背景:RheumwebbianumRoyle(RW)由于其5000年的药用和烹饪种植历史而具有重要的民族药理学意义。在传统和当代医疗实践中展示治疗优势,RW表现出关键的药理作用,包括抗癌活性,胃肠控制,抗炎特性,和抑制纤维化。尽管它在民族药理学中具有广泛的生物活性,其对结直肠癌(CRC)的疗效尚不完全清楚.
目的:这项研究首次旨在研究源自RW根茎的各种提取物对CRC发展的化学预防能力。
方法:使用不同的溶剂制备了四种类型的RW提取物:己烷,乙酸盐,乙醇和甲醇。评价所有四种提取物对HCT-116人CRC细胞的细胞毒性。使用1,2-二甲基肼(DMH)诱导的大鼠CRC模型在不同剂量的体内进一步研究了有希望的提取物,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。
结果:细胞活力:体外评估表明,用RW的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,将生存能力降低高达85%和90%,分别,200μg/ml。
结果:组织病理学分析显示,与仅DMH处理的动物相比,RW提取物处理组的结肠组织形态显著改善。RW治疗组显示结构异常减少,拥塞,炎性细胞浸润,隐窝脓肿的形成,和发育不良。相比之下,仅DMH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,隐窝脓肿的形成,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。血液学,和肝脏参数:在DMH诱导的结直肠癌大鼠模型中,明显的血液学失衡,包括红细胞减少49.13%,血红蛋白中32.18%,和26.79%的血细胞比容,白细胞增加79.62%,血小板增加68.96%。施用RW根茎提取物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治疗显著降低血清ALT和AST水平,分别增长了36.78%和33.12%,分别,由于DMH暴露。RW干预还减轻了动脉粥样硬化的发作,血清总胆固醇和甘油三酯水平显着降低。比较分析表明,RW处理的DMH组有效地恢复了血脂谱,与仅DMH组相反,后者表现出指示结肠癌的标志物。氧化应激:DMH处理组显示MDA水平显著增加195.59%,表明自由基产生增加,再加上SOD水平下降(33%),CAT(48%),GSH(58%),和GR活性(49%),表示氧化应激。在DMH处理的大鼠中用RW提取物处理显著降低MDA水平和增强SOD,CAT,GSH,和GR活动。这些结果强调了RW提取物的抗氧化功效。
结论:本研究强调了RW根茎提取物在抑制结直肠癌发展中的显著潜力。进一步的调查是必要的,以确定活性成分负责这些有希望的结果,将RW定位为对抗结肠癌的天然和潜在药物。
BACKGROUND: 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.
OBJECTIVE: This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development.
METHODS: 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.
RESULTS: 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.
RESULTS: 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.
CONCLUSIONS: 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.