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纳米结构的α-山竹素-氧化铜复合物通过凋亡基因调控对口腔致病生物膜和口腔癌的双重作用

Dual Action of Nanostructured α-Mangostin-Copper Oxide Complexes Against Dental Pathogen Biofilms and Oral Cancer via Apoptosis Gene Modulation.

作者信息

Rafi Shaik Mohammed, Ramasamy Mohankumar, Jain Divya, Muthu Kesavan, Manivannan Chandrakumar, Althaf Hussain Shaik, Deepak Paramasivam, Thiyagarajulu Nathiya, Guru Ajay, Perianaika Matharasi Antonyraj Anahas, Melo Coutinho Henrique Douglas

机构信息

Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.

Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603 203, Chengalpattu District, Tamil Nadu, India.

出版信息

Chem Biodivers. 2025 Mar;22(3):e202401961. doi: 10.1002/cbdv.202401961. Epub 2025 Jan 13.

DOI:10.1002/cbdv.202401961
PMID:39434420
Abstract

The development of effective treatments for dental pathogens and oral cancer remains a significant challenge. Copper oxide nanoparticles (CuO NPs) are recognized for their strong antimicrobial properties, attributed to the synthesis of oxygen-dependent radicals. α-Mangostin (MG), a natural xanthone from mangosteen fruit, is well-known for its antioxidant, antimicrobial, and anticancer potential. The combination of CuO NPs with MG would offer a synergistic approach to enhance therapeutic efficacy. CuO-MG NPs were synthesized and characterized for their size, morphology, and surface properties. The antimicrobial efficacy of these nanoparticles was tested against oral pathogens, including Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans, and Candida albicans. Antioxidant activity was assessed using superoxide anion and hydroxyl radical anion. The anticancer potential was evaluated by examining apoptosis induction in oral cancer cell lines, focusing on the expression of key apoptotic markers such as Caspase-3, Caspase-8, and FasL. Molecular docking simulations were performed to understand the interaction between MG and biofilm receptors. The CuO-MG NPs evidenced significant antimicrobial efficacy against all tested oral pathogens, with enhanced efficacy attributed to the combined effects of CuO-induced oxidative stress and the antimicrobial properties of MG. Antioxidant assays demonstrated a dose-dependent increase in radical scavenging activity. In oral cancer cells, CuO-MG NPs significantly reduced cell viability and induced apoptosis, as evidenced by the up-regulation of Caspase-3, Caspase-8, and FasL. Molecular docking studies revealed strong binding affinities of MG to key biofilm receptors, disrupting pathogen adhesion and biofilm formation. The combination of CuO NPs and MG offers a powerful and multifaceted therapeutic approach to oral healthcare. CuO-MG NPs demonstrate synergistic antimicrobial, antioxidant, and anticancer properties, offering a potential approach for the management of oral infections and oral cancer. Further preclinical and clinical studies are recommended to ensure their safety and stability in medical applications.

摘要

开发针对牙科病原体和口腔癌的有效治疗方法仍然是一项重大挑战。氧化铜纳米颗粒(CuO NPs)因其强大的抗菌性能而受到认可,这归因于氧依赖性自由基的合成。α-山竹黄酮(MG)是一种来自山竹果实的天然氧杂蒽酮,以其抗氧化、抗菌和抗癌潜力而闻名。CuO NPs与MG的组合将提供一种协同方法来提高治疗效果。合成了CuO-MG NPs,并对其尺寸、形态和表面性质进行了表征。测试了这些纳米颗粒对包括金黄色葡萄球菌、粪肠球菌、变形链球菌和白色念珠菌在内的口腔病原体的抗菌效果。使用超氧阴离子和羟基自由基阴离子评估抗氧化活性。通过检查口腔癌细胞系中的凋亡诱导情况来评估抗癌潜力,重点关注关键凋亡标志物如半胱天冬酶-3、半胱天冬酶-8和FasL的表达。进行了分子对接模拟以了解MG与生物膜受体之间的相互作用。CuO-MG NPs对所有测试的口腔病原体均显示出显著的抗菌效果,其增强的效果归因于CuO诱导的氧化应激和MG的抗菌特性的综合作用。抗氧化试验表明自由基清除活性呈剂量依赖性增加。在口腔癌细胞中,CuO-MG NPs显著降低细胞活力并诱导凋亡,半胱天冬酶-3、半胱天冬酶-8和FasL的上调证明了这一点。分子对接研究揭示了MG与关键生物膜受体的强结合亲和力,破坏了病原体的粘附和生物膜形成。CuO NPs与MG的组合为口腔保健提供了一种强大且多方面的治疗方法。CuO-MG NPs表现出协同的抗菌、抗氧化和抗癌特性,为口腔感染和口腔癌的管理提供了一种潜在方法。建议进一步进行临床前和临床研究,以确保其在医学应用中的安全性和稳定性。

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