Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Preparation and characterization of biomimetic liposomes coated with erythrocyte membrane co-loading triptolide and celastrol / 药学学报

Drug combination can effectively enhance the anti-tumor effect, reduce the drug dose, and improve medication safety. The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo. Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f. Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect, but they are limited by poor water solubility and low tumor tissue delivery rate. In this study, a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology, particle size, potential, drug release, serum stability, and other properties. The immunogenicity, uptake behavior, and anti-cell proliferation ability of the biomimetic liposome was compared. All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (Chengdu, China). The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol (C+T/RBCm@Lip) in this study had an average particle size of 119.12 ± 2.78 nm and a spherical "core-shell" structure. The zeta potential value was -16.9 ± 1.2 mV, and the drug release behavior in vitro was slow. In addition, the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein, had good stability in serum, and could effectively avoid the recognition and clearance of macrophages, without causing immunogenicity in vivo. The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes, and the inhibitory effect on proliferation of HepG2 cells was enhanced. In conclusion, the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol, and could enhance the inhibitory effect on the growth of HepG2 liver cancer cells, providing a new idea for the anti-tumor application of Tripterygium wilfordii Hook f.

Research Progress on Mechanism of Yiguanjian Intervention in Liver Cirrhosis / 中国实验方剂学杂志

Liver cirrhosis caused by the repeated action of one or more causes is a pathological stage characterized by diffuse fibrosis of the liver parenchyma， formation of false lobules and regenerative nodules， portal hypertension which caused by abnormal blood vessels inside and outside the liver. The progression of cirrhosis to decompensation is characterized by severe liver damage， with ascites， gastroesophageal varices bleeding， hepatic encephalopathy and other complications， and most of the treatments are symptomatic， with high mortality and poor prognosis. At present， the traditional Chinese medicine treatment of decompensated cirrhosis can not only effectively improve liver function， but also significantly improve the 5-year survival rate of patients， which suggests that Chinese medicine has potential advantages in preventing and treating end-stage liver disease， and promoting liver cirrhosis tissue reconstruction. Modern Chinese medicine doctors believe that liver cirrhosis is mainly caused by Qi Yin deficiency （liver， spleen， kidney），internal invasion of damp-heat epidemic toxin， and collateral stasis. Deficiency of liver and kidney Yin is a common symptom of decompensated cirrhosis. Yiguanjian， one of Kidney-Nourishing and Liver-Replenishing decoction in traditional Chinese medicine ， is the representative prescription for modern clinical treatment of chronic liver disease with "deficiency of liver and kidney Yin" syndrome. Yiguanjian， created by WEI Yu-zhen （WEI Zhi-xiu）in the Qing Dynasty， Contained in "Xu Ming Yi Lei An ". Clinical studies show that Yiguanjian can effectively improve liver function in patients with liver cirrhosis， promote ascites resolution， and reduce the occurrence of hepatic encephalopathy and other related complications. Experimental research has suggested that Yiguanjian has the characteristics of multi-path， multi-level， and multi-target comprehensive regulation. The mechanism of prevention and treatment of liver cirrhosis may be mainly related to anti-oxidative stress， improving liver inflammation， improving liver cell biosynthesis， inhibiting hepatic stellate cell activation， reducing collagen deposition， improving sinusoidal vascularization and promoting liver cell regeneration. This paper reviews the progress of clinical and experimental research of Yiguanjian in the treatment of liver cirrhosis in the past 5 years， to provide some references for the clinical application and in-depth study of Yiguanjian.