Hypoglycemic and hypolipidemic effects of unsaponifiable matter from okra seed in diabetic rats.

BACKGROUND/OBJECTIVES: Okra seed is a rich source of various nutritional and bioactive constituents, but its mechanism of action is still unclear. The aim of this study was to evaluated the effects on glucose uptake and serum lipid profiles of unsaponifiable matter (USM) from okra seed in adipocytes and diabetic animal models. MATERIALS/METHODS: USM was prepared from okra seed powder by saponification. The contents of phytosterols and vitamin E in USM were measured. 3T3-L1 preadipocytes were cultured for 6 days with different concentrations of USM (0-200 µg/mL). The diabetic rats were administered with or without USM for 5 wk. RESULTS: In the USM, the contents of phytosterols and vitamin E were 394.13 mg/g USM and 31.16 mg/g USM, respectively. USM showed no cytotoxicity and led to an approximately 1.4-fold increase in glucose uptake in 3T3-L1 adipocytes. The treatment of USM also increased the expressions of peroxisome proliferator-activated receptor-γ and glucose transporter-4 in a dose-dependent manner in adipocytes. The body weight change was not significantly different in all diabetic rats. However, blood glucose and the weights of liver and adipose tissues were significantly reduced compared to those in the control diabetic rats. Treatment with USM decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the control group. The USM group also showed significantly decreased atherogenic indices and cardiac risk factors. CONCLUSION: These results suggest that USM from okra seed improves the hypoglycemic and hypolipidemic effects in diabetic rats, and provides valuable information for improving the functional properties of okra seed.

Efficacy and Safety of Fibroblast Growth Factor-21 Analogs for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.

Fibroblast growth factor (FGF)-21 analogs are potential therapeutic candidates for metabolic dysfunction-associated steatohepatitis (MASH). This systematic review and meta-analysis aimed to assess the efficacy and safety of the FGF-21 analogs, efruxifermin, pegbelfermin, and pegozafermin for MASH treatment. A comprehensive systematic review and meta-analysis of randomized controlled trials from five major databases was conducted. Primary efficacy outcomes focused on liver histological improvement, while secondary efficacy outcomes encompassed reductions in liver fat content and improvements in biochemical parameters. Safety outcomes examined included treatment-emergent adverse events (TEAEs), treatment-related TEAEs, TEAEs leading to discontinuation, and serious TEAEs. Eight eligible studies involving 963 patients were included in this review. Compared with the placebo group, the FGF-21 analog-treated group exhibited significantly improved primary efficacy outcomes, specifically ≥1 stage improvement in fibrosis with no worsening of MASH (risk ratio [RR] = 1.83; 95% confidence interval [CI] = 1.27-2.62) and at least two-point improvement in the non-alcoholic fatty liver disease activity score with no worsening of fibrosis (RR = 2.85; 95% CI = 2.06-3.95). Despite an increased risk of TEAEs (RR = 1.17; 95% CI = 1.08-1.27) and treatment-related adverse events (RR = 1.75; 95% CI = 1.40-2.19), FGF-21 analogs exhibited an acceptable safety profile. FGF-21 analogs were significantly better in achieving liver histological improvements and beneficial biochemical outcomes compared with placebo, with a tolerable safety pattern. These findings shed light on the efficacy and safety of FGF-21 analogs and provide valuable evidence for their application as MASH therapeutics.

Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy.

In this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various analytical approaches to obtain information for selecting a suitable polymer. Based on the calculation of the Hansen solubility parameter and the identification of the single glass transition temperature (Tg), the miscibility between bisacodyl and all the investigated polymers was confirmed. Additionally, the drug-polymer molecular interaction was identified based on the comprehensive results of dynamic vapor sorption (DVS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and a comparison of the predicted and experimental values of Tg. In particular, the hydroxypropyl methylcellulose (HPMC)-based solid dispersions, which exhibited large deviation between the calculated and experimental values of Tg and superior physical stability after DVS experiments, were selected as the most appropriate solubilized bisacodyl formulations due to the excellent inhibitory effects on precipitation based on the results of the non-sink dissolution test. Furthermore, it was shown that the enteric-coated tablets containing HPMC-bisacodyl at a 1:4 ratio (w/w) had significantly improved in vivo therapeutic laxative efficacy compared to preparations containing un-solubilized raw bisacodyl in constipation-induced rabbits. Therefore, it was concluded that the pre-formulation strategy, using several analyses and approaches, was successfully applied in this study to investigate the miscibility and interaction of drug-polymer systems, hence resulting in the manufacture of favorable solid dispersions with favorable in vitro and in vivo performances using hot-melt extrusion processes.