Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garn...Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garnered considerable attention is programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1).The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system.Furthermore,it controls the phenotype and functionality of innate and adaptive immune components.A range of monoclonal antibodies,including avelumab,atezolizumab,camrelizumab,dostarlimab,durvalumab,sinitilimab,toripalimab,and zimberelimab,have been developed for targeting the interaction between PD-1 and PD-L1.These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system.Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints.This could contribute to the existing arsenal of anticancer drugs.Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis,promoting tumor cell apoptosis,influencing cell proliferation,and eventually leading to tumor cell death and inhibiting cancer progression.However,there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer.Hence,this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules.Moreover,the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules.Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.展开更多
Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable att...Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.Therefore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.展开更多
Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Tolllike receptor 4(TLR4)i...Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Tolllike receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or viruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.展开更多
Although non-alcoholic fatty liver disease(NAFLD)presents as an intricate condition characterized by a growing prevalence,the often-recommended lifestyle interventions mostly lack high-level evidence of efficacy and t...Although non-alcoholic fatty liver disease(NAFLD)presents as an intricate condition characterized by a growing prevalence,the often-recommended lifestyle interventions mostly lack high-level evidence of efficacy and there are currently no effective drugs proposed for this indication.The present review delves into NAFLD pathology,its diverse underlying physiopathological mechanisms and the available in vitro,in vivo,and clinical evidence regarding the use of natural compounds for its management,through three pivotal targets(oxidative stress,cellular inflammation,and insulin resistance).The promising perspectives that natural compounds offer for NAFLD management underscore the need for additional clinical and lifestyle intervention trials.Encouraging further research will contribute to establishing more robust evidence and practical recommendations tailored to patients with varying NAFLD grades.展开更多
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...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.展开更多
Cancer is generally regarded as the result of abnormal growth of cells. According to World Health Organization, cancer is the leading cause of mortality worldwide. Mother nature provides a large source of bioactive co...Cancer is generally regarded as the result of abnormal growth of cells. According to World Health Organization, cancer is the leading cause of mortality worldwide. Mother nature provides a large source of bioactive compounds with excellent therapeutic efficacy. Numerous phytochemicals from nature have been investigated for anticancer properties. In this review article, we discuss several natural compounds, which have shown anti-cancer activity. Natural compounds induce cell cycle arrest, activate intrinsic and extrinsic apoptosis pathways, generate Reactive Oxygen Species(ROS), and down-regulate activated signaling pathways, resulting in inhibition of cell proliferation, progression and metastasis of cancer. Several preclinical studies have suggested that natural compounds can also increase the sensitivity of resistant cancers to available chemotherapy agents. Furthermore, combining FDA approved anti-cancer drugs with natural compounds results in improved efficacy. On the basis of these exciting outcomes of natural compounds against several cancer types, several agents have already advanced to clinical trials. In conclusion, preclinical results and clinical outcomes against cancer suggest promising anticancer efficacy of agents from natural sources.展开更多
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 perso...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.展开更多
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 possi...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.展开更多
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 contrib...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.展开更多
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.,a...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.展开更多
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 th...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.展开更多
The increasing incidence of melanoma poses significant challenges for conventional treatment approaches,plagued by drug resistance and adverse side effects.Natural marine-derived compounds have gained prominence in me...The increasing incidence of melanoma poses significant challenges for conventional treatment approaches,plagued by drug resistance and adverse side effects.Natural marine-derived compounds have gained prominence in melanoma research for their unique bioactivities and diversity.This review delves into the therapeutic potential of these compounds in melanoma treatment,emphasizing their distinctive advantages such as multi-target mechanisms and immune modulation,which distinguish them from traditional therapies.Additionally,we discuss the challenges in translating these agents into clinical applications,including formulation stability,bioavailability,and regulatory hurdles.Recent advancements in preclinical models such as organoids and completed clinical trials further support the exploration of marine-derived compounds in melanoma management.By consolidating current research,this review underscores the potential of these agents to enhance treatment efficacy and foster new therapeutic strategies.展开更多
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 peripher...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.展开更多
Oral diseases include periodontal and oral tumors.Current treatment methods rely largely on surgical interventions and mechanical cleaning,with a lack of targeted pharmacological therapies.Regardless,natural active co...Oral diseases include periodontal and oral tumors.Current treatment methods rely largely on surgical interventions and mechanical cleaning,with a lack of targeted pharmacological therapies.Regardless,natural active compounds have now become a new focus of research for the treatment of oral diseases owing to their low toxicity,favorable biocompatibility,and multi-target effects.This review summarizes the research progress regarding the role and application potential of natural active compounds,such as berberine and curcumin,in the prevention and treatment of oral diseases.展开更多
Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the community.To date,effective therapy for stroke has been limited by its complex pathological...Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the community.To date,effective therapy for stroke has been limited by its complex pathological mechanisms.Autophagy refers to an intracellular degrading process with the involvement of lysosomes.Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents.Increasing evidence support that autophagy protects neuronal cells from ischemic injury.However,under certain circumstances,autophagy activation induces cell death and aggravates ischemic brain injury.Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke.In the present work,we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.展开更多
Coronaviruses(CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.Co Vs are known t...Coronaviruses(CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.Co Vs are known to cause various potentially lethal human respiratory infectious diseases,such as severe acute respiratory syndrome(SARS),Middle East respiratory syndrome(MERS),and the very recent coronavirus disease 2019(COVID-19)outbreak.Unfortunately,neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs.Therefore,effective prevention and treatment medications against human coronavirus are in urgent need.In the past decades,many natural compounds have been reported to possess multiple biological activities,including antiviral properties.In this article,we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS,and discussed their potential use for the treatment of COVID-19.展开更多
The plant plasma membrane(PM)H^(+)-ATPase is an essential enzyme controlling plant growth and development.It is an important factor in response to abiotic and biotic stresses and is subject to tight regulation.We are ...The plant plasma membrane(PM)H^(+)-ATPase is an essential enzyme controlling plant growth and development.It is an important factor in response to abiotic and biotic stresses and is subject to tight regulation.We are in demand for new sustainable natural growth regulators and as a key enzyme for regulation of transport into the plant cell the PM H^(+)-ATPase is a potential target for these.In this review,we have evaluated the known non-protein natural compounds with regulatory effects on the PM H^(+)-ATPase,focusing on their mechanism of action and their potential as biologicals/growth regulators in plant production of future sustainable agriculture.展开更多
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 b...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.展开更多
Liver diseases are most common disorders in the world and characterized by rapid changes from steatosis to chronic hepatitis,fi brosis,cirrhosis,and hepatocellular carcinoma(HCC).Natural products that attained great a...Liver diseases are most common disorders in the world and characterized by rapid changes from steatosis to chronic hepatitis,fi brosis,cirrhosis,and hepatocellular carcinoma(HCC).Natural products that attained great attention is to be used in the prevention and treatment of multiple diseases in humans.Several researches have been reported numerous natural and phytochemical compounds that may counteract or prevent the hepatic injury and primary liver cancer.The conservative treatment of liver toxicity and HCC may face awkward challenges in chemotherapy such as therapeutic failure or drug resistance.Accordingly,there is an actual need for safe and effective therapeutic and preventive modalities for liver disorders.The present review aims to focus on the potential protective and therapeutic effects of natural compounds in the prevention and treatment of hepatotoxicity and HCC.It also demonstrates the mechanism of the natural products in enzymatic regulation of antioxidants and its role in apoptosis and proliferation of cancerous lesions of hepatocytes.Accordingly,it highlights the promising role of natural bioactive compounds and provides the rational for further transitional researches,and emphasize on the scientifi c validation of natural compounds for therapeutic portfolio for clinical use in liver diseases.展开更多
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 whe...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.展开更多
基金support provided by the Department of Science and Technology,Science and Engineering Research Board(DST-SERB),the Anusandhan National Research Foundation(ANRF),State University Research Excellence(SERB-SURE),Ministry of Science and Technology,Govt.of India(SUR/2022/001353).
文摘Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garnered considerable attention is programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1).The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system.Furthermore,it controls the phenotype and functionality of innate and adaptive immune components.A range of monoclonal antibodies,including avelumab,atezolizumab,camrelizumab,dostarlimab,durvalumab,sinitilimab,toripalimab,and zimberelimab,have been developed for targeting the interaction between PD-1 and PD-L1.These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system.Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints.This could contribute to the existing arsenal of anticancer drugs.Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis,promoting tumor cell apoptosis,influencing cell proliferation,and eventually leading to tumor cell death and inhibiting cancer progression.However,there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer.Hence,this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules.Moreover,the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules.Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.
基金supported by the National Natural Science Foundation of China(Grant No.:82174222)Shandong Province Natural Science Foundation,China(Grant No.:ZR2021LZY015).
文摘Breast cancer(BC)is one of the most prevalent malignant tumors affecting women worldwide,with its incidence rate continuously increasing.As a result,treatment strategies for this disease have received considerable attention.Research has highlighted the crucial role of the Hedgehog(Hh)signaling pathway in the initiation and progression of BC,particularly in promoting tumor growth and metastasis.Therefore,molecular targets within this pathway represent promising opportunities for the development of novel BC therapies.This study aims to elucidate the therapeutic mechanisms by which natural compounds modulate the Hh signaling pathway in BC.By conducting a comprehensive review of various natural compounds,including polyphenols,terpenes,and alkaloids,we reveal both common and unique regulatory mechanisms that influence this pathway.This investigation represents the first comprehensive analysis of five distinct mechanisms through which natural compounds modulate key molecules within the Hh pathway and their impact on the aggressive behaviors of BC.Furthermore,by exploring the structure-activity relationships between these compounds and their molecular targets,we shed light on the specific structural features that enable natural compounds to interact with various components of the Hh pathway.These novel insights contribute to advancing the development and clinical application of natural compound-based therapeutics.Our thorough review not only lays the groundwork for exploring innovative BC treatments but also opens new avenues for leveraging natural compounds in cancer therapy.
基金sponsored by the National Natural Science Foundation of China(Grant No.:32371185)the Shanghai Science and Technology Plan Project,China(Project No.:23010504200)+3 种基金the“Shuguang Program”(Program No.:20SG50)funded by Shanghai Education Development FoundationShanghai Municipale Education Commission,China,the Shanghai Talent Development Fund,China(Grant No.:2020125)the Key Lab of Exercise and Health Sciences of Ministry of Education(Shanghai University of Sport,China)(Grant No.:2022KF001)the Shanghai Key Lab of Human Performance(Shanghai University of Sport,China)(Grant No.:11DZ2261100).
文摘Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Tolllike receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or viruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.
基金funded by the multidisciplinary inter-institute“Health-Bioscience”projects 2020—QUINOACT.
文摘Although non-alcoholic fatty liver disease(NAFLD)presents as an intricate condition characterized by a growing prevalence,the often-recommended lifestyle interventions mostly lack high-level evidence of efficacy and there are currently no effective drugs proposed for this indication.The present review delves into NAFLD pathology,its diverse underlying physiopathological mechanisms and the available in vitro,in vivo,and clinical evidence regarding the use of natural compounds for its management,through three pivotal targets(oxidative stress,cellular inflammation,and insulin resistance).The promising perspectives that natural compounds offer for NAFLD management underscore the need for additional clinical and lifestyle intervention trials.Encouraging further research will contribute to establishing more robust evidence and practical recommendations tailored to patients with varying NAFLD grades.
基金Part of this manuscript was supported by Grant from the Instituto Mexicano del Seguro Social,projects FIS/IMSS/PROT/G15/1414
文摘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.
基金supported in part by NIH/National Cancer Institute R01 grant CA129038(to S.K.S)MEST grant 2012–0005755(to S.H.K)
文摘Cancer is generally regarded as the result of abnormal growth of cells. According to World Health Organization, cancer is the leading cause of mortality worldwide. Mother nature provides a large source of bioactive compounds with excellent therapeutic efficacy. Numerous phytochemicals from nature have been investigated for anticancer properties. In this review article, we discuss several natural compounds, which have shown anti-cancer activity. Natural compounds induce cell cycle arrest, activate intrinsic and extrinsic apoptosis pathways, generate Reactive Oxygen Species(ROS), and down-regulate activated signaling pathways, resulting in inhibition of cell proliferation, progression and metastasis of cancer. Several preclinical studies have suggested that natural compounds can also increase the sensitivity of resistant cancers to available chemotherapy agents. Furthermore, combining FDA approved anti-cancer drugs with natural compounds results in improved efficacy. On the basis of these exciting outcomes of natural compounds against several cancer types, several agents have already advanced to clinical trials. In conclusion, preclinical results and clinical outcomes against cancer suggest promising anticancer efficacy of agents from natural sources.
文摘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.
文摘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.
基金supported by the grant from Grant-in-Aid for Scientific Research(B)(JSPS KAKENHI Grant Number 24300139)Challenging Exploratory Research(JSPS KAKENHI Grant Number 25640019)from the Ministry of Education,Culture,Sports,Science,and Technology of Japan
文摘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.
文摘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.
文摘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.
文摘The increasing incidence of melanoma poses significant challenges for conventional treatment approaches,plagued by drug resistance and adverse side effects.Natural marine-derived compounds have gained prominence in melanoma research for their unique bioactivities and diversity.This review delves into the therapeutic potential of these compounds in melanoma treatment,emphasizing their distinctive advantages such as multi-target mechanisms and immune modulation,which distinguish them from traditional therapies.Additionally,we discuss the challenges in translating these agents into clinical applications,including formulation stability,bioavailability,and regulatory hurdles.Recent advancements in preclinical models such as organoids and completed clinical trials further support the exploration of marine-derived compounds in melanoma management.By consolidating current research,this review underscores the potential of these agents to enhance treatment efficacy and foster new therapeutic strategies.
文摘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.
基金supported by grants from the Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Oral diseases include periodontal and oral tumors.Current treatment methods rely largely on surgical interventions and mechanical cleaning,with a lack of targeted pharmacological therapies.Regardless,natural active compounds have now become a new focus of research for the treatment of oral diseases owing to their low toxicity,favorable biocompatibility,and multi-target effects.This review summarizes the research progress regarding the role and application potential of natural active compounds,such as berberine and curcumin,in the prevention and treatment of oral diseases.
基金funded by the National Natural Science Foundation of China(81822044,81773703 and 81630098)the Fundamental Research Funds for the Central Universities(2019XZZX004-17,China)
文摘Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the community.To date,effective therapy for stroke has been limited by its complex pathological mechanisms.Autophagy refers to an intracellular degrading process with the involvement of lysosomes.Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents.Increasing evidence support that autophagy protects neuronal cells from ischemic injury.However,under certain circumstances,autophagy activation induces cell death and aggravates ischemic brain injury.Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke.In the present work,we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.
文摘Coronaviruses(CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.Co Vs are known to cause various potentially lethal human respiratory infectious diseases,such as severe acute respiratory syndrome(SARS),Middle East respiratory syndrome(MERS),and the very recent coronavirus disease 2019(COVID-19)outbreak.Unfortunately,neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs.Therefore,effective prevention and treatment medications against human coronavirus are in urgent need.In the past decades,many natural compounds have been reported to possess multiple biological activities,including antiviral properties.In this article,we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS,and discussed their potential use for the treatment of COVID-19.
基金supported by the Novo Nordic Foundatioin grant number NNF19OC0056457the Danish Council for Independent Research,Technology and Production Sciences(FTP)grant no.DFF-4184-00548 COMBAT。
文摘The plant plasma membrane(PM)H^(+)-ATPase is an essential enzyme controlling plant growth and development.It is an important factor in response to abiotic and biotic stresses and is subject to tight regulation.We are in demand for new sustainable natural growth regulators and as a key enzyme for regulation of transport into the plant cell the PM H^(+)-ATPase is a potential target for these.In this review,we have evaluated the known non-protein natural compounds with regulatory effects on the PM H^(+)-ATPase,focusing on their mechanism of action and their potential as biologicals/growth regulators in plant production of future sustainable agriculture.
基金This work was supported by the Italian Ministero dell’Istruzione,dell’Universitáe della Ricerca PRIN 2017SNRXH3(to EO and SN)PRA_2018_20 University of Pisa(to EO).
文摘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.
文摘Liver diseases are most common disorders in the world and characterized by rapid changes from steatosis to chronic hepatitis,fi brosis,cirrhosis,and hepatocellular carcinoma(HCC).Natural products that attained great attention is to be used in the prevention and treatment of multiple diseases in humans.Several researches have been reported numerous natural and phytochemical compounds that may counteract or prevent the hepatic injury and primary liver cancer.The conservative treatment of liver toxicity and HCC may face awkward challenges in chemotherapy such as therapeutic failure or drug resistance.Accordingly,there is an actual need for safe and effective therapeutic and preventive modalities for liver disorders.The present review aims to focus on the potential protective and therapeutic effects of natural compounds in the prevention and treatment of hepatotoxicity and HCC.It also demonstrates the mechanism of the natural products in enzymatic regulation of antioxidants and its role in apoptosis and proliferation of cancerous lesions of hepatocytes.Accordingly,it highlights the promising role of natural bioactive compounds and provides the rational for further transitional researches,and emphasize on the scientifi c validation of natural compounds for therapeutic portfolio for clinical use in liver diseases.
文摘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.
