Kadi M Alharbi, Shahad A Alshehri, Wasayf A Almarwani, Khulud K Aljohani, Ajwan Z Albalawi, Areej S Alatawi, Shekha M Al-Atwi, Lama S Alhwyty, Hanan M Hassan, Mohammed M H Al-Gayyar
{"title":"环黄芪醇通过减少氧化应激、炎症和细胞凋亡对大鼠阿尔茨海默病的影响","authors":"Kadi M Alharbi, Shahad A Alshehri, Wasayf A Almarwani, Khulud K Aljohani, Ajwan Z Albalawi, Areej S Alatawi, Shekha M Al-Atwi, Lama S Alhwyty, Hanan M Hassan, Mohammed M H Al-Gayyar","doi":"10.2174/0115672050315334240508162754","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>As individuals age, they may develop Alzheimer's disease (AD), which is characterized by difficulties in speech, memory loss, and other issues related to neural function. Cycloastragenol is an active ingredient of Astragalus trojanus and has been used to treat inflammation, aging, heart disease, and cancer.</p><p><strong>Objectives: </strong>This study aimed to explore the potential therapeutic benefits of cycloastragenol in rats with experimentally induced AD. Moreover, the underlying molecular mechanisms were also evaluated by measuring Nrf2 and HO-1, which are involved in oxidative stress, NFκB and TNF-α, which are involved in inflammation, and BCL2, BAX, and caspase-3, which are involved in apoptosis.</p><p><strong>Methods: </strong>Sprague-Dawley rats were given 70 mg/kg of aluminum chloride intraperitoneally daily for six weeks to induce AD. Following AD induction, the rats were given 25 mg/kg of cycloastragenol daily by oral gavage for three weeks. Hippocampal sections were stained with hematoxylin/ eosin and with anti-caspase-3 antibodies. The Nrf2, HO-1, NFκB, TNF-α, BCL2, BAX, and caspase-3 gene expressions and protein levels in the samples were analyzed.</p><p><strong>Results: </strong>Cycloastragenol significantly improved rats' behavioral test performance. It also strengthened the organization of the hippocampus. Cycloastragenol significantly improved behavioral performance and improved hippocampal structure in rats. It caused a marked decrease in the expression of NFκB, TNF-α, BAX, and caspase-3, which was associated with an increase in the expression of BCL2, Nrf2, and HO-1.</p><p><strong>Conclusion: </strong>Cycloastragenol improved the structure of the hippocampus in rats with AD. It enhanced the outcomes of behavioral tests, decreased the concentration of AChE in the brain, and exerted antioxidant and anti-inflammatory effects. Antiapoptotic effects were also noted, leading to significant improvements in cognitive function, memory, and behavior in treated rats.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"141-154"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of Cycloastragenol on Alzheimer's Disease in Rats by Reducing Oxidative Stress, Inflammation, and Apoptosis.\",\"authors\":\"Kadi M Alharbi, Shahad A Alshehri, Wasayf A Almarwani, Khulud K Aljohani, Ajwan Z Albalawi, Areej S Alatawi, Shekha M Al-Atwi, Lama S Alhwyty, Hanan M Hassan, Mohammed M H Al-Gayyar\",\"doi\":\"10.2174/0115672050315334240508162754\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>As individuals age, they may develop Alzheimer's disease (AD), which is characterized by difficulties in speech, memory loss, and other issues related to neural function. Cycloastragenol is an active ingredient of Astragalus trojanus and has been used to treat inflammation, aging, heart disease, and cancer.</p><p><strong>Objectives: </strong>This study aimed to explore the potential therapeutic benefits of cycloastragenol in rats with experimentally induced AD. Moreover, the underlying molecular mechanisms were also evaluated by measuring Nrf2 and HO-1, which are involved in oxidative stress, NFκB and TNF-α, which are involved in inflammation, and BCL2, BAX, and caspase-3, which are involved in apoptosis.</p><p><strong>Methods: </strong>Sprague-Dawley rats were given 70 mg/kg of aluminum chloride intraperitoneally daily for six weeks to induce AD. Following AD induction, the rats were given 25 mg/kg of cycloastragenol daily by oral gavage for three weeks. Hippocampal sections were stained with hematoxylin/ eosin and with anti-caspase-3 antibodies. The Nrf2, HO-1, NFκB, TNF-α, BCL2, BAX, and caspase-3 gene expressions and protein levels in the samples were analyzed.</p><p><strong>Results: </strong>Cycloastragenol significantly improved rats' behavioral test performance. It also strengthened the organization of the hippocampus. Cycloastragenol significantly improved behavioral performance and improved hippocampal structure in rats. It caused a marked decrease in the expression of NFκB, TNF-α, BAX, and caspase-3, which was associated with an increase in the expression of BCL2, Nrf2, and HO-1.</p><p><strong>Conclusion: </strong>Cycloastragenol improved the structure of the hippocampus in rats with AD. It enhanced the outcomes of behavioral tests, decreased the concentration of AChE in the brain, and exerted antioxidant and anti-inflammatory effects. 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引用次数: 0
摘要
背景：随着年龄的增长，人们可能会患上阿尔茨海默病（AD），其特征是语言障碍、记忆力减退以及其他与神经功能有关的问题。环黄芪醇是黄芪的一种活性成分，已被用于治疗炎症、衰老、心脏病和癌症：本研究旨在探讨环黄芪醇对实验诱导的注意力缺失症大鼠的潜在治疗作用。此外，还通过测定参与氧化应激的Nrf2和HO-1、参与炎症的NFκB和TNF-α以及参与细胞凋亡的BCL2、BAX和caspase-3，对其潜在的分子机制进行了评估：连续六周每天腹腔注射 70 毫克/千克氯化铝诱导 Sprague-Dawley 大鼠产生 AD。诱导AD后，每天给大鼠灌胃25毫克/千克环黄芪醇，连续三周。海马切片用苏木精/伊红和抗天冬酶-3抗体染色。对样本中的Nrf2、HO-1、NFκB、TNF-α、BCL2、BAX和caspase-3基因表达和蛋白水平进行了分析：结果：环黄芪醇能明显改善大鼠的行为测试表现。结果：环黄芪醇能明显改善大鼠的行为测试表现，还能增强海马的组织结构。环黄芪醇能明显改善大鼠的行为表现并改善海马结构。环黄芪醇能显著降低NFκB、TNF-α、BAX和caspase-3的表达，同时增加BCL2、Nrf2和HO-1的表达：结论：环黄芪醇能改善AD大鼠的海马结构。结论：环黄芪醇能改善 AD 大鼠海马的结构，提高行为测试的结果，降低大脑中 AChE 的浓度，并发挥抗氧化和抗炎作用。它还具有抗细胞凋亡的作用，从而显著改善了治疗大鼠的认知功能、记忆力和行为。
Effects of Cycloastragenol on Alzheimer's Disease in Rats by Reducing Oxidative Stress, Inflammation, and Apoptosis.
Background: As individuals age, they may develop Alzheimer's disease (AD), which is characterized by difficulties in speech, memory loss, and other issues related to neural function. Cycloastragenol is an active ingredient of Astragalus trojanus and has been used to treat inflammation, aging, heart disease, and cancer.
Objectives: This study aimed to explore the potential therapeutic benefits of cycloastragenol in rats with experimentally induced AD. Moreover, the underlying molecular mechanisms were also evaluated by measuring Nrf2 and HO-1, which are involved in oxidative stress, NFκB and TNF-α, which are involved in inflammation, and BCL2, BAX, and caspase-3, which are involved in apoptosis.
Methods: Sprague-Dawley rats were given 70 mg/kg of aluminum chloride intraperitoneally daily for six weeks to induce AD. Following AD induction, the rats were given 25 mg/kg of cycloastragenol daily by oral gavage for three weeks. Hippocampal sections were stained with hematoxylin/ eosin and with anti-caspase-3 antibodies. The Nrf2, HO-1, NFκB, TNF-α, BCL2, BAX, and caspase-3 gene expressions and protein levels in the samples were analyzed.
Results: Cycloastragenol significantly improved rats' behavioral test performance. It also strengthened the organization of the hippocampus. Cycloastragenol significantly improved behavioral performance and improved hippocampal structure in rats. It caused a marked decrease in the expression of NFκB, TNF-α, BAX, and caspase-3, which was associated with an increase in the expression of BCL2, Nrf2, and HO-1.
Conclusion: Cycloastragenol improved the structure of the hippocampus in rats with AD. It enhanced the outcomes of behavioral tests, decreased the concentration of AChE in the brain, and exerted antioxidant and anti-inflammatory effects. Antiapoptotic effects were also noted, leading to significant improvements in cognitive function, memory, and behavior in treated rats.
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