Smart Farm Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do, 25451, South Korea.
BMC Complement Med Ther. 2021 Jan 25;21(1):44. doi: 10.1186/s12906-021-03212-6.
Nonalcoholic steatohepatitis (NASH), a liver disease caused by a nonalcoholic fatty liver, is increasing in incidence worldwide. Owing to the complexity of its pathogenic mechanisms, there are no therapeutic agents for this disease yet. The ideal drug for NASH needs to concurrently decrease hepatic lipid accumulation and exert anti-inflammatory, antifibrotic, and antioxidative effects in the liver. Because of their multipurpose therapeutic effects, we considered that medicinal herbs are suitable for treating patients with NASH.
We determined the efficacy of the alcoholic extract of Lysimachia vulgaris var. davurica (LV), an edible medicinal herb, for NASH treatment. For inducing NASH, C57BLKS/J lar-Lepr/Lepr (db/db) male mice were fed with a methionine-choline deficient (MCD) diet ad libitum. After 3 weeks, the LV extract and a positive control (GFT505) were administered to mice by oral gavage for 3 weeks with a continued MCD diet as needed.
In mice with diet-induced NASH, the LV extract could relieve the disease symptoms; that is, the extract ameliorated hepatic lipid accumulation and also showed antioxidative and anti-inflammatory effects. The LV extract also activated nuclear factor E2-related factor 2 (Nrf2) expression, leading to the upregulation of antioxidants and detoxification signaling. Moreover, the extract presented remarkable efficacy in alleviating liver fibrosis compared with GFT505. This difference was caused by significant LV extract-mediated reduction in the mRNA expression of fibrotic genes like the alpha-smooth muscle actin and collagen type 3 alpha 1. Reduction of fibrotic genes may thus relate with the downregulation of transforming growth factor beta (TGFβ)/Smad signaling by LV extract administration.
Lipid accumulation and inflammatory responses in the liver were alleviated by feeding LV extract to NASH-induced mice. Moreover, the LV extract strongly prevented liver fibrosis by blocking TGFβ/Smad signaling. Hence, LV showed sufficient potency for use as a therapeutic agent against NASH.
非酒精性脂肪性肝炎（NASH）是一种由非酒精性脂肪肝引起的肝脏疾病，其发病率在全球范围内呈上升趋势。由于其发病机制复杂，目前尚无治疗该疾病的药物。NASH 的理想药物需要同时减少肝脏脂质堆积，并在肝脏发挥抗炎、抗纤维化和抗氧化作用。由于具有多方面的治疗作用，我们认为草药适合治疗 NASH 患者。
我们确定了毛茛科珍珠菜属植物糙叶景天（LV）的酒精提取物治疗 NASH 的疗效。为了诱导 NASH，将 C57BLKS/J lar-Lepr/Lepr（db/db）雄性小鼠用蛋氨酸-胆碱缺乏（MCD）饮食自由喂养。3 周后，LV 提取物和阳性对照（GFT505）通过口服灌胃给予继续 MCD 饮食的小鼠 3 周。
在饮食诱导的 NASH 小鼠中，LV 提取物可缓解疾病症状；即，该提取物可改善肝脂质堆积，并具有抗氧化和抗炎作用。LV 提取物还激活核因子 E2 相关因子 2（Nrf2）表达，上调抗氧化和解毒信号。此外，与 GFT505 相比，LV 提取物在缓解肝纤维化方面表现出显著疗效。这种差异是由于 LV 提取物显著降低了纤维化基因（如α-平滑肌肌动蛋白和胶原 3α1）的 mRNA 表达所致。LV 提取物的减少可能与 TGFβ/Smad 信号通路的下调有关。
LV 提取物喂养 NASH 诱导的小鼠可减轻肝脏脂质堆积和炎症反应。此外，LV 提取物通过阻断 TGFβ/Smad 信号强烈预防肝纤维化。因此，LV 具有作为 NASH 治疗剂的足够效力。
