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.

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.

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.

Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.

Current status of drug therapy for alveolar echinococcosis

Alveolar echinococcosis(AE)is a chronic zoonotic parasitic disease caused by infection with Echinococcus multilocularis.AE is associated with a high mortality rate and poses a significant threat to human health.The primary treatment for AE is surgical resection of the lesions;however,owing to its long incubation period and insidious disease progression,many patients are diagnosed only after the onset of complications such as liver cirrhosis,jaundice,and portal hypertension,which preclude curative surgical intervention.For patients who are unwilling or unable to undergo surgery,lifelong administration of anti-AE medications is necessary.Benzimidazole compounds,such as albendazole and mebendazole,are the current mainstays of treatment,offering good efficacy.Nevertheless,these medications primarily inhibit parasite proliferation rather than eradicate the infection,and their long-term use can lead to significant drug-related toxic effects.Consequently,there is an urgent need to develop new therapeutic strategies that convey better efficacy and reduce the adverse effects associated with current treatments.Recent advancements in AE therapy include novel synthetic compounds such as antiviral agents,antibiotics,antineoplastic agents,immunosuppressants,and antiangiogenic agents,as well as natural compounds derived from traditional Chinese and Tibetan medicine.These new drugs show promising clinical potential because they interfere with parasitic metabolic pathways and cellular structures.This review aims to discuss recent research on AE drug therapy,including mechanisms of action,dosing regimens,signalling pathways,and therapeutic outcomes,with a goal of providing new insights and directions for the development of anti-AE drugs and summarizing current advancements in AE pharmacotherapy.

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.

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.

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.

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.

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.

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 Compound Curcumin Corrects the Gating Defect of G551DMutant Cystic Fibrosis Transmembrane Conductance Regulator

In the present study, we identified the natural compound curcumin to be an effective G551D-CFTR activator by cell-based fluorescent assay and electrophysiological measurement. We demonstrated that curcumin can restore the impaired chloride conductance of G551D mutant CFTR. The activity is rapid, reversible, and cAMP-dependent. Our study identified a new natural lead compound for the pharmacological therapy of cystic fibrosis caused by G551D mutation of CFTR.

Natural Compound Formula RM88 Significantly Reduces Blood Alcohol Concentration in Humans

There is extensive worldwide use for the social consumption of alcohol. Abuse of alcohol causes substantial personal, psychological and medical health issues. In addition, there are significant national economic costs from lost productivity. However, there are limited pharmaceutical drugs for the treatment of alcohol overuse. Historically, many cultures have used herbs and other natural compounds to reduce problematic alcohol induced behaviour but the evidence is anecdotal. This study investigated if a natural compound formula (RM88) that was developed could reduce blood alcohol concentration (BAC) in a controlled case series. Thirteen subjects (5 males, 8 females, age range 18 to 85 years) completed 16 paired sessions of alcohol only versus RM88 with alcohol. Subjects consumed one to three standard drinks of beer, wine or spirits (14.7 to 29.4 gm alcohol). Measurements were made by a fuel cell breathalyzer for a period of 90 minutes. Summated BAC showed a reduction in 94% (15/16) of paired test sessions (BAC reduction range 23% - 79%, mean 50.9% ± 16.5%, p = 0.0005). Data normalized to 20 gm alcohol (two standard drinks) showed a significance of p = 0.00026. One subject on prednisone and hydroxychloroquine drugs had increased BAC from RM88. The average reductions of BAC for the beverages were spirits 34% (n = 3), beer 36% (n = 3), and wine 52% (n = 10). RM88 showed that this combination of natural compounds was very effective in reducing maximal peak concentrations of alcohol.

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.

The Natural Law of Transition of a Charged Particle into a Compound State under the Action of an Electroscalar Field

This article is the continuation of article [1] where the experimental facts of observation of the electroscalar radiation in the spectrum of the Sun have been presented [2]. This radiation comes into the world having a long wavelength, being longitudinal and extraordinarily penetrating. In accordance with the principle of least action, the Lagrangian of the electroscalar field and the tensor of energy-moment are determined using the variation the potential and coordinates. The equation of motion the charged particle in electroscalar field is determined and the energy of particle has the negative sign with respect to the mechanical energy of particle and the energy of electromagnetic field. So, this is decreasing the electrical potential of particle during the propagation. The electroscalar energy of charged particle and field’s force acting on the particle during their motion change the particle’s electrical status which, in its turn, may trigger the transition of the particle into a compound state during interaction with any object. Due to the continuity this process can lead the particle to the state which enters into a compound state with a negative energy for a different particle’s velocity. This state is the physical vacuum’s state. Analysis of the solar spectrum demonstrates that scattering and absorption of electroscalar wave go on the cavities of solids. The spreading out of electroscalar field obeys to the law of plane wave and the transfer the energy and information can occur in vacuum and any medium.

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.

The medicinal chemistry of Urtica dioica L.:from preliminary evidence to clinical studies supporting its neuroprotective activity

Urtica dioica is a perennial herb from the family of Urticaceae that is commonly known as stinging nettle.This plant is widespread in Europe,Africa,America,and a part of Asia,as it adapts to different environments and climatic condi-tions.The leaves,stalk,and bark of U.dioica found applications in the field of nutrition,cosmetics,textile,pest control and pharmacology.In this connection,bioactive chemical constituents such as flavonoids,phenolic acids,amino acids,carotenoids,and fatty acids have been isolated from the plant.With this review,we aim at providing an updated and comprehensive overview of the contributions in literature reporting computational,in vitro,pre-clinical and clini-cal data supporting the therapeutic applications of U.dioica.Experimental evidence shows that U.dioica constituents and extracts can provide neuroprotective effects by acting through a combination of different molecular mecha-nisms,that are discussed in the review.These findings could lay the basis for the identification and design of more effective tools against neurodegenerative diseases.

A network pharmacology approach to explore the mechanism of action of Yiqi Fumai lyophilized injection in the treatment of novel coronavirus disease

Background:Shengmai decoction,which has been included in the diagnosis and treatment of coronavirus disease 2019(COVID-19),is effective in the early treatment of patients with severe COVID-19.Yiqi Fumai lyophilized injection(YQFM)is a modern Chinese medicine preparation of the Shengmai decoction.The mechanism of its intervention at the molecular level in the severe stage of COVID-19 remains unclear.Therefore,it is necessary to investigate the mechanism of YQFM in the treatment of patients with severe COVID-19.Methods:The corresponding target genes of the main active ingredients in YQFM and COVID-19 were obtained by using multiple databases and literature retrieval.A protein-protein interaction network was constructed,and enrichment analysis of the target was performed using Cytoscape 3.8.1.Lastly,the docking of all the identified compounds with angiotensin-converting enzyme II was confirmed by applying molecular docking technology.Results:YQFM has anti-inflammatory effects on RAW267.4 macrophages.The main active compounds of YQFM are all effective anti-inflammatory agents,and these active compounds also show beneficial physiological functions,such as anti-oxidation,anti-bacterial,and anticancer activities.Gene Ontology analysis showed enrichment in the following pathways:lipopolysaccharides,interleukins,NF-kappa B,interleukin-2 and others,revealing that YQFM may play a role in the treatment of patients with severe COVID-19 through these pathways.Conclusion:YQFM has multicomponent and multitarget characteristics,and it could reduce lung injury by inhibiting inflammatory reactions,promoting antiviral activities,and regulating immunity,among other functions,to treat patients with severe COVID-19.

Herbal compounds as promising therapeutic agents in precision medicine strategies for cancer:A systematic review

Background:The field of personalized medicine has gained increasing attention in cancer care,with the aim of tailoring treatment strategies to individual patients for improved outcomes.Herbal medicine,with its long-standing historical use and extensive bioactive compounds,offers a rich source of potential treatments for various diseases,including cancer.Objective:To provide an overview of the current knowledge and evidence associated with incorporating herbal compounds into precision medicine strategies for cancer diseases.Additionally,to explore the general characteristics of the studies included in the analysis,focusing on their key features and trends.Search strategy:A comprehensive literature search was conducted from multiple online databases,including Pub Med,Scopus,Web of Science,and CINAHL-EBSCO.The search strategy was designed to identify studies related to personalized cancer medicine and herbal interventions.Inclusion criteria:Publications pertaining to cancer research conducted through in vitro,in vivo,and clinical studies,employing natural products were included in this review.Data extraction and analysis:Two review authors independently applied inclusion and inclusion criteria,data extraction,and assessments of methodological quality.The quality assessment and biases of the studies were evaluated based on modified Jadad scales.A detailed quantitative summary of the included studies is presented,providing a comprehensive description of their key features and findings.Results:A total of 121 studies were included in this review for analysis.Some of them were considered as comprehensive experimental investigations both in vitro and in vivo.The majority(n=85)of the studies included in this review were conducted in vitro,with 44 of them specifically investigating the effects of herbal medicine on animal models.Additionally,7 articles with a combined sample size of 31,271 patients,examined the impact of herbal medicine in clinical settings.Conclusion:Personalized medication can optimize the use of herbal medicine in cancer treatment by considering individual patient factors such as genetics,medical history,and other treatments.Additionally,active phytochemicals found in herbs have shown potential for inhibiting cancer cell growth and inducing apoptosis,making them a promising area of research in preclinical and clinical investigations.