A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids.

Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600 mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study's hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600 mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26 nmol/g and 4.13 nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota.

Graded levels of Eimeria infection modulated gut physiology and temporarily ceased the egg production of laying hens at peak production.

An experiment was conducted to investigate the changes in gastrointestinal physiology, including intestinal leakage, immune response, oxidative stress, along with performance traits, of Hy-Line W-36 laying hens following Eimeria infection at peak egg production. A total of 360 laying hens, at 25 wk of age, were assigned randomly to 5 treatment groups, each consisting of 6 replicate cages, including a nonchallenged control group. The other 4 groups were inoculated with graded levels of mixed Eimeria species as high, medium-high, medium-low, and low doses, respectively. The body weight (BW) and body weight gain (BWG) of laying hens were measured from 0 to 14 days postinoculation (DPI). Average daily feed intake (ADFI) and hen-day egg production (HDEP) were measured from 0 to 15 and 0 to 28 DPI, respectively. Gut permeability was measured on 5 DPI, whereas oxidative stress, immune response, and expression of nutrient transporter genes were measured on 6 and 14 DPI. A significant linear reduction in BW and BWG was observed with increased Eimeria inoculation dosage on both 6 and 14 DPI (P < 0.001, P-Lin < 0.0001). An interaction between the Eimeria dosages and DPI was observed for ADFI (P < 0.0001). Feed intake in the challenged groups decreased starting at 4 DPI, with the most significant drop occurring at 7 DPI, which did not recover until 15 DPI. Following the challenge, gastrointestinal physiology shifted toward the host defense against the Eimeria infection by upregulating mRNA expression of tight junction proteins and immune responses while downregulating the expression of key nutrient transporters on 6 and 14 DPI (P < 0.05). An interaction between the Eimeria inoculation dosage and DPI was also observed for daily HDEP (P < 0.0001). Overall, HDEP was lower in the challenged groups compared to the control. Daily HDEP in the challenged groups dropped from 8 DPI and became similar to the control birds only after 24 DPI. Egg production temporarily ceased in most of the laying hens infected with the high and medium-high dosages of Eimeria. In conclusion, Eimeria infection activated the host immune response, negatively affecting the gastrointestinal health, growth performance, and temporarily ceased the egg production of Hy-Line W-36 laying hens when infected at peak production.

Molecular dynamics simulations assisted investigation of phytochemicals as potential lead candidates against anti-apoptotic Bcl-B protein.

Due to the multifarious nature of cancer, finding a single definitive cure for this dreadful disease remains an elusive challenge. The dysregulation of the apoptotic pathway or programmed cell death, governed by the Bcl-2 family of proteins plays a crucial role in cancer development and progression. Bcl-B stands out as a unique anti-apoptotic protein from the Bcl-2 family that selectively binds to Bax which inhibits its pro-apoptotic function. Although several inhibitors are reported for Bcl-2 family proteins, no specific inhibitors are available against the anti-apoptotic Bcl-B protein. This study aims to address this research gap by using virtual screening of an in-house library of phytochemicals from seven anti-cancer medicinal plants to identify lead molecules against Bcl-B protein. Through pharmacokinetic analysis and molecular docking studies, we identified three lead candidates (Enterolactone, Piperine, and Protopine) based on appreciable drug-likeliness, ADME properties, and binding affinity values. The identified molecules also exhibited specific interactions with critical amino acid residues of the binding cleft, highlighting their potential as lead candidates. Finally, molecular dynamics simulations and MM/PBSA based binding free energy analysis revealed that Enterolactone (CID_114739) and Piperine (CID_638024) molecules were on par with Obatoclax (CID_11404337), which is a known inhibitor of the Bcl-2 family proteins.Communicated by Ramaswamy H. Sarma.

Modulation of terpenoid indole alkaloid pathway via elicitation with phytosynthesized silver nanoparticles for the enhancement of ajmalicine, a pharmaceutically important alkaloid.

MAIN CONCLUSION: The use of silver nanoparticles as elicitors in cell cultures of Rauwolfia serpentina resulted in increased levels of ajmalicine, upregulated structural and regulatory genes, elevated MDA content, and reduced activity of antioxidant enzymes. These findings hold potential for developing a cost-effective method for commercial ajmalicine production. Plants possess an intrinsic ability to detect various stress signals, prompting the activation of defense mechanisms through the reprogramming of metabolites to counter adverse conditions. The current study aims to propose an optimized bioprocess for enhancing the content of ajmalicine in Rauwolfia serpentina callus through elicitation with phytosynthesized silver nanoparticles. Initially, callus lines exhibiting elevated ajmalicine content were established. Following this, a protocol for the phytosynthesis of silver nanoparticles using seed extract from Rauwolfia serpentina was successfully standardized. The physicochemical attributes of the silver nanoparticles were identified, including their spherical shape, size ranging from 6.7 to 28.8 nm in diameter, and the presence of reducing-capping groups such as amino, carbonyl, and amide. Further, the findings indicated that the presence of 2.5 mg L-1 phytosynthesized silver nanoparticles in the culture medium increased the ajmalicine content. Concurrently, structural genes (TDC, SLS, STR, SGD, G10H) and regulatory gene (ORCA3) associated with the ajmalicine biosynthetic pathway were observed to be upregulated. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were observed. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were also observed. Our results strongly recommend the augmentation of ajmalicine content in the callus culture of R. serpentina through supplementation with silver nanoparticles, a potential avenue for developing a cost-effective process for the commercial production of ajmalicine.

Effect of supplementation of fennel seed powder on intake, growth performance, gut health and economics in goats.

The aim of this study was to evaluate the effect of fennel seed powder (FSP) at varying levels on intake, growth, gut health, body condition, body measurements and economics in post weaned male goats. For this experiment a total of 30 post weaned male kids of Barbari goats with statistically similar body weight (P = 0.575) and age (3-4 months) were randomly distributed in three comparable groups each having 10 kids. Three groups viz. control (no supplementation), T1 (0.5% of DM in diet) and T2 (1.0% of DM in diet) were formed and the study continued up to 5 months. Statistical analysis of results showed significant effect of FSP supplementation on intake, growth, body condition, and gut health and body measurements in goats of treatment groups. Significantly highest body weight (BW), average daily gain (ADG) and dry matter intake (DMI) (P < 0.001) was reported in T2 group, followed by T1 than control group goats. Further, feed conversion ratio (FCR), feed conversion efficiency (FCE%) and body condition score of treatment groups (T1 and T2) was improved significantly (P < 0.001) than control group goats. However, FCR and FCE% in T1 and T2 differed non- significantly (P > 0.05). Analysis of fecal samples indicated significantly higher (P < 0.001) fecal dry matter (FDM%), fecal consistency score (FS) in T1 and T2 group than control group whereas parasitic fecal egg count per gram (EPG) was significantly lower in T1 and T2 group than control group. However, EPG in T1 and T2 differed non- significantly (P > 0.05). Body measures differed significantly (P < 0.05) among groups. Economic evaluation of FSP supplemented showed that T1 and T2 group fetched INR 462 and 501 per goat on selling over control group (1USD = 82.54 INR). It can be concluded from this study that supplementation of FSP @ 1.0% of DM in diet may economically improve intake, growth, gut health, body condition, body measurements and economics in post weaned male Barbari goats.

Preparation, Characterization, and Antioxidant Activity of L-Ascorbic Acid/HP-ß-Cyclodextrin Inclusion Complex-Incorporated Electrospun Nanofibers.

L-Ascorbic acid (LAA) is a key vitamin, implicated in a variety of physiological processes in humans. Due to its free radical scavenging activity, it is extensively employed as an excipient in pharmaceutical products and food supplements. However, its application is greatly impeded by poor thermal and aqueous stability. Herein, to improve the stability and inhibit oxidative degradation, we prepared LAA-cyclodextrin inclusion complex-incorporated nanofibers (NFs). The continuous variation method (Job plot) demonstrated that LAA forms inclusions with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) at a 2:1 molar stoichiometric ratio. The NFs were prepared via the single step electrospinning technique, without using any polymer matrix. The solid-state characterizations of LAA/HP-ß-CD-NF via powder x-ray diffractometry (PXRD), Fourier-transform infrared (FT-IR) analysis, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and nuclear magnetic resonance (1H NMR and 2D-NOESY) spectroscopy, reveal the effective encapsulation of the LAA (guest molecule) inside the HP-ß-CD (host) cavity. The SEM micrograph reveals an average fiber diameter of ~339 nm. The outcomes of the thermal investigations demonstrated that encapsulation of LAA within HP-ß-CD cavities provides improved thermal stability of LAA (by increasing the thermal degradation temperature). The radical scavenging assay demonstrated the enhanced antioxidant potential of LAA/HP-ß-CD-NF, as compared to native LAA. Overall, the study shows that cyclodextrin inclusion complex-incorporated NFs, are an effective approach for improving the limitations associated with LAA, and provide promising avenues in its therapeutic and food applications.

Network pharmacology-based anti-pancreatic cancer potential of kaempferol and catechin of Trema orientalis L. through computational approach.

In pancreatic cancer, healthy cells in the pancreas begin to malfunction and proliferate out of control. According to our conventional knowledge, many plants contain several novel bioactive compounds, having pharmaceutical applications for the treatment of disease like pancreatic cancer. The methanolic fraction of fruit extract of Trema orientalis L. (MFETO) was analysed through HRMS. In this in silico study, pharmacokinetic and physicochemical properties of the identified flavonoids from MFETO were screened out by ADMET analysis. Kaempferol and catechin followed Lipinski rules and showed no toxicity in Protox II. Targets of these compounds were taken from SwissTarget prediction and TCMSP whilst targets for pancreatic cancer were taken from GeneCards and DisGeNET databases. The protein-protein interaction (PPI) network of common genes was generated through STRING and then exported to the Cytoscape to get top 5 hub genes (AKT1, SRC, EGFR, TNF, and CASP3). The interaction between compounds and hub genes was analysed using molecular docking, and high binding affinity between them can be visualised by Biovia discovery studio visualizer. Our study shows that, five hub genes related to pancreatic cancer play an important role in tumour growth induction, invasion and migration. Kaempferol effectively check cell migration by inhibiting ERK1/2, EGFR-related SRC, and AKT pathways by scavenging ROS whilst catechin inhibited TNFα-induced activation and cell cycle arrest at G1 and G2/M phases by induction of apoptosis of malignant cells. Kaempferol and catechin containing MFETO can be used for formulation of potent drugs for pancreatic cancer treatment in future.

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise.

Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year, with an estimated 5-year survival rate of 30%-35% after diagnosis. Hepatocellular carcinoma (HCC) constitutes a significant subtype of liver cancer (approximate75%) and is considered primary liver cancer. Treatment for liver cancer mainly depends on the stage of its progression, where surgery including, hepatectomy and liver transplantation, and ablation and radiotherapy are the prime choice. For advanced liver cancer, various drugs and immunotherapy are used as first-line treatment, whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins. Sorafenib and lenvatinib are first-line therapies, while regorafenib and ramucirumab are second-line therapy. Various metabolic and signaling pathways such as Notch, JAK/ STAT, Hippo, TGF-ß, and Wnt have played a critical role during HCC progression. Dysbiosis has also been implicated in liver cancer. Drug-induced toxicity is a key obstacle in the treatment of liver cancer, necessitating the development of effective and safe medications, with natural compounds such as resveratrol, curcumin, diallyl sulfide, and others emerging as promising anticancer agents. This review highlights the current status of liver cancer research, signaling pathways, therapeutic targets, current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.

Phytochemicals, Antioxidant, Anti-inflammatory Studies, and Identification of Bioactive Compounds Using GC-MS of Ethanolic Novel Polyherbal Extract.

Hyperglycemia is the hallmark of diabetes, which is a collection of related metabolic disorders. Over time, diabetes can cause a variety of problems, including cardiovascular disease, nephropathy, neuropathy, and retinopathy. Ethanolic novel polyherbal extract (PHE) was prepared by mixing equal amounts of the following ingredients: Terminalia chebula Retz. (TC), Terminalia bellerica Roxb. (TB), Berberis aristata DC. (BA), Nyctanthes arbostratis L. (NA), Premna integrifolia L. (PI), and Andrographis paniculata Nees. (AP). Analysis of PHE results revealed phytochemicals like glycosides, flavonoids, alkaloids, tannins, phytosterols, and saponins. The aim of the study was to prepare an ethanolic extract of PHE using the cold maceration technique, and identify bioactive molecules from gas chromatography-mass spectrometry (GC-MS) analysis, and evaluate biological responses by using in vitro studies like antioxidant and anti-inflammatory activity. PHE was found to contain a total of 35 phytochemicals in GC-MS of which 22 bioactive compounds were obtained in good proportion. There are a few new ones, including 2-buten-1-ol, 2-ethyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl (17.22%), 1, 2, 5, 6-tetrahydrobenzonitrile (4.26%), 4-piperidinamine, 2, 2, 6, 6-tetramethyl-(0.07%), undecanoic acid, 5-chloro-, chloromethyl ester (0.41%), are identified. Antioxidant activity was estimated using EC50 values of 392.143 µg/ml, which were comparable to the standard value of EC50 310.513 µg/ml obtained using DPPH. Antioxidant activity was estimated with EC50 392.143 µg/ml, comparable to standard EC50 310.513 µg/ml using DPPH. In vitro anti-inflammatory potential was found with IC50 of 91.449 µg/ml, comparable to standard IC50 89.451 µg/ml for membrane stabilization and IC50 of 36.940 µg/ml, comparable to standard IC50 35.723 µg/ml for protein denaturation assays. As a result, the findings of this study show an enrichment of bioactive phytochemicals that can be used to investigate biological activity. To better understand how diabetes receptors work, in silico studies like docking could be carried out.

Chlorogenic Acid: A Dietary Phenolic Acid with Promising Pharmacotherapeutic Potential.

Phenolic acids are now receiving a great deal of interest as pervasive human dietary constituents that have various therapeutic applications against chronic and age-related diseases. One such phenolic acid that is being utilized in traditional medicine is chlorogenic acid (CGA). It is one of the most readily available phytochemicals that can be isolated from the leaves and fruits of plants, such as coffee beans (Coffea arabica L.), apples (Malus spp.), artichoke (Cynara cardunculus L.), carrots (Daucus carota L.), betel (Piper betle L.), burdock (Arctium spp.), etc. Despite its low oral bioavailability (about 33%), CGA has drawn considerable attention due to its wide range of biological activities and numerous molecular targets. Several studies have reported that the antioxidant and anti-inflammatory potentials of CGA mainly account for its broad-spectrum pharmacological attributes. CGA has been implicated in exerting a beneficial role against dysbiosis by encouraging the growth of beneficial GUT microbes. At the biochemical level, its therapeutic action is mediated by free radical scavenging efficacy, modulation of glucose and lipid metabolism, down-regulation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1ß, and interferon-gamma (IFN-γ), upregulation of nuclear factor erythroid 2-related factor 2 (Nrf-2), and inhibition of the activity of nuclear factor- κß (NF-κß), thus helping in the management of diabetes, cardiovascular diseases, neurodegenerative disorders, cancer, hypertension etc. This review highlights the natural sources of CGA, its bioavailability, metabolism, pharmacotherapeutic potential, and underlying mechanisms of action for the clinical usefulness of CGA in the management of health disorders.

Assessment of diversity in anti-nutrient profile, resistant starch, minerals and carbohydrate components in different ricebean (Vigna umbellata) accessions.

Ricebean accessions (n = 38) cultivated in India were evaluated for their comprehensive nutrient, anti-nutrients and mineral composition. Protein and total dietary fibre ranged between 23.23 and 27.33 and 12.27 to 16.69 g/100 g, respectively. Among the oligosaccharides, verbascose was not detected, however, raffinose and stachyose ranged between 47 and 186 and 117 to 5765 mg/100 g, respectively. Among the free sugars, sucrose was found dominating (up to 370 mg/100 g). Resistant starch (4.13 to 8.62 %), iron (3.49 to 7.46 mg/100 g), zinc (1.90 to 3.72 mg/100 g) and selenium (0.28 to 4.48 µg/100 g) varied significantly (p < 0.05) among ricebean samples. Phytic acid, saponin, trypsin inhibitor and oxalate analysed in ricebean accessions ranged between 303 and 760 mg/100 g, 19 to 46 mg/g, 309 to 1076 mg/100 g and 219 to 431 mg/100 g, respectively. Multivariate analysis using hierarchical clustering analysis (HCA), and principal component analysis (PCA) was employed to decipher the diversity of nutrients and anti-nutrients across the ricebean accessions. Based on HCA, dendrogram-1 (nutrients) and dendrogram-2 (minerals, anti-nutrients) were produced, having four clusters in each. In the dendrogram-1 and 2, the largest cluster had (n = 21) and (n = 15) accessions, respectively. The PCA analyse the uncorrelated set of variables (principal components) and it condenses a large set of data variables. Based on the eigenvalue >1, a total of eight PCs were formed contributing total variance of 78.8 %. The factor loading contribution in the PC1 and PC2 were from iron, fructose, glucose, raffinose and total dietary fibre, selenium (Se) and protein, respectively.

Antimicrobial and immunomodulatory effects of tannic acid supplementation in broilers infected with Salmonella Typhimurium.

Infection by Salmonella Typhimurium, a food-borne pathogen, can reduce the poultry production efficiency. The objective of this study was to investigate the effects of tannic acid (TA) supplementation on growth performance, Salmonella colonization, gut barrier integrity, serum endotoxin levels, antioxidant capacity, gut health, and immune function in broilers infected with the Salmonella enterica serovar Typhimurium nalidixic acid resistant strain (STNR). A total of 546 one-day-old broilers were arbitrarily allocated into 6 treatments including 1) Sham-challenged control (SCC; birds fed a basal diet and administrated peptone water); 2) Challenged control (CC; birds fed a basal diet and inoculated with 108 STNR); 3) Tannic acid 0.25 (TA0.25; CC + 0.25 g/kg TA); 4) TA0.5 (CC + 0.5 g/kg TA); 5) TA1 (CC + 1 g/kg TA); and 6) TA2 (CC + 2 g/kg TA). On D 7, supplemental TA linearly reduced STNR colonization in the ceca (P < 0.01), and TA1 and TA2 group had significantly lower reduced STNR colonization in the ceca (P < 0.01). On D 7 to 21, average daily gain tended to be linearly increased by supplemental TA (P = 0.097). The serum endotoxin levels were quadratically decreased by supplemental TA on D 21 (P < 0.05). Supplemental TA quadratically increased ileal villus height (VH; P < 0.05), and the TA0.25 group had higher ileal VH compared to the CC group (P < 0.05). Supplemental TA linearly increased percentage of peripheral blood CD8+ T cells on D 18 (P < 0.01). The TA0.5 group had significantly lower lymphocyte numbers compared to the CC groups (P < 0.05). The abundance of monocytes linearly increased with TA supplementation (P < 0.01). Therefore, broilers fed TA had reduced STNR colonization, increased growth performance, decreased serum endotoxin levels, enhanced gut health in the broilers, and stimulated the immune system in broilers infected with STNR. Supplementation of TA (1-2 g/kg) enhanced growth performance and gut health via antimicrobial and immunostimulatory effects in broilers infected with STNR.

Functional role of branched chain amino acids in poultry: a review.

This review provides insight into the effects of the branched-chain amino acids (BCAA: leucine, isoleucine, and valine) on the growth, production performance, immunity, and intestinal health of poultry. Besides providing nitrogen substrates and carbon framework for energy homeostasis and transamination, BCAA also function as signaling molecules in the regulation of glucose, lipid, and protein synthesis via protein kinase B and as a mechanistic target of the rapamycin (AKT-mTOR) signaling pathway that is important for muscle accretion. The level of leucine is generally high in cereals and an imbalance in the ratio among the 3 BCAA in a low protein diet would produce a negative effect on poultry growth performance. This occurs due to the structural similarity of the 3 BCAA, which leads to metabolic competition and interference with the enzymatic degradation pathway. Emerging evidence shows that the inclusion of BCAA is essential for the proper functioning of the innate and adaptive immune system and the maintenance of intestinal mucosal integrity. The recommended levels of BCAA for poultry are outlined by NRC (1994), but commercial broilers and laying hen breed standards also determine their own recommended levels. In this review, it has been noted that the requirement for BCAA is influenced by the diet type, breed, and age of the birds. Additionally, several studies focused on the effects of BCAA in low protein diets as a strategy to reduce nitrogen excretion. Notably, there is limited research on the inclusion ratio of BCAA in a supplemental form as compared to the ingredient-bound form which would affect the dynamics of utilization in different disease-challenged conditions, especially those affecting digesta passage ratio. In summary, this review encompasses the role of BCAA as functional AA and discusses their physiological effects on the productivity and health of poultry. The observations and interpretations of this review can guide future research to adjust the recommended levels of BCAA in feeding programs in the absence of subtherapeutic antibiotics in poultry.

Sensing of mercury ion using light induced aqueous leaf extract mediated green synthesized silver nanoparticles of Cestrum nocturnum L.

In this study, a simple, one-pot, and eco-friendly biosynthesis of silver nanoparticles (AgNPs) was accomplished with the use of aqueous leaves extract of Cestrum nocturnum L.(AECN). Different techniques like ultraviolet-visible (UV-Vis) spectrophotometry, Fourier transform infrared (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning area electron diffraction were used to investigate the optical, operational, and physical properties of the green synthesized AECN-AgNPs.The AECN-AgNPs were further used for the detection of Hg2+ by UV-Vis and electrochemical methods. The disintegration of the AECN-AgNPs solution caused the formation of an Ag-Hg amalgam, which caused discoloration of the solution. Sensing performance for a variety of metals such as Na+, K+, Mg2+, Ca2+, Ni2+, Cu 2+, Fe3+, Zn2+, Co2+, Cd2+, Pb2+, As3+, and Mn2+ at 10-mM concentrations was measured in order to determine the selectivity of the sensor towards the Hg2+. For the electrochemical determination of 2 + Hg2+ , AECN-AgNPs were immobilized on a glassy carbon (GC) electrode, and the resulting modified electrode (GC/AECN-AgNPs) was characterized by cyclic voltammetry. This phenomenon is advantageously used for the sensitive determination of trace level Hg2+. GC/AECN-AgNPs demonstrated a linear calibration range of 100 nM to 10 µM and a limit of detection of 21 nM for Hg2+ determination.

Evaluation of antidiabetic activity of dietary phenolic compound chlorogenic acid in streptozotocin induced diabetic rats: Molecular docking, molecular dynamics, in silico toxicity, in vitro and in vivo studies.

BACKGROUND: Chlorogenic acid is amongst the well-known polyphenolic compounds being used in human food and beverages. Its presence has been reported in tea leaves, roasted green beans, coffee, cocoa, berry fruits, apples, citrus fruits, and pears. OBJECTIVE: The present study aims to elucidate the effectiveness of chlorogenic acid on in silico and in vitro inhibition of glucose metabolising enzymes (α-amylase and α-glucosidase) and on blood-based markers associated with diabetic complications in vivo. METHODS: Docking and molecular dynamics studies were performed using GLIDE (Schrodinger, LLC, NY, 2019-2) and Maestro-Desmond Interoperability Tools, version 4.1 (Schrödinger, NY, 2015), respectively. α-Amylase and α-glucosidase inhibitory activities of chlorogenic acid were measured in vitro. Diabetes was induced in adult Wistar rats by injecting streptozotocin (50 mg/kg). Biochemical assays were performed using standard kits. RESULT: The in silico studies for α-amylase and α-glucosidase with chlorogenic acid suggested that the ligand was stable and strongly bound with the above-mentioned proteins. During in vitro studies, chlorogenic acid inhibited both the enzymes in a dose-dependent manner (5-30 µg/mL). In addition, chlorogenic acid treatment for 28 days significantly suppressed the increase in blood glucose, total cholesterol, triglyceride, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, γ-glutamyl transferase, alkaline phosphatase, total bilirubin, creatinine, urea, uric acid, and feed intake levels in diabetic rats. Chlorogenic acid also caused significant improvement in body weight, serum HDL-cholesterol, total protein, and albumin levels leading to betterment in atherogenic indices related to diabetes-associated cardiovascular risks. CONCLUSION: The findings indicated that chlorogenic acid inhibited α-amylase and α-glucosidase and significantly decreased diabetes associated hyperglycemia, hyperlipidemia, and hepatorenal damage, making it a possible functional food ingredient and drug candidate for the management of diabetes and related complications.

Effects of Dietary Fiber on Nutrients Utilization and Gut Health of Poultry: A Review of Challenges and Opportunities.

Many fibrous ingredients incorporated in poultry feed to reduce production costs have low digestibility and cause poor growth in poultry. However, all plant-based fibers are not equal, and thus exert variable physiological effects on the birds, including but not limited to, digestibility, growth performance, and microbial fermentation. Several types of fibers, especially oligosaccharides, when supplemented in poultry diets in isolated form, exhibit prebiotic effects by enhancing beneficial gut microbiota, modulating gut immunity, boosting intestinal mucosal health, and increasing the production of short-chain fatty acids (SCFA) in the gut. Recently, poultry producers are also facing the challenge of limiting the use of antibiotic growth promoters (AGP) in poultry feed. In addition to other alternatives in use, exogenous non-starch polysaccharides digesting enzymes (NSPase) and prebiotics are being used to provide substrates to support the gut microbiome. We also conducted a meta-analysis of different studies conducted in similar experimental conditions to evaluate the variability and conclusiveness in effects of NSPase on growth performance of broilers fed fibrous ingredients. This review presents a holistic approach in discussing the existing challenges of incorporating high-fiber ingredients in poultry feed, as well as strategies to fully utilize the potential of such ingredients in improving feed efficiency and gut health of poultry.

Cross-sectional Study of Calcium Phosphate Product and Intact Parathyroid Hormone Levels in Predialysis and Postdialysis Patients with Stage 5 Chronic Kidney Disease.

Chronic kidney disease (CKD) gradually deteriorates the mineral homeostasis, with a disruption of normal serum phosphorus, calcium, and intact parathyroid hormone (iPTH). Hemodialysis is one of the replacement therapies used to treat CKD patients to achieve normal kidney function. The present study aimed to evaluate the impact of dialysis on serum levels of calcium, phosphorus, and iPTH in CKD patients. A cross-sectional observational study was conducted between May 2015 and April 2017 in patients with CKD stage 5. The demographic characteristics including age, sex, body weight, and estimated glomeruli filtration rate were recorded. Serum levels of calcium, phosphorus, and iPTH were measured. A total of 100 patients divided into predialysis (n = 50) and postdialysis group (n = 50) with the mean age 50.34 and 51.88 years were included in this study, respectively. Mean levels of serum calcium and iPTH in the postdialysis patients were significantly lower than predialysis patients (P = 0.0183 and P <0.001). The proportion of patients (74%) with serum phosphorus level >4.5 mg/dL was significantly higher in postdialysis group (0.003). The risk of having high level of iPTH was 3.20 times more among the patients with level of phosphorus between 2.5 and 4.5 mg/dL [odds ratio (OR), 3.20; 95% confidence interval (CI), 1.16-8.80; P = 0.02] and 2.82 times more among patients with level of calcium <8.5 mg/dL (OR, 2.82; 95% CI, 1.13-7.01; P = 0.02). Overall observations suggest a significant reduction in levels of serum calcium and iPTH after dialysis in patients with CKD stage 5.

Comparative structural and functional analysis of STL and SLL, chitin-binding lectins from Solanum spp.

Therapeutically important chitin-binding lectins have been already reported in the literature for Solanum tuberosum and Solanum lycopersicum, but their structural data are unavailable. Therefore, we have done comparative structural and functional analysis of chitin-binding lectins from S. tuberosum (STL) and S. lycopersicum (SLL). From the sequence analysis, it has been observed that there is high percentage of proline residues in STL and SLL, 21% and 30% respectively. We utilized the hybrid homology modeling-ab initio approaches to predict the 3D structures of STL and SLL, which are used for in silico interaction studies with N,N'-Diacetylchitobiose, Triacetylchitotriose and Tetra-N-acetylglucosamine. The best STL-glycan and SLL-glycan complexes were subjected to Molecular dynamics simulation to understand and compare the structural stability and the binding patterns of glycans toward STL and SLL. We observed that the structural stability of the STL and SLL had been improved significantly due to the binding of glycans. Together with the results of global, essential dynamics and MM-PBSA analysis, indicated that N,N'-Diacetylchitobiose has more binding affinity towards STL, whereas Triacetylchitotriose has more binding affinity with SLL. This comprehensive and comparative structural and functional analysis provides critical insights about the structures and their binding sites, binding orientation, and binding affinity of chitin oligomers towards the structures of STL and SLL. These findings can be used to design further experimental studies to explore the potential therapeutic properties of STL and SLL. Communicated by Ramaswamy H. Sarma.

A comprehensive review on promising anti-viral therapeutic candidates identified against main protease from SARS-CoV-2 through various computational methods.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has shown an exponential trend of infected people across the planet. Crediting its virulent nature, it becomes imperative to identify potential therapeutic agents against the deadly virus. The 3-chymotrypsin-like protease (3CLpro) is a cysteine protease which causes the proteolysis of the replicase polyproteins to generate functional proteins, which is a crucial step for viral replication and infection. Computational methods have been applied in recent studies to identify promising inhibitors against 3CLpro to inhibit the viral activity. This review provides an overview of promising drug/lead candidates identified so far against 3CLpro through various in silico approaches such as structure-based virtual screening (SBVS), ligand-based virtual screening (LBVS) and drug-repurposing/drug-reprofiling/drug-retasking. Further, the drugs have been classified according to their chemical structures or biological activity into flavonoids, peptides, terpenes, quinolines, nucleoside and nucleotide analogues, protease inhibitors, phenalene and antibiotic derivatives. These are then individually discussed based on the various structural parameters namely estimated free energy of binding (ΔG), key interacting residues, types of intermolecular interactions and structural stability of 3CLpro-ligand complexes obtained from the results of molecular dynamics (MD) simulations. CONCLUSION: The review provides comprehensive information of potential inhibitors identified through several computational methods thus far against 3CLpro from SARS-CoV-2 and provides a better understanding of their interaction patterns and dynamic states of free and ligand-bound 3CLpro structures.

Influence of pre and postpartum alpha-tocopherol supplementation on milk yield, milk quality, and udder health of Jersey crossbred cows at tropical lower Gangetic region.

BACKGROUND AND AIM: Alpha-tocopherol supplementation influences milk yield, milk quality, and udder health of dairy cows, which needs to be investigated for Jersey crossbred cows at hot-humid climate. Therefore, the present study was framed with an objective to study the effect of pre and postpartum Alpha-tocopherol supplementation on milk yield, milk quality, and udder health status of Jersey crossbred cows at tropical climate. MATERIALS AND METHODS: For this study, 19 similar parity, body condition score, and production level dairy animals were separated randomly into three groups, namely, Control, T1 and T2. Control group (no supplementation) was compared with two treatment groups, namely, T1 and T2. Supplementation of Alpha-tocopherol was done in concentrate fed to the animals (at 1 g/cow/day) 30 days prepartum to 30 days postpartum in T1 and 30 days prepartum to 60 days postpartum in T2 groups. Observations were taken for different parameters up to 5 months of lactation. RESULTS: Statistically analyzed data revealed that overall significantly (p<0.01) more milk production was found in T2, followed by T1 than the control group. Overall significantly (p<0.01) lower somatic cell counts and modified California mastitis tests were recorded in T2, followed by T1 than the control group. Overall significantly (p<0.01), better milk quality in terms of methylene blue reduction test was found in T2, followed by T1 than control groups. Differences in the milk composition of all three groups were non-significant (p>0.05). CONCLUSION: Supplementation of Alpha-tocopherol during prepartum to initial lactation period may enhance milk yield, milk quality, and udder health status of Jersey crossbred cows at the tropical lower Gangetic region.