Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extra...Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.展开更多
Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This...Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking.A total of 17 bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified.The KEGG pathway analysis showed that the PI3K/Akt signaling pathway,MAPK signaling pathway,AMPK signaling pathway,and nuclear factor kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi.According to molecular docking analysis,the phytochemicals of Chenpi can bind to central anti-obesity targets.Based on the ADMET analysis and network pharmacology results,tangeretin exhibited the lowest predicted toxicity and potential for anti-obesity effects.In the in vitro lipid accumulation model,tangeretin effectively suppressed the free fatty acid-induced lipid in Hep G2 cells by upregulating the PI3K/Akt/GSK3βsignaling pathway based on the result of q-PCR and Western blotting.The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi,also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.展开更多
The increasing incidence of neurodegenerative diseases(NDs)and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies.Medicinal plants,renowned for their long...The increasing incidence of neurodegenerative diseases(NDs)and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies.Medicinal plants,renowned for their long-standing use in traditional medicine,offer a hopeful avenue for discovering new neuroprotective agents.This study emphasizes the potential neuroprotective characteristics of edible fruit plants in Bangladesh,specifically focusing on their traditional folk medicine uses for neurological disorders.This study provides an in-depth overview of the different types of edible fruit trees in Bangladesh and their phytochemicals,including flavonoids,terpenoids,and phenolic acids.This work examines the scientific data supporting the neuroprotective properties of bioactive chemicals from plants.It further explores the mechanisms by which these compounds work to counteract oxidative stress,decrease inflammation,and stimulate neurogenesis.Moreover,the study investigates toxicological characteristics and bioactive components of some fruits,emphasizing the importance of further investigation to measure their safety profile comprehensively.This thorough study highlights the potential benefits of Bangladesh's edible fruit trees as a rich source of neuroprotective chemicals.It also shows that additional research might lead to novel approaches for improving brain functioning and preventing NDs.展开更多
Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper(L.)(P.hydropiper)against bacterial virulence proteins through molecular docking(MD)and experimental validation.Method...Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper(L.)(P.hydropiper)against bacterial virulence proteins through molecular docking(MD)and experimental validation.Methods Six bioactive compounds from P.hydropiper were investigated:catechin(CAT1),hyperin(HYP1),ombuin(OMB1),pinosylvin(PSV1),quercetin 3-sulfate(QSF1),and scutellarein(SCR1).Their binding affinities and potential binding pockets were assessed through MD against four bacterial target proteins with Protein Data Bank identifiers(PDB IDs):topoisomerase IV from Escherichia coli(E.coli)(PDB ID:3FV5),Staphylococcus aureus(S.aureus)gyrase ATPase binding domain(PDB ID:3U2K),CviR from Chromobacterium violaceum(C.violaceum)(PDB ID:3QP1),and glycosyl hydrolase from Pseudomonas aeruginosa(P.aeruginosa)(PDB ID:5BX9).Molecular dynamics simulations(MDS)were performed on the most promising compound-protein complexes for 50 nanoseconds(ns).Drug-likeness was evaluated using Lipinski's Rule of Five(RO5),followed by absorption,distribution,metabolism,excretion,and toxicity(ADMET)analysis using SwissADME and pkCSM web servers.Antibacterial activity was evaluated through disc diffusion assays,testing both individual compounds and combinations with conventional antibiotics[cefotaxime(CTX1,30μg/disc),ceftazidime(CAZ1,30μg/disc),and piperacillin(PIP1,100μg/disc)].Results MD revealed strong binding affinity(ranging from-9.3 to-5.9 kcal/mol)for all compounds,with CAT1 showing exceptional binding to 3QP1(-9.3 kcal/mol)and 5BX9(-8.4 kcal/mol).MDS confirmed the stability of CAT1-protein complexes with binding free energies of-84.71 kJ/mol(5BX9-CAT1)and-95.59 kJ/mol(3QP1-CAT1).Five compounds(CAT1,SCR1,PSV1,OMB1,and QSF1)complied with Lipinski's RO5 and showed favorable ADMET profiles.All compounds were non-carcinogenic,with CAT1 classified in the lowest toxicity class(VI).In antibacterial assays,CAT1 demonstrated significant activity against both gram-positive bacteria[Streptococcus pneumoniae(S.pneumoniae),S.aureus,and Bacillus cereus(B.cereus)][zone diameter of inhibition(ZDI):10-22 mm]and gram-negative bacteria[Acinetobacter baumannii(A.baumannii),E.coli,and P.aeruginosa](ZDI:14-27 mm).Synergistic effects were observed when CAT1 was combined with antibiotics and the growth inhibitory indices(GII)was 0.69-1.00.Conclusion P.hydropiper bioactive compounds,particularly CAT1,show promising antibacterial potential through multiple mechanisms,including direct inhibition of bacterial virulence proteins and synergistic activity with conventional antibiotics.The favorable pharmacological properties and low toxicity profiles support their potential development as therapeutic agents against bacterial infections.展开更多
Skin,the largest organ in the human body,consists of three distinct layers and is a barrier against hazardous environmental exposures to safeguard overall body health.While the superficial layers of skin and their app...Skin,the largest organ in the human body,consists of three distinct layers and is a barrier against hazardous environmental exposures to safeguard overall body health.While the superficial layers of skin and their appendages,like hair,are constantly diminished,skin stem cells continuously regenerate new hair and skin cells to replace them.As we age,the regenerative capacity of skin stem cells is reduced,and skin wound healing and hair generation efficiency is compromised.At the same time,the production of collagen that supports the skin's structure,elasticity,texture,and appearance is reduced,leading to signs of skin aging such as wrinkles,sagging,and loss of skin firmness,which make skin vulnerable to hazardous environmental perturbations.In addition to a sophisticated local neuroendocrine system,several genes such as SOX9,NOTCH,TGFBs,CTGF,AGR3,DSTYK,TPCN2,and collagen,play vital roles in skin integrity and health.Environmental factors such as contaminants,toxins,sun or UV radiation,infections,and skin microbiome dysbiosis negatively impact skin health,primarily by affecting skin stem cells and/or critical genes supporting skin health.Conversely,various nutritional elements,phytochemicals(e.g.,curcumin,quercetin,rosemary,phenolic acids,and sesamin),as well as skin and gut microbiome parameters,help support skin health and prevent skin diseases or premature skin aging.This narrative review explores these topics and introduces potential remedies to promote skin health and mitigate skin aging and diseases.展开更多
Nuclear factor kB(NF-kB)is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions.NF-kB consists of five transcription factors that execute both cytoplasmic and nuclear sign...Nuclear factor kB(NF-kB)is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions.NF-kB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells.NF-kB is the only signaling molecule that governs both pro-and antiapoptotic,and pro-and anti-inflammatory responses.This is due to the canonical and non-canonical components of the NF-kB signaling pathway.Together,these pathways orchestrate cancer-related inflammation,hyperplasia,neoplasia,and metastasis.Non-canonical NF-kB pathways are particularly involved in the chemoresistance of cancer cells.In view of its pivotal role in cancer progression,NF-kB represents a potentially significant therapeutic target for modifying tumor cell behavior.Several phytochemicals are known to modulate NF-kB pathways through the stabilization of its inhibitor,IkB,by inhibiting phosphorylation and ubiquitination thereof.Several natural pharmacophores are known to inhibit the nuclear translocation of NF-kB and associated pro-inflammatory responses and cell survival pathways.In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-kB component,we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-kB signaling pathways for controlling the fate of tumor cells for cancerdirected interventions.展开更多
Medicinal plants of Moraceae family have been well-recognized traditionally due to their versatile applications in various fields including agriculture, cosmetic and food as well as in pharmaceutical industries. Their...Medicinal plants of Moraceae family have been well-recognized traditionally due to their versatile applications in various fields including agriculture, cosmetic and food as well as in pharmaceutical industries. Their biomedical and medicinal importance is reflected from their broad range of pharmacological activities for treatment of various inflammatory conditions, cancer, infectious diseases, and gastrointestinal disorders. The present review was aimed to summarize and critically discuss the biomedical implications of Morus species, their bioactive compounds, and phytochemicals. Bioactivity guided fractionation of these medicinal plants revealed that different types of bioactive phytochemicals and secondary metabolites such as steroids, saponins, alkaloids, glycosides and phenolic compounds including terpenoids, flavonoids, anthocyanins and tannins were present. The critical analysis of the literature revealed that the aqueous, methanolic, and ethanolic extracts of Morus species and their bioactive compounds exhibit remarkable anti-oxidative,anti-diabetic, anti-stress, nephroprotective, antimicrobial, anti-mutagenic, anticancer,anxiolytic, hepatoprotective, anthelmintic, antimicrobial, immune-modulatory and cholesterol lowering effects. Based on the literature review and bioactivity guided investigation of Morus species and their phytomedicinal effects, we anticipate that these herbal products hold excellent potential for future research.展开更多
Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis ...Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.展开更多
Although the incidence of colorectal cancer(CRC) has been declining in recent decades,it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone ...Although the incidence of colorectal cancer(CRC) has been declining in recent decades,it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits,vegetables,and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits,vegetables,and spices which exhibit chemopreventive potential. In this review article,chemopreventive effects of phytochemicals including curcumin,polysaccharides(apple polysaccharides and mushroom glucans),saponins(Paris saponins,ginsenosides and soy saponins),resveratrol,and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC.展开更多
Whole grain has a wide range of phytochemicals exhibiting health benefits of lowering risk of chronic diseases.As commonly consumed grain product,corn has unique profiles of nutrients and phytochemicals when compared ...Whole grain has a wide range of phytochemicals exhibiting health benefits of lowering risk of chronic diseases.As commonly consumed grain product,corn has unique profiles of nutrients and phytochemicals when compared with other whole grains.Corn nutrients and phytochemicals include vitamins(A,B,E,and K),minerals(Mg,P,and K),phenolic acids(ferulic acid,coumaric acid,and syringic acid),carotenoids and flavonoids(anthocyanins),and dietary fiber.More and more scientific evidences have shown that regular consumption of whole grain corn lowers the risk of developing chronic diseases such as cardiovascular disease,type 2 diabetes,and obesity and improves digestive health.Further studies on bioactive compounds of corn related to health are needed.展开更多
The National Cancer Institute had projected breast cancer(BC) as one of the topmost prevalent malignancies around the globe.In many cases,BC becomes resistant to chemotherapy,radiation and hormonal therapies.Tradition...The National Cancer Institute had projected breast cancer(BC) as one of the topmost prevalent malignancies around the globe.In many cases,BC becomes resistant to chemotherapy,radiation and hormonal therapies.Traditional BC therapies are associated with adverse side effects,drug resistance and recurrence.Extensive research work has shown that these dietary phytochemicals(DPs) may exert therapeutic effects by regulating the miRNA expression.A large number of DPs have been researched as miRNA regulatory agents against BC and some other DPs have not yet been tested against BC.We have discussed the effects of curcumin,diallyl disulphide,3,3′ diindolylmethane,ellagic acid,genistein,indole-3-carbinol,quercetin,resveratrol,and sulforaphane on regulation of expression of BC miRNAs in a wide range of in vitro and in vivo models.We have also shown some of the possible DPs(Oleanolic acid,capsaicin,benzyl isothiocyanate,epigallocatechin gallate,phenethyl isothiocyanate and ursolic acid) that have shown miRNA regulatory activities and have not yet been tested against BC miRNAs.Finally,current limitations,challenges,future perspectives of DPs and BC research are also critically discussed.展开更多
Food-microbiota-host interactions provide an overarching framework for understanding the function of the gut microbiota axis.Diet is a major modulator of gut microbiota.Plant-based foods are rich in phytochemicals;the...Food-microbiota-host interactions provide an overarching framework for understanding the function of the gut microbiota axis.Diet is a major modulator of gut microbiota.Plant-based foods are rich in phytochemicals;therefore,it is essential to assess such foods and elucidate the mechanisms underlying their action.In this review,we summarize the role of gut microbiota in the communication between the gut and the brain,liver,lung,kidney,and joints,as well as the role of the gut microbiota axis in diseases involving these organs.In addition,we assess the effects of phytochemicals from plant-based foods on the gut microbiota axis via different pathways.展开更多
Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer prop...Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e.展开更多
Colorectal cancer(CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cu...Colorectal cancer(CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but also causes side effects. Many studies have shown that adequate intake of fruits and vegetables in the diet may have a protective effect on CRC occurrence, possibly due to the special biological protective effect of the phytochemicals in these foods. Numerous in vitro and in vivo studies have demonstrated that phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles by regulating specific signaling pathways and molecular markers to inhibit the occurrence and development of CRC. This review summarizes the progress on CRC prevention using the phytochemicals sulforaphane, curcumin and resveratrol, and elaborates on the specific underlying mechanisms. Thus, we believe that phytochemicals might provide a novel therapeutic approach for CRC prevention, but future clinical studies are needed to confirm the specific preventive effect of phytochemicals on cancer.展开更多
Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiatio...Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals(capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-induced experimental tumors and/or associated biomarkers and processes in rodents at several organ sites. The observed anti-initiating, anti-promoting and anti-progression activity of dietary phytochemicals in carcinogen-induced experimental models involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases resulting to effects on multiple genes and cell signaling pathways. Results from clinical trials using these compounds have not shown them to be chemopreventive. This may be due to our:(1) inability to reproduce the exposure conditions, i.e., levels, complexity, other host and lifestyle factors; and(2) lack of understanding about the mechanisms of action and agent-mediated toxicity in several organs and physiological processes in the host. Current research efforts in addressing the issues of exposure conditions, bioavailability, toxicity and the mode of action of dietary phytochemicals may help address the reason for observed mismatch that may ultimately lead to identification of new chemopreventive agents for protection against broad spectrum of exposures.展开更多
Prostate cancer is the second leading cancer among men in the United States. Several studies have correlated the development of prostate cancer with diet and life-style. Therefore, a balanced diet and improved life st...Prostate cancer is the second leading cancer among men in the United States. Several studies have correlated the development of prostate cancer with diet and life-style. Therefore, a balanced diet and improved life style might inhibit prostate cancer progression. Cancer chemoprevention has emerged as an important factor in controlling cancer development through natural or synthetic compounds. Oxidative stress is among the factors contributing to prostate cancer development. The transcription factor nuclear factor(erythroid-derived 2)-like 2(Nrf2) controls detoxifying antioxidant enzymes expression by binding to the antioxidant response element(ARE) in the promoter of these genes to activate their expression. Many natural products can fight oxidative stress and protects cells from DNA damage by activating the Nrf2/ARE pathway. High consumption of fruits and vegetables can reduce disease incidence and invasive tumors. In this review, the roles of important fruit and vegetable phytochemicals in regulating prostate cancer progression and tumor growth are discussed.展开更多
Coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),has affected millions of people globally.It was declared a pandemic by the World Health Organization in...Coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),has affected millions of people globally.It was declared a pandemic by the World Health Organization in March 2020.The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a“cytokine storm”and the high oxidative stress responsible for the associated symptomatology.Not only respiratory symptoms are reported,but gastrointestinal symptoms(diarrhea,vomiting,and nausea)and liver abnormalities(high levels of aspartate aminotransferase,alanine aminotransferase transaminases,and bilirubin)are observed in at least 30%of patients.Reduced food intake and a delay in medical services may lead to malnutrition,which increases mortality and poor outcomes.This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury,taking energy and nutrient requirements and their impact on the immune response into account.The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.展开更多
To determine the significance of germination on phytochemical constituents and non-enzymatic antioxidant activ- ities of Ceiba pentandra seed extracts. Phytochemicals and antioxidant activities of raw and germinating ...To determine the significance of germination on phytochemical constituents and non-enzymatic antioxidant activ- ities of Ceiba pentandra seed extracts. Phytochemicals and antioxidant activities of raw and germinating seeds of Ceiba pentandra were estimated by different methods. The levels of phytochemical constituents were influenced by germination and increased except alkaloids and tannins, which were decreased significantly during germination. Among non-enzymatic antioxidants like DPPH, FRAP, reducing assay and hydroxyl radical scavenging activity all showed improved activity compared with non-germinating seeds. This may be due to various reactive oxygen species (ROS) that were generated as by-products of metabolism during germination. This group of ROS included superoxide radicals (O2), hydrogen peroxide radicals (HzOz) and hydroxyl radicals (OH). The formation of these oxygen radicals resulted in the accumulation of lipid hydroperoxides by radical chain oxidation via phospholipids peroxy radicals within membranes. Therefore, it was hypothesized that this could be related to the increase of anti- oxidant activity in large unilamellar vesicles observed in germinated seeds. The implication of this study is that the Ceiba pentandra seeds as natural antioxidant agents and put forward the possibility of employing for therapeutic potential.展开更多
Islet amyloid polypeptide(IAPP),or amylin,has been identifi ed as a key factor in the development of type 2 diabetes(T2D).IAPP aggregates,which form amyloid fi brils,contribute to cytotoxicity of the pancreatic β-cel...Islet amyloid polypeptide(IAPP),or amylin,has been identifi ed as a key factor in the development of type 2 diabetes(T2D).IAPP aggregates,which form amyloid fi brils,contribute to cytotoxicity of the pancreatic β-cells,resulting in loss of function and subsequent reduction in insulin production.As a result,surviving β-cells overcompensate for this reduction of insulin production,further contributing to the loss of function because of increased stress,thus leading to insulin resistance.Endogenously,IAPP monomers function in a variety of roles;however,aggregation renders them non-functional.The use of naturally occurring compounds,including peptides and phytochemicals,has been explored as a way to mitigate or inhibit IAPP fi bril formation.This review discusses the structure,endogenous roles and mechanism of IAPP fi bril formation,recent advances on inhibitors of IAPP fi bril formation,and new insights on the future development and application of foodderived inhibitors towards T2D management.展开更多
基金United Arab Emirates University,Grant/Award Number:12R104 and 12R121。
文摘Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
基金supported by the Guangdong Provincial Key Laboratory IRADS(2022B1212010006,R0400001-22)。
文摘Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking.A total of 17 bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified.The KEGG pathway analysis showed that the PI3K/Akt signaling pathway,MAPK signaling pathway,AMPK signaling pathway,and nuclear factor kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi.According to molecular docking analysis,the phytochemicals of Chenpi can bind to central anti-obesity targets.Based on the ADMET analysis and network pharmacology results,tangeretin exhibited the lowest predicted toxicity and potential for anti-obesity effects.In the in vitro lipid accumulation model,tangeretin effectively suppressed the free fatty acid-induced lipid in Hep G2 cells by upregulating the PI3K/Akt/GSK3βsignaling pathway based on the result of q-PCR and Western blotting.The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi,also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.
文摘The increasing incidence of neurodegenerative diseases(NDs)and the constraints of existing treatment methods have spurred a keen interest in investigating alternative therapies.Medicinal plants,renowned for their long-standing use in traditional medicine,offer a hopeful avenue for discovering new neuroprotective agents.This study emphasizes the potential neuroprotective characteristics of edible fruit plants in Bangladesh,specifically focusing on their traditional folk medicine uses for neurological disorders.This study provides an in-depth overview of the different types of edible fruit trees in Bangladesh and their phytochemicals,including flavonoids,terpenoids,and phenolic acids.This work examines the scientific data supporting the neuroprotective properties of bioactive chemicals from plants.It further explores the mechanisms by which these compounds work to counteract oxidative stress,decrease inflammation,and stimulate neurogenesis.Moreover,the study investigates toxicological characteristics and bioactive components of some fruits,emphasizing the importance of further investigation to measure their safety profile comprehensively.This thorough study highlights the potential benefits of Bangladesh's edible fruit trees as a rich source of neuroprotective chemicals.It also shows that additional research might lead to novel approaches for improving brain functioning and preventing NDs.
基金Research Grants of Senior Research Fellowship in favor of first author(Gloak Majumdar)from Council of Scientific and Industrial Research(CSIR,New Delhi,Government of India)(CSIR-SRF)with Award No.09/1151/(0008)2020-EMR-I.
文摘Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper(L.)(P.hydropiper)against bacterial virulence proteins through molecular docking(MD)and experimental validation.Methods Six bioactive compounds from P.hydropiper were investigated:catechin(CAT1),hyperin(HYP1),ombuin(OMB1),pinosylvin(PSV1),quercetin 3-sulfate(QSF1),and scutellarein(SCR1).Their binding affinities and potential binding pockets were assessed through MD against four bacterial target proteins with Protein Data Bank identifiers(PDB IDs):topoisomerase IV from Escherichia coli(E.coli)(PDB ID:3FV5),Staphylococcus aureus(S.aureus)gyrase ATPase binding domain(PDB ID:3U2K),CviR from Chromobacterium violaceum(C.violaceum)(PDB ID:3QP1),and glycosyl hydrolase from Pseudomonas aeruginosa(P.aeruginosa)(PDB ID:5BX9).Molecular dynamics simulations(MDS)were performed on the most promising compound-protein complexes for 50 nanoseconds(ns).Drug-likeness was evaluated using Lipinski's Rule of Five(RO5),followed by absorption,distribution,metabolism,excretion,and toxicity(ADMET)analysis using SwissADME and pkCSM web servers.Antibacterial activity was evaluated through disc diffusion assays,testing both individual compounds and combinations with conventional antibiotics[cefotaxime(CTX1,30μg/disc),ceftazidime(CAZ1,30μg/disc),and piperacillin(PIP1,100μg/disc)].Results MD revealed strong binding affinity(ranging from-9.3 to-5.9 kcal/mol)for all compounds,with CAT1 showing exceptional binding to 3QP1(-9.3 kcal/mol)and 5BX9(-8.4 kcal/mol).MDS confirmed the stability of CAT1-protein complexes with binding free energies of-84.71 kJ/mol(5BX9-CAT1)and-95.59 kJ/mol(3QP1-CAT1).Five compounds(CAT1,SCR1,PSV1,OMB1,and QSF1)complied with Lipinski's RO5 and showed favorable ADMET profiles.All compounds were non-carcinogenic,with CAT1 classified in the lowest toxicity class(VI).In antibacterial assays,CAT1 demonstrated significant activity against both gram-positive bacteria[Streptococcus pneumoniae(S.pneumoniae),S.aureus,and Bacillus cereus(B.cereus)][zone diameter of inhibition(ZDI):10-22 mm]and gram-negative bacteria[Acinetobacter baumannii(A.baumannii),E.coli,and P.aeruginosa](ZDI:14-27 mm).Synergistic effects were observed when CAT1 was combined with antibiotics and the growth inhibitory indices(GII)was 0.69-1.00.Conclusion P.hydropiper bioactive compounds,particularly CAT1,show promising antibacterial potential through multiple mechanisms,including direct inhibition of bacterial virulence proteins and synergistic activity with conventional antibiotics.The favorable pharmacological properties and low toxicity profiles support their potential development as therapeutic agents against bacterial infections.
文摘Skin,the largest organ in the human body,consists of three distinct layers and is a barrier against hazardous environmental exposures to safeguard overall body health.While the superficial layers of skin and their appendages,like hair,are constantly diminished,skin stem cells continuously regenerate new hair and skin cells to replace them.As we age,the regenerative capacity of skin stem cells is reduced,and skin wound healing and hair generation efficiency is compromised.At the same time,the production of collagen that supports the skin's structure,elasticity,texture,and appearance is reduced,leading to signs of skin aging such as wrinkles,sagging,and loss of skin firmness,which make skin vulnerable to hazardous environmental perturbations.In addition to a sophisticated local neuroendocrine system,several genes such as SOX9,NOTCH,TGFBs,CTGF,AGR3,DSTYK,TPCN2,and collagen,play vital roles in skin integrity and health.Environmental factors such as contaminants,toxins,sun or UV radiation,infections,and skin microbiome dysbiosis negatively impact skin health,primarily by affecting skin stem cells and/or critical genes supporting skin health.Conversely,various nutritional elements,phytochemicals(e.g.,curcumin,quercetin,rosemary,phenolic acids,and sesamin),as well as skin and gut microbiome parameters,help support skin health and prevent skin diseases or premature skin aging.This narrative review explores these topics and introduces potential remedies to promote skin health and mitigate skin aging and diseases.
文摘Nuclear factor kB(NF-kB)is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions.NF-kB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells.NF-kB is the only signaling molecule that governs both pro-and antiapoptotic,and pro-and anti-inflammatory responses.This is due to the canonical and non-canonical components of the NF-kB signaling pathway.Together,these pathways orchestrate cancer-related inflammation,hyperplasia,neoplasia,and metastasis.Non-canonical NF-kB pathways are particularly involved in the chemoresistance of cancer cells.In view of its pivotal role in cancer progression,NF-kB represents a potentially significant therapeutic target for modifying tumor cell behavior.Several phytochemicals are known to modulate NF-kB pathways through the stabilization of its inhibitor,IkB,by inhibiting phosphorylation and ubiquitination thereof.Several natural pharmacophores are known to inhibit the nuclear translocation of NF-kB and associated pro-inflammatory responses and cell survival pathways.In view of this and the high degree of specificity exhibited by various phytochemicals for the NF-kB component,we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-kB signaling pathways for controlling the fate of tumor cells for cancerdirected interventions.
基金Universiti Teknologi MARA for providing LESTARI grant(600-IRMI/DANA 5/3/LESTARI(0007/2016))and support in writing the present review article.
文摘Medicinal plants of Moraceae family have been well-recognized traditionally due to their versatile applications in various fields including agriculture, cosmetic and food as well as in pharmaceutical industries. Their biomedical and medicinal importance is reflected from their broad range of pharmacological activities for treatment of various inflammatory conditions, cancer, infectious diseases, and gastrointestinal disorders. The present review was aimed to summarize and critically discuss the biomedical implications of Morus species, their bioactive compounds, and phytochemicals. Bioactivity guided fractionation of these medicinal plants revealed that different types of bioactive phytochemicals and secondary metabolites such as steroids, saponins, alkaloids, glycosides and phenolic compounds including terpenoids, flavonoids, anthocyanins and tannins were present. The critical analysis of the literature revealed that the aqueous, methanolic, and ethanolic extracts of Morus species and their bioactive compounds exhibit remarkable anti-oxidative,anti-diabetic, anti-stress, nephroprotective, antimicrobial, anti-mutagenic, anticancer,anxiolytic, hepatoprotective, anthelmintic, antimicrobial, immune-modulatory and cholesterol lowering effects. Based on the literature review and bioactivity guided investigation of Morus species and their phytomedicinal effects, we anticipate that these herbal products hold excellent potential for future research.
文摘Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.
基金Supported by Postdoctoral Science Foundation of China,No.2012M512102,No.2013T60964National Nature Science Foundation of China,No.81302787
文摘Although the incidence of colorectal cancer(CRC) has been declining in recent decades,it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits,vegetables,and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits,vegetables,and spices which exhibit chemopreventive potential. In this review article,chemopreventive effects of phytochemicals including curcumin,polysaccharides(apple polysaccharides and mushroom glucans),saponins(Paris saponins,ginsenosides and soy saponins),resveratrol,and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC.
文摘Whole grain has a wide range of phytochemicals exhibiting health benefits of lowering risk of chronic diseases.As commonly consumed grain product,corn has unique profiles of nutrients and phytochemicals when compared with other whole grains.Corn nutrients and phytochemicals include vitamins(A,B,E,and K),minerals(Mg,P,and K),phenolic acids(ferulic acid,coumaric acid,and syringic acid),carotenoids and flavonoids(anthocyanins),and dietary fiber.More and more scientific evidences have shown that regular consumption of whole grain corn lowers the risk of developing chronic diseases such as cardiovascular disease,type 2 diabetes,and obesity and improves digestive health.Further studies on bioactive compounds of corn related to health are needed.
文摘The National Cancer Institute had projected breast cancer(BC) as one of the topmost prevalent malignancies around the globe.In many cases,BC becomes resistant to chemotherapy,radiation and hormonal therapies.Traditional BC therapies are associated with adverse side effects,drug resistance and recurrence.Extensive research work has shown that these dietary phytochemicals(DPs) may exert therapeutic effects by regulating the miRNA expression.A large number of DPs have been researched as miRNA regulatory agents against BC and some other DPs have not yet been tested against BC.We have discussed the effects of curcumin,diallyl disulphide,3,3′ diindolylmethane,ellagic acid,genistein,indole-3-carbinol,quercetin,resveratrol,and sulforaphane on regulation of expression of BC miRNAs in a wide range of in vitro and in vivo models.We have also shown some of the possible DPs(Oleanolic acid,capsaicin,benzyl isothiocyanate,epigallocatechin gallate,phenethyl isothiocyanate and ursolic acid) that have shown miRNA regulatory activities and have not yet been tested against BC miRNAs.Finally,current limitations,challenges,future perspectives of DPs and BC research are also critically discussed.
基金supported by the National Key Research and Development Program(2021YFE0190100)National Natural Science Foundation of China(81760776,81874336)。
文摘Food-microbiota-host interactions provide an overarching framework for understanding the function of the gut microbiota axis.Diet is a major modulator of gut microbiota.Plant-based foods are rich in phytochemicals;therefore,it is essential to assess such foods and elucidate the mechanisms underlying their action.In this review,we summarize the role of gut microbiota in the communication between the gut and the brain,liver,lung,kidney,and joints,as well as the role of the gut microbiota axis in diseases involving these organs.In addition,we assess the effects of phytochemicals from plant-based foods on the gut microbiota axis via different pathways.
文摘Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e.
基金Supported by the National Natural Science Foundation of China,No.81372681the Key Research Development Program of Shandong Province,No.2015GGH318014
文摘Colorectal cancer(CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but also causes side effects. Many studies have shown that adequate intake of fruits and vegetables in the diet may have a protective effect on CRC occurrence, possibly due to the special biological protective effect of the phytochemicals in these foods. Numerous in vitro and in vivo studies have demonstrated that phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles by regulating specific signaling pathways and molecular markers to inhibit the occurrence and development of CRC. This review summarizes the progress on CRC prevention using the phytochemicals sulforaphane, curcumin and resveratrol, and elaborates on the specific underlying mechanisms. Thus, we believe that phytochemicals might provide a novel therapeutic approach for CRC prevention, but future clinical studies are needed to confirm the specific preventive effect of phytochemicals on cancer.
文摘Chemoprevention is one of the cancer prevention approaches wherein natural/synthetic agent(s) are prescribed with the aim to delay or disrupt multiple pathways and processes involved at multiple steps, i.e., initiation, promotion, and progression of cancer. Amongst environmental chemopreventive compounds, diet/beverage-derived components are under evaluation, because of their long history of exposure to humans, high tolerability, low toxicity, and reported biological activities. This compilation briefly covers and compares the available evidence on chemopreventive efficacy and probable mechanism of chemoprevention by selected dietary phytochemicals(capsaicin, curcumin, diallyl sulphide, genistein, green/black tea polyphenols, indoles, lycopene, phenethyl isocyanate, resveratrol, retinoids and tocopherols) in experimental systems and clinical trials. All the dietary phytochemicals covered in this review have demonstrated chemopreventive efficacy against spontaneous or carcinogen-induced experimental tumors and/or associated biomarkers and processes in rodents at several organ sites. The observed anti-initiating, anti-promoting and anti-progression activity of dietary phytochemicals in carcinogen-induced experimental models involve phytochemical-mediated redox changes, modulation of enzymes and signaling kinases resulting to effects on multiple genes and cell signaling pathways. Results from clinical trials using these compounds have not shown them to be chemopreventive. This may be due to our:(1) inability to reproduce the exposure conditions, i.e., levels, complexity, other host and lifestyle factors; and(2) lack of understanding about the mechanisms of action and agent-mediated toxicity in several organs and physiological processes in the host. Current research efforts in addressing the issues of exposure conditions, bioavailability, toxicity and the mode of action of dietary phytochemicals may help address the reason for observed mismatch that may ultimately lead to identification of new chemopreventive agents for protection against broad spectrum of exposures.
基金supported in part by Institutional Funds and from the National Cancer Institute(Grant No.R01-CA118947,R01-CA152826)the National Center for Complementary and Alt ernative Medicines and the Office of Dietary Supplements(Grant No.R01AT007065)
文摘Prostate cancer is the second leading cancer among men in the United States. Several studies have correlated the development of prostate cancer with diet and life-style. Therefore, a balanced diet and improved life style might inhibit prostate cancer progression. Cancer chemoprevention has emerged as an important factor in controlling cancer development through natural or synthetic compounds. Oxidative stress is among the factors contributing to prostate cancer development. The transcription factor nuclear factor(erythroid-derived 2)-like 2(Nrf2) controls detoxifying antioxidant enzymes expression by binding to the antioxidant response element(ARE) in the promoter of these genes to activate their expression. Many natural products can fight oxidative stress and protects cells from DNA damage by activating the Nrf2/ARE pathway. High consumption of fruits and vegetables can reduce disease incidence and invasive tumors. In this review, the roles of important fruit and vegetable phytochemicals in regulating prostate cancer progression and tumor growth are discussed.
基金SIP Project,No.SIP-20200341 and No.SIP-20200453Consejo Nacional de Ciencia y Tecnología(CONACyT)Grants,No.PAACTI 312807.
文摘Coronavirus disease 2019(COVID-19),which is caused by severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2),has affected millions of people globally.It was declared a pandemic by the World Health Organization in March 2020.The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a“cytokine storm”and the high oxidative stress responsible for the associated symptomatology.Not only respiratory symptoms are reported,but gastrointestinal symptoms(diarrhea,vomiting,and nausea)and liver abnormalities(high levels of aspartate aminotransferase,alanine aminotransferase transaminases,and bilirubin)are observed in at least 30%of patients.Reduced food intake and a delay in medical services may lead to malnutrition,which increases mortality and poor outcomes.This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury,taking energy and nutrient requirements and their impact on the immune response into account.The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.
文摘To determine the significance of germination on phytochemical constituents and non-enzymatic antioxidant activ- ities of Ceiba pentandra seed extracts. Phytochemicals and antioxidant activities of raw and germinating seeds of Ceiba pentandra were estimated by different methods. The levels of phytochemical constituents were influenced by germination and increased except alkaloids and tannins, which were decreased significantly during germination. Among non-enzymatic antioxidants like DPPH, FRAP, reducing assay and hydroxyl radical scavenging activity all showed improved activity compared with non-germinating seeds. This may be due to various reactive oxygen species (ROS) that were generated as by-products of metabolism during germination. This group of ROS included superoxide radicals (O2), hydrogen peroxide radicals (HzOz) and hydroxyl radicals (OH). The formation of these oxygen radicals resulted in the accumulation of lipid hydroperoxides by radical chain oxidation via phospholipids peroxy radicals within membranes. Therefore, it was hypothesized that this could be related to the increase of anti- oxidant activity in large unilamellar vesicles observed in germinated seeds. The implication of this study is that the Ceiba pentandra seeds as natural antioxidant agents and put forward the possibility of employing for therapeutic potential.
基金Authors acknowledge the financial support from the Natural Sciences and Engineering Research Council of Canada(NSERC)(grant number RGPIN-2018-06839)the University Research Chairs Program of the University of Ottawa,Canada.
文摘Islet amyloid polypeptide(IAPP),or amylin,has been identifi ed as a key factor in the development of type 2 diabetes(T2D).IAPP aggregates,which form amyloid fi brils,contribute to cytotoxicity of the pancreatic β-cells,resulting in loss of function and subsequent reduction in insulin production.As a result,surviving β-cells overcompensate for this reduction of insulin production,further contributing to the loss of function because of increased stress,thus leading to insulin resistance.Endogenously,IAPP monomers function in a variety of roles;however,aggregation renders them non-functional.The use of naturally occurring compounds,including peptides and phytochemicals,has been explored as a way to mitigate or inhibit IAPP fi bril formation.This review discusses the structure,endogenous roles and mechanism of IAPP fi bril formation,recent advances on inhibitors of IAPP fi bril formation,and new insights on the future development and application of foodderived inhibitors towards T2D management.