Zoology Department, Faculty of Science, Helwan University, Cairo, 11795, Egypt.
Chemistry Department, Faculty of Science, Helwan University, Cairo, 11795, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Jun;394(6):1091-1102. doi: 10.1007/s00210-020-02043-5. Epub 2021 Jan 8.
The hepatoprotective activity of heliomycin obtained from the culture broth of actinomycete AB5 against diethylnitrosamine (DEN)-induced hepatic cancer in Wistar rats was estimated. Heliomycin exhibited a significant decrease in the levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) compared to the positive control. For instance, the heliomycin group after 20 weeks showed a significant decline in ALT, AST, and ALP values (70.75 ± 5.12, 140.25 ± 11.75, and 163.25 ± 18.66, respectively) compared to the positive control group (170.00 ± 9.55, 252.75 ± 12.33, and 278.00 ± 21.32, respectively). Additionally, the isolated compound showed a highly significant decrease in serum alpha-fetoprotein (AFP) levels. After 8, 16, and 20 weeks, the mean values of AFP in the heliomycin group revealed a highly significant decrease (33.62 ± 2.46, 30.00 ± 4.05, and 28.50 ± 2.64, respectively) compared to the positive control group (49.45 ± 3.03, 81.90 ± 6.70, and 90.75 ± 5.12, respectively). The histopathological investigation of liver sections supported the results of biochemical analysis. It was demonstrated that heliomycin showed histological improvement of hepatocytes and marked increase of nuclear pyknotic with clear cytoplasm, which is a sign of improving the apoptotic pathway of malignant cells. It also displayed marked fibrosis at most of the malignant cells and the development of some regenerative nodules. Heliomycin showed moderate immunoreactivity with alpha-fetoprotein (AFP), and proliferation cell nuclear antigen (PCNA) compared to the positive control group. To the best of our knowledge, this is the first study to report the anticancer activity of heliomycin against hepatocellular carcinoma in vivo.
从放线菌 AB5 的发酵液中获得的赫里亚霉素对 Wistar 大鼠二乙基亚硝胺（DEN）诱导肝癌的保肝活性进行了评估。与阳性对照组相比，赫里亚霉素显著降低了丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）的水平。例如，赫里亚霉素组在 20 周后，ALT、AST 和 ALP 值显著下降（分别为 70.75±5.12、140.25±11.75 和 163.25±18.66），与阳性对照组（分别为 170.00±9.55、252.75±12.33 和 278.00±21.32）相比。此外，该分离化合物还显著降低了血清甲胎蛋白（AFP）水平。在第 8、16 和 20 周时，赫里亚霉素组的 AFP 平均值显著下降（分别为 33.62±2.46、30.00±4.05 和 28.50±2.64），与阳性对照组（分别为 49.45±3.03、81.90±6.70 和 90.75±5.12）相比具有统计学意义。肝组织切片的组织病理学检查支持生化分析的结果。结果表明，赫里亚霉素可改善肝细胞的组织学，细胞质清晰，核固缩明显，这是改善恶性细胞凋亡途径的标志。它还显示出在大多数恶性细胞上有明显的纤维化和一些再生结节的发育。与阳性对照组相比，赫里亚霉素对甲胎蛋白（AFP）和增殖细胞核抗原（PCNA）的免疫反应呈中度。据我们所知，这是首次报道赫里亚霉素在体内对肝癌的抗癌活性。
