Mahanta, S. | bioRxiv Science

bioRxiv2022

In silico analysis of Bacopa monnieri (L.) Wettst. compounds for drug development against Neurodegenerative Disorders

Neurotrophins play a crucial role in the development and regulation of neurons. Alterations in the functioning of these Neurotrophins leads to several Neurodegenerative Disorders. Albeit engineered medications which are accessible for the treatment of Neurodegenerative Disorders, due to their numerous side-effects, it becomes imperative to formulate and synthesize novel drug candidates. Plants could be utilized as an alternative for these manufactured medications because of their low incidental effects in contrast with the engineered drugs. Bacopa monnieri has been traditionally known to be utilized to treat Neurodegenerative Disorders. Therefore, in current study an in-silico based study was carried out to evaluate the pharmacological effect of Bacopa monnieri. Molecular Docking was carried out to screen the active phytochemicals of Bacopa monnieri which can act as potential drug candidates against the causative proteins of Neurodegenerative Disorders. A total of 105 biologically active phytochemicals from Bacopa monnieri were docked against the receptors of brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, and nerve growth factor. Based on molecular docking study it was observed that the phytocompounds Vitamin E, Benzene propanoic acid, 3,5-bis(1,1dimethylethyl)4-hydroxy-, methyl ester (BPA), Stigmasterol, and Nonacosane of Bacopa monnieri significantly fits to the active residues of the four selected drug targets. Further Molecular Dynamics simulation study was performed to examine the stability of the binding of these phytochemicals with the selected targets. Drug likeness properties as well as related physico-chemical properties were analyzed through ADMETox study. Our findings suggested that the phytocompounds Vitamin E, BPA, Stigmasterol and Nonacosane significantly bind against brain-derived neurotrophic factor, neurotrophin-3, neurotrophin4, and nerve growth factor, respectively which may be the potential drug candidates for the treatment of neurodegenerative disorders. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/486025v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@2c39aforg.highwire.dtl.DTLVardef@17f4fd9org.highwire.dtl.DTLVardef@1534e13org.highwire.dtl.DTLVardef@2ad383_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2020

Exploration of endo-xylanase from novel strain of Bacillus velezensis AG20 isolated from the cave of Meghalaya

Cave sets the example of extreme ecological niche and habitat for diversified microorganisms. Present study involved in the isolation of endoxylanase producing novel strain Bacillus velezensis AG20 from the Krem Phyllut cave, Meghalaya, India. Culture dependent studies, molecular phylogentics, RNA secondary folding pattern based on 16S rDNA substantiated the identity of this novel strain. Bacillus velezensis AG20 revealed the superbug quality having resistance against various class of broad-spectrum antibiotics. Bacillus velezensis AG20 revealed biofilm formation over the cell surface in FESEM. Highest cell biomass and xylanase production supported in TB medium, further purified partially to 5.3 fold with 21% yield. Molecular weight of the purified xylanase found to be 45 kDa. Enzyme kinetics and pattern of hydrolysis revealed the evidence for the selection of linear birchwood xylan with Vmax = 21.0 {+/-} 3.0 U/ml, Km = 1.25 mg/ml, Kcat = 1.75/s at optimum pH 7 and temperature 50{degrees}C also found significant statistically in Taguchis orthogonal design. Conversely, ruled out any exoacting activity against synthetic pNP-xylopyranoside substrate. Endo-xylanase isolated from Bacillus velezensis AG20 was moderately thermostable over temperatures 50 and 60{degrees}C. Time dependent hydrolysis of agro-waste sugar cane bagasse depicted the production of xylooligosaccharides (XOS) predominantly xylobiose, xylotriose and xylotetrose. Purified mixed XOS hold their prebiotic potential by promoting the growth of probiotics Bifidobacterium and Lactobacillus as well as high stability (~90%) against systemic fluids. Mixed XOS (300 g/ml) displayed anti-proliferation activities by reducing the growth of HT-29 and Caco-2 cells significantly 90% and 75%, respectively, after 48 h. IMPORTANCEExtremophiles dwelling inside the caves have laden with the extraordinary capabilities of bioconversion by nature. The pristine ecological niche inside the cave, absence of proper light and air, supports the livelihood of novel microorganisms. In India, Meghalaya is hoisting longest caves in the East Khasi Hills, providing conducive environment for novel bacterial strains. With the prime objective of isolating novel bacterial strains that produce extracellular xylanase our studies have been carried out. Considering the present industrial demand for nutraceutical, prebiotics, anti-proliferating agents and biofuels by the conversion of lignocellulosic biomass (LCB), novel enzymes are required. Xylanases from bacterial origin play a significant role in conversion of LCB into oligosaccharides. Therefore, exploration and characterization of xylanase producing novel isolate from cave may pave the new arena for the production of prebiotic and anti-inflammatory oligosaccharides from agro-waste.

microbiology↗