Résumé
Objective:To study the effect of Biejia Jianwan on expressions of signal molecules and target genes of transforming growth factor-β (TGF-β)/Smad pathway in diethylnitrosamine (DEN)-induced rat hepatocellular carcinoma, and explore the mechanisms of Biejia Jianwan suppressing the invasion of hepatocellular carcinoma. Method:The rats were divided into three group, namely normal group, model group and Biejia Jianwan group (2.2 g·kg-1·d-1). Rats in Biejia Jianwan group and model group received intraperitoneal injections of DEN to induce sequential chronic inflammation, cirrhosis and hepatocellular carcinoma. At the sign of cirrhosis, rats in Biejia Jianwan group began taking Biejia Jianwan by gavage for 6 weeks. Rat blood was collected to measure serum levels of biochemical markers of liver function tests, including alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), albumin(Alb), γ-glutamyl transpeptadase(GGT), alkaline phosphatase(ALP). Rat livers were fixed in formalin and stained with hematoxylin-eosin (HE)staining， quantitative real-time PCR was used to test the mRNA expressions of TGF-β1， and Western blot was used to test protein expressions of TGF-β1, Smad2/3, p-Smad2/3, N-cadherin, E-cadherin and Vimentin. Result:All of the levels of biochemical markers showed no difference in Biejia Jianwan group and model group. Biejia Jianwan could improve the pathological changes of balloon-like degeneration, edema, and necrosis in liver cancer tissues. Importantly, the treatment dramatically decreased the mRNA expression of TGF-β1(P<0.01), and the protein expressions of TGF-β1, p-Smad2(P<0.01). Besides, the protein expression of N-cadherin and Vimentin were decreased significantly (P<0.01). Conclusion:Biejia Jianwan can inhibit epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cells activated via TGF-β/Smad pathway by reducing TGF-β1 expression, so as to suppress the metastasis and invasion of hepatocellular carcinoma.
Résumé
Objective::To systematically review the evolution of Biejia Jianwan in Medical Treasures of the Golden Chamber and its clinical application in ancient and modern times, in order to analyze its application and transformation in modern times. For one thing, it provided ideas for the secondary development of Biejia Jianwan, for another, it provided reference for the transformation and application of classical famous prescriptions. Method::Ancient and modern literature of Biejia Jianwan were collected and summarized to study the ancient and modern clinical application of Biejia Jianwan, and its origin, evolution of prescription meanings and changes of main indications. Based on market research, the market transformation of Biejia Jianwan, and its research and development process and market application were analyzed. Result::Biejia Jianwan has been applied in past dynasties since the Medical Treasures of the Golden Chamber, but with insignificant changes and simple indications. In fact, Biejia Jianwan was specially developed for the treatment of malaria with abdominal mass. According to the drug dosage ratio, Trinycis Carapax and Chixiao are the main drugs in Biejia Jianwan, and insect drugs are also used. Modern literature analysis shows that Biejia Jianwan is mainly used to treat liver diseases, such as liver fibrosis, cirrhosis and liver cancer, whether in clinical or experimental studies. It was found that when Biejia Jianwan was transformed from a classical prescription into a Chinese patent medicine mainly based on its composition, dosage and preparation of the original prescription recorded in the Medical Treasures of the Golden Chamber. Chinese patent medicine preparations have been included in many diseases diagnosis and treatment, medication guidelines and expert consensus. Compared with other traditional Chinese medicines, Biejia Jianwan is more widely used in clinic with lower costs. Conclusion::Biejia Jianwan is used to treat malaria with abdominal mass in ancient times, but in modern times it is mostly used to treat liver diseases, such as liver fibrosis, with a definite efficacy. In addition, Biejia Jianwan have been successfully transformed into a modern Chinese patent medicine preparation, and achieved a better response in the market, providing a reference for the transformation and application of other classical prescriptions.