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Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms
PURPOSE: 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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801896/ https://www.ncbi.nlm.nih.gov/pubmed/35115763 http://dx.doi.org/10.2147/DDDT.S343928 |
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author | Wang, Jinghui Zhang, Yuhua Zhang, Meifeng Sun, Si Zhong, Yang Han, Lei Xu, Yitong Wan, Dong Zhang, Junhui Zhu, Huifeng |
author_facet | Wang, Jinghui Zhang, Yuhua Zhang, Meifeng Sun, Si Zhong, Yang Han, Lei Xu, Yitong Wan, Dong Zhang, Junhui Zhu, Huifeng |
author_sort | Wang, Jinghui |
collection | PubMed |
description | PURPOSE: 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. |
format | Online Article Text |
id | pubmed-8801896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-88018962022-02-02 Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms Wang, Jinghui Zhang, Yuhua Zhang, Meifeng Sun, Si Zhong, Yang Han, Lei Xu, Yitong Wan, Dong Zhang, Junhui Zhu, Huifeng Drug Des Devel Ther Original Research PURPOSE: 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. Dove 2022-01-25 /pmc/articles/PMC8801896/ /pubmed/35115763 http://dx.doi.org/10.2147/DDDT.S343928 Text en © 2022 Wang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wang, Jinghui Zhang, Yuhua Zhang, Meifeng Sun, Si Zhong, Yang Han, Lei Xu, Yitong Wan, Dong Zhang, Junhui Zhu, Huifeng Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms |
title | Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms |
title_full | Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms |
title_fullStr | Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms |
title_full_unstemmed | Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms |
title_short | Feasibility of Catalpol Intranasal Administration and Its Protective Effect on Acute Cerebral Ischemia in Rats via Anti-Oxidative and Anti-Apoptotic Mechanisms |
title_sort | feasibility of catalpol intranasal administration and its protective effect on acute cerebral ischemia in rats via anti-oxidative and anti-apoptotic mechanisms |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801896/ https://www.ncbi.nlm.nih.gov/pubmed/35115763 http://dx.doi.org/10.2147/DDDT.S343928 |
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