1.Effects of sinomenine hydrochloride on adjuvant arthritis rats based on NLRP3/Gasdermin D/Caspase-1/Interleukin-1β pyroptosis path-way
Yuxiang XU ; Ying TIAN ; Qian XU ; Zijing GE ; Lusha YAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(9):1174-1181
AIM:To investigate the protective ef-fect of sinomenine hydrochloride(SIN)on adjuvant arthritis(AA)rats by regulating the NLRP3/Gasder-min D/Caspase-1/Interleukin-1β pyroptosis path-way.METHODS:Sixty rats were randomly divided into 6 groups,10 rats in each group:Con group(normal rats),AA group(AA rat model),L-SIN group(AA rats were intragastrically administered with 100 mg/kg SIN),M-SIN group(AA rats were intra-gastrically administered with 200 mg/kg SIN),H-SIN group(AA rats were intragastrically administered with 400 mg/kg SIN),ACG group(positive drug group:AA rats were intragastrically administered with 150 mg/kg Wantong Jingu Tablets).Observe the degree of joint swelling and arthritis index.HE was used to observe the pathological changes of the right ankle joint tissue of rats.The levels of in-flammatory factors and oxidative stress-related in-dicators in synovial tissue were detected.Western Blot was used to detect the expression levels of NL-RP3/Gasdermin D/Caspase-1/Interleukin-1β pyrop-tosis pathway-related proteins.RESULTS:Com-pared with Con group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in AA group were signifi-cantly increased(P<0.05).Compared with AA group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NL-RP3,GSDMD,Caspase-1 and IL-1β protein expres-sion levels were significantly decreased in SIN treat-ment group with the increase of treatment dose(P<0.05).Compared with AA group and L-SIN group,the degree of joint swelling,arthritis index,inflam-matory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in ACG group were significantly decreased(P<0.05).Compared with H-SIN group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Cas-pase-1 and IL-1β protein expression levels in ACG group were significantly increased(P<0.05).CON-CLUSION:SIN can alleviate the inflammatory injury of AA rats and reduce the levels of inflammatory factors and oxidative stress,thus exerting a protec-tive effect on AA rats.The mechanism may be based on the NLRP3/Gasdermin D/Caspase-1/Inter-leukin-1β pyroptosis pathway.
2.Effects of sinomenine hydrochloride on adjuvant arthritis rats based on NLRP3/Gasdermin D/Caspase-1/Interleukin-1β pyroptosis path-way
Yuxiang XU ; Ying TIAN ; Qian XU ; Zijing GE ; Lusha YAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(9):1174-1181
AIM:To investigate the protective ef-fect of sinomenine hydrochloride(SIN)on adjuvant arthritis(AA)rats by regulating the NLRP3/Gasder-min D/Caspase-1/Interleukin-1β pyroptosis path-way.METHODS:Sixty rats were randomly divided into 6 groups,10 rats in each group:Con group(normal rats),AA group(AA rat model),L-SIN group(AA rats were intragastrically administered with 100 mg/kg SIN),M-SIN group(AA rats were intra-gastrically administered with 200 mg/kg SIN),H-SIN group(AA rats were intragastrically administered with 400 mg/kg SIN),ACG group(positive drug group:AA rats were intragastrically administered with 150 mg/kg Wantong Jingu Tablets).Observe the degree of joint swelling and arthritis index.HE was used to observe the pathological changes of the right ankle joint tissue of rats.The levels of in-flammatory factors and oxidative stress-related in-dicators in synovial tissue were detected.Western Blot was used to detect the expression levels of NL-RP3/Gasdermin D/Caspase-1/Interleukin-1β pyrop-tosis pathway-related proteins.RESULTS:Com-pared with Con group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in AA group were signifi-cantly increased(P<0.05).Compared with AA group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NL-RP3,GSDMD,Caspase-1 and IL-1β protein expres-sion levels were significantly decreased in SIN treat-ment group with the increase of treatment dose(P<0.05).Compared with AA group and L-SIN group,the degree of joint swelling,arthritis index,inflam-matory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in ACG group were significantly decreased(P<0.05).Compared with H-SIN group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Cas-pase-1 and IL-1β protein expression levels in ACG group were significantly increased(P<0.05).CON-CLUSION:SIN can alleviate the inflammatory injury of AA rats and reduce the levels of inflammatory factors and oxidative stress,thus exerting a protec-tive effect on AA rats.The mechanism may be based on the NLRP3/Gasdermin D/Caspase-1/Inter-leukin-1β pyroptosis pathway.

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