Calotropis gigantea (L.) 干燥。 （C. gigantea）是一种传统药用植物，以其治疗糖尿病的功效以及显着的抗氧化、抗炎和抗癌特性而闻名。 II 型糖尿病 (T2DM) 的特点是慢性代谢紊乱，与高血糖和胰岛素反应受损导致肝细胞癌 (HCC) 风险升高相关。 C. gigantea 的民族药理学功效的科学验证为缓解 T2DM 并发症中的癌症进展提供了优势，丰富了现有知识，并可能有助于未来的临床癌症治疗。本研究旨在研究 C. gigantea 茎皮提取物的二氯甲烷部分的预防潜力（ CGDCM）针对二乙基亚硝胺（DEN）诱导的 T2DM 大鼠肝癌，旨在降低与糖尿病相关的癌症发病率，同时验证 C. gigantea 的民族药理学功效。给自发性糖尿病 Torii（SDT）大鼠施用 DEN 诱导肝癌（SDT-DEN-VEH） ，然后用 CGDCM 治疗。二甲双胍用作阳性对照（SDT-DEN-MET）。所有治疗均在初次 DEN 注射后持续 10 周。对糖尿病相关参数进行定量，包括血糖、胰岛素和糖化血红蛋白 (HbA1c) 的血清水平，以及肝功能酶（天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶和 γ-谷氨酰转移酶）。评估血清炎症生物标志物白细胞介素-6 (IL-6) 和肿瘤坏死因子-α (TNF-α)。分析肝组织样本的炎症蛋白表达（IL-6、TNF-α、转化生长因子-β1 (TGF-β1) 和 α-平滑肌肌动蛋白 (α-SMA)）。进行组织病理学评估以评估肝坏死、炎症和纤维化。使用免疫组织化学法测定肝细胞增殖的 Ki-67 表达。用 CGDCM 治疗的 SDT-DEN 诱导的 HCC 大鼠表现出血糖水平降低、胰岛素水平升高和 HbA1c 水平降低。 CGDCM 治疗还降低了 SDT-DEN-VEH 大鼠肝脏中升高的 IL-6、TNF-α、TGF-β1 和 α-SMA 水平。此外，CGDCM 治疗可防止肝细胞损伤、纤维化和细胞增殖。 CGDCM 治疗未观察到对正常器官的不良影响，表明其治疗与糖尿病相关的 HCC 并发症是安全的。此外，SD 大鼠接受 2.5 mg/kg CGDCM 治疗时没有出现不良反应，这进一步支持了其安全使用的观点。这些研究结果表明，C. gigantea 茎皮提取物对 T2DM 患者 HCC 并发症的发展具有预防作用，扩大其民族药理学优势的潜在益处。版权所有 © 2024。由 Elsevier B.V. 出版。

Calotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments.This study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy.Spontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression.Rats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-β1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage.These findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages.Copyright © 2024. Published by Elsevier B.V.