Drug Design, Development and Therapy (Jan 2022)
Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms
Abstract
Jinghui Wang,1 Yuhua Zhang,2 Meifeng Zhang,1 Si Sun,1 Yang Zhong,1 Lei Han,1 Yitong Xu,1 Dong Wan,3 Junhui Zhang,4 Huifeng Zhu1 1College of Pharmaceutical Sciences & College of Chinese Medicine, Southwest University, Chongqing, 400715, People’s Republic of China; 2Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, 445000, People’s Republic of China; 3Department of Emergency and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Health Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Huifeng ZhuCollege of Pharmaceutical Sciences and Traditional Chinese Medicine, Southwest University, Chongqing, 400715, People’s Republic of ChinaEmail [email protected] ZhangHealth Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaEmail [email protected]: Catalpol is the main active component of Rehmannia glutinosa, which has a variety of pharmacological activities, including anti-inflammatory and anti-oxidative effects. This study investigates the feasibility of catalpol intranasal administration and its protective effect on acute cerebral ischemia in rats via anti-oxidative and anti-apoptotic mechanisms.Patients and Methods: This study investigates the method of catalpol intranasal administration to evaluate the nasal mucosal toxicity, brain targeting and pharmacokinetics of catalpol. The protective effect of catalpol of intranasal administration on stroke-induced brain injury in rats and its mechanisms on oxidative stress pathway Nrf2/HO-1 and apoptosis were also investigated using middle cerebral artery occlusion (MCAO).Results: The results showed that catalpol intranasal administration was safe and feasible with no hemolysis, no bad effect on the maxillary ciliary movement of bullfrog. After intranasal administration, the brain targeting index (DTI) of catalpol was greater than 1, which indicated that catalpol had good brain targeting after intranasal administration. The bioavailability of catalpol administered intranasally was higher than that of in plasma. In MACO model, catalpol intranasal administration could significantly reduce cerebral infarction volume, neurological dysfunction and brain edema. In addition, catalpol intranasal administration can also reduce the brain cell’s occurrence of apoptosis, promote the expression of Bcl-2 protein and inhibit the expression of Bax protein, reduce oxidative stress damage via up-regulating expression of Nrf2 and HO-1, increasing the activities of SOD and decreasing the activities of MDA.Conclusion: Collectively, catalpol intranasal administration has good safety, stability and brain targeting. It can effectively protect the brain injury of the rat model of acute cerebral ischemia and provide the possibility of drug administration in the acute stage of cerebral ischemia, especially before entering the hospital.Keywords: catalpol, cerebral ischemia, intranasal administration, oxidative stress, apoptosis, neuroprotection
