摘要Type Ⅰ interferon(IFN)is considered as a bridge between innate and adaptive immunity.Proper activation or inhibi-tion of type Ⅰ IFN signaling is essential for host defense against pathogen invasion,tumor cell proliferation,and overactive immune re-sponses.Due to intricate and diverse chemical structures,natural products and their derivatives have become an invaluable source in-spiring 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 1 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.