In Silico and In Vitro Study of Isoquercitrin against Kidney Cancer and Inflammation by Triggering Potential Gene Targets.

Kidney cancer has emerged as a major medical problem in recent times. Multiple compounds are used to treat kidney cancer by triggering cancer-causing gene targets. For instance, isoquercitrin (quercetin-3-O-ß-d-glucopyranoside) is frequently present in fruits, vegetables, medicinal herbs, and foods and drinks made from plants. Our previous study predicted using protein-protein interaction (PPI) and molecular docking analysis that the isoquercitrin compound can control kidney cancer and inflammation by triggering potential gene targets of IGF1R, PIK3CA, IL6, and PTGS2. So, the present study is about further in silico and in vitro validation. We performed molecular dynamic (MD) simulation, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, cytotoxicity assay, and RT-PCR and qRT-PCR validation. According to the MD simulation (250 ns), we found that IGF1R, PIK3CA, and PTGS2, except for IL6 gene targets, show stable binding energy with a stable complex with isoquercitrin. We also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the final targets to determine their regulatory functions and signaling pathways. Furthermore, we checked the cytotoxicity effect of isoquercitrin (IQ) and found that 5 µg/mL and 10 µg/mL doses showed higher cell viability in a normal kidney cell line (HEK 293) and also inversely showed an inhibition of cell growth at 35% and 45%, respectively, in the kidney cancer cell line (A498). Lastly, the RT-PCR and qRT-PCR findings showed a significant decrease in PTGS2, PIK3CA, and IGF1R gene expression, except for IL6 expression, following dose-dependent treatments with IQ. Thus, we can conclude that isoquercitrin inhibits the expression of PTGS2, PIK3CA, and IGF1R gene targets, which in turn controls kidney cancer and inflammation.

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases.

Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development, as well as ginsenoside-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bioconversion processes. Current research shows that CK has a wide range of pharmacological actions, including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, and anti-inflammatory and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signaling pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

Potential of Gut Microbial Metabolites in Treating Osteoporosis and Obesity: A Network Pharmacology and Bioinformatics Approach.

BACKGROUND The gut microbial metabolites demonstrate significant activity against metabolic diseases including osteoporosis (OP) and obesity, but active compounds, targets, and mechanisms have not been fully identified. Hence, the current investigation explored the mechanisms of active metabolites and targets against OP and obesity by using network pharmacology approaches. MATERIAL AND METHODS The gutMGene database was used to collect gut microbial targets-associated metabolites; DisGeNET and OMIM databases were used to identify targets relevant to OP and obesity. A total of 63 and 89 overlapped targets were considered the final OP and obesity targets after creating a Venn diagram of metabolites-related targets and disease-related targets. Furthermore, the top 20% of degrees, betweenness, and closeness were used to form the sub-network of protein-protein interaction of these targets. Finally, the biotransformation-increased receptors and biological mechanisms were identified and validated using ADMET properties analysis, molecular docking, and molecular dynamic simulation. RESULTS GO, KEGG pathway analysis, and protein-protein interactions were performed to establish metabolites and target networks. According to the enrichment analysis, OP and obesity are highly linked to the lipid and atherosclerosis pathways. Moreover, ADMET analysis depicts that the major metabolites have drug-likeliness activity and no or less toxicity. Following that, the molecular docking studies showed that compound K and TP53 target have a remarkable negative affinity (-8.0 kcal/mol) among all metabolites and targets for both diseases. Finally, the conformity of compound K against the targeted protein TP53 was validated by 250ns MD simulation. CONCLUSIONS Therefore, we summarized that compound K can regulate TP53 and could be developed as a therapy option for OP and obesity.

Clinically proven natural products, vitamins and mineral in boosting up immunity: A comprehensive review.

Background: and Purposes: The terminology "immune boost-up" was the talk of the topic in this Covid-19 pandemic. A significant number of the people took initiative to increase the body's defense capacity through boosting up immunity worldwide. Considering this, the study was designed to explain the natural products, vitamins and mineral that were proved by clinical trail as immunity enhancer. Methods: Information was retrieved from SciVerse Scopus ® (Elsevier Properties S. A, USA), Web of Science® (Thomson Reuters, USA), and PubMed based on immunity, nutrients, natural products in boosting up immunity, minerals and vitamins in boosting up immunity, and immune booster agents. Result: A well-defined immune cells response provide a-well functioning defense system for the human physiological system. Cells of the immune system must require adequate stimulation so that these cells can prepare themselves competent enough to fight against any unintended onslaught. Several pharmacologically active medicinal plants and plants derived probiotics or micronutrients have played a pivotal role in enhancing the immune boost-up process. Their role has been well established from the previous study. Immune stimulating cells, especially cells of acquired immunity are closely associated with the immune-boosting up process because all the immunological reactions and mechanisms are mediated through these cells. Conclusion: This article highlighted the mechanism of action of different natural products, vitamins and mineral in boosting up the immunity of the human body and strengthening the body's defense system. Therefore, it is recommended that until the specific immune-boosting drugs are available in pharma markets, anyone can consider the mentioned products as dietary supplements to boost up the immunity.

A review on Impact of dietary interventions, drugs, and traditional herbal supplements on the gut microbiome.

The gut microbiome is the community of healthy, and infectious organisms in the gut and its interaction in the host gut intestine (GI) environment. The balance of microbial richness with beneficial microbes is very important to perform healthy body functions like digesting food, controlling metabolism, and precise immune function. Alternately, this microbial dysbiosis occurs due to changes in the physiochemical condition, substrate avidity, and drugs. Moreover, various categories of diet such as "plant-based", "animal-based", "western", "mediterranean", and various drugs (antibiotic and common drugs) also contribute to maintaining microbial flora inside the gut. The imbalance (dysbiosis) in the microbiota of the GI tract can cause several disorders (such as diabetes, obesity, cancer, inflammation, and so on). Recently, the major interest is to use prebiotic, probiotic, postbiotic, and herbal supplements to balance such microbial community in the GI tract. But, there has still a large gap in understanding the microbiome function, and its relation to the host diet, drugs, and herbal supplements to maintain the healthy life of the host. So, the present review is about the updates on the microbiome concerns related to diet, drug, and herbal supplements, and also gives research evidence to improve our daily habits regarding diet, drugs, and herbal supplements. Because our regular dietary plan and traditional herbal supplements can improve our health by balancing the bacteria in our gut.

Effects of Green Tea (-)-Epigallocatechin-3-Gallate (EGCG) on Cardiac Function - A Review of the Therapeutic Mechanism and Potentials.

Heart disease, the leading cause of death worldwide, refers to various illnesses that affect heart structure and function. Specific abnormalities affecting cardiac muscle contractility and remodeling and common factors including oxidative stress, inflammation, and apoptosis underlie the pathogenesis of heart diseases. Epidemiology studies have associated green tea consumption with lower morbidity and mortality from cardiovascular diseases, including heart and blood vessel dysfunction. Among the various compounds found in green tea, catechins are believed to play a significant role in producing benefits to cardiovascular health. Comprehensive literature reviews have been published to summarize the tea catechins' antioxidative, anti-inflammatory, and anti-apoptosis effects in various diseases, such as cardiovascular diseases, cancers, and metabolic diseases. However, recent studies on tea catechins, especially the most abundant (-)-Epigallocatechin-3-Gallate (EGCG), revealed their capabilities in regulating cardiac muscle contraction by directly altering myofilament Ca2+ sensitivity on force development and Ca2+ ion handling in cardiomyocytes under both physiological and pathological conditions. In vitro and in vivo data also demonstrated that green tea extract or EGCG protected or rescued cardiac function, independent of their well-known effects against oxidative stress and inflammation. This mini-review will focus on the specific effects of tea catechins on heart muscle contractility at the molecular and cellular level, revisit their effects on oxidative stress and inflammation in various heart diseases, and discuss EGCG's potential as one of the lead compounds for new drug discovery for heart diseases.

Prevalence of anemia and associated risk factors among pregnant women attending antenatal care in Bangladesh: a cross-sectional study.

BACKGROUND: Anemia has created attention worldwide because of its adverse effects on the mother and the fetus during pregnancy. A large body of evidence has shown that pregnant women are the most vulnerable group to anemia. OBJECTIVES: This study aims to determine the prevalence of anemia, and associated risk factors, among pregnant women attending antenatal care (ANC) at government and private hospitals in Bangladesh. METHODS: This cross-sectional study included 424 pregnant women, who visited hospitals for ANC from January to July 2019. We used a simple random sampling technique to select study subjects. Data were collected using a structured questionnaire and participant's current medical record cards. SPSS software was used for analyzing data. RESULTS: The prevalence of anemia was 62.5% and significantly (P < 0.001) higher in the subjects attending ANC in government hospitals (68.7%) than in private (55.0%) hospitals. The prevalence of the severity of anemia was 28.3% mild, 36.9% moderate, and 3.40% severe in government hospitals while in private hospitals was 14.7% mild, 39.8% moderate, and 0.5% severe anemia. Anemia was significantly associated with maternal age 20-25 years [adjusted odds ratio (AOR) = 1.9] and 26-30 years (AOR = 2.37), monthly family income (300-500) US$ (AOR = 2.76), and ANC in government hospitals (AOR = 2.02), the parity [multiparous (AOR = 1.92)], gravidity [multigravid (AOR = 1.63)], contraception [no contraception (AOR = 2.50), and iron supplement [no iron supplement (AOR = 0.64). CONCLUSIONS: The result suggests that pregnant women should receive routine ANC and recognize iron supplementation during pregnancy. Finally, the results of this study are particularly relevant for pregnant women who are receiving ANC.

Anti-hyperglycemic effect of the immature endosperm of sugar palm (Borassus flabellifer) fruit on type 2 diabetes mellitus patients-a case study.

AIM: This study aimed to investigate the nutrient contents and the anti-hyperglycemic effect of the immature endosperm of sugar palm (IESP) (Borassus flabellifer L.) fruit on type-2 diabetes mellitus (T2DM) patients. METHODS: This is a short type case study where patients (n = 30) with T2DM were randomly selected and fed IESP (100 mL) twice a day after a regular meal and continued this experiment up to 4th weeks. RESULT: The mean fasting blood glucose (FBG) level was markedly reduced from 1st week (15.74 mmol/L) to 4th week (10.53 mmol/L) among the patients who had normal body mass index (18.5-24.9). Only 16.67% diabetic patients had irregular FBG levels where 10% were in the previous stages after finishing the experimental period, and exceptionally in the case of 6.67% diabetic patients, this therapeutic juice was unsuccessful because of their irregular intake of insulin. The IESP was more effective on female (p ≤ 0.001) patients than males (p ≤ 0.05). CONCLUSION: The IESP could be considered as anti-hyperglycemic fruit, and this might be due to its nutrient contents, especially phytochemicals, fiber, sodium, potassium, copper, and zinc.

Evaluation of cytotoxic, analgesic, antidiarrheal and phytochemical properties of Hygrophila spinosa (T. Anders) whole plant.

BACKGROUND: Synthetic drugs are going to be replaced by plant-derived traditional drugs due to their cost effectiveness, relatively less harmfulness, and efficacy against multidrug resistance organisms. Hygrophila spinosa (Acanthaceae) has been used in a wide range of ailments including flatulence, diarrhea, dysentery, gonorrhea, and menorrhagia. Therefore, we investigated the cytotoxic, antinociceptive, and antidiarrheal effects of H. spinosa ethanol extract (EExHs). METHODS: Preliminary phytochemical screening was accomplished by established methods modified in experimental protocol. EExHs was undertaken for cytotoxic assay by Brine shrimp lethality bioassay, antinociceptive action by acetic acid induced writhing test, and antidiarrheal activity by castor oil induced antidiarrheal test. Data were analyzed by GraphPad Prism 6.0 software using Dunnett's test for multiple comparisons. RESULTS: Reducing sugar, steroid, glycoside, tannin, alkaloid, saponins, and flavonoids were found to be present in EExHs. Lethal concentration (LC50) of EExHs for brine shrimps was 50.59 µg/mL which was relatively lower than that of the standard drug vincristine sulfate. In acetic acid induced writhing test, oral administration of EExHs at three different doses (125, 250, and 500 mg/kg) decreased writhing in dose-dependent manner while the highest dose (500 mg/kg) achieved the maximum percentages of pain inhibition (58.8%). Diclofenac sodium (25 mg/kg) was used as a reference antinociceptive drug. The antidiarrheal action of EExHs was not found to be very promising for further use; however, the pure compounds from EExHs could be analyzed to justify the effects. CONCLUSIONS: This research demonstrates that the secondary metabolites guided cytotoxic and analgesic effects could be extensively studied in multiple models to confirm the effects.

Solanum tuberosum lectin inhibits Ehrlich ascites carcinoma cells growth by inducing apoptosis and G2/M cell cycle arrest.

Recently, a lectin was purified from the potato cultivated in Bangladesh locally known as Sheel. In the present study cytotoxicity of the lectin against Ehrlich ascites carcinoma (EAC) cells was studied by MTT assay in vitro in RPMI-1640 medium and 8.0-36.0 % cell growth inhibition was observed at the range of 2.5-160 µg/ml protein concentration when incubated for 24 h. The lectin-induced apoptosis in EAC cells was confirmed by fluorescence and optical microscope. The apoptotic cell death was also confirmed by using caspase inhibitors. Cells growth inhibition caused by the lectin (36 %) was remarkably decreased to 7.6 and 22.3 % respectively in the presence of caspase-3 and -8 inhibitors. RT-PCR was used to evaluate the expression of apoptosis-related genes Bcl-X, p53, and Bax. An intensive expression of Bcl-X gene was observed in untreated control EAC cells with the disappeared of the gene in Sheel-treated EAC cells. At the same time, Bax gene expression appeared only in Sheel-treated EAC cells and the expression level of the p53 gene was increased remarkable after the treatment of EAC cells with the lectin. The lectin showed strong agglutination activity against EAC cells. Flow cytometry was used to study the cell cycle phases of EAC cells and it was observed that the lectin arrested the G2/M phase. In conclusion, Sheel lectin inhibited EAC cells growth by inducing apoptosis.

Purification and characterization of a novel chitinase from Trichosanthes dioica seed with antifungal activity.

Chitinases are a group of enzymes that show differences in their molecular structure, substrate specificity, and catalytic mechanism and widely found in organisms like bacteria, yeasts, fungi, arthropods actinomycetes, plants and humans. A novel chitinase enzyme (designated as TDSC) was purified from Trichosanthes dioica seed with a molecular mass of 39±1 kDa in the presence and absence of ß-mercaptoethanol. The enzyme was a glycoprotein in nature containing 8% neutral sugar. The N-terminal sequence was determined to be EINGGGA which did not match with other proteins. Amino acid analysis performed by LC-MS revealed that the protein was rich in leucine. The enzyme was stable at a wide range of pH (5.0-11.0) and temperature (30-90 °C). Chitinase activity was little bit inhibited in the presence of chelating agent EDTA (ethylenediaminetetraaceticacid), urea and Ca(2+). A strong fluorescence quenching effect was found when dithiothreitol and sodium dodecyl sulfate were added to the enzyme. TDSC showed antifungal activity against Aspergillus niger and Trichoderma sp. as tested by MTT assay and disc diffusion method.

New insights into seaweed polyphenols on glucose homeostasis.

CONTEXT: Polyphenol-rich marine macroalgae are gaining dietary importance due to their influence over diabetes mellitus and the role as a vital source of high-value nutraceuticals. Their assorted beneficial effects on human health include competitive inhibition of digestive enzymes, varying the activity of hepatic glucose-metabolizing enzymes, lowering the plasma glucose levels, and lipid peroxidation, delaying the aging process. OBJECTIVE: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes. METHODS: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment. RESULTS: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included. CONCLUSION: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.

Genotypic differences in zinc efficiency of Chinese maize evaluated in a pot experiment.

BACKGROUND: Zinc (Zn) deficiency, a major problem limiting crop production worldwide, is common on calcareous soils of China. Using such a Zn-deficient soil supplied adequately with plant mineral nutrients, with or without Zn, 30 Chinese maize genotypes were grown for 30 days in a greenhouse pot experiment and assessed for Zn efficiency (ZE), measured as relative biomass under Zn-limiting compared with non-limiting conditions. RESULTS: Substantial variation in tolerance to low Zn nutritional status was observed within the maize genotypes. Tolerant genotypes did not show Zn deficiency symptoms at the studied early seedling growth, and there was a well-defined relationship between shoot dry matter and the ZE trait. ZE values ranged on average from 45 to 100% for shoot dry weight. Under low available soil Zn conditions, shoot and root dry weights, shoot Zn concentration and content, leaf superoxide dismutase (SOD) activity, leaf area and plant height were all correlated with ZE. Shoot Zn and phosphorus (P) concentrations were negatively correlated. CONCLUSION: Three genotypes (L55 × 178, L114 × 178 and Zhongnong 99) were identified as highly Zn-efficient and three (L53 × 178, L105 × 178 and L99 × 178) as very low in ZE. This selection allows further work to evaluate ZE based on grain yield and grain Zn concentration, including field experiments likely to benefit farmers producing maize on Chinese soils low in available Zn.

Protective effects of the dietary supplementation of turmeric (Curcuma longa L.) on sodium arsenite-induced biochemical perturbation in mice.

The present study was undertaken to evaluate the protective effect of turmeric powder on arsenic toxicity through mice model. Swiss albino male mice were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were treated with turmeric powder (T, 50 mg/kg body weight/day), sodium arsenite (Sa, 10 mg/kg body weight/day) and turmeric plus Sa (T+Sa), respectively. Results showed that oral administration of Sa reduced the weight gain of the mice compared to the control group and food supplementation of turmeric prevented the reduction of weight gain. Turmeric abrogated the Sa-induced elevation of serum urea, glucose, triglyceride (TG) level and alanine aminotransferase (ALT) activity except the activity of alkaline phosphatase (ALP). Turmeric also prevented the Sa-induced perturbation of serum butyryl cholinesterase activity (BChE). Therefore, ameliorating effect of turmeric on Sa-treated mice suggested the future application of turmeric to reduce or to prevent arsenic toxicity in human.