Department of Surgery, Division of Hepatobiliary Surgery, Faculty of Medicine, Al-Baha University, Al-Baha, Saudi Arabia.
Department of Medical Parasitology, Faculty of Medicine, Al-Baha University, Al-Baha, Saudi Arabia.
PLoS Negl Trop Dis. 2023 Jun 20;17(6):e0011426. doi: 10.1371/journal.pntd.0011426. eCollection 2023 Jun.
Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni.
Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF β1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed.
A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-β1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05).
Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.
血吸虫病是全球最普遍的寄生虫感染之一。吡喹酮（PZQ）耐药性可能对疾病的控制能力构成威胁。关于 Ziziphus spina-christi 叶提取物（ZLE）在治疗肝血吸虫病中的作用知之甚少。然而，尚无研究探讨 ZLE 的抗血管生成和抗增殖活性是否可能成为减轻这种情况下肝损伤的机制。因此，本研究旨在评估 ZLE 作为一种抗血管生成和抗增殖剂在感染 S. mansoni 的仓鼠中的治疗潜力。
使用 50 只仓鼠并将其分为 5 组（每组 10 只仓鼠）；未感染未治疗（对照组）、未感染 ZLE 治疗、感染未治疗、感染 PZQ 治疗和感染 ZLE 治疗。通过免疫组织化学表达 VEGF、Ki-67 和 TGFβ1 在肝切片中评估药物的抗血管生成和抗纤维化作用。还测量肝匀浆中的一些氧化应激参数（NO、GSH、GST 和 SOD），并评估血清肝酶。
与未感染未治疗组相比，ZLE 和 PZQ 治疗组的虫体负荷、肉芽肿大小、肉芽肿面积和数量均显著降低，且与 PZQ 治疗组相比，ZLE 治疗组的肉芽肿数量和组织卵负荷降低更为显著（p<0.05）。ZLE 对肉芽肿具有显著的抗血管生成和抗纤维化作用，其 VEGF 和 TGF-β1 的表达明显低于未感染未治疗组和 PZQ 治疗组。ZLE 表现出抗增殖活性，其阳性 Ki-67 肝细胞百分比明显低于未感染未治疗组。此外，ZLE 表现出强大的抗氧化作用，其肝匀浆中的 NO 和 GSH、GST 和 SOD 的保存明显低于未感染未治疗组和 PZQ 治疗组（p<0.05）。
我们的结果表明，ZLE 作为一种有前途的肝保护治疗工具，可用于治疗血吸虫性肝纤维化，因为它在感染 S. mansoni 的仓鼠中具有抗血管生成、抗增殖、抗纤维化和抗氧化作用，为其在传统医学中的应用提供了科学依据。
