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利用绵头雪莲乙醇根提取物对小鼠模型的乳腺肿瘤进展进行调节

Modulation of mammary tumour progression using murine model by ethanol root extract of Saussurea costus (falc.) lipsch.

机构信息

Department of Veterinary Pathology, Dr. G.C Negi College of Veterinary and Animal Sciences, CSK Himachal Pradesh Agricultural University, Palampur, Himachal Pradesh, 176062, India.

Department of Veterinary Pharmacology and Toxicology, Dr. G.C Negi College of Veterinary and Animal Sciences, CSK Himachal Pradesh Agricultural University, Palampur, Himachal Pradesh, 176062, India.

出版信息

J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117302. doi: 10.1016/j.jep.2023.117302. Epub 2023 Oct 18.

DOI:10.1016/j.jep.2023.117302
PMID:37858751
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Breast cancer is a major cause of death among human females across the globe. The anti-neoplastic agents or therapies used for the treatment of cancers can enhance longevity but are subsequently observed to deteriorate the quality of life due to the extensive side effects produced. Saussurea costus is a potential medicinal plant of the Himalayas with noticeable ethnopharmacological properties. The phytochemicals present in Saussurea costus are responsible for anti-carcinogenic potential and warranted nil or minimal side effects of Saussurea costus and directed to use this plant as a preventive or therapeutic drug candidate against cancers.

AIM OF THE STUDY

The present study was planned to evaluate the anti-neoplastic activity of Saussurea costus root extract (SL) in rat mammary tumour model.

MATERIALS AND METHODS

The anti-neoplastic activity of SL root extract at 3 different doses (100, 250 and 500 mg/kg BW) for 18 weeks against 12-dimethylbenz (a) anthracene (DMBA)-induced mammary tumours in Sprague Dawley (SD) female rats was analyzed through serum biochemistry (ALT, AST, ALP, Total protein, Creatinine and BUN), oxidative stress parameters (Lipid peroxidation, Catalase and Reduced glutathione), pro-inflammatory cytokines (TNF-α and NF-κB), immunohistochemical markers (Ki-67, MMP-9 and VEGF), real-time PCR (PCNA, p53, bax, bcl-2 and caspase-3, genes) and molecular docking.

RESULTS

Inhibition of tumour parameters, minimal alteration in the liver (ALT, AST and ALP) and kidney enzymes (Creatinine and BUN), decreased activity of MDA, elevated levels of GSH and catalase, reduction in the levels of pro-inflammatory cytokines i.e. TNF-α and NF-κB, reduced gross and histomorphological changes, declined expression of Ki-67, MMP-9 and VEGF in vivo rat model, mRNA expression of cancer-related genes and docking of dehydrocostus lactone and costunolide with NF-κB and TNF-α demonstrated the chemopreventive action of SL root extract.

CONCLUSIONS

The in-vivo trial elucidates anti-neoplastic activity of Saussurea costus root extract as demonstrated through the reduction of biochemical indices, oxidative stress parameters, histological changes, pro-inflammatory cytokines (NF-κB and TNF-α), cellular proliferation (Ki-67), metastases (MMP-9) and neovascularization (VEGF) markers with highest anti-neoplastic effect of SL extract at the dose of 500 mg/kg body weight. Therefore, the present study signifies the need to use the active principles present in the root extract of Saussurea costus against breast cancer as a therapeutic regimen.

摘要

民族药理学相关性

乳腺癌是全球女性死亡的主要原因之一。用于治疗癌症的抗肿瘤药物或疗法可以延长寿命,但随后由于产生广泛的副作用而观察到生活质量恶化。藏红花是喜马拉雅山地区具有显著民族药理学特性的潜在药用植物。藏红花中的植物化学物质负责抗癌潜力,并保证藏红花的副作用为零或最小,将其用作预防或治疗癌症的候选药物。

研究目的

本研究旨在评估藏红花根提取物(SL)在大鼠乳腺肿瘤模型中的抗肿瘤活性。

材料和方法

通过血清生化(ALT、AST、ALP、总蛋白、肌酐和 BUN)、氧化应激参数(脂质过氧化、过氧化氢酶和还原型谷胱甘肽)、促炎细胞因子(TNF-α 和 NF-κB)、免疫组织化学标志物(Ki-67、MMP-9 和 VEGF)、实时 PCR(PCNA、p53、bax、bcl-2 和 caspase-3 基因)和分子对接分析 SL 根提取物在 3 个不同剂量(100、250 和 500mg/kg BW)下对 12-二甲基苯(a)蒽(DMBA)诱导的 Sprague Dawley(SD)雌性大鼠乳腺肿瘤的抗肿瘤活性。

结果

肿瘤参数的抑制、肝脏(ALT、AST 和 ALP)和肾脏酶(肌酐和 BUN)的最小改变、MDA 活性降低、GSH 和过氧化氢酶水平升高、促炎细胞因子水平降低,即 TNF-α 和 NF-κB,减少体内大鼠模型的大体和组织形态学变化,Ki-67、MMP-9 和 VEGF 的表达降低,癌症相关基因的 mRNA 表达以及脱氢藏红花内酯和木香烃内酯与 NF-κB 和 TNF-α 的对接表明 SL 根提取物具有化学预防作用。

结论

体内试验阐明了藏红花根提取物的抗肿瘤活性,通过降低生化指标、氧化应激参数、组织学变化、促炎细胞因子(NF-κB 和 TNF-α)、细胞增殖(Ki-67)、转移(MMP-9)和新生血管生成(VEGF)标志物来证明,500mg/kg 体重的 SL 提取物具有最高的抗肿瘤作用。因此,本研究表明需要使用藏红花根提取物中的活性成分来治疗乳腺癌。

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