Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu, 600 034, India.
Division of Taxonomy & Biodiversity, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu, 600 034, India.
Biomed Pharmacother. 2017 Nov;95:402-411. doi: 10.1016/j.biopha.2017.08.071. Epub 2017 Sep 12.
The prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) is increasing and there is an increasing interest in natural products to treat NAFLD. This study aimed to evaluate the hepatoprotective effect of andrographolide and two of its derivatives; in one the OH group at C-14 was removed and in the other OH groups at C-3 and C-19 were protected. Andrographolide (AN) was isolated from the aerial parts of Andrographis paniculata Wall. Isoandrographolide (IAN) and 3,19-acetonylidene andrographolide (ANA) were derivatized from AN. Drug likeness of the compounds was studied using DataWarrior. The effect of the compounds in ameliorating hepatic steatosis and lipotoxicity was assessed using palmitate-oleate induced steatotic HepG2 cell lines. In vivo efficacy of the compounds was assessed by using HFD fed rats. IAN showed comparatively high drug score and low irritability than AN. MTT assay indicated that the treatment with IAN had comparatively less toxicity than AN and ANA to HepG2 cells. The treatment with IAN significantly reduced the lipid accumulation and the leakage of LDH and transaminases, while the treatments with AN and ANA did not prohibit the leakage. In the in vivo experiment, the treatment with IAN showed comparatively better hepatoprotection by reducing the serum lipid, transaminases and ALP levels than with AN and ANA. Our results showed that IAN could be a promising lead to treat NAFLD with comparatively low toxicity and improved efficacy.
非酒精性脂肪性肝病（NAFLD）的患病率正在上升，人们对天然产物治疗 NAFLD 的兴趣也在日益增加。本研究旨在评估穿心莲内酯及其两种衍生物的肝保护作用；一种是 C-14 上的 OH 基团被去除，另一种是 C-3 和 C-19 上的 OH 基团被保护。穿心莲内酯（AN）从穿心莲的地上部分中分离得到。异穿心莲内酯（IAN）和 3,19-乙酰亚基穿心莲内酯（ANA）是从 AN 衍生而来的。使用 DataWarrior 研究了化合物的药物相似性。使用棕榈酸-油酸诱导的脂肪变性 HepG2 细胞系评估了化合物改善肝脂肪变性和脂肪毒性的作用。使用 HFD 喂养的大鼠评估了化合物的体内功效。IAN 显示出相对较高的药物评分和比 AN 更低的刺激性。MTT 测定表明，IAN 处理对 HepG2 细胞的毒性比 AN 和 ANA 处理相对较小。IAN 处理显著减少了脂质积累和 LDH 和转氨酶的漏出，而 AN 和 ANA 处理并没有阻止漏出。在体内实验中，IAN 处理通过降低血清脂质、转氨酶和碱性磷酸酶水平，表现出比 AN 和 ANA 处理更好的保肝作用。我们的结果表明，IAN 可能是一种有前途的治疗 NAFLD 的先导化合物，具有相对较低的毒性和改善的疗效。
