Interactions of naturally occurring compounds with antimicrobials

Antibiotics are among the most often used medications in human healthcare and agriculture.Overusing these substances can lead to complications such as increasing antibiotic resistance in bacteria or a toxic effect when administering large amounts.To solve these problems,new solutions in antibacterial therapy are needed.The use of natural products in medicine has been known for centuries.Some of them have antibacterial activity,hence the idea to combine their activity with commercial antibiotics to reduce the latter's use.This review presents collected information on natural compounds(terpenes,alkaloids,flavonoids,tannins,sulfoxides,and mycotoxins),of which various drug interactions have been observed.Many of the indicated compounds show synergistic or additive interactions with antibiotics,which suggests their potential for use in antibacterial therapy,reducing the toxicity of the antibiotics used and the risk of further development of bacterial resistance.Unfortunately,there are also compounds which interact antagonistically,potentially hindering the therapy of bacterial infection.Depending on its mechanism of action,each compound can behave differently in combination with different antibiotics and when acting against various bacterial strains.

Plant-derived natural compounds in the treatment of arsenic-induced toxicity

Arsenic toxicity,imposed mainly by arsenic-contaminated groundwater,is considered a critical threat to global communal health,as there is no specific and proven conventional therapy for chronic arsenic toxicity,i.e.,arsenicosis,which is an insidious global public health menace affecting 50 countries.Alternative options should,therefore,be explored for the mitigation of arsenicosis.Literature survey reveals several natural compounds from plants possess significant protective efficacy against arsenic toxicity in chiefly preclinical and few clinical investigations.The studies on the ameliorative effects of plant-derived natural compounds against arsenic toxicity published in the last 25 years are collated.Forty-eight plant-based natural compounds possess alleviative effects on experimental arsenic-induced toxicity in animals,six of which have been reported to be clinically effective in humans.A potential nutraceutical or therapeutic candidate against arsenicosis for humans may thus be developed with the help of recent advancements in research in this area,along with the currently available treatments.

A Review of Textile Fabrication Using Bioactive Compounds Derived from Natural Products

Antimicrobial-treated textiles should exhibit efficacy against a broad spectrum of bacterial and fungal species,all while maintaining user safety with a non-toxic profile.Natural antimicrobial compounds play a vital role in textile finishing processes.The proliferation of synthetic antimicrobial agents introduces environmental and consumer safety concerns.Given these potential hazards associated with synthetic agents,the utilization of natural antimicrobial agents is gaining traction,as they tend to have fewer adverse effects on users and are more environmentally sustainable.Numerous natural antimicrobial compounds,sourced from plants such as neem,basil,turmeric,aloe vera,and clove oil,have been developed,showcasing inherent antimicrobial properties.This review article highlights the importance of incorporating bioactive components in the creation of antibacterial textile fabrics.

Rapid discovery of a novel “green” and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen“green”natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by downregulating GST expression.Considering the high GST levels in HCC patients,this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Tracing of natural gas migration by light hydrocarbons:A case study of the Dongsheng gas field in the Ordos Basin,NW China

Based on the analysis of light hydrocarbon compositions of natural gas and regional comparison in combination with the chemical components and carbon isotopic compositions of methane,the indication of geochemical characteristics of light hydrocarbons on the migration features,dissolution and escape of natural gas from the Dongsheng gas field in the Ordos Basin is revealed,and the effect of migration on specific light hydrocarbon indexes is further discussed.The study indicates that,natural gas from the Lower Shihezi Formation(Pix)in the Dongsheng gas field displays higher iso-C5-7contents than n-C5-7contents,and the C6-7light hydrocarbons are composed of paraffins with extremely low aromatic contents(<0.4%),whereas the C7light hydrocarbons are dominated by methylcyclohexane,suggesting the characteristics of coal-derived gas with the influence by secondary alterations such as dissolution.The natural gas from the Dongsheng gas field has experienced free-phase migration from south to north and different degrees of dissolution after charging,and the gas in the Shiguhao area to the north of the Borjianghaizi fault has experienced apparent diffusion loss after accumulation.Long-distance migration in free phase results in the decrease of the relative contents of the methylcyclohexane in C7 light hydrocarbons and the toluene/n-heptane ratio,as well as the increase of the n-heptane/methylcyclohexane ratio and heptane values.The dissolution causes the increase of isoheptane values of the light hydrocarbons,whereas the diffusion loss of natural gas in the Shiguhao area results in the increase of n-C5-7contents compared to the iso-C5-7contents.

In silico evaluation of kuwanon compounds as antiviral agents targeting H9N2 influenza virus

Background:The threat of avian influenza a subtype avian influenza A(H9N2)virus remains a significant concern,necessitating the exploration of novel antiviral agents.This study employs network pharmacology and computational analysis to investigate the potential of kuwanons,a natural compounds against H9N2 influenza virus.Methods:Leveraging comprehensive databases and bioinformatics tools,we elucidate the molecular mechanisms underlying Kuwanons pharmacological effects against H9N2 influenza virus.Network pharmacology identifies H9N2 influenza virus targets and compounds through integrated protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes analyses.Molecular docking studies were performed to assess the binding affinities and structural interactions of Kuwanon analogues with key targets,shedding light on their potential inhibitory effects on viral replication and entry.Results:Compound-target network analysis revealed complex interactions(120 nodes,163 edges),with significant interactions and an average node degree of 2.72.Kyoto Encyclopedia of Genes and Genomes analysis revealed pathways such as Influenza A,Cytokine-cytokine receptor interaction pathway in H9N2 influenza virus.Molecular docking studies revealed that the binding free energy for the docked ligands ranged between-5.2 and-9.4 kcal/mol for the human interferon-beta crystal structure(IFNB1,Protein Data Bank:1AU1)and-5.4 and-9.6 kcal/mol for Interleukin-6(IL-6,PDB:4CNI).Conclusion:Our findings suggest that kuwanon exhibits promising antiviral activity against H9N2 influenza virus by targeting specific viral proteins,highlighting its potential as a natural therapeutic agent in combating avian influenza infections.

Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review

Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.

Natural compounds and extracts from Mexican medicinal plants with anti-leishmaniasis activity: An update

Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceraltype leishmaniasis are recorded and 60000 persons died from the disease. In Mexico,cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major,while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC_(50)≤30 mg/mL or m M have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.

Cancer chemoprevention through the induction of apoptosis by natural compounds

As cell and tissue homeostasis are mediated by the balance between proliferation and apoptosis, controlling this balance is important for cancer chemoprevention. Cancer chemoprevention can be achieved by the use of natural, synthetic or biologic compounds that reverse, suppress or prevent the development of epithelial malignancies. Natural compounds including flavonoids are able to reduce oxidative stress, which is the most likely mechanism mediating the protective effects against cancer development. In addition, in vitro and in vivo studies have suggested that flavonoids, such as (-)-epigallocatechin-3-gallete (EGCG), quercetin, and curcumin, act by induction of apoptosis. Several natural compounds inhibit cell proliferation and angiogenesis. Certain natural products have been shown to inhibit the activation of nuclear factor kappa B (NF-κB) and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Understanding the mechanism of these natural products will contribute to the development of more specific preventive strategies against cancer development. Here we focus on the ability of natural cancer chemopreventive agents to induce apoptosis, and attempt to provide evidence for the preventive and therapeutic effects of natural compounds, EGCG, quercetin, and curcumin, in a succinct manner highlightingκand Akt signaling pathways in vivo.

Transient Folate Deprivation in Combination with Small-molecule Compounds Facilitates the Generation of Somatic Cell-derived Pluripotent Stem Cells in Mice

Induced pluripotent stem cells （iPSCs） can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical re- search. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel ap- proach to generating iPSCs. In this study, a new combination of small-molecule compounds （SMs） （so- dium butyrate, A-83-01, CHIR99021, Y-27632） under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts （MEFs） in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs The resulting cell lines resembled mouse embryonic stem （ES） cells with respect to proliferation rate, morphology, pluripotency-associatedmarkers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcino- genicity and the use of exogenous reprogramming factors.

Natural compounds may contribute in preventing SARS-CoV-2 infection:a narrative review

Coronavirus pandemic infection is the most important health issue worldwide.Coronavirus disease 2019 is a contagious disease characterized by severe acute respiratory syndrome coronavirus 2.To date,excluding the possibility of vaccination,against SARS-CoV-2 infection it is possible to act only with supportive care and non-virus-specific treatments in order to improve the patient’s symptoms.Pharmaceutical industry is investigating effects of medicinal plants,phytochemical extracts and aromatic herbs to find out natural substances which may act as antiviral drugs.Several studies have revealed how these substances may interfere with the viral life cycle,viral entry,replication,assembly or discharge,as well as virus-specific host targets or stimulating the host immune system,reducing oxidative stress and inflammatory response.A natural compound can be used as a prophylaxis by people professionally exposed to the risk of contagion and/or positive patients not in intensive care.The aim of this paper is to perform a narrative review of current literature in order to summarize the most studied natural compounds and their modes of action.

Neuroglobin and neuroprotection:the role of natural and synthetic compounds in neuroglobin pharmacological induction

Neuroglobin(Ngb)is a 17 kDa monomeric hexa-coordinated heme protein belonging to the globin family.Ngb is mainly expressed in neurons of the central and peripheral nervous system,although moderate levels of Ngb have been detected in non-nervous tissues.In the past decade,Ngb has been studied for its neuroprotective role in a large number of neurological disorders such as Alzheimer’s disease,Huntington’s disease,brain ischemia and hypoxia.This review discusses and summarizes the natural compounds and the small synthetic molecules capable of modulating Ngb expression that exhibits a protective role against various neurodegenerative diseases.

Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases

It has been suggested that altered levels/function of brain-derived neurotrophic factor （BDNF） play a role in the pathophysiology of neurodegenerative diseases including Alzheimer＇s disease. BDNF positively contributes to neural survival and synapse maintenance via stimulating its high affinity receptor TrkB, making upregulation of BDNF and/or activation of BDNF-related intracellnlar signaling an attractive approach to treating neurodegenerative diseases. In this short review, I briefly introduce small natural compounds such as flavonoids that successfully increase activation of the BDNF system and discuss their beneficial effects against neurodegeneration.

Natural Products as Potential Lead Compounds for Drug Discovery Against SARS-CoV-2

For the past 2 years,the coronavirus responsible for the COVID-19 infection has become a world pandemic,ruining the lives and economies of several nations in the world.This has scaled up research on the virus and the resulting infection with the goal of developing new vaccines and therapies.Natural products are known to be a rich source of lead compounds for drug discovery,including against infectious diseases caused by microbes(viruses,bacteria and fungi).In this review article,we conducted a literature survey aimed at identifying natural products with inhibitory concentrations against the coronaviruses or their target proteins,which lie below 10μM.This led to the identification of 42 compounds belonging to the alkaloid,flavonoid,terpenoid,phenolic,xanthone and saponin classes.The cut off concentration of 10μM was to limit the study to the most potent chemical entities,which could be developed into therapies against the viral infection to make a contribution towards limiting the spread of the disease.

Research Progress on Toxicity of Natural Compounds

There are many active substances in natural resources.After years of research,researchers at home and abroad have extracted active compounds and proved that these compounds have low toxicity and high efficiency,but the toxicity of these compounds cannot be ignored.In this paper,the research progress on the toxicity of compounds isolated from various natural substances is reviewed,which provides a reference for the further development and rational utilization of natural compounds.

Role of natural products and intestinal flora on type 2 diabetes mellitus treatment

Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.

A Cocktail of Natural Compounds Holds Promise for New Immunotherapeutic Potential in Head and Neck Cancer

Objective: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas(HNSC). Methods: Gene expression data of HNSC samples and peripheral blood mononuclear cells(PBMCs) of HNSC patients were collected from Gene Expression Omnibus(GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres(DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. Results: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expressions of all 110 commonly DEGs were altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. Conclusions: This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

Natural Compound Curcumin—a Channel Potentiator Rather Than a Corrector of the Defective Intracellular Processing of △F508 Mutant Cystic Fibrosis Transmembrane Conductance Regulator

Cystic fibrosis（CF） is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator（CFTR） chloride channel. The most common point mutation AF508, which leads to impaired intracellular processing and channel gating of CFTR, appears in about 90% CF patients. The natural compound curcumin was reported to correct the processing defect of AF508-CFTR and proposed as a potential therapeutic drug to cure CF. In the present study, we analyzed the effect of curcumin on AF508-CFTR and demonstrated that curcumin can restore the impaired chloride conductance of AF508 mutant CFTR. The activity is rapid, reversible and cAMP-dependent. However, we couldn＇t reproduce the previously reported correction of the defective membrane trafficking of AF508-CFTR by curcumin. Therefore, curcumin may not be a superior lead compound for developing anti-CF drugs.

Prioritised identification of structural classes of natural products from higher plants in the expedition of antimalarial drug discovery

The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria.Urgent measures need to be taken to curb this impending challenge.The higher plant-derived sesquiterpene,quinoline alkaloids,and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed.Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed.The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P.falciparum.To identify these novel scaffolds,we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data.Natural products were assigned to different structural classes using NPClassifier.To identify the most promising chemical scaffolds,we then correlated natural compound class with bioactivity and other data,namely(i)potency,(ii)resistance index,(iii)selectivity index and(iv)physicochemical properties.We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data.From this analysis we identified the top-ranked natural product pathway as the alkaloids.The top three ranked super classes identified were(i)pseudoalkaloids,(ii)naphthalenes and(iii)tyrosine alkaloids and the top five ranked classes(i)quassinoids(of super class triterpenoids),(ii)steroidal alkaloids(of super class pseudoalkaloids)(iii)cycloeudesmane sesquiterpenoids(of super class triterpenoids)(iv)isoquinoline alkaloids(of super class tyrosine alkaloids)and(v)naphthoquinones(of super class naphthalenes).Launched chemical space of these identified classes of compounds was,by and large,distinct from that of‘legacy’antimalarial drugs.Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs.These molecules have the potential to be developed into new antimalarial drugs.

Advances in research on the anticancer mechanism of the natural compound cucurbitacin from Cucurbitaceae plants:a review

Cucurbitacins are highly oxidized tetracyclic triterpenoids that are widely found in plants belonging to Cucurbitaceae family and exert various pharmacological effects.Many cucurbitacin derivatives are available,of which cucurbitacins B,D,E,and I are important members of the cucurbitacin family and exert anticancer effects against various cancers.This review summarizes the advances in research on cucurbitacins B,D,E,and I in inducing tumor cell apoptosis,cytoskeletal destruction,cell cycle arrest,and autophagy and in regulating various cancer-related signaling pathways.In addition,this review summarizes the latest research on the synergistic effects of the combination of cucurbitacins and clinically approved chemotherapeutic drugs.The findings summarized in this review suggest that cucurbitacins are multi-targeting and multi-functional anticancer drugs and that their complex anticancer mechanisms should be examined in future studies.Because of their proven benefits,cucurbitacins have the potential to be used as anticancer drugs in the clinical setting.