Moharana Alok Kumar, Gaur Mahendra, Mohapatra Tapas Kumar, Dash Rudra Narayan, Subudhi Bharat Bhusan
Drug Development and Analysis Lab, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, 751029, India.
Nityananada College of Pharmacy, Sergarh, Balasore, Odisha, 756060, India.
Curr Comput Aided Drug Des. 2025;21(2):194-210. doi: 10.2174/0115734099307360240731052835.
Arthritis is the cause of morbidity associated with Chikungunya virus (CHIKV) infection. It persists even after the virus has been cleared from the body. MBZM-NIBT was earlier shown to inhibit (CHIKV) infection and .
The objective of this study is to determine the ability of MBZM-N-IBT to manage arthritis independent of CHIKV infection.
The acute toxicity of MBZM-N-IBT was determined to find a permissible oral dose. Effects against inflammation and arthritis were determined in relevant preclinical models. Network pharmacology was used to propose possible modes of action.
It showed no acute toxicity orally, with an estimated LD of more than 5000 mg/kg in rats. It significantly reduced inflammation. Its effect against Complete Freund's Adjuvant (CFA) induced arthritis was comparable to that of Diclofenac sodium. Network pharmacology analysis revealed that MBZM-N-IBT can potentially interfere with multiple targets and pathways. MMP12 and CTSD were found to be the most probable hub targets of MBZM-N-IBT for its effect against arthritis.
In conclusion, MBZM-N-IBT is safe at 50 mg/kg and can manage arthritis independent of CHIKV infection through modulation of multiple pathways and arthritis-associated targets.
关节炎是与基孔肯雅病毒(CHIKV)感染相关的发病原因。即使病毒已从体内清除,关节炎仍会持续存在。先前研究表明MBZM-NIBT可抑制CHIKV感染。
本研究的目的是确定MBZM-N-IBT在不依赖CHIKV感染的情况下控制关节炎的能力。
测定MBZM-N-IBT的急性毒性以确定允许的口服剂量。在相关临床前模型中确定其对炎症和关节炎的影响。采用网络药理学方法推测可能的作用模式。
口服时无急性毒性,大鼠的估计半数致死量超过5000 mg/kg。它能显著减轻炎症。其对完全弗氏佐剂(CFA)诱导的关节炎的作用与双氯芬酸钠相当。网络药理学分析表明,MBZM-N-IBT可能会干扰多个靶点和途径。发现基质金属蛋白酶12(MMP12)和组织蛋白酶D(CTSD)是MBZM-N-IBT抗关节炎作用最可能的核心靶点。
总之,MBZM-N-IBT在50 mg/kg时是安全的,并且可以通过调节多种途径和与关节炎相关的靶点来控制不依赖CHIKV感染的关节炎。