Alpha glucosidase inhibitory properties of a few bioactive compounds isolated from black rice bran: combined in vitro and in silico evidence supporting the antidiabetic effect of black rice.

In view of the recent reports of the antidiabetic effect of the black rice bran extract, an attempt has been made in the present work to evaluate the potential α-glucosidase inhibitory activity of a few selected bioactive compounds present in the pericarp of the black rice. Out of the six bioactive compounds from black rice bran selected for the study, two compounds viz. cyanidin-3-glucoside and 6'-O-feruloylsucrose were identified as novel and highly potent α-glucosidase inhibitors via their in vitro and in silico screenings. The enzyme inhibition assay was corroborated by molecular docking and molecular dynamics simulation studies. Molecular docking studies suggested high binding energies and good binding interactions of these compounds with the active site residues of the receptor protein. A good agreement was found between the results of both modes of evaluation. The experimental results proved that the black rice bran extract can show 62% of alpha glucosidase inhibiting enzyme activity as compared to that of the popular drug Acarbose. While both the docking scores and binding affinity values indicate the formation of a ligand-enzyme complex by the major components of the extract, the molecular dynamics study further indicates the stability of the complex. The pharmacokinetic (ADMET properties) studies of these active compounds also support their use as safe oral anti-diabetic drugs. Thus, the results obtained from these studies of alpha glucosidase inhibition by bioactive compounds present in black rice bran indicate that these bioactive compounds can produce significant antidiabetic activity by inhibiting the active site of the target enzyme and hence these compounds can be used as leads for the synthesis of new antidiabetic drugs.

Resveratrol-loaded chitosan-pectin core-shell nanoparticles as novel drug delivery vehicle for sustained release and improved antioxidant activities.

Resveratrol, chemically known as 3,5,4'-trihydroxy-trans-stilbene, is a natural polyphenol with promising multi-targeted health benefits. The optimal therapeutic uses of resveratrol are limited due to its poor solubility, rapid metabolism and low bioavailability. To address the issues, we have encapsulated resveratrol inside the nanosized core made of chitosan and coated this core with pectin-shell in order to fabricate a drug delivery vehicle which can entrap resveratrol for a longer period of time. The core-shell nanoparticles fabricated in this way were characterized with the help of Fourier transform infrared spectrometer, field-emission scanning electron microscope, field-emission transmission electron microscopy/selected area electron diffraction, high-resolution transmission electron microscope, dynamic light scattering and zeta potential measurements. In vitro drug release study showed the ability of the core-shell nanoparticles to provide sustained release of resveratrol for almost 30 h. The release efficiency of the drug was found to be pH dependent, and a sequential control over drug release can be obtained by varying the shell thickness. The resveratrol encapsulated in a nanocarrier was found to have a better in vitro antioxidant activity than free resveratrol as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. This work finally offers a novel nano-based drug delivery system.

Disruption of androgen receptor signaling by chlorpyrifos (CPF) and its environmental degradation products: a structural insight.

Androgen-disruptors are chemicals that interfere with the biosynthesis, metabolism or function of endogenous androgens affecting normal male reproductive development and health. Several epidemiological studies have indicated a link between exposure to androgen disrupting chemicals with reduced sperm counts and increased infertility. The actions of androgens within target cells are transduced by the androgen receptors (ARs). Chlorpyrifos (CPF), a chlorinated organophosphorus pesticide, is known to cause impairment in both male and female reproductive systems. Recent publications have shown molecular interactions of CPF and its environmental degradation products with human progesterone receptor and human estrogen receptor. Exposure to CPF causes a marked reduction in sperm counts with lowering in serum testosterone level, which suggests possible molecular interaction of CPF with AR. The investigation to reveal the possibility and the extent of binding of CPF and some of its degradation products (chlorpyrifos-oxon [CPYO], desethyl chlorpyrifos [DEC], trichloromethoxypyridine [TMP] and trichloropyridinol [TCP]) with AR using molecular docking simulation are reported. The findings of the present docking, binding energy and molecular dynamics studies reveal that CPF and its degradation products may bind to ARs and act as a potent androgen disruptor.Communicated by Ramaswamy H. Sarma.