Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
Animal Laboratory Center, 302 Hospital of People's Liberation Army, Beijing, People's Republic of China.
BMC Complement Altern Med. 2018 Jul 9;18(1):212. doi: 10.1186/s12906-018-2276-8.
Liuweiwuling tablets (LWWL) are an herbal product that exerts remarkable effects on liver protection and aminotransferase levels, and they have been approved by the Chinese State Food and Drug Administration (CFDA). Clinical studies have found that LWWL can inhibit collagen production and reduce the levels of liver fibrosis markers in the serum. Thus, LWWL is expected to have beneficial effects in the treatment of liver fibrosis. The purpose of this study was to evaluate the pharmacological effects of LWWL.
Hepatic fibrosis was induced in rats via carbon tetrachloride (CCl) treatment. The rats were treated twice weekly for 8 weeks with either 2 mL·kg body weight of a 50% solution of CCl in olive oil or olive oil alone by oral gavage. A subset of rats received daily intraperitoneal injections of either colchicine (0.2 mg/kg per day), LWWL (0.4, 1.6, or 6.4 g/kg per day), or vehicle (N = 12 for all groups) during weeks 9-12. The rats were sacrificed after 12 weeks. Pathological changes in hepatic tissue were examined using hematoxylin and eosin (H&E) and Sirius Red staining. Immunohistochemistry was performed to observe α-smooth muscle actin (α-SMA) and collagen type I (collagen I) protein expression. Western blotting was also used to detect α-SMA protein expression. Real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect transforming growth factor-1 (TGF-β1), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinase-1 (TIMP1), and tissue inhibitor of metalloproteinase-2 (TIMP2) mRNA expression.
LWWL significantly reversed histological fibrosis and liver injury, reduced the hydroxyproline content in liver tissue, and decreased α-SMA and collagen I expression. LWWL also suppressed hepatic stellate cell (HSC) activation by reducing the expression of the profibrogenic factors TGF-β1 and PDGF. The expression levels of TIMP1 and TIMP2, which regulate extracellular matrix (ECM) degradation, were decreased after CCl injury in LWWL-treated rats.
These data suggest that LWWL may serve as a promising therapeutic agent to reduce fibrogenesis.
六味五灵片（LWWL）是一种具有显著保肝和降低转氨酶作用的中药，已获得中国国家食品药品监督管理局（CFDA）批准。临床研究发现，LWWL 可抑制胶原生成，降低血清肝纤维化标志物水平。因此，LWWL 有望在肝纤维化治疗中发挥有益作用。本研究旨在评估 LWWL 的药理作用。
采用四氯化碳（CCl）诱导大鼠肝纤维化。大鼠每周两次通过灌胃给予 50% CCl 在橄榄油中的溶液 2 mL·kg 体重或仅给予橄榄油 8 周。部分大鼠在第 9-12 周每天给予腹腔注射秋水仙碱（0.2 mg/kg 体重/天）、LWWL（0.4、1.6 或 6.4 g/kg 体重/天）或载体（各组均为 N = 12）。12 周后处死大鼠。用苏木精和伊红（H&E）及天狼猩红染色观察肝组织的病理变化。免疫组化观察α-平滑肌肌动蛋白（α-SMA）和 I 型胶原（collagen I）蛋白表达。Western blot 法检测 α-SMA 蛋白表达。实时定量逆转录聚合酶链反应（RT-qPCR）检测转化生长因子-β1（TGF-β1）、血小板衍生生长因子（PDGF）、金属蛋白酶组织抑制剂-1（TIMP1）和金属蛋白酶组织抑制剂-2（TIMP2）mRNA 表达。
LWWL 可显著逆转肝纤维化和肝损伤的组织学变化，降低肝组织羟脯氨酸含量，减少 α-SMA 和 collagen I 表达。LWWL 通过降低促纤维化因子 TGF-β1 和 PDGF 的表达抑制肝星状细胞（HSC）活化。LWWL 治疗大鼠 CCl 损伤后，调节细胞外基质（ECM）降解的 TIMP1 和 TIMP2 表达水平降低。
这些数据表明，LWWL 可能是一种有前途的抗纤维化治疗药物。
