Biochanin A induces a brown-fat phenotype via improvement of mitochondrial biogenesis and activation of AMPK signaling in murine C3H10T1/2 mesenchymal stem cells.

In this study, we investigated the effect of Biochanin A (BioA), an O-methylated isoflavone on the brown-fat phenotype formation and on the associated thermogenic program including mitochondrial biogenesis and lipolysis in C3H10T1/2 MSCs. Our data demonstrates that Treatment with BioA in an adipogenic differentiation cocktail induced formation of brown-fat-like adipocytes from C3H10T1/2 MSCs without treatment with a known browning inducer (rosiglitazone or T3) at an early stage of differentiation. The formation of brown-fat-like adipocytes by BioA treatment was evidenced by upregulation of key thermogenic markers: Ucp1, Pgc1α, Prdm16, and Pparγ. BioA also increased the expression of beige (Cd137 and Fgf21) and brown (Elovl3 and Zic1)-specific markers. Additionally, BioA treatment promoted mitochondrial biogenesis, judging by the upregulation of genes; Cox8b, Cidea, Dio2, Sirt1, Opa1, and Fis1. BioA treatment increased the amount of mitochondrial DNA and its encoded proteins: oxidative phosphorylation complexes (I-V); this change was associated with high oxygen consumption by C3H10T1/2 MSCs. A small-interfering-RNA-induced gene knockdown and experiments with dorsomorphin-driven competitive inhibition revealed that BioA exerts the thermogenic action via activation of AMPK signaling. Our study shows the mechanism of BioA-induced promotion of a brown-fat phenotype. Nonetheless, clinical research is necessary to validate BioA as a brown-fat-like signature inducer.

A systematic review on antioxidant and antiinflammatory activity of Sesame (Sesamum indicum L.) oil and further confirmation of antiinflammatory activity by chemical profiling and molecular docking.

Traditionally, sesame oil (SO) has been used as a popular food and medicine. The review aims to summarize the antioxidant and antiinflammatory effects of SO and its identified compounds as well as further fatty acid profiling and molecular docking study to correlate the interaction of its identified constituents with cyclooxygenase-2 (COX-2). For this, a literature study was made using Google Scholar, Pubmed, and SciFinder databases. Literature study demonstrated that SO has potential antioxidant and antiinflammatory effects in various test systems, including humans, animals, and cultured cells through various pathways such as inhibition of COX, nonenzymatic defense mechanism, inhibition of proinflammatory cytokines, NF-kB or mitogen-activated protein kinase signaling, and prostaglandin synthesis pathway. Fatty acid analysis of SO using gas chromatography identified known nine fatty acids. In silico study revealed that sesamin, sesaminol, sesamolin, stigmasterol, Δ5-avenasterol, and Δ7-avenasterol (-9.6 to -10.7 kcal/mol) were the most efficient ligand for interaction and binding with COX-2. The known fatty acid also showed binding efficiency with COX-2 to some extent (-6.0 to -8.4 kcal/mol). In summary, it is evident that SO may be one of promising traditional medicines that we could use in the prevention and management of diseases associated with oxidative stress and inflammation.

Agathisflavone: Botanical sources, therapeutic promises, and molecular docking study.

In this article, we have summarized the biological sources and pharmacological activities of agathisflavone along with molecular docking studies to correlate the interaction of this biflavonoid and biomacromolecules involving in its biological effects observed in database-oriented scientific reports. For this, an up-to-date (from 1991 to October 2018) search was done on the databases such as PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society, Clinicaltrials.gov, and Google Scholar databases. The findings suggest that agathisflavone possesses antioxidant, anti-inflammatory, antiviral, antiparasitic, cytotoxic, neuroprotective, and hepatoprotective activities. An in silico study of agathisflavone against 17 essential proteins/enzymes revealed that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are the most efficient enzymes for the interaction and binding of this biflavonoid for its anti-inflammatory activity. In conclusion, agathisflavone may be one of the promising plant-derived lead compounds in the treatment of oxidative stress, inflammatory diseases, microbial infection, hepatic and neurological diseases and disorders, and cancer. © 2019 IUBMB Life, 71(9):1192-1200, 2019.

Preparation and evaluation of SEDDS of simvastatin by in vivo, in vitro and ex vivo technique.

The objective of this work was to formulate a Self Emulsifying Drug Delivery System (SEDDS) of simvastatin, a poorly soluble drug and to evaluate by in vivo, in vitro and ex vivo techniques. Oils and surfactants were screened out depending upon their solubilizing capacity. Among all of the solvents, Capryol 90 showed good solubilizing capacity. It dissolved 105 mg/ml of simvastatin. Tween-80 also showed good solubilizing capacity which was 117 mg/ml. The two excipients were used to prepare simvastatin SEDDS. Formulations were initially checked for the color, clarity and sedimentation. The SEDDS formulations were transparent and clear. Formulation F2 containing 7:3 (m/m) mixture of Capryol 90/Tween-80 produced smallest micro-emulsion with particles size of 0.074 µm and drug release was higher than other formulation (102% within 20 min). Ex vivo study of the SEDDS formulation was evaluated using guinea pig intestinal sac. Drug diffused from F2 formulation was significantly higher than pure drug (p < 0.001). In vivo study of SEDDS was performed in albino mice using plasma cholesterol level as a pharmacodynamic marker parameter. The test formulation (F2) appeared remarkable reduction in plasma cholesterol level, after oral administration which showed that SEDDS may be an effective technique for the oral administration of simvastatin.