Metformin Hydrochloride Loaded Mucoadhesive Microspheres and Nanoparticles for Anti-Hyperglycemic and Anticancer Effects Using Factorial Experimental Design.

Background: Metformin hydrochloride (HCl) microspheres and nanoparticles were formulated to enhance bioavailability and minimize side effects through sustained action and optimized drug-release characteristics. Initially, the same formulation design with different ratios of metformin HCl and Eudragit RSPO was used to formulate four batches of microspheres and nanoparticles using solvent evaporation and nanoprecipitation methods, respectively. Methods: The produced formulations were evaluated based on particle size and shape (particle size distribution (PSD), scanning electron microscope (SEM)), incompatibility (differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)), drug release pattern, permeation behavior, in vivo hypoglycemic effects, and in vitro anticancer potential. Results: Compatibility studies concluded that there was minimal interaction between metformin HCl and the polymer, whereas SEM images revealed smoother, more spherical nanoparticles than microspheres. Drug release from the formulations was primarily controlled by the non-Fickian diffusion process, except for A1 and A4 by Fickian, and B3 by Super case II. Korsmeyer-Peppas was the best-fit model for the maximum formulations. The best formulations of microspheres and nanoparticles, based on greater drug release, drug entrapment, and compatibility characteristics, were attributed to the study of drug permeation by non-everted intestinal sacs, in vivo anti-hyperglycemic activity, and in vitro anticancer activity. Conclusion: This study suggests that the proposed metformin HCl formulation can dramatically reduce hyperglycemic conditions and may also have anticancer potential.

Improvement of lipid profile and hepatic oxidative stress in high-fat-diet induced hyperlipidemic Swiss albino rats by Piper betle juice: evidences from in vivo and in silico studies.

Piper betle L. leaves are very popular and traditionally used to chew with betel nut in many Asian countries. In this study, P. betle leaves juice (PBJ) was subjected to evaluation for its antihyperlipidemic activity in the high-fat-diet-induced hyperlipidemic rats model. Swiss albino rats were allowed to high-fat- diet for one month, followed by concurrent administration of PBJ for another month. The rats were then sacrificed and collected blood, tissues and organs. Pharmacokinetic, toxicological studies and molecular docking studies were performed using SwissADME, admetSAR and schrodinger suit-2017. Our investigation showed a promising effect of PBJ on body weight, lipid profile, oxidative and antioxidative enzymes, and the principle enzyme responsible for the synthesis of cholesterol. PBJ at 0.5 - 3.0 mL/rat significantly reduced body weight of hyperlipidemic rats compared to control. PBJ at the doses of 1.0, 1.5, 2.0, and 3.0 mL/rat significantly (p<0.05, p<0.01, p<0.001) improved the levels of TC, LDL-c, TG, HDL-c and VLDL-c. Similarly, PBJ doses starting from 1.0 mL/rat to 3.0 mL/rat reduced the oxidative biomarkers AST, ALT, ALP, and creatinine. The level of HMG-CoA was significantly reduced by PBJ doses 1.5, 2, and 3 ml/rat. A number of compounds have been found to have good pharmacokinetic profile and safety and 4-coumaroylquinic acid exerted the best docking score among them. Thus our findings clearly demonstrated the potential lipid-lowering activities of PBJ both in vivo and in silico studies. PBJ can be a good candidate for the development of antihyperlipidemic medication or as an alternative medicine.

Evaluation of Wound-Healing and Antioxidant Effects of Marantodes pumilum (Blume) Kuntze in an Excision Wound Model.

Marantodes pumilum (MP) is a great source of herbal medicine used traditionally by both men and women for various purposes. MP may have potential wound-healing effects due to its diverse biological properties. An extensive study was conducted in a normal male rat model for determining the effects of MP var. pumila (MPvp) and var. alata (MPva) on the wound healing process. Here, 126 male Sprague-Dawley rats were divided randomly into seven groups as follows: sham-operated (SH), vehicle dressing (VD), flavine dressing (FD), MPvp leaves (PL), MPvp roots (PR), MPva leaves (AL), and MPva roots (AR). The parameters studied were the percentage of wound contraction, histomorphology study by hematoxylin and eosin (H&E), Masson-Goldner trichrome (MGT), and immunohistochemistry (IHC) staining. In addition, the levels of enzymatic antioxidants and malondialdehyde were also measured in the wound tissue homogenates. Wounds treated with extracts (PL, PR, AL, and AR) showed significantly faster healing (p < 0.05) compared to untreated and control groups (SH, VD, and FD). Histological analysis among MP-treated groups revealed better re-epithelialization, higher collagen deposition, enhanced fibronectin content and fibroblast cells, and higher fiber transformation from collagen-III to collagen-I, accompanied with a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. MP has antioxidant effects that may enhance wound healing in the rat model.

The Pharmacological Potential of Oil Palm Phenolics (OPP) Individual Components.

The oil palm tree (Elaeis guineensis) from the family Arecaceae is a high oil-producing agricultural crop. A significant amount of vegetation liquor is discarded during the palm oil milling process amounting to 90 million tons per year around the world. This water-soluble extract is rich in phenolic compounds known as Oil Palm Phenolics (OPP). Several phenolic acids including the three isomers of caffeoylshikimic acid (CFA), p-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA) and hydroxytyrosol are among the primary active ingredients in the OPP. Previous investigations have reported several positive pharmacological potentials by OPP such as neuroprotective and atheroprotective effects, anti-tumor and reduction in Aß deposition in Alzheimer's disease model. In the current review, the pharmacological potential for CFA, PHBA, PCA and hydroxytyrosol is carefully reviewed and evaluated.