidemia accounts for about 17 million deaths worldwide each year. High cost and side effects have limited the use of conventional anti-lipidaemic agents in some cases, majority of whom resort to traditional medicine. The current research focused on validating the safety and efficacy of a herbal product, 'LIPO A' used in the management of hyperlipidaemia. Induction of hyperlipidaemia was achieved by oral administration of 3 mL of cholesterol in coconut oil for 4 weeks in male Sprague Dawley rats with water available as 40 % sucrose. Subsequently, the animals were treated with 100, 200 and 400 mg/kg of the product 'LIPO A' for 4 additional weeks with atorvastatin as reference drug (at 2 mg/kg body weight). Blood samples were taken for serum biochemistry and atherogenic ratios were then calculated. 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) scavenging assay, total antioxidant capacity, physicochemical and phytochemical analysis were also carried out using standard methods. Treatment resulted in a dose-dependent reduction in total cholesterol with maximum reduction of 46.01 % at 400 mg/kg compared to atorvastatin with 49.30 %. There were significant changes in the low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (LDL-c/HDL-c) and Total Cholesterol (TC/HDL-c) ratios which measures the atherogenic and coronary risk indices respectively. Acute and subacute toxicity studies did not reveal any signs of toxicity. High Performance Liquid Chromatography (HPLC) fingerprint revealed six well resolved peaks with two prominent compounds with retention times 24.88 and 23.95 min, which could serve as quality control markers for the product. The herbal product showed considerable antihyperlipidemic and antioxidant actions in rodent models and lend credence to its use in traditional medicine for hyperlipidaemia.

Myrianthus libericus: Possible mechanisms of hypoglycaemic action and in silico prediction of pharmacokinetics and toxicity profile of its bioactive metabolite, friedelan-3-one.

The hypoglycaemic and anti-hyperlipidaemic effects of the 70% ethanol stem bark extract of Myrianthus libericus (MLB), used traditionally in the management of diabetes in Ghana, was evaluated in this study using streptozotocin (45 mg/kg)-induced diabetic rats. In vitro hypoglycaemic activities of the extract and one of its principal compounds, friedelan-3-one were then investigated using α-amylase inhibitory and glucose uptake assay in C2C12 myotubes. In silico analysis of the pharmacokinetic and toxicity properties of the compound was also performed. MLB significantly (p < 0.001) reduced the elevated blood glucose levels and corrected considerably (p < 0.01) the altered serum lipid profiles of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Together with friedelan-3-one, the extract markedly inhibited the activity of α-amylase and promoted glucose uptake in C2C12 cells. Whereas MLB significantly (p < 0.001) up-regulated PI3K and PPARγ transcripts with a corresponding increase in GLUT-4 transcripts within the muscle cells, friedelan-3-one only up-regulated PI3K and GLUT-4 transcripts to promote glucose transport. Friedelan-3-one was shown to be non-carcinogenic, non-hepatotoxic, has decent oral bioavailability and a good compound for optimisation into a drug candidate. The study has demonstrated that MLB possess hypoglycaemic and anti-hyperlipidaemic activities and could be used as a therapeutic agent in the management of diabetes mellitus.