Studies On The Action Mechanism And Serum Pharmacochemistry Of Zuojin Pill In Treating Stomach Heat Syndrome

Objective To explore the mechanisms of action of Zuojin pill on stomach heat(SH)syndrome in rats by anti-inflammatory,antioxidant and anti-apoptotic activities as well as restoration of metabolic perturbations.To carry out a preliminary study on serum pharmacochemistry of Zuojin pill and to further explore its prototype components and metabolites in rats through analyzing the constituents absorbed into blood.Method The rats were randomly divided into normal group,model group and Zuojin pill group.Rats of model group were established by gavage decoction of pepper and absolute ethanol.Furthermore,Establishing typical 1H-NMR spectra of rat urine and feces to analysis potential biomarkers associated with SH;The contents or activities of inflammatory factors such as interleukin(IL)-2,IL-6,IL-10,IL-1 β,and(Myeloperoxidase)MPO and oxidative stress factors such as glutathione(GSH),glutathione-S-transferase(GST),Nitric Oxide(NO),glutathione peroxidase(GSH-Px),catalase(CAT),superoxide dismutase(SOD),and malondialdehyde(MDA)as well as apoptotic factors such as B-cell lymphoma-2(Bcl-2)and Bax in rat serum and gastric were determined by chemocolorimetry and enzyme-linked immunosorbent assay(ELISA).The prototype components and metabolites in rat serum were identified through analysis and comparison of the HPLC fingerprints of Zuojin pill,rat serum obtained after oral administration of Zuojin pill or single crude drug and blank serum.Result Zuojin pill could significantly reverse the pathological process of SH.All potential biomarkers associated with SH in rats were significantly reversed by Zuojin pill except creatinine and uridine in urine(succinate,2-oxoglutarate,citrate,creatine,creatinine,taurine and uridine)and β-glucose in feces(n-butyrate,propionate,threonine/lactate,β-glucose,uracl).Pretreatment of rats with Zuojin pill normalized the SH-induced significant changes in gastric levels of oxidative stress(GSH,MDA,GST,GPx,CAT,NOand SOD),inflammatory(IL-2,IL-6,IL-10,MPO,and IL-1β)and apoptotic(Bcl-2 and Bax)markers;.After rats were administered with Zuojin pill,14 transitional constituents in blood were detected,among which 9 were metabolites and 5 were prototype constituents.Conclusion Zuojin Pill could exerted beneficial effect on SH through reversing tricarboxylic acid cycle,metabolism of gut microbiota,antioxidant,anti-inflammat ory and anti-apoptotic activities.Pharmacodynamic material basis of Zuojin pill treating SH has been preliminary explaned.