When human immune function is compromised,infections caused by pathogenic fungi are often difficult to cure,with invasive fungal diseases frequently associated with high mortality rates.Presently,the types of antifung...When human immune function is compromised,infections caused by pathogenic fungi are often difficult to cure,with invasive fungal diseases frequently associated with high mortality rates.Presently,the types of antifungal drugs available for clinical use are limited,and their toxicity and safety issues can lead to adverse effects for patients.The emergence of drug-resistant strains and the“super fungus”Candida auris has further complicated treatment.Consequently,the identification of new antifungal medications and the formulation of effective combination therapy strategies have emerged as pivotal research priorities within this discipline.Natural products are specialized small molecules that are produced in nature and play pivotal roles in numerous cellular processes and are considered to be among the most significant pharmaceutical agents in the field of human healthcare.Accordingly,the objective of this paper is to review natural products and relevant compounds that exhibit antifungal activity by targeting key components of the fungal cell walls or cell membranes.We focused on the most recent research findings from 2022 to 2025 concerning antifungal natural products derived from plants,fungi,and bacteria,and conducted a comprehensive summary of the sources and types of natural products,along with their antifungal mechanisms of action.Furthermore,we analyzed the application prospects of combining novel natural products with existing antifungal drugs from the perspective of compensatory mechanisms of fungal cell structures,thus establishing new treatment strategies for fungal infections.展开更多
Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional deterioration.Rece...Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional deterioration.Recently,ferroptosis,a newly recognized form of programmed cell death,has been implicated in IRI.Rehmanniae Radix Praeparata(RRP),extensively used in Chinese herbal medicine for its hepatoprotective,anti-inflammatory,and antioxidant properties,presents a potential therapeutic approach.However,the mechanisms by which RRP mitigates HIRI,particularly through the regulation of ferroptosis,remain unclear.In this study,we developed a HIRI mouse model and monocrotaline(MCT)-and erastin-induced in vitro hepatocyte injury models.We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI.The RRP aqueous extract was characterized by the presence of acteoside,rehmannioside D,and 5-hydroxymethylfurfural.Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress,reduced intracellular iron accumulation,and attenuated HIRI-induced liver damage.Additionally,RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in vitro.Mechanistically,the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake,promoting hepcidin-and ferroportin-mediated iron efflux,and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression.Moreover,siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract's inhibitory effect on ferroptosis.In conclusion,our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI,highlighting the restoration of iron metabolic balance.These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.展开更多
Type I interferon(IFN)is considered as a bridge between innate and adaptive immunity.Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion,tumor cell prolifera...Type I interferon(IFN)is considered as a bridge between innate and adaptive immunity.Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion,tumor cell proliferation,and overactive immune responses.Due to intricate and diverse chemical structures,natural products and their derivatives have become an invaluable source inspiring innovative drug discovery.In addition,some natural products have been applied in clinical practice for infection,cancer,and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted.However,whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated.In the current review,we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity,including both agonism/activation and antagonism/inhibition,and their potential application as therapies.Furthermore,the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified.In conclusion,natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection,cancer,and autoimmune diseases.展开更多
基金supported by the National Natural Science Foundation of China(No.82322075).
文摘When human immune function is compromised,infections caused by pathogenic fungi are often difficult to cure,with invasive fungal diseases frequently associated with high mortality rates.Presently,the types of antifungal drugs available for clinical use are limited,and their toxicity and safety issues can lead to adverse effects for patients.The emergence of drug-resistant strains and the“super fungus”Candida auris has further complicated treatment.Consequently,the identification of new antifungal medications and the formulation of effective combination therapy strategies have emerged as pivotal research priorities within this discipline.Natural products are specialized small molecules that are produced in nature and play pivotal roles in numerous cellular processes and are considered to be among the most significant pharmaceutical agents in the field of human healthcare.Accordingly,the objective of this paper is to review natural products and relevant compounds that exhibit antifungal activity by targeting key components of the fungal cell walls or cell membranes.We focused on the most recent research findings from 2022 to 2025 concerning antifungal natural products derived from plants,fungi,and bacteria,and conducted a comprehensive summary of the sources and types of natural products,along with their antifungal mechanisms of action.Furthermore,we analyzed the application prospects of combining novel natural products with existing antifungal drugs from the perspective of compensatory mechanisms of fungal cell structures,thus establishing new treatment strategies for fungal infections.
基金supported by Beijing Nova Program(No.Z201100006820025)the National Natural Science Foundation of China(No.82274186)+3 种基金the Fundamental Research Funds for the Central Universities(No.2023-JYB-JBZD-046)the National High-Level Talents Special Support Program to LI Xiaojiaoyanthe National Key Research and Development Program on Modernization of Traditional Chinese Medicine(No.2022YFC3502100)Beijing Municipal Science&Technology Commission(No.7212174)。
文摘Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional deterioration.Recently,ferroptosis,a newly recognized form of programmed cell death,has been implicated in IRI.Rehmanniae Radix Praeparata(RRP),extensively used in Chinese herbal medicine for its hepatoprotective,anti-inflammatory,and antioxidant properties,presents a potential therapeutic approach.However,the mechanisms by which RRP mitigates HIRI,particularly through the regulation of ferroptosis,remain unclear.In this study,we developed a HIRI mouse model and monocrotaline(MCT)-and erastin-induced in vitro hepatocyte injury models.We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI.The RRP aqueous extract was characterized by the presence of acteoside,rehmannioside D,and 5-hydroxymethylfurfural.Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress,reduced intracellular iron accumulation,and attenuated HIRI-induced liver damage.Additionally,RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in vitro.Mechanistically,the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake,promoting hepcidin-and ferroportin-mediated iron efflux,and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression.Moreover,siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract's inhibitory effect on ferroptosis.In conclusion,our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI,highlighting the restoration of iron metabolic balance.These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.
基金This work was supported by Beijing Nova Program of Science&Technology(Nos.Z201100006820025 and Z211100002121167)the Young Elite Scientists Sponsorship Program from CACM(No.CACM-2020-QNRC2-04)the National Natural Science Foundation of China(No.82004029).
文摘Type I interferon(IFN)is considered as a bridge between innate and adaptive immunity.Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion,tumor cell proliferation,and overactive immune responses.Due to intricate and diverse chemical structures,natural products and their derivatives have become an invaluable source inspiring innovative drug discovery.In addition,some natural products have been applied in clinical practice for infection,cancer,and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted.However,whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated.In the current review,we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity,including both agonism/activation and antagonism/inhibition,and their potential application as therapies.Furthermore,the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified.In conclusion,natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection,cancer,and autoimmune diseases.
