Protective effects and mechanisms of Lizhong decoction(理中汤) against non-alcoholic fatty liver disease in a rat model

OBJECTIVE: To investigate the protective effects and molecular mechanisms of Lizhong decoction( 理中汤, LZD) against non-alcoholic fatty liver disease(NAFLD). METHODS: Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined. RESULTS: Rats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage,inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor(PPAR)-γ expression, and suppressed dipeptidyl peptidase 4(DPP4) expression in the liver. CONCLUSION: It was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.

Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling

Objective:To elucidate the mechanism of Lizhong Decoction(LZD)in treating dextran sodium sulfate(DSS)-induced colitis in mice based on metabonomics.Methods:Thirty-six mice were randomly divided into 6 groups,including normal,model,low-(1.365 g/kg),medium-(4.095 g/kg)and high dose(12.285 g/kg)LZD and salazosulfadimidine(SASP)groups,6 mice in each group.Colitis model mice were induced by DSS admistration for 7 days,and treated with low,medium and high dose LZD extract and positive drug SASP.Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass(UPLC-Q-TOF/MS)combined with Metabolynxsoftware.Results:The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment(P<0.05).Potential biomarkers(9 in serum and 4 in urine)were screened and tentatively identified.The endogenous metabolites were mainly involved in primary bile acid,sphingolipid,linoleic acid,arachidonic acid,amino acids(alanine,aspartate,and glutamate),butanoate and glycerophospholipid metabolism in plasma,and terpenoid backbone biosynthesis,glycerophospholipid and tryptophan metabolism in urine.After LZD treatment,these markers notably restored to normal levels.Conclusions:The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics,which laid a foundation for further exploring the pathological and physiological mechanism,early diagnosis,and corresponding drug development of colitis.