Department of Pathology, College of Korean Medicine, Dongguk University, Goyang, 10326, Republic of Korea.
Department of Diagnostics, College of Korean Medicine, Dongguk University, Goyang, 10326, Republic of Korea.
Sci Rep. 2019 Jun 21;9(1):9055. doi: 10.1038/s41598-019-45099-x.
New drug development is a challenging process that requires high-risk, huge costs and long lead times. Therefore, drug repurposing is considered a strategic and economic way towards successful drug development. Sochehwan (SCH) is a herbal formula well known as a digestive aid in traditional oriental medicine, is referred to in classic medical texts, and is available as an over-the-counter drug for indications of digestive ailments. Interestingly, another medical text written in earlier age describes different indication of SCH yet to be examined. We conducted a series of investigations using maturated adipocytes, free fatty acid (FFA) induced hepatic steatosis model in vitro and high-fat diet (HFD) mice model in vivo. Exposure to SCH regulated expression of adipogenic genes and proteins, significantly inhibiting formation of lipid droplets in 3T3-L1 cells. Similarly, SCH treatment modulated proteins related with energy metabolism decreasing lipid accumulation in FFA induced HepG2 cells. Furthermore, HFD-fed c57BL/6 J mice supplemented with SCH exhibited significant changes in serum glucose and lipid profiles. Histologic analysis of mice liver and adipose tissue showed that SCH administration attenuated hepatic steatosis and hypertrophy of adipose tissue. In overall, the results show that SCH can potentially be used to treat metabolic syndrome (MetS) by enhancing glucose metabolism and inhibiting lipogenesis through activating AMP-activated protein kinase (AMPK) and its downstream signaling. Furthermore, it seems to be a feasible drug repurposing strategy for drugs originating from alternative medicine to revise the value for buried indications of some herbal prescription in old traditional Chinese Medicine (TCM) classics.
新药开发是一个具有挑战性的过程,需要高风险、高成本和长周期。因此,药物重定位被认为是成功开发药物的一种战略和经济途径。芍合丸(SCH)是一种传统东方医学中的助消化草药配方,在经典医学文献中有记载,并且作为一种非处方药用于治疗消化疾病。有趣的是,另一部更早时期的医学文献描述了 SCH 尚未被检验的其他适应症。我们使用成熟的脂肪细胞、游离脂肪酸(FFA)诱导的肝脂肪变性模型进行了一系列体外研究,并在高脂肪饮食(HFD)小鼠模型中进行了体内研究。暴露于 SCH 调节了脂肪生成基因和蛋白的表达,显著抑制了 3T3-L1 细胞中脂滴的形成。同样,SCH 处理调节了与能量代谢相关的蛋白,减少了 FFA 诱导的 HepG2 细胞中的脂质积累。此外,用 SCH 补充高脂肪饮食喂养的 c57BL/6J 小鼠的血清葡萄糖和脂质谱发生了显著变化。对小鼠肝脏和脂肪组织的组织学分析表明,SCH 给药可减轻肝脂肪变性和脂肪组织肥大。总的来说,这些结果表明,SCH 可通过激活 AMP 激活的蛋白激酶(AMPK)及其下游信号通路来增强葡萄糖代谢和抑制脂肪生成,从而潜在地用于治疗代谢综合征(MetS)。此外,对于来源于替代医学的药物,这似乎是一种可行的药物重定位策略,可以重新评估一些古老的中医经典中的草药方剂的潜在适应症。