Majhi Praful Kumar, Sayyad Samir, Gaur Mahendra, Kedar Gangadhar, Rathod Shankar, Sahu Rajanikant, Pradhan Prasanna Kumar, Tripathy Shyamalendu, Ghosh Goutam, Subudhi Bharat Bhusan
Drug Development and Analysis Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha 751029, India.
Vitely Bio LLP, Ahmedabad , Gujarat 380054, India.
ACS Omega. 2024 May 22;9(22):23634-23648. doi: 10.1021/acsomega.4c01219. eCollection 2024 Jun 4.
(Willd.) Miers (Menispermaceae) is a traditional rejuvenator and a conventional medicine used to manage oxidative stress-related diseases, including those associated with the central nervous system. Decreased dextromethorphan (DEM) metabolism is necessary for high bioavailability and application against Alzheimer's disease (AD). Since stem extract (TCE) can potentially inhibit several metabolic enzymes, it can also enhance dextromethorphan bioavailability. This study investigates the potential of TCE to improve DEM's bioavailability and efficacy for the management of AD. analysis was carried out to find the inhibition potential of phytocomponents of for CYP2D6 and CYP3A4. The LC-MS method was revalidated for the analysis of DEM and metabolite dextrorphan (DEX) in the presence of quinidine (QN). The ratio of DEM to DEX was estimated with varying doses of TCE following pharmacokinetic analysis. Network pharmacology analysis was carried out to understand the complementary potential of phytocomponents. This was further validated in the scopolamine-induced dementia model through behavioral and histopathological analyses. TCE (100 mg/kg) for 14 days increased the DEM to DEX ratio by 2.8-fold compared to QN treatment. While was comparable to that of QN treatment at this dose (100 mg/kg) of TCE, it increased significantly at the higher dose (400 mg/kg) of TCE pretreatment. All other pharmacokinetic parameters were also enhanced at this dose with a 4.7-fold increase in DEM/DEX compared with QN. Network pharmacology analysis indicated the ability of TCE to target multiple factors associated with AD. Furthermore, it improved spatial memory and reduced hyperactivity in rodents better than the combination of QN and DEM.
（威尔德）米尔斯（防己科）是一种传统的回春剂和用于治疗与氧化应激相关疾病（包括与中枢神经系统相关疾病）的传统药物。右美沙芬（DEM）代谢降低对于高生物利用度以及用于治疗阿尔茨海默病（AD）至关重要。由于[植物名称]茎提取物（TCE）可能抑制多种代谢酶，它也可以提高右美沙芬的生物利用度。本研究调查TCE提高DEM生物利用度以及治疗AD疗效的潜力。进行分析以发现[植物名称]植物成分对CYP2D6和CYP3A4的抑制潜力。在奎尼丁（QN）存在的情况下，重新验证了用于分析DEM和代谢物右啡烷（DEX）的LC-MS方法。药代动力学分析后，用不同剂量的TCE估计DEM与DEX的比率。进行网络药理学分析以了解植物成分的互补潜力。通过行为和组织病理学分析在东莨菪碱诱导的痴呆模型中进一步验证了这一点。与QN治疗相比，TCE（100mg/kg）给药14天使DEM与DEX的比率增加了2.8倍。虽然在该剂量（100mg/kg）的TCE下[某个指标]与QN治疗相当，但在较高剂量（400mg/kg）的TCE预处理时它显著增加。在该剂量下，所有其他药代动力学参数也得到增强，与QN相比，DEM/DEX增加了4.7倍。网络药理学分析表明TCE能够靶向与AD相关的多个因素。此外，与QN和DEM的组合相比，它在啮齿动物中更好地改善了空间记忆并减少了多动。
