Wang Kun, Jin Ruo-Min, Chen Chang-Xun
Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Zhongguo Zhong Yao Za Zhi. 2013 Jul;38(14):2365-9.
To observe the effect of ingredients in Huanglian Jiedu decoction (HLJDT) combined with Gardeniae Fructus on the hepatic toxicity of Gardeniae Fructus and its mechanism.
Rats were given Gardeniae Fructus and HLJDT decoction at the dose of 10 times of clinical dosage for 3 days. Their ALT AST, ALP, TBA were detected, and their liver weight index was calculated. SOD activity, MDA content, GSH-PX activity, TNF-alpha content in hepatic tissues were determined. The cell apoptosis in liver tissue was determined by TUNEL, and the expressions of apoptosis related proteins Bax, Bcl-2 were measured by immunohistochemical method.
Compared with the normal control group, the Gardeniae Fructus group showed significant increase in the liver weight index, ALT, AST, TBA and ALP, notable decrease in SOD, SOD/MDA and GSH-PX, and remarkable rise in MDA, TNF-a concentration, accumulated optical density, apoptosis index, Bax and Bax/Bcl-2. Compare with that in the Gardeniae Fructus group, the liver index, ALT, AST, TBA, ALP reduced obviously; SOD, SOD/MDA and GSH-PX markedly increased; MDA and TNF-alpha significantly reduced; the accumulated optical density and apoptosis index significantly reduced; and Bax/Bcl-2 was much lower in HLJDT group.
The hepatic toxicity caused by Gardeniae Fructus may be related to inflammation, oxidative stress-induced hepatocyte necrosis and apoptosis. Other ingredients in HLJDT, apart from Gardeniae Fructus, can decrease the hepatic toxicity caused by Gardeniae Fructus by increasing the enzyme activity eliminating radicals and inhibiting hepatocyte injury caused by inflammatory reaction against Gardeniae Fructus.
观察黄连解毒汤(HLJDT)配伍栀子对栀子肝毒性的影响及其作用机制。
以10倍临床剂量给予大鼠灌胃栀子及HLJDT水煎剂,连续3天。检测大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆汁酸(TBA)水平,并计算肝脏重量指数。测定肝组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH-PX)活性、肿瘤坏死因子-α(TNF-α)含量。采用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL)检测肝组织细胞凋亡情况,免疫组织化学法检测凋亡相关蛋白Bax、Bcl-2的表达。
与正常对照组比较,栀子组大鼠肝脏重量指数、ALT、AST、TBA、ALP显著升高,SOD、SOD/MDA、GSH-PX显著降低,MDA、TNF-α浓度、累积光密度、凋亡指数、Bax、Bax/Bcl-2显著升高。与栀子组比较,HLJDT组大鼠肝脏指数、ALT、AST、TBA、ALP明显降低;SOD、SOD/MDA、GSH-PX显著升高;MDA、TNF-α明显降低;累积光密度和凋亡指数明显降低;Bax/Bcl-2明显降低。
栀子所致肝毒性可能与炎症、氧化应激诱导的肝细胞坏死及凋亡有关。黄连解毒汤中除栀子外的其他成分可通过提高自由基清除酶活性及抑制针对栀子的炎症反应所致肝细胞损伤,降低栀子的肝毒性。