The Study On Curative Effect And Mechanism Of Fufang Huzhang Decoction In The Treatment Of NAFLD

Part one:Clinical study the therapeutic effects of Fufang huzhang decoction in the treatment of NAFLDBackground:Non-alcoholic fatty liver disease(NAFLD)is a great health burden,though the current intervention measures are not effective.Adiponectin is one of the key adipocytokines in the pathogenesis of NAFLD.Increasing evidence has demonstrated that herbal medicines are capable of attenuating NAFLD development and progression.Fufang huzhang decoction(FFHZ)is an empirical prescription for treating NAFLD in our clinical practice.But the mechanism remains unclear.Objectives:To observe the therapeutic effects of FFHZ on the treatment of NAFLD and determine the mediators involved.Methods:A total of 80 patients with NAFLD were randomly divided into treatment group(treated with FFHZ,n=40)and control group(treated with polyene phosphatidylcholine capsules,n=40)for 3 months.Parameters include Chinese medicine symptom score,body mass index,waist circumference,serologic tests(blood glucose,lipid profile,insulin,adiponectin)were measured.The insulin sensitivity was evaluated by HOMA-IR index.The serum adiponectin were evaluated by ELISA.The fat contents in livers were evaluated by quantitative ultrasound.Results:The baseline characteristics had no significant difference between the two groups.After 3 months of treatment,obvious improvement of Chinese medicine symptom score was observed in the treatment group.The total effective rate of treatment group was superior to the control group(P<0.05).Serum liver enzymes(ALT,AST,GGT)in the two groups decreased after treatment significantly(P<0.05),but the effect of FFHZ is more potent than polyene phosphatidyl choline(P<0.05).No change of TC,HDL-C and LDL-C could be demonstrated after treatment in the two groups.TG in treatment group decreased significantly(P<0.05),but TG in control group remained relatively stable(P>0.05).Significant reduction of HOMA-IR index was detected in treatment group(P<0.05),while no improvement was seen in control group(P>0.05).The serum adiponectin levels increased significantly(P<0.05)after FFHZ treatment,but the serum adiponectin of control group kept at low levels(P>0.05).The fat contents in livers were significantly lower in the treatment group after FFHZ treatment and they also were lower than those in the control group(P<0.05).Conclusion:1.FFHZ was effective in treating NAFLD and was found to be superior to polyene phosphatidylcholine capsules in reducing HOMA-IR index and fat contents in livers.2.FFHZ attenuates NAFLD by induction of adiponectin signaling.Part two:Fufang huzhang decoction improve NAFLD by modulating the FGF21-adiponectin axisBackground:Our clinic study had found Fufang huzhang decoction(FFHZ)was effective in treating NAFLD and it attenuated NAFLD by induction of adiponectin signaling.But the mechanism is not well understood.Adiponectin is a downstream effector of fibroblast growth factor 21(FGF21),which is a metabolic hormone with pleiotropic effects on regulating glucose and lipid homeostasis and insulin sensitivity.Dysfunctional FGF21-adiponectin axis play an important role in the pathogenesis of NAFLD.Objective:To investigate the effect of FFHZ on FGF21-adiponectin axis in NAFLD rats.Methods:A total of 50 6-week-old male SD rats were randomly divided into normal control group(normal diet,n=20),model group(high fat diet,n=30)for8 weeks.Then the rats(10 rats/group)were sacrificed for detecting baseline characteristics.The rats in model group were randomly divided into model control group(normal diet,n= 10),treatment group(normal diet + FFHZ,n=10)for 12 weeks.Parameters include body weight,liver weight,serologic tests(blood glucose,ALT,lipid profile)and TG contents in livers were measured.The liver pathological changes were characterized by cell steatosis and inflammatory.Serum adiponectin,FGF21 and insulin were evaluated by ELISA.The insulin sensitivity was evaluated by HOMA-IR index.The expression of adiponectin mRNA in periepididymal adipose tissues was detected by realtime PCR.Results:High fat diet increased liver weights,and serum TG concentrations.After treatment,serum ALT and AST in the treatment group decreased significantly(P<0.05).No change of serum TC could be demonstrated after treatment in the three groups.Serum TG in treatment group decreased significantly(P<0.05),but TG in model control group remained relatively stable(P>0.05).Significant reduction of HOMA-IR index was detected in treatment group(P<0.05),while no improvement was seen in model control group(P>0.05).The TG contents in livers were significantly decreased in the treatment group after FFHZ treatment and they also were lower than those in the model control group(P<0.05).The liver cell steatosis and inflammatory improved after FFHZ treatment.An elevated serum Fgf21 level was associated with decreased expression of adiponectin in the NAFLD rats.The serum FGF21 levels decreased significantly(P<0.05)after FFHZ treatment,but the serum FGF21 of model control group kept at high levels(P>0.05).At the same time,the serum adiponect in levels increased significantly(P<0.05)after FFHZ treatment and the serum adiponectin of control group kept at low levels(P>0.05).Conclusion:1.FFHZ has definite protective effect on rats with NAFLD.2.The mechanism may be the upregulation of expression of adiponectin mRNA by decrease FGF21 resistance.