In vitro Antioxidant and in vivo Hepatoprotective Activities of Root Bark Extract and Solvent Fractions of Croton macrostachyus Hochst. Ex Del. (Euphorbiaceae) on Paracetamol-Induced Liver Damage in Mice.

BACKGROUND: Liver disease is a major public health threat, particularly in developing countries. Several medicinal plants and formulations have been claimed to have liver protective activities. The present study aimed to evaluate in vitro antioxidant and in vivo hepatoprotective activities of root bark extracts of Croton macrostachyus (Euphorbiaceae). METHODS: Free radical scavenging activity of crude extract and solvent fractions of the plant was conducted using the DPPH assay method. Hepatoprotective activities of the crude extract and solvent fractions of the plant were carried out based on paracetamol-induced liver damage in mice. Serum biomarkers (AST, ALT, ALP, total bilirubin and total protein) were assessed to find out the effect. Histopathological examination was also carried out for all groups of mice to further confirm the findings. RESULTS: Antioxidant assay revealed that the crude extract, aqueous fraction and chloroform fraction of Croton macrostachyus exhibited free radical scavenging activity with IC50 values of 128.6, 168.9, and 406 µg/mL, respectively. Pretreatment of the mice with the crude extract and solvent fractions of Croton macrostachyus significantly reduced ALP (p<0.001), ALT (p<0.001), and AST (p<0.001) levels at all the administered doses compared to the toxic group. The crude extract and chloroform fraction decreased total bilirubin level at doses of 200 mg/kg (P<0.05) and 400 mg/kg (P<0.001). Pretreatment of the mice with 400 mg/kg of the crude extract and aqueous fraction elevated total protein value compared to the paracetamol treated group (P<0.05). The hepatoprotective activities of the plant extracts were confirmed by histopathological studies. CONCLUSION: From this study, it can be concluded that the crude extract and solvent fractions of Croton macrostachyus demonstrated antioxidant and hepatoprotective activities.

Drug Interactions of Metformin Involving Drug Transporter Proteins.

Metformin is a most widely used medication all around the world to treat Type 2 diabetes mellitus. It is also found to be effective against various conditions including, Prediabetes, Gestational diabetes mellitus (GDM), Polycystic Ovarian Syndrome (PCOS), Obesity, Cancer, etc. It is a cationic drug and it depends Organic Cation Transporters (OCTs) and Multidrug and Toxin Extruders (MATEs) mostly for its pharmacokinetics movement. The probability of drug interaction increases with the number of concomitant medications. This article focuses the drug interactions of metformin and most of them are linked to the inhibition of OCTs and MATEs leading to increased plasma metformin concentrations and subsequent elevation of risk of Metformin Associated Lactic Acidosis (MALA). By identifying the drugs inhibiting OCTs and MATEs, the healthcare professionals can predict the drug interactions of metformin.