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.

A computational insight into the molecular interactions of chlorpyrifos and its degradation products with the human progesterone receptor leading to endocrine disruption.

Chlorpyrifos (CPF) is a widely used pesticide effective against a large number of target pests, which is used by farmers to protect food crops. Based on earlier epidemiologic reports, which indicate that CPF might interfere with the progesterone signaling pathway and can affect conception, the present study was undertaken to evaluate the binding interaction of CPF with the human progesterone receptor (hPR). Progesterone is one of the important hormones of the reproductive system and through its receptor, PR, the progesterone signaling pathway regulates important reproductive functions including reproductive cyclicity and initiation and continuation of pregnancy. The binding interactions of four major degradation products of CPF, viz. chlorpyrifos-oxon (CPYO), des-ethyl chlorpyrifos (DEC), 3,5,6-trichloro-2-methoxypyridine (TMP), 3,5,6-trichloro-2-pyridinol (TCP), were also studied to evaluate the possibility of endocrine disruption caused by these metabolites. Docking studies revealed that CPF, CPYO, and DEC were able to involve important interacting amino acid residues of the hPR during molecular interactions and are capable of competing with progesterone. Thus, CPF and its degradation products can act as potential xenoligands for the hPR and can disrupt normal progesterone signaling pathway.

Molecular interactions of chlorpyrifos and its environmental degradation products with human sex hormone-binding globulin: an in silico study.

In recent years, there has been a widespread interest and awareness about health issues posed by endocrine-disrupting chemicals present in the environment. These chemicals, often present in food and many consumer products, can interfere with hormone biosynthesis and metabolism and may result in deviation from normal homeostatic control. Chlorpyrifos (CPF), a major endocrine-disrupting chemical is used worldwide as an agricultural insecticide against a broad spectrum of insect pests in rice cultivation and to control termites. The insecticide mostly undergoes environmental degradation to chlorpyrifos-oxon (CPYO), des-ethyl chlorpyrifos (DEC), 3,5,6-trichloro-2-methoxypyridine (TMP) and 3,5,6-trichloro-2-pyridinol (TCP). Results from several epidemiological studies suggest that exposure to CPF can result in reproductive disorders, including infertility in male and female. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The objective of the present study involved computational approaches to apprehend the mechanism of molecular interaction of CPF and its four degradation products (CPYO, DEC, TMP, TCP) with human SHBG using molecular docking simulation. All five compounds (CPF, CPYO, DEC, TMP, TCP) showed high binding affinity with SHBG; however, the binding affinity values were higher (more negative) for CPF, CPYO, DEC and TMP than for TCP indicating that CPF, CPYO, DEC and TMP formed a tight interaction with SHBG. From the results obtained with the docking analysis, it can be opined that CPF, CPYO, DEC and TMP could possibly act as potential endocrine disruptors for androgen signaling.

Effect of Mimosa pudica root extract on vaginal estrous and serum hormones for screening of antifertility activity in albino mice.

BACKGROUND: Several plants are traditionally used as birth control agents by the rural people in India. Mimosa pudica is one of the folk medicinal plants commonly used as antifertility agent in some places in India. The present work was carried out to evaluate the claimed antifertility effect of the plant by carrying out pharmacological studies with the root extract of the plant. STUDY DESIGN: Air-dried roots of M. pudica were extracted using methanol. Dried methanol extract of the root was administered orally to Swiss albino mice for 21 consecutive days. Estrous cycle, reproductive hormones (LH, FSH, prolactin, estradiol and progesterone) and number of litters produced were studied in both control and extract-administered groups by using standard methods. Phytochemical studies of the methanolic root extract were carried out using qualitative and thin-layer chromatography methods. RESULTS: M. pudica root extract, when administered orally at a dose of 300 mg/kg body weight/day, prolonged the length of the estrous cycle with significant increase in the duration of the diestrous phase and reduced the number of litters in albino mice. The number of litters was increased in the posttreatment period. The analysis of the principal hormones (LH, FSH, prolactin, estradiol and progesterone) involved in the regulation of the estrous cycle showed that the root extract altered gonadotropin release and estradiol secretion. CONCLUSIONS: The root extract of M. pudica has antifertility effect as it prolongs the estrous cycle and disturbs the secretion of gonadotropin hormones in albino mice. The decrease in FSH level in the proestrus and estrus stages in the extract-administered group compared with those of control animals indicates the disturbance of estrous cycle and ovulation through suppression of FSH.

Antifertility activity of the methanolic leaf extract of Cissampelos pareira in female albino mice.

meenakshi Cissampelos pareira Linn. is one of the folk medicinal plants commonly used as antifertility agent in some places of India. The aim of the present study was to evaluate the validity of the antifertility effect of the leaf extract. Cissampelos pareira leaf extract, when administered orally, altered the estrous cycle pattern in female mice, prolonged the length of estrous cycle with significant increase in the duration of diestrus stage and reduced significantly the number of litters in albino mice. The analysis of the principal hormones involved in estrous cycle regulation showed that the plant extract altered gonadotropin release (LH, FSH and prolactin) and estradiol secretion. The results indicated the antifertility effect of Cissampelos pareira leaf extract in female albino mice. The oral LD50 of the extract was found to be 7.3 g/kg in mice.