College of Pharmacy, Beihua University, Jilin, Jilin Province 132013, China.
College of Pharmacy, Baicheng Medical College, Baicheng, Jilin Province 137099, China.
Food Funct. 2023 Jun 19;14(12):5606-5619. doi: 10.1039/d3fo01315d.
Ginseng, when used as a food and nutritional supplement, has the ability to regulate human immunity. Here, the potential anti-hepatic fibrosis effect of ginsenoside Rd (Rd), one of the protopanaxadiol types of ginsenoside, was investigated. We established a hepatic fibrosis model using intraperitoneal injection of thioacetamide (TAA) for five weeks in mice. In addition, an model was established by using TGF-β to activate hepatic stellate cells (HSCs), treated with Rd and an estrogen-related receptor α (ERRα) inhibitor (XCT-790). The ERRα knockdown (shRNA-ERRα) of the primary mouse hepatocytes was used to establish hepatocyte injury by TGF-β, and they were then incubated in Rd. The Rd significantly alleviated the histopathological changes, and reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The Rd could upregulate the ERRα and downregulate the fibrosis markers in the livers of mice. In TAA-induced mice, the Rd inhibited the purinergic ligand-gated ion channel 7 receptor (P2X7r)-mediated NLRP3 inflammasome activation, consequently reversing the liver inflammatory response. The Rd significantly increased the expression of ERRα and suppressed the extracellular matrix (ECM) in the HSCs or primary hepatocytes. The Rd significantly decreased the P2X7r-mediated NLRP3 inflammasome activation, consequently reversing the inflammatory response, including the production of IL-1β, IL-23 in the activated HSCs and primary hepatocytes. The Rd could ameliorate the damage of the hepatocytes and further inhibit the entry of IL-1β and IL-18 into the extracellular matrix. The Rd reduced the inflammatory reaction by regulating the ERRα-P2X7r signaling pathway while suppressing the fibrogenesis, which suggests that the Rd can serve as a novel dietary supplement approach to combat hepatic fibrosis.
人参作为一种食品和营养补充剂，具有调节人体免疫力的能力。在这里，我们研究了人参皂苷 Rd（Rd）作为一种原人参二醇型人参皂苷，对肝纤维化的潜在抑制作用。我们通过向小鼠腹腔注射硫代乙酰胺（TAA）建立了肝纤维化模型，持续五周。此外，我们还通过使用 TGF-β激活肝星状细胞（HSCs），并用 Rd 和雌激素相关受体α（ERRα）抑制剂（XCT-790）进行处理，建立了肝纤维化模型。我们使用 TGF-β诱导原发性小鼠肝细胞损伤，敲低 ERRα（shRNA-ERRα），并在 Rd 孵育。Rd 显著减轻了组织病理学变化，并降低了血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平。Rd 可上调 ERRα，下调肝脏纤维化标志物。在 TAA 诱导的小鼠中，Rd 抑制嘌呤能配体门控离子通道 7 受体（P2X7r）介导的 NLRP3 炎性体激活，从而逆转肝脏炎症反应。Rd 显著增加 ERRα的表达，并抑制 HSCs 或原发性肝细胞的细胞外基质（ECM）。Rd 显著降低 P2X7r 介导的 NLRP3 炎性体激活，从而逆转炎症反应，包括激活的 HSCs 和原发性肝细胞中 IL-1β和 IL-23 的产生。Rd 可以减轻肝细胞损伤，进一步抑制 IL-1β和 IL-18 进入细胞外基质。Rd 通过调节 ERRα-P2X7r 信号通路来减轻炎症反应，同时抑制纤维化，这表明 Rd 可以作为一种新的饮食补充剂方法来对抗肝纤维化。
