School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India; Department of Clinical Biochemistry, University of Kashmir, J&K, India.
Department of Clinical Biochemistry, University of Kashmir, J&K, India.
J Ethnopharmacol. 2024 Dec 5;335:118652. doi: 10.1016/j.jep.2024.118652. Epub 2024 Aug 2.
Rheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood.
This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development.
Four types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations.
Cell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml.
Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts.
This study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer.
Webbian 大黄（RW）因其 5000 年的药用和食用栽培历史而具有重要的民族药理学意义。RW 在传统和现代医学实践中表现出治疗优势，具有抗癌活性、胃肠道控制、抗炎特性和抑制纤维化等关键药理作用。尽管 RW 在民族药理学中具有广泛的生物活性，但它对结直肠癌（CRC）的疗效仍不完全清楚。
本研究首次旨在研究 RW 根茎的各种提取物对 CRC 发展的化学预防作用。
使用不同溶剂（己烷、乙酸乙酯、乙醇和甲醇）从 RW 根茎中制备了四种类型的提取物。所有四种提取物均在 HCT-116 人 CRC 细胞上进行了细胞毒性评估。有前途的提取物在不同剂量下进一步在体内使用 1,2-二甲基肼（DMH）诱导的大鼠 CRC 模型进行研究，以评估抗氧化和抗癌特性以及它们对相关肝恶化和血液学改变的影响。
细胞活力：体外评估表明，RW 甲醇和乙醇提取物处理后，HCT-116 细胞活力呈剂量和时间依赖性降低，在 200μg/ml 时分别降低了 85%和 90%。
组织病理学分析显示，RW 提取物处理组的结肠组织形态有显著改善，与仅用 DMH 处理的动物相比。RW 处理组显示出结构异常、充血、炎症细胞浸润、隐窝脓肿形成和发育不良的减少。相比之下，仅用 DMH 处理的组表现出不规则的腺体结构、粘膜破坏、广泛的炎症细胞浸润、隐窝脓肿形成和发育不良。这些结果突出了 RW 甲醇和乙醇提取物在减轻结肠癌相关组织病理学改变方面的潜力。
在 DMH 诱导的结直肠癌大鼠模型中，明显存在血液学失衡，包括红细胞减少 49.13%、血红蛋白减少 32.18%、血细胞比容减少 26.79%，白细胞增加 79.62%，血小板增加 68.96%。RW 根茎提取物的给药有效地将这些血液学参数恢复到与对照组相当的水平。此外，RW 治疗显著降低了血清 ALT 和 AST 水平，分别增加了 36.78%和 33.12%，这是由于 DMH 暴露引起的。RW 干预还减轻了动脉粥样硬化的发生，这表现在血清总胆固醇和甘油三酯水平的显著降低。比较分析表明，RW 处理的 DMH 组有效地恢复了脂质谱，与仅用 DMH 处理的组形成对比，后者表现出提示结肠癌的标志物。
DMH 处理组的 MDA 水平显著增加了 195.59%，表明自由基生成增加，同时 SOD（33%）、CAT（48%）、GSH（58%）和 GR 活性（49%）降低，表明氧化应激。RW 提取物在 DMH 处理的大鼠中的治疗显著降低了 MDA 水平并增强了 SOD、CAT、GSH 和 GR 活性。这些结果强调了 RW 提取物的抗氧化功效。
本研究强调了 RW 根茎提取物在抑制结直肠癌发展方面的重要潜力。需要进一步研究以确定这些有希望结果的活性成分，将 RW 定位为对抗结肠癌的天然潜在药物。
