Background. Traditional herbal medicine practitioners in the Ashanti region of Ghana use the fruit peels of Citrus limon (L.) Osbeck (C. limon) in preventive and curative treatment of many cancers including liver cancer. This ethnobotanical claim remains to be verified scientifically. Aim of the Study. This study investigated prophylactic hepatoprotective and anti-HCC effects of C. limon peel extract (LPE) in CCl₄/olive oil-induced HCC-like rats. Materials and Methods. After preparation of LPE, it was subjected to phytochemical screening using standard phytochemical methods. A total of 30 healthy adult male Sprague-Dawley rats (weighing 150-200 g) were randomly assigned into six groups of 5 rats each. Rats in the control group received olive oil (5 mL/kg ip) twice weekly for 16 weeks. Rats in the model group received CCl₄/olive oil (2 mL/kg, ip) twice weekly for 16 weeks. Rats in capecitabine (10 mg/kg po) and LPE (50, 100, and 200 mg/kg po) groups received CCl₄/olive oil (2 mL/kg, i.p) in the morning and their respective treatments in the afternoon twice a week for 16 weeks. Rats in all groups had free access to food and water ad libitum. Body weight and survival rates were monitored. Rats were sacrificed under deep anesthesia, blood was collected, and liver and other organs were isolated. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), prothrombin time, bilirubin, C-reactive protein (CRP), alpha- (α-) fetoprotein (AFP), and liver histology were assessed. Results. Alkaloids, tannins, flavonoids, terpenoids, and saponins were detected in LPE. Model rats demonstrated increased serum levels of AFP, CRP, ALP, GGT, ALT, and AST, prothrombin time, total bilirubin, direct bilirubin, blood lymphocyte, and monocyte counts, but decreased serum albumin and total protein compared to control rats. Unlike the control, model rats demonstrated fat accumulation in periportal and centrilobular hepatocytes and neoplastic transformation. Semiquantitation of periodic acid Schiff- (PAS-) stained liver sections showed decreased glycogen storage in hepatocytes of model rats compared to control rats. Compared to the model, LPE treatment protected against CCl4-induced hepatocarcinogenesis, which was evidenced by decreased AFP, CRP, liver enzymes, total and direct bilirubin, prothrombin time, and blood lymphocyte and monocyte counts; attenuation of fat accumulation; and increased glycogen storage, albumin, and total protein. Conclusion. LPE abates CCl₄-induced hepatocarcinogenesis by attenuating liver inflammation and improving metabolic, biosynthetic, and detoxification functions of the liver. The prophylactic hepatoprotective and anti-hepatocarcinogenic effects of LPE are attributable to its phytochemical composition raising hopes of finding potential anticancer bioactive compounds from C. limon fruit peels.

中文翻译：

---

柠檬 (L.) Osbeck 果皮提取物可减轻四氯化碳诱导的 Sprague-Dawley 大鼠肝癌发生

背景。加纳阿散蒂地区的传统草药从业者使用柠檬(L.) Osbeck ( C. limon )的果皮来预防和治疗包括肝癌在内的多种癌症。这一民族植物学主张仍有待科学验证。研究目的。本研究调查了柠檬皮提取物 (LPE) 对 CCl ₄ /橄榄油诱导的 HCC 样大鼠的预防性保肝和抗 HCC 作用。材料和方法。LPE制备后，使用标准植物化学方法对其进行植物化学筛选。将30只健康成年雄性Sprague-Dawley大鼠(体重150-200g)随机分为6组，每组5只。对照组的大鼠每周两次接受橄榄油（5 mL/kg ip ），持续 16 周。模型组大鼠每周两次接受CCl ₄ /橄榄油（2 mL/kg，腹腔注射），持续16周。卡培他滨（10 mg/kg po）和LPE（50、100和200 mg/kg po）组大鼠早上接受CCl ₄ /橄榄油（2 mL/kg，ip），下午分别接受两次治疗一周，持续 16 周。各组大鼠均可自由采食和饮水。监测体重和存活率。在深度麻醉下处死大鼠，采集血液，分离肝脏和其他器官。天冬氨酸转氨酶 (AST)、丙氨酸转氨酶 (ALT)、碱性磷酸酶 (ALP)、γ-谷氨酰转移酶 (GGT)、凝血酶原时间、胆红素、C 反应蛋白 (CRP)、α- ( α -) 甲胎蛋白 (AFP) 和评估肝脏组织学。结果。LPE 中检测到生物碱、单宁、类黄酮、萜类化合物和皂苷。与对照大鼠相比，模型大鼠血清 AFP、CRP、ALP、GGT、ALT 和 AST、凝血酶原时间、总胆红素、直接胆红素、血液淋巴细胞和单核细胞计数升高，但血清白蛋白和总蛋白降低。与对照组不同，模型大鼠表现出门静脉周围和小叶中心肝细胞的脂肪积累以及肿瘤转化。高碘酸希夫 (PAS) 染色肝切片的半定量显示，与对照大鼠相比，模型大鼠肝细胞中的糖原储存减少。与模型相比，LPE 治疗可预防 CCl4 诱导的肝癌发生，AFP、CRP、肝酶、总胆红素和直接胆红素、凝血酶原时间以及血液淋巴细胞和单核细胞计数下降即可证明这一点；减少脂肪堆积；并增加糖原储存、白蛋白和总蛋白。结论。LPE通过减轻肝脏炎症和改善肝脏的代谢、生物合成和解毒功能来减轻 CCl _{4诱导的肝癌发生。}LPE 的预防性保肝和抗肝癌作用归因于其植物化学成分，这提高了从柠檬果皮中寻找潜在抗癌生物活性化合物的希望。