Significance of Soy-Based Fermented Food and Their Bioactive Compounds Against Obesity, Diabetes, and Cardiovascular Diseases.

Soybean-based fermented foods are commonly consumed worldwide, especially in Asia. These fermented soy-products are prepared using various strains of Bacillus, Streptococcus, Lactobacillus, and Aspergillus. The microbial action during fermentation produces and increases the availability of various molecules of biological significance, such as isoflavones, bioactive peptides, and dietary fiber. These dietary bio active compounds are also found to be effective against the metabolic disorders such as obesity, diabetes, and cardiovascular diseases (CVD). In parallel, soy isoflavones such as genistein, genistin, and daidzin can also contribute to the anti-obesity and anti-diabetic mechanisms, by decreasing insulin resistance and oxidative stress. The said activities are known to lower the risk of CVD, by decreasing the fat accumulation and hyperlipidemia in the body. In addition, along with soy-isoflavones fermented soy foods such as Kinema, Tempeh, Douchi, Cheonggukjang/Chungkukjang, and Natto are also rich in dietary fiber (prebiotic) and known to be anti-dyslipidemia, improve lipolysis, and lowers lipid peroxidation, which further decreases the risk of CVD. Further, the fibrinolytic activity of nattokinase present in Natto soup also paves the foundation for the possible cardioprotective role of fermented soy products. Considering the immense beneficial effects of different fermented soy products, the present review contextualizes their significance with respect to their anti-obesity, anti-diabetic and cardioprotective roles.

Anti-diabetic prospects of dietary bio-actives of millets and the significance of the gut microbiota: A case of finger millet.

Finger millet (Eleusine coracana) is a staple food in several parts of the world because of its high nutritional value. In addition to its high nutrient content, finger millet contains numerous bioactive compounds, including polyphenol (10.2 mg/g TAE), flavonoid (5.54 mg/g CE), phytic acid (0.48%), and dietary fiber (15-20%). Polyphenols are known for their anti-oxidant and anti-diabetic role. Phytic acid, previously considered an anti-nutritive substance, is now regarded as a nutraceutical as it reduces carbohydrate digestibility and thus controls post-prandial glucose levels and obesity. Thus, finger millet is an attractive diet for patients with diabetes. Recent findings have revealed that the anti-oxidant activity and bio-accessibility of finger millet polyphenols increased significantly (P < 0.05) in the colon, confirming the role of the gut microbiota. The prebiotic content of finger millet was also utilized by the gut microbiota, such as Faecalibacterium, Eubacterium, and Roseburia, to generate colonic short-chain fatty acids (SCFAs), and probiotic Bifidobacterium and Lactobacillus, which are known to be anti-diabetic in nature. Notably, finger millet-induced mucus-degrading Akkermansia muciniphila can also help in alleviate diabetes by releasing propionate and Amuc_1100 protein. Various millet bio-actives effectively controlled pathogenic gut microbiota, such as Shigella and Clostridium histolyticum, to lower gut inflammation and, thus, the risk of diabetes in the host. In the current review, we have meticulously examined the role of gut microbiota in the bio-accessibility of millet compounds and their impact on diabetes.

Chemo-informatics guided study of natural inhibitors targeting rho GTPase: a lead for treatment of glaucoma.

Glaucoma, the most perilous disease leading to blindness is a result of optical neuropathy. Accumulation of aqueous humor in the posterior chamber due to a large difference in the rate of formation and its drainage in the anterior chamber causes an increase in intraocular pressure (IOP) leading to damage of nerve cells. A literature survey has revealed that inhibition of the Rho guanosine triphosphatases (rho GTPase) pathway by specific inhibitors leads to the relaxation of contractile cells involved in the aqueous outflow pathway. Relaxation of the strained contractile cells results in increased outflow thereby releasing IOP. In the present study molecular docking has been used to screen twenty seven bioactive (17 natural compounds and 10 conventional drugs) compounds that may play a significant role in relaxing contractile cells by inhibiting rho-GTPase protein. Docking results showed that among all-natural bioactive compounds Cyanidin and Delphinidine have a good binding affinity (- 8.4 kcal/mol) than the top screened conventional drug molecule Mitomycin, (- 6.3 kcal/mol) when docked with rho-GTPase protein. Cyanidin and Delphinidin belong to anthocyanidin, a glycoside form of anthocyanins from Vaccinium myrtillus L. and Punica granatum. The resembling potential of Cyanidin and Delphinidin concerning the drug Mitomycin was confirmed through simulation analysis. Molecular dynamics study (MDS) for 100 ns, showed that the rho GTPase-Delphinidine complex structure was energetically more stable than rho GTPase-Cyaniding complex in comparison to rho GTPase-Mitomycin complex. The comparative study of both the selected hits (Cyanidin and Delphinidin) was assessed by RMSD, RMSF, Rg, SASA, H-bond, PCA MM/PBSA analysis. The analysis revealed that Delphinidine is more potent to inhibit the rho GTPase as compare to Cyaniding and available conventional drugs in terms of stability and binding free energy. Based on the results, these molecules have good pharmacokinetic and pharmacodynamics properties and will prove to be a promising lead compound as a future drug for Glaucoma.

Computational analysis of microarray data of Arabidopsis thaliana challenged with Alternaria brassicicola for identification of key genes in Brassica.

BACKGROUND: Alternaria blight, a recalcitrant disease caused by Alternaria brassicae and Alternaria brassicicola, has been recognized for significant losses of oilseed crops especially rapeseed-mustard throughout the world. Till date, no resistance source is available against the disease; hence, plant breeding methods cannot be used to develop disease-resistant varieties. Therefore, in the present study, efforts have been made to identify resistance and defense-related genes as well as key components of JA-SA-ET-mediated pathway involved in resistance against Alternaria brasscicola through computational analysis of microarray data and network biology approach. Microarray profiling data from wild type and mutant Arabidopsis plants challenged with Alternaria brassicicola along with control plant were obtained from the Gene Expression Omnibus (GEO) database. The data analysis, including DEGs extraction, functional enrichment, annotation, and network analysis, was used to identify genes associated with disease resistance and defense response. RESULTS: A total of 2854 genes were differentially expressed in WT9C9; among them, 1327 genes were upregulated and 1527 genes were downregulated. A total of 1159 genes were differentially expressed in JAM9C9; among them, 809 were upregulated and 350 were downregulated. A total of 2516 genes were differentially expressed in SAM9C9; among them, 1355 were upregulated and 1161 were downregulated. A total of 1567 genes were differentially expressed in ETM9C9; among them, 917 were upregulated and 650 were downregulated. Besides, a total of 2965 genes were differentially expressed in contrast WT24C24; among them, 1510 genes were upregulated and 1455 genes were downregulated. A total of 4598 genes were differentially expressed in JAM24C24; among them, 2201 were upregulated and 2397 were downregulated. A total of 3803 genes were differentially expressed in SAM24C24; among them, 1819 were upregulated and 1984 were downregulated. A total of 4164 genes were differentially expressed in ETM24C24; among them, 1895 were upregulated and 2269 were downregulated. The upregulated genes of Arabidopsis thaliana were mapped and annotated with CDS sequences of Brassica rapa obtained from PlantGDB database. Additionally, PPI network of these genes were constructed to investigate the key components of hormone-mediated pathway involved in resistance during pathogenesis. CONCLUSION: The obtained information from present study can be used to engineer resistance to Alternaria blight caused by Alternaria brasscicola through molecular breeding or genetic manipulation-based approaches for improving Brassica oilseed productivity.

In silico identification of mimicking molecule(s) triggering von Willebrand factor in human: a molecular drug target for regulating coagulation pathway.

Blood coagulation is a complex and dynamic process wherein the body activates its emergency mechanism to stop bleeding and wound healing via the interactions of prothrombotic and antithrombotic agents. von Willebrand factor (VWF) is a complex glycoprotein and initial component of the hemostasis pathway which serves a multipurpose role in blood coagulation process. There are reports of various plants that contain several bioactive compounds possessing properties of inducing blood coagulation directly or indirectly. In the present study, efforts have been made to identify bioactive compounds that may play a significant role in regulation of the coagulation cascade by accelerating VWF and thus enhance the hemostasis process. An antidiuretic peptide drug, Desmopressin, works on VWF and releases them in circulation. Forty-seven compounds from different plant sources were screened through molecular docking, out of which two compounds, Emodin and Peruvianoside II, showed more binding affinity than the reference drug Desmopressin. Emodin and Peruvianoside II showed binding energies -7.2 and -7.0 kcal/mol, respectively, when docked with VWF, whereas Desmopressin displayed less binding energy (-6.9 kcal/mol). Emodin belongs to anthraquinone from Rumex hastasus and Peruvianoside II belongs to flavanone glycosides from Thevetia peruviana. The mimicking potential of top identified molecules with respect to the drug was confirmed through simulation analysis. Besides, the molecular dynamics simulation (MDS) study (for 20 ns) showed that the Peruvianoside II protein complex was energetically more stable than Emodin protein complex. Based on the results, Peruvianoside II possesses great potential and thus may be considered for development of drugs for hemostasis.

Augmentation of crop productivity through interventions of omics technologies in India: challenges and opportunities.

With the continuous increase in the population of developing countries and decline of natural resources, there is an urgent need to qualitatively and quantitatively augment crop productivity by using new tools and technologies for improvement of agriculturally important traits. The new scientific and technological omics-based approaches have enabled us to deal with several issues and challenges faced by modern agricultural system and provided us novel opportunities for ensuring food and nutritional security. Recent developments in sequencing techniques have made available huge amount of genomic and transcriptomic data on model and cultivated crop plants including Arabidopsis thaliana, Oryza sativa, Triticum aestivum etc. The sequencing data along with other data generated through several omics platforms have significantly influenced the disciplines of crop sciences. Gene discovery and expression profiling-based technologies are offering enormous opportunities to the scientific community which can now apply marker-assisted selection technology to assess and enhance diversity in their collected germplasm, introgress essential traits from new sources and investigate genes that control key traits of crop plants. Utilization of omics science and technologies for crop productivity, protection and management has recently been receiving a lot of attention; the majority of the efforts have been put into signifying the possible applications of various omics technologies in crop plant sciences. This article highlights the background of challenges and opportunities for augmentation of crop productivity through interventions of omics technologies in India.

Identification of new drug-like compounds from millets as Xanthine oxidoreductase inhibitors for treatment of Hyperuricemia: A molecular docking and simulation study.

Xanthine oxidoreductase plays an important role in formation of uric acid and its regulation during purine catabolism. Uncontrolled expression of this enzyme is responsible for overproduction and deposition of uric acid in blood that is potentially injurious because it can breakdown DNA and protein molecules, triggering many diseases. Human Xanthine oxidoreductase (HsXOR) is considered to be a pharmacological target for the treatment of hyperuricemia. Many of the HsXOR-inhibitor drugs such as Febuxostat and Allopurinol are known to have significant adverse effects. Therefore, there is an urgent need to develop new HsXOR-inhibitor drugs with less or no toxicity for the long-term treatment or prevention of hyperuricemia-related diseases. Many nutritious and medical functions have been reported in millets. Present work deals with identification of millet derived compounds in terms of their interaction with target, HsXOR through molecular docking and dynamic simulation studies. Of thirty two chosen compounds, Luteolin and Quercitin showed more binding affinity with HsXOR than reference drugs, Febuxostat and Allopurinol. Molecular dynamics simulations (20 ns long) revealed that Luteolin-protein complex was energetically more stable than Quercitin-protein complex. The millet derived compounds i.e. Luteolin and Quercitin showed binding energy -9.7 kcal/mol whereas the known drugs i.e. Febuxostat and Allopurinol showed binding energy -8.0 kcal/mol and -5.5 kcal/mol respectively. Based on the study, Luteolin possess high potential to be considered for trial as an inhibitor of HsXOR as it may regulate the pathway by inhibiting HsXOR. Further investigations are proposed to consider Luteolin for developing future drugs from millets and other natural sources.

Modeling of the jasmonate signaling pathway in Arabidopsis thaliana with respect to pathophysiology of Alternaria blight in Brassica.

The productivity of Oilseed Brassica, one of the economically important crops of India, is seriously affected by the disease, Alternaria blight. The disease is mainly caused by two major necrotrophic fungi, Alternaria brassicae and Alternaria brassicicola which are responsible for significant yield losses. Till date, no resistant source is available against Alternaria blight, hence plant breeding methods can not be used to develop disease resistant varieties. Jasmonate mediated signalling pathway, which is known to play crucial role during defense response against necrotrophs, could be strengthened in Brassica plants to combat the disease. Since scanty information is available in Brassica-Alternaria pathosystems at molecular level therefore, in the present study efforts have been made to model jasmonic acid pathway in Arabidopsis thaliana to simulate the dynamic behaviour of molecular species in the model. Besides, the developed model was also analyzed topologically for investigation of the hubs node. COI1 is identified as one of the promising candidate genes in response to Alternaria and other linked components of plant defense mechanisms against the pathogens. The findings from present study are therefore informative for understanding the molecular basis of pathophysiology and rational management of Alternaria blight for securing food and nutritional security.

In Silico Identification of Mimicking Molecules as Defense Inducers Triggering Jasmonic Acid Mediated Immunity against Alternaria Blight Disease in Brassica Species.

Alternaria brassicae and Alternaria brassicicola are two major phytopathogenic fungi which cause Alternaria blight, a recalcitrant disease on Brassica crops throughout the world, which is highly destructive and responsible for significant yield losses. Since no resistant source is available against Alternaria blight, therefore, efforts have been made in the present study to identify defense inducer molecules which can induce jasmonic acid (JA) mediated defense against the disease. It is believed that JA triggered defense response will prevent necrotrophic mode of colonization of Alternaria brassicae fungus. The JA receptor, COI1 is one of the potential targets for triggering JA mediated immunity through interaction with JA signal. In the present study, few mimicking compounds more efficient than naturally occurring JA in terms of interaction with COI1 were identified through virtual screening and molecular dynamics simulation studies. A high quality structural model of COI1 was developed using the protein sequence of Brassica rapa. This was followed by virtual screening of 767 analogs of JA from ZINC database for interaction with COI1. Two analogs viz. ZINC27640214 and ZINC43772052 showed more binding affinity with COI1 as compared to naturally occurring JA. Molecular dynamics simulation of COI1 and COI1-JA complex, as well as best screened interacting structural analogs of JA with COI1 was done for 50 ns to validate the stability of system. It was found that ZINC27640214 possesses efficient, stable, and good cell permeability properties. Based on the obtained results and its physicochemical properties, it is capable of mimicking JA signaling and may be used as defense inducers for triggering JA mediated resistance against Alternaria blight, only after further validation through field trials.

Computer aided screening of natural compounds targeting the E6 protein of HPV using molecular docking.

The cancer profile in the Indian state of Uttarakhand reveals that the breast cancer is the most prevalent type of cancers in females followed by cervical and ovarian type. Literature survey shows that the E6 protein of Human Papilloma Virus-16 (HPV-16) is responsible for causing several forms of cancer in human. Therefore, it is of interest to screen HPV-16 E6 target protein with known natural compounds using computer aided molecular modeling and docking tools. The complete structure of E6 is unknown. Hence, the E6 structure model was constructed using different online servers followed by molecular docking of Colchine, Curcumin, Daphnoretin, Ellipticine and Epigallocatechin-3-gallate; five known natural compounds with best E6 protein model predicted by Phyre2 server. The screening exercise shows that Daphnoretin (with binding free energy of -8.3 kcal/mol), a natural compound derived from Wikstroemia indica has the top binding properties. Thus, it is of interest to consider the compound for further validation.

Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer.

The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation.

Effects of fluoride on germination, early growth and antioxidant enzyme activities of legume plant species Prosopis juliflora.

Prosopis juliflora (Mimosoideae) is a fast growing and drought resistant tree of semi-arid region of India where fluoride (F) toxicity is a common problem. In the present investigations this species was fluoride tested to check their capacity as bioindicator plant and its efficiency to accumulate. To achieve this aim, P. juliflora seedlings grown in hydroponic culture containing different concentrations of F were analyzed for germination percentage together with some biochemical parameters viz, antioxidant enzyme activities, total chlorophyll and accumulation of F in different plant parts. After 15 days of treatment, root growth (r = -0.928, p < 0.01), shoot growth (r = -0.976, p < 0.01), vigor index (r = -0.984, p < 0.01) were in decreasing trend with increasing concentration of NaF. Both catalase (3.2 folds) and peroxidase (2.7 folds) enzymes activity increased with increase in F concentration. Plant accumulated larger portion of the F in the roots (1024.63 microg g(-1) d.wt.) followed by shoot (492.30 microg g(-1) d.wt.). As P. juliflora did not show any morphological changes (marginal and tip chlorosis of leaf portions, necrosis and together these features are referred to as leaf "tip-burn") therefore, this species may be used as suitable bioindicator species for potentially F affected areas. Further, higher accumulation of F in roots indicates that P. juliflora is a suitable species for the removal of F in phytoremediation purposes.

Mapping of fluoride endemic area and assessment of F(-1) accumulation in soil and vegetation.

The prevalence of fluorosis is mainly due to the consumption of more fluoride (F(-1)) through drinking water, vegetables, and crops. The objective of the study was mapping of F(-1) endemic area of Newai Tehsil, Tonk district, Rajasthan, India. For the present study, water, soil (0-45 cm), and vegetation samples were collected from 17 villages. Fluoride concentration in water samples ranged from 0.3 to 9.8 mg/l. Out of 17 villages studied, the amounts of F(-1) content of eight villages were found to exceed the permissible limits. Labile F(-1) content and total F(-1) content in soil samples ranges 11.00-70.05 mg/l and 50.3-179.63 µg g(-1), respectively. F(-1) content in tree species was found in this order Azadirachta indica 47.32-55.76 µg g(-1) > Prosopis juliflora 40.16-49.63 µg g(-1) > Acacia tortilis 34.39-43.60 µg g(-1). While in case of leafy vegetables, F(-1) content order was Chenopodium album 54.23-98.42 µg g(-1) > Spinacea oleracea 30.41-64.09 µg g(-1) > Mentha arvensis 35.48-51.97 µg g(-1). The order of F(-1) content in crops was found as 41.04 µg g(-1) Pennisetum glaucum > 13.61 µg g(-1) Brassica juncea > 7.98 µg g(-1) Triticum sativum in Krishi Vigyan Kendra (KVK) farms. Among vegetation, the leafy vegetables have more F(-1) content. From the results, it is suggested that the people of KVK farms should avoid the use of highly F(-1) containing water for irrigation and drinking purpose. It has been recommended to the government authority to take serious steps to supply drinking water with low F(-1) concentration for the fluorosis affected villages. Further, grow more F(-1) hyperaccumulator plants in F(-1) endemic areas to lower the F(-1) content of the soils.

Organ-wise accumulation of fluoride in Prosopis juliflora and its potential for phytoremediation of fluoride contaminated soil.

Fluoride (F) contamination is a global environmental problem, as there is no cure of fluorosis available yet. Prosopis juliflora is a leguminous perennial, phreatophyte tree, widely distributed in arid and semi-arid regions of world. It extensively grows in F endemic areas of Rajasthan (India) and has been known as a "green" solution to decontaminate cadmium, chromium and copper contaminated soils. This study aims to check the tolerance potential of P. juliflora to accumulate fluoride. For this work, P. juliflora seedlings were grown for 75 d on soilrite under five different concentrations of F viz., control, 25, 50, 75 and 100 mg NaF kg(-1). Organ-wise accumulation of F, bioaccumulation factor (BF), translocation factor (TF), growth ratio (GR) and F tolerance index (TI) were examined. Plant accumulated high amounts of F in roots. The organ-wise distribution showed an accumulation 4.41 mg kg(-1)dw, 12.97 mg kg(-1)dw and 16.75 mg kg(-1)dw F, in stem, leaves and roots respectively. The results indicated significant translocation of F from root into aerial parts. The bioaccumulation and translocation factor values (>1.0) showed high accumulation efficiency and tolerance of P. juliflora to F. It is concluded that P. juliflora is a suitable candidate for phytoremediation purpose and can be explored further for the decontamination of F polluted soils.

Effect of fluoride pollution on genetic diversity of a medicinal tree, Syzygium cumini.

Syzygium cumini Linn. (Myrtaceae) is a medicinal tree (Jamun) used worldwide in treatment of diabetes. However, no molecular data is available on genetic polymorphism and its relationship, if any with fluoride pollution. In the present study, the genetic variability of two populations of S. cumini growing in fluoride rich soils and normal soils located in Rajasthan and Haryana regions of India, respectively was determined using random amplified polymorphic DNA (RAPD) markers. Different measures of diversity in Rajasthan populations: Shannon's index of phenotypic diversity (I) = 0.440; Nei's genetic diversity (h) = 0.292; effective number of alleles per locus (Ne) = 1.497; total species diversity (Hsp) = 0.307 and within population diversity (Hpop) = 0.158 showed high diversity in comparison to Haryana populations. Thus, it seems that Rajasthan population responds with increased genetic variation resulting possibly from new mutation that affect allele frequencies as a consequence of adaptation to contaminated environment. This may imply that the increased diversity levels may act as a buffer to combat fluoride stress. Cluster analysis and principal component analysis (PCA) results showed mixing between the populations.