Narayanan Kannan Badri
School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Gyeongbuk, Republic of Korea.
Research Institute of Cell Culture, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Gyeongbuk, Republic of Korea.
Pharmaceutics. 2025 May 2;17(5):606. doi: 10.3390/pharmaceutics17050606.
Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating the repair process. While inflammation is a fundamental component of the body's defense and healing process, its dysregulation can lead to pathological consequences, contributing to various acute and chronic diseases, such as autoimmune disorders, cancer, metabolic syndromes, cardiovascular diseases, neurodegenerative conditions, and other systemic complications. Generally, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), antihistamines, biologics, and colchicine are used as pharmacological agents in the management of inflammatory diseases. However, these conventional treatments often have limitations, including adverse side effects, long-term toxicity, and drug resistance. In contrast, enzyme-based therapeutics have emerged as a promising alternative due to their high specificity, catalytic efficiency, and ability to modulate inflammatory pathways with reduced side effects. These enzymes function by scavenging reactive oxygen species (ROS), inhibiting cytokine transcription, degrading circulating cytokines, and blocking cytokine release by targeting exocytosis-related receptors. Additionally, their role in tissue repair and regeneration further enhances their therapeutic potential. Most natural anti-inflammatory enzymes belong to the oxidoreductase class, including catalase and superoxide dismutase, as well as hydrolases such as trypsin, chymotrypsin, nattokinase, bromelain, papain, serratiopeptidase, collagenase, hyaluronidase, and lysozyme. Engineered enzymes, such as Tobacco Etch Virus (TEV) protease and botulinum neurotoxin type A (BoNT/A), have also demonstrated significant potential in targeted anti-inflammatory therapies. Recent advancements in enzyme engineering, nanotechnology-based enzyme delivery, and biopharmaceutical formulations have further expanded their applicability in treating inflammatory diseases. This review provides a comprehensive overview of both natural and engineered enzymes, along with their formulations, used as anti-inflammatory therapeutics. It highlights improvements in stability, efficacy, and specificity, as well as minimized immunogenicity, while discussing their mechanisms of action and clinical applications and potential future developments in enzyme-based biomedical therapeutics.
炎症是免疫系统针对各种有害刺激的多方面生物学反应，这些刺激包括病原体（如细菌和病毒）、细胞损伤、毒素以及天然/合成刺激物。这种保护机制对于消除损伤原因、清除受损细胞以及启动修复过程至关重要。虽然炎症是身体防御和愈合过程的基本组成部分，但其失调会导致病理后果，引发各种急性和慢性疾病，如自身免疫性疾病、癌症、代谢综合征、心血管疾病、神经退行性疾病以及其他全身并发症。一般来说，非甾体抗炎药（NSAIDs）、皮质类固醇、改善病情抗风湿药（DMARDs）、抗组胺药、生物制剂和秋水仙碱被用作治疗炎症性疾病的药物。然而，这些传统治疗方法往往存在局限性，包括不良副作用、长期毒性和耐药性。相比之下，基于酶的疗法因其高特异性、催化效率以及以降低副作用的方式调节炎症途径的能力，已成为一种有前景的替代方法。这些酶通过清除活性氧（ROS）、抑制细胞因子转录、降解循环中的细胞因子以及通过靶向与胞吐相关的受体来阻断细胞因子释放发挥作用。此外，它们在组织修复和再生中的作用进一步增强了其治疗潜力。大多数天然抗炎酶属于氧化还原酶类，包括过氧化氢酶和超氧化物歧化酶，以及水解酶，如胰蛋白酶、糜蛋白酶、纳豆激酶、菠萝蛋白酶、木瓜蛋白酶、舍雷肽酶、胶原酶、透明质酸酶和溶菌酶。工程酶，如烟草蚀纹病毒（TEV）蛋白酶和A型肉毒杆菌神经毒素（BoNT/A），在靶向抗炎治疗中也显示出巨大潜力。酶工程、基于纳米技术的酶递送和生物药物制剂方面的最新进展进一步扩大了它们在治疗炎症性疾病中的适用性。这篇综述全面概述了天然酶和工程酶及其制剂作为抗炎治疗药物的情况。它强调了在稳定性、疗效和特异性方面的改进，以及免疫原性的最小化，同时讨论了它们的作用机制、临床应用以及基于酶的生物医学治疗的潜在未来发展。
