Majed Ferial, Nafees Sana, Rashid Summya, Ali Nemat, Hasan Syed Kazim, Ali Rashid, Shahid Ayaz, Sultana Sarwat
Department of Medical Elementology and Toxicology, Faculty of Science, Section of Molecular Carcinogenesis and Chemoprevention, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
Toxicol Int. 2015 Jan-Apr;22(1):21-9. doi: 10.4103/0971-6580.172252.
The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of Terminalia chebula (TC) against chemically-induced skin tumorigenesis in Swiss albino mice. It is used as herbal medicine because it exhibits antioxidant, anti-inflammatory, and anticarcinogenic activity. However, the précised underlying mechanism remains to be elucidated.
In light of the important role of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (i-NOS), ornithine decarboxylase (ODC), proinflammatory cytokines, oxidative stress in carcinogenesis, chemopreventive efficacy of TC against 7,12-dimethylbenz[a] anthracene (DMBA), and croton oil-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective antioxidant enzymes activity, lipid peroxidation (LPO), inflammatory responses, and expression of various molecular markers in skin tissues.
We found that topical application of TC at dose of 30 mg/kg b. wt. mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Histological findings further supported the protective effects of TC against DMBA/croton oil-induced cutaneous damage.
The findings of the present study suggest that the chemopreventive effect of TC is associated with upregulation of endogenous cytoprotective machinery and downregulation of inflammatory mediators (interleukin (IL)-6, COX-2, i-NOS, ODC, and NF-κB).
本研究旨在探讨诃子(Terminalia chebula,TC)对瑞士白化小鼠化学诱导皮肤肿瘤发生的抗肿瘤潜力的潜在分子机制。它作为草药使用,因为它具有抗氧化、抗炎和抗癌活性。然而,确切的潜在机制仍有待阐明。
鉴于核因子-κB(NF-κB)、环氧化酶-2(COX-2)、诱导型一氧化氮合酶(i-NOS)、鸟氨酸脱羧酶(ODC)、促炎细胞因子、氧化应激在致癌过程中的重要作用,从细胞保护抗氧化酶活性、脂质过氧化(LPO)、炎症反应以及皮肤组织中各种分子标志物的表达方面,研究了诃子对7,12-二甲基苯并[a]蒽(DMBA)和巴豆油诱导的两阶段皮肤致癌的化学预防效果。
我们发现以30mg/kg体重的剂量对小鼠局部应用诃子可有效抑制氧化应激以及炎症介质的失调激活和肿瘤发生。组织学结果进一步支持了诃子对DMBA/巴豆油诱导的皮肤损伤的保护作用。
本研究结果表明,诃子的化学预防作用与内源性细胞保护机制的上调以及炎症介质(白细胞介素(IL)-6、COX-2、i-NOS、ODC和NF-κB)的下调有关。