Mohammed Hamdoon A, Ewees Mohamed G, Mahmoud Nesreen I, Ali Hussein M, Amin Elham, Abdel-Bakky Mohamed S
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.
Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
Pharmaceuticals (Basel). 2023 Oct 16;16(10):1470. doi: 10.3390/ph16101470.
Forssk. ex JF Gmel. (SV), a traditional known plant, has shown in vitro cytotoxic activity against HepG2 and HepG-2/ADR (doxorubicin-resistant cells) liver cell carcinoma cell lines, as well as hepatoprotection against paracetamol and carbon tetrachloride (CCl4)-induced liver injury. The current study evaluated the protective effect of SV, administered against N-diethylnitrosamine (NDEA)-induced HCC in rats. The possible modulatory effect of SV on the PI3K/HIF-1α/c-MYC/iNOS pathway was investigated. Sixty male adult albino rats (200 ± 10 g) were equally classified into five groups. Group I served as a control; Group 2 (SV control group) received SV (p.o., 200 mg/kg body weight); Group 3 (NDEA-administered rats) received freshly prepared NDEA solution (100 mg/L); and Groups 4 and 5 received simultaneously, for 16 weeks, NDEA + SV extract (100 and 200 mg/kg, orally). NDEA-treated rats displayed significant increases in serum levels of AFP, CEA, PI3K, malondialdehyde (MDA), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGFR), with increased liver tissue protein expression of fibrinogen concomitant and significantly decreased concentrations of antioxidant parameters (catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH)) in comparison to normal rats. On the flip side, AFP, CEA, PI3K, MDA, EGFR, and VEGFR serum levels were significantly reduced in rats that received NDEA with SV, both at low (SV LD) and high (SV HD) doses, accompanied by significant improvements in antioxidant parameters compared to the NDEA-treated group. Conclusions: SV possesses a significant hepatoprotective effect against NDEA-induced HCC via inhibiting the PI3K/HIF-1α/c-MYC/iNOS pathway, suggesting that SV could be a promising hepatocellular carcinoma treatment.
福斯克（由 JF 格梅尔修订）（SV）是一种传统的知名植物，已显示出对肝癌细胞系 HepG2 和 HepG-2/ADR（多柔比星耐药细胞）的体外细胞毒性活性，以及对扑热息痛和四氯化碳（CCl4）诱导的肝损伤的肝保护作用。本研究评估了 SV 对 N-二乙基亚硝胺（NDEA）诱导的大鼠肝癌的保护作用。研究了 SV 对 PI3K/HIF-1α/c-MYC/iNOS 通路的可能调节作用。60 只成年雄性白化大鼠（200±10 克）平均分为五组。第一组作为对照组；第二组（SV 对照组）接受 SV（口服，200 毫克/千克体重）；第三组（给予 NDEA 的大鼠）接受新鲜配制的 NDEA 溶液（100 毫克/升）；第四组和第五组同时接受 NDEA + SV 提取物（100 和 200 毫克/千克，口服），持续 16 周。与正常大鼠相比，经 NDEA 处理的大鼠血清甲胎蛋白（AFP）、癌胚抗原（CEA）、PI3K、丙二醛（MDA）、表皮生长因子受体（EGFR）和血管内皮生长因子（VEGFR）水平显著升高，肝组织纤维蛋白原蛋白表达增加，抗氧化参数（过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH））浓度显著降低。另一方面，在接受低剂量（SV LD）和高剂量（SV HD）NDEA 与 SV 的大鼠中，AFP、CEA、PI3K、MDA、EGFR 和 VEGFR 血清水平显著降低，与 NDEA 处理组相比，抗氧化参数有显著改善。结论：SV 通过抑制 PI3K/HIF-1α/c-MYC/iNOS 通路对 NDEA 诱导的肝癌具有显著的肝保护作用，表明 SV 可能是一种有前途的肝细胞癌治疗药物。
