Mohagheghzadeh Ala, Badr Parmis, Mohagheghzadeh Abdolali, Hemmati Shiva
Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
Pharmaceuticals (Basel). 2023 Jun 15;16(6):887. doi: 10.3390/ph16060887.
Any defects in bile formation, secretion, or flow may give rise to cholestasis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. As the pathogenesis of hepatic disorders is multifactorial, targeting parallel pathways potentially increases the outcome of therapy. has been famed for its anti-depressive effects. However, according to traditional Persian medicine, it helps with jaundice and acts as a choleretic medication. Here, we will discuss the underlying molecular mechanisms of for its use in hepatobiliary disorders. Differentially expressed genes retrieved from microarray data analysis upon treatment with safe doses of extract and intersection with the genes involved in cholestasis are identified. Target genes are located mainly at the endomembrane system with integrin-binding ability. Activation of α5β1 integrins, as osmo-sensors in the liver, activates a non-receptor tyrosine kinase, c-SRC, which leads to the insertion of bile acid transporters into the canalicular membrane to trigger choleresis. upregulates CDK6 that controls cell proliferation, compensating for the bile acid damage to hepatocytes. It induces ICAM1 to stimulate liver regeneration and regulates nischarin, a hepatoprotective receptor. The extract targets the expression of conserved oligomeric Golgi (COG) and facilitates the movement of bile acids toward the canalicular membrane via Golgi-derived vesicles. In addition, induces SCP2, an intracellular cholesterol transporter, to maintain cholesterol homeostasis. We have also provided a comprehensive view of the target genes affected by 's main metabolites, such as hypericin, hyperforin, quercitrin, isoquercitrin, quercetin, kaempferol, rutin, and -coumaric acid to enlighten a new scope in the management of chronic liver disorders. Altogether, standard trials using as a neo-adjuvant or second-line therapy in ursodeoxycholic-acid-non-responder patients define the future trajectories of cholestasis treatment with this product.
胆汁形成、分泌或流动中的任何缺陷都可能导致胆汁淤积、肝纤维化、肝硬化和肝细胞癌。由于肝脏疾病的发病机制是多因素的，针对平行途径可能会提高治疗效果。[药物名称]因其抗抑郁作用而闻名。然而，根据传统波斯医学，它有助于治疗黄疸，并作为一种利胆药物。在此，我们将讨论[药物名称]用于肝胆疾病的潜在分子机制。从用安全剂量的[药物名称]提取物处理后的微阵列数据分析中检索出差异表达基因，并与胆汁淤积相关基因进行交叉分析，从而确定目标基因。目标基因主要位于具有整合素结合能力的内膜系统。α5β1整合素作为肝脏中的渗透压感受器被激活后，会激活非受体酪氨酸激酶c-SRC，进而导致胆汁酸转运体插入胆小管膜以触发胆汁分泌。[药物名称]上调控制细胞增殖的CDK6，以补偿胆汁酸对肝细胞的损伤。它诱导ICAM1以刺激肝脏再生并调节一种肝脏保护受体nischarin。该提取物靶向保守寡聚高尔基体（COG）的表达，并通过高尔基体衍生的囊泡促进胆汁酸向胆小管膜的移动。此外，[药物名称]诱导细胞内胆固醇转运体SCP2以维持胆固醇稳态。我们还全面介绍了受[药物名称]的主要代谢产物如金丝桃素、贯叶连翘素、槲皮苷、异槲皮苷、槲皮素、山奈酚、芦丁和对香豆酸影响 的目标基因，为慢性肝病的治疗开辟新的视野。总之，在熊去氧胆酸无反应患者中使用[药物名称]作为新辅助或二线治疗的标准试验确定了该产品治疗胆汁淤积的未来方向。
