Anti-Inflammatory Activity Evaluation Of A Series Of Natural Products And Mechanism Exploration Of Paeonilactone B

Inflammation is a non-specific defensive immune response.based on the vascular system,it is involved in important life processes such as infection clearance,tissue regeneration and repair and so on.However,persistent or excessive inflammatory reactions can cause tissue damage and drive the occurrence and development of many diseases.Developing new anti-inflammatory drugs from traditional Chinese medicine ingredients has always been a hot topic in drug research.In this paper,the anti-inflammatory activity of a series of natural products was screened using an anti-inflammatory model of macrophages induced by LPS,including Valeriana officinalis Linn.,Valeriana jatamansi Jones.,Valeriana officinalis L.var.latifolia Miq.,Stellera chamaejasme L.,Paeoniae radix rubra,Pogostemonis herba,Prunella vulgaris L.,Mosla chinensis Maxim.,Elsholtzia densa Benth.,Ryopteris crassirhizoma Rhizoma.,Osmundae Rhizoma.,Tripterygium wilfordii Hook.f.,and a total of 378 compounds.Twenty-nine monomeric compounds,including flavonoids,monoterpenes,triterpenes and diterpenes,were found to have anti-inflammatory potential in vitro.Paeonilactone compound 229（paeonilactone B）isolated from Paeoniae Radix could significantly inhibit the production of NO in LPS stimulated macrophages with an IC₅₀ value of 6.08±1.81μmol/L.The compound can also significantly inhibit the secretion of various cytokines such as IL-1β,IL-6,IL-18 and TNF-αin activated macrophages,as well as the production of i NOS and COX-2 proteases.Further mechanism studies showed that it inhibited the phosphorylation of JNK,ERK1/2,p38MAPK,IκBα,NF-κB/p65and STAT3,suggesting that the compound may down-regulate the secretion of inflammatory factors by inhibiting MAPKs and NF-κB signaling pathways,STAT3 activation and NLRP3 expressionin in LPs-activated macrophages,thus exerting anti-inflammatory activity.In addition,compound 229 also inhibited the production of NO,TNF-αand IL-18 in macrophages infected with influenza virus A/WSN/33/2009 H1N1（WSN）,and decreased the expression of i NOS and COX-2,but had no effect on the secretion of IL-1βand IL-6.These results indicated that compound 229 also showed anti-inflammatory potential in macrophages infected with influenza virus.