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山石榴提取物通过抑制氧化应激和细胞因子对乳腺癌模型的化学预防作用。

Chemopreventive effects of Melastoma malabathricum L. extract in mammary tumor model via inhibition of oxidative stress and inflammatory cytokines.

机构信息

Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Prayagraj, Uttar Pradesh, 211007, India.

School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, 440-746, Republic of Korea.

出版信息

Biomed Pharmacother. 2021 May;137:111298. doi: 10.1016/j.biopha.2021.111298. Epub 2021 Mar 2.

Abstract

The objective of this study was to evaluate the anticancer effects of Melstoma malabathricum L. (MM) MDA-MB-231 human breast cancer and in vivo mammary tumor model and decipher the potential mechanism. The phyto-constituents in the extract have been identified by liquid chromatography-mass spectrometry (LC-MS). The anti-cancer activity of MM extract was tested on MDA-MB-231 human breast cancer cells. Chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was used for the induction of breast cancer in rodents. Burden, volume, tumor incidence, pro-inflammatory cytokines, antioxidant parameters and mitochondrial parameters were estimated. Histological analysis was determined in mammary gland, vagina, uterus, heart, liver, lung and renal tissues. LC-MS showed the 21 phyto-constituents present in the extract of MM. MM extract showed the potent cytotoxicity against MDA-MB-231 cells and exhibited the IC value (14.6 μM). MM extract significantly decreased the body weight and altered the organ weight such as ovary, uterus, liver, spleen, lungs, renal, adrenal and brain tissue. MM extract significantly down-regulated the tumor incidence, tumor burden and average tumor weight at dose dependently manner. MM extract significantly altered the antioxidants activity in term of augmented the level of superoxide dismutase (SOD), catalase (CAT) and suppressed the level of malonaldehyde (MDA); pro-inflammatory cytokines levels such as reduced the level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in the serum, hepatic and mammary gland tissue in DMBA induced mammary gland tumor rats. MM extract significantly (P < 0.001) enhanced the activity of mitochondrial parameters include Isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), Malate dehydrogenase (MDH) and alpha-keto glutaraldehyde dehydrogenase (α-KGDH). The histopathological finding exhibited that MM extract has a marked reduced effect on mammary glands, mammary gland, vagina, uterus, heart, liver, lung and renal.These data provide the scientific evidence that MM extract might be used as a traditional medicine to cure the breast cancer.

摘要

本研究旨在评估马六甲巴戟天(MM)MDA-MB-231 人乳腺癌及体内乳腺肿瘤模型的抗癌作用,并揭示其潜在机制。采用液相色谱-质谱联用(LC-MS)鉴定提取物中的植物成分。在 MDA-MB-231 人乳腺癌细胞上测试 MM 提取物的抗癌活性。化学致癌物 7,12-二甲基苯并(a)蒽(DMBA)用于诱导啮齿动物乳腺癌。估计负担、体积、肿瘤发生率、促炎细胞因子、抗氧化参数和线粒体参数。对乳腺、阴道、子宫、心脏、肝脏、肺和肾脏组织进行组织学分析。LC-MS 显示 MM 提取物中存在 21 种植物成分。MM 提取物对 MDA-MB-231 细胞表现出强烈的细胞毒性,并表现出 IC 值(14.6μM)。MM 提取物显著降低了体重,并改变了卵巢、子宫、肝脏、脾脏、肺、肾、肾上腺和脑组织等器官的重量。MM 提取物在剂量依赖性方式下显著降低肿瘤发生率、肿瘤负担和平均肿瘤重量。MM 提取物显著改变了抗氧化剂活性,增加了超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的水平,并抑制了丙二醛(MDA)的水平;血清、肝和乳腺组织中的促炎细胞因子水平如肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平降低在 DMBA 诱导的乳腺肿瘤大鼠中。MM 提取物显著(P<0.001)增强了线粒体参数的活性,包括异柠檬酸脱氢酶(ICDH)、琥珀酸脱氢酶(SDH)、苹果酸脱氢酶(MDH)和α-酮戊二酸脱氢酶(α-KGDH)。组织病理学发现表明,MM 提取物对乳腺、乳腺、阴道、子宫、心脏、肝脏、肺和肾脏有明显的减轻作用。这些数据为 MM 提取物可能作为治疗乳腺癌的传统药物提供了科学依据。

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