Phytochemicals of Aloe barbadensis miller as Potential Inhibitors of Uropathogenic Escherichia coli for Urinary Tract Infection Therapy: An in Silico Approach

Urinary tract infections (UTIs) are common infections caused by normal skin or rectum bacteria that get into the urethra and infect the urinary tract. Although the infection can affect various parts of the tract, bladder infections are the most prevalent kind. Uropathogenic Escherichia Coli (UPEC) is the most common pathogen associated with UTI development. Therefore, inhibiting the UPEC protein target (PDB ID: 8BVD) appears to be a promising therapeutic strategy. Therefore, in this study, molecular docking and dynamics were conducted to examine the antibacterial activity of Aloe barbadensis miller against UPEC bacteria. The Aloe barbadensis miller natural compounds licochalcone A, palmidin B and palmidin C were downloaded from PubChem with amoxicillin, which was used as a control drug and studied against the target molecule. The potential parameters examined were the docking scores, absorption, distribution, metabolism, excretion, toxicity (ADMET), bioavailability, root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, radius of gyration, and potential energy of the system. Docking scores showed that all ligands demonstrated an admirable candidature as an inhibitor to 8BVD molecule, and the score hierarchy is licochalcone A (-6.4 kcal/mol), palmidin C (-6.1 kcal/mol), palmidin B (-6.0 kcal/mol), and amoxicillin (-5.9 kcal/mol). All ligands appeared to have good drug-like properties and oral bioavailability. Molecular dynamic studies showed that all ligands exhibited an excellent nominee as inhibitors in their vicinity at 20 ns. However, there is a relatively high fluctuation of palmidin B compared with other compounds, which seems to be more stable. This work suggests that the selected phytoconstituents could be used as inhibitors of the 8BVD protein in the fight against UTIs. However, further investigation on the clinical and experimental validation of UTI treatment’s specific mechanisms and effects is still welcomed.

Gut microbiota axis:potential target of phytochemicals from plant-based foods

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.

Phytopharmacological potential of different species of Morus alba and their bioactive phytochemicals:A review

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.

Role of dietary phytochemicals in modulation of miRNA expression:Natural swords combating breast cancer

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.

Role of phytochemicals in colorectal cancer prevention

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.

Cancer Therapy with Phytochemicals: Present and Future Perspectives

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.

Research progress on chemopreventive effects of phytochemicals on colorectal cancer and their mechanisms

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.

Corn phytochemicals and their health benefits

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.

Phytochemicals as inhibitors of tumor necrosis factor alpha and neuroinflammatory responses in neurodegenerative diseases

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.

Phytochemicals targeting NF-kB signaling:Potential anti-cancer interventions

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.

Phytochemicals in diets for breast cancer prevention:The importance of resveratrol and ursolic acid

Breast cancer is the second leading cause of death from cancer in women in the United States.A growing emphasis is being placed on alternative medicine and dietary approaches toward prevention of potential diseases.Phytochemicals are bioactive compounds that are naturally present in foods that,when acting in synergy,bestow potential anti-cancer properties.Resveratrol,a phytoalexin,and ursolic acid,a pentacyclic triterpenoid,are two bioactive compounds that are at the forefront in scientific research.Previous animal studies have documented the anti-cancer properties of resveratrol on breast cancer cells and research groups have recently been able to identify the anti-cancer,anti-inflammatory and induction of apoptosis properties of resveratrol along with the signal transduction pathways that the compound affects.Ursolic acid has been cast into the limelight with the recent discovery documenting its anti-inflammation and anti-cancer activities by targeting signal pathways,especially in the prevention of breast cancer.©2012 Production and hosting by Elsevier B.V.on behalf of Beijing Academy of Food Sciences.

Understanding the molecular mechanisms of cancer prevention by dietary phytochemicals:From experimental models to clinical trials

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.

Potential of peptides and phytochemicals in attenuating different phases of islet amyloid polypeptide fi brillation for type 2 diabetes management

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.

Elevated CO₂Levels Affect Phytochemicals and Nutritional Quality of Food Crops

Rising atmospheric CO2 levels pose many challenges to global climate, thus to all forms of life including plants. The impact of elevated CO2 on plant growth and development and the nutritional quality in relation to major nutrients in many crops has been explored extensively. However, information on the elevated CO2 effects on the health-promoting phytochemicals in food crops is rather limited. Major nutrients in food crops including protein, phosphorus, potassium, calcium, iron, zinc and other micronutrients in many food crops are known to be suppressed at elevated CO2 levels. Elevated CO2 increases carbohydrate accumulation but decreases nitrogen accumulation in plants thus affecting their C-N ratio. A number of studies show that high C-N ratio and nitrogen limiting conditions in plants can result in the accumulation of carbon-based secondary metabolites, many of which are health-promoting phytochemicals and allelochemicals involved in plants’ defense against pathogens and herbivory. Although the results from these studies are variable, it can be concluded that while elevated CO2 is known to suppress the content of major nutrients, it may actually have a favorable impact on the accumulation of carbon-based phytochemicals in food crops.

Dramatic Improvement in Physical Well-Being of Terminal AIDS Patients Following Administration of Phytochemicals

Phytochemicals (PHT) are biologically active chemicals produced by plants, non-essential nutrients, with medicinal properties. In this short communication we report the dramatic improvement in the physical and clinical well-being of 9 terminal AIDS patients that received Phyto V7, a PHT mix, for a period of 3 months. All patients living in the Dr. Cruz Jiminian Foundation (hospice) in Santo Domingo, Dominican Republic, were in an emaciated condition—most could not eat, sit down, shower, stand up or dress alone;all had high viremia (from ~50,000 to above 500,000;243,816 ± 176,724 HIV-1 RNA copies/ml) and very low CD4+ T-cells counts (142 ± 51 counts/mm3). The clinical status of all patients was C3 according to the United States Centers for Disease Control (CDC) status index. As antiretroviral treatment was not available to the Foundation at the time of the study, the only treatment that they received was Phyto V7 supplementation. Each individual received 5 tablets 3 times a day, each tablet containing 750 mg of Phyto V7. At the end of the 3 months, Phyto V7 supplementation radically improved the well-being of all 9 patients. All patients could eat, sit down, shower, stand up and dress alone. This study supports the notion that PHT supplementation can improve significantly the well-being of terminally ill AIDS patients and is the foundation to conducting further control studies to substantiate this notion.

Provenance variations in proximate principles,mineral matter,total phenols and phytochemicals of Melia dubia drupes:an unexplored alternate livestock feed stock

This research was carried out on nine provenances from the north Western Ghats to quantify proximate principles,mineral matter,total phenols and other phytochemicals in Melia dubia drupe pulp.Drupe biometric,biomass attributes,proximate principles,mineral matter and total phenols diff ered signifi cantly among the provenances.The average drupe length and width was 26.5 and 22.3 mm,respectively.Average drupe and pulp fresh weight,pulp dry weight and stone weight were 783.1,552.1,165.1,and 179.8 g/100 drupes,respectively.Pulp,dry matter and moisture per cent were 70.5%,29.9%and 70.0%,respectively.Average crude fi bre,protein,ether extract,total ash and nitrogen-free extract were 8.3%,7.6%,5.1%,6.3%,and 72.6%,respectively.Average Ca,Mg,P and K levels were 0.5%,0.2%,0.2%,and 2.0%,respectively.Total phenols were 0.4%.Cluster analysis showed that the study area may be divided into three distinct provenances,each having diff erent drupe traits and proximate composition,including mineral components.Gas-chromatography mass-spectrometry analysis revealed 27 phytochemicals,many of which possess benefi cial biological attributes.The implications of this provenance variation study should be useful for future improvement in terms of better drupe pulp nutrition for livestock feed.Further study suggests that M.dubia pulp could be categorized as a good feed source with low fi bre,energy,fat and mineral levels.All proximate parameters,mineral matter content and total phenols are within prescribed limits.

Potential bioactive phytochemicals, antioxidant properties and anticancer pathways of Nymphaea nouchali

Objective:To investigate bioactive phytochemicals and antioxidant activities of Nymphaea nouchali and to explore its anticancer pathways by a network pharmacology approach.Methods:Using a spectrophotometer and high-performance liquid chromatography-diode array detector(HPLC-DAD),we quantified bioactive phytochemicals in methanolic extract of Nymphaea nouchali tuber.The extracts were investigated for in vitro antioxidant properties.Targets of these bioactive phytochemicals were predicted and anticancer-associated pathways were analyzed by a network pharmacology approach.Moreover,we identified the predicted genes associated with cancer pathways and the hub genes in the protein-protein interaction network of predicted genes.Results:Quantitative results indicated the total phenolics,total flavonoids,and total proanthocyanidins in the methanolic extract of Nymphaea nouchali tuber.HPLC-DAD analysis showed rutin(39.44 mg),catechin(39.20 mg),myricetin(30.77 mg),ellagic acid(11.05 mg),gallic acid(3.67 mg),vanillic acid(0.75 mg),rosmarinic acid(4.81 mg),p-coumaric acid(3.35 mg),and quercetin(0.90 mg)in 1 g of dry extract.The extract showed the radical scavenging activities of 2,2-diphenyl-1-picrylhydrazyl,2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)and N,N-dimethyl-pphenylenediamine.By using network pharmacology,we predicted 130 target genes associated with cancer pathways.The top hub genes(IL6,AKT1,EGFR,JUN,PTGS2,MAPK3,CASP3,and CXCL8)were also identified,which were associated with cancer pathways and interacted with bioactive phytochemicals of the methanolic extract of Nymphaea nouchali tuber.Conclusions:Our study provides insights into the mechanism of anticancer activities of the methanolic extract of Nymphaea nouchali tuber.

Liver disorders in COVID-19,nutritional approaches and the use of phytochemicals

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.

Assessment of phytochemicals and antioxidant activities of raw and germinating Ceiba pentandra (kapok) seeds

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.

Embryo and Endosperm Phytochemicals from Polyembryonic Maize Kernels and Their Relationship with Seed Germination

Because of the growing worldwide demand for maize grain,new alternatives have been sought for breeding of this cereal,e.g.,development of polyembryonic varieties,which agronomic performance could positively impact the grain yield per unit area,and nutritional quality.The objectives of this study were to(1)determine the phytochemicals present in the embryo and endosperm of grain from maize families with high,low,and null polyembryony frequency,which were planted at different locations,and(2)state the relationship between these compounds and seed germination.The extracted phytochemicals from corn were identified by HPLC-MS.The results showed that the genotype with the highest presence of phytochemicals was the brachytic population with high polyembryony called“BAP”,which also required less water during the germination process.The number of phytochemicals in both embryo and endosperm tissues was not related to the sowing location where they came from or the type of polyembryony.The number of different phytochemicals depended on the grain tissue from where they were extracted.The chemical compounds found in the different maize tissues were related to the development of the plant,either in roots or nibs because these are mainly associated with the lignin synthesis.