Comparative study of anti-inflammatory effects of different processed products through the COX-2/PGE2 signaling pathway: based on network pharmacology and molecular docking

Background:Radix Aconiti Lateralis Preparata(Fu-zi)is a traditional Chinese medicinal herb,which has been widely used in the clinic and has potent anti-inflammatory activities.we aimed to explore the mechanisms of extract containing alkaloids from different Fu-zi Processed Products(FPP)in treating inflammation,especially rheumatoid arthritis(RA).Methods:Firstly,using network pharmacology technology,the ingredients,and targets of Fu-zi were obtained by searching and screening,the targets involving RA were acquired,the intersection targets were constructed a"component-target-pathway"network.A comprehensive investigation was conducted on the anti-rheumatoid arthritis mechanisms of 5 FPPs in lipopolysaccharide(LPS)induced RAW264.7 cells,which serve as a model for RA.The production of NO and inflammatory cytokines were measured by ELISA kit.Quantitative Real-time PCR(qRT-PCR)was utilized to measure the mRNA levels.COX-2/PGE2 signaling pathway-associated proteins were determined by western blot.Results:According to a network pharmacological study,16 chemical components and 43 common targets were found in Fu-zi and 6 key targets including PTGS2 were closely related to the mechanism of Fu-zi in treating RA.The in vitro study revealed that the levels of NO,TNF-α,and IL-1βwere substantially decreased by the 5 FPPs.The 5 FPPs significantly suppressed the expression of proteins COX-2,iNOS,and NF-κB,with particularly notable effects observed for PFZ and XFZ.Conclusion:Altogether,these results demonstrated that the 5 PPS containing alkaloids have a good anti-RA-related inflammatory effect,and the mechanism may be related to COX-2/PGE2 signaling pathway,particularly,Fu-zi prepared utilizing a traditional Chinese technique.

Hypothesis of the osthol intervention in osteoarthritis treatment through COX-2 specific pathway

Osteoarthritis(OA)is a joint degenerative disease characterized by softening and peeling of articular cartilage,reactive hyperplasia of subchondral bone,and narrowing of joint space,which seriously affects the quality of daily life of patients.Drug therapy is one of the effective means to treat osteoarthritis,it mainly includes the use of nonsteroidal antiinflammatory drugs,hormones and painkillers.These methods have a certain effect on alleviating symptoms,but there are also some obvious adverse reactions,and are not easy to take for a long time.Osthol is a natural coumarin isolated from Pinaceae plants.It has pharmacological effects such as anti-inflammatory,antioxidant and neuroprotective.A large number of studies and experiments show that Osthol has a good effect in the treatment of osteoarthritis,and no obvious harmful effect has been found.Therefore,by analyzing and sorting out the relevant experiments and literatures published in recent years,this paper puts forward some scientific hypotheses on the possible specific ways of regulating COX-2 mRNA expression,one of the important roles of Osthol in the treatment of osteoarthritis,in order to clarify the possible potential mechanism and inspire subsequent related research.