Pharmaceutical Research and Technology Institute, Kindai University.
Antiaging Center, Kindai University.
Biol Pharm Bull. 2023;46(6):848-855. doi: 10.1248/bpb.b23-00167.
A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100 mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.
西藏獐牙菜根茎的甲醇提取物（车前科）对 D-半乳糖胺（D-GalN）/脂多糖（LPS）诱导的小鼠肝损伤具有保护作用。我们之前从提取物中分离出了 46 种化合物，包括几种类型的环烯醚萜苷、苯乙醇苷和芳烃等。其中，獐牙菜苦苷、獐牙菜苦苷元和 4-羟基-3-甲氧基苯乙酮在 50-100mg/kg 的剂量下具有积极的保肝作用，经口（p.o.）。为了表征这些分离物的作用机制，并阐明苯乙醇苷对其保肝作用的结构要求，我们在体外研究中评估了它们对（i）D-GalN 诱导的小鼠原代肝细胞毒性、（ii）LPS 诱导的小鼠腹腔巨噬细胞一氧化氮（NO）产生和（iii）TNF-α 诱导的 L929 细胞毒性的影响。这些分离物降低了 D-GalN 引起的细胞毒性，而不抑制 LPS 诱导的巨噬细胞活化，还降低了肝细胞对 TNF-α 的敏感性。此外，还评估了苯乙醇苷对 D-GalN 诱导的小鼠原代肝细胞毒性的保护作用的结构要求。
