Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats
Abstract Background Alzheimer’s disease (AD) pathogenesis is associated with amyloid-β (Aβ)-induced neuroinflammation. In AD, the activation of microglia caused by Aβ accumulation is followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necro...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | https://doi.org/10.1186/s12906-022-03591-4 |
| _version_ | 1818147410228019200 |
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| author | Nutchareeporn Nillert Chantana Boonyarat Jariya Umka Welbat Komsun Bunreungthong Ploenthip Puthongking Wanassanun Pannangrong |
| author_facet | Nutchareeporn Nillert Chantana Boonyarat Jariya Umka Welbat Komsun Bunreungthong Ploenthip Puthongking Wanassanun Pannangrong |
| author_sort | Nutchareeporn Nillert |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) pathogenesis is associated with amyloid-β (Aβ)-induced neuroinflammation. In AD, the activation of microglia caused by Aβ accumulation is followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), and ultimately leads to cognitive impairments. Clausena harmandiana (CH) is a medicinal plant in the Rutaceae family and has been used in folk medicine to relieve illnesses such as stomachache and headache, and as a health tonic. Interestingly, CH root extract (CHRE) has several anti-inflammatory and other pharmacological activities, but there are no studies in AD-like animal models. Objectives This study aims to evaluate the effects of CHRE on cognitive impairments, increased Aβ1–42 protein levels, and neuroinflammation in Aβ1–42-induced rats. Methods Forty-eight adult male Sprague-Dawley rats (250–300 g) were randomly divided into 6 groups (n = 8) of the sham control, V + Aβ, CB + Aβ CHRE125 + Aβ, CHRE250 + Aβ, and CHRE500 + Aβ. Sodium carboxymethylcellulose, Celebrex (10 mg/kg BW) and CHRE (125, 250, and 500 mg/kg BW) were given orally or without any treatment for 35 days. On day 21, aggregated Aβ1–42 at a concentration of 1 μg/μl were injected into both lateral ventricles (1 μl/side) of all treated rats, while sterilized normal saline were injected to untreated rats. Ten days later, the novel object recognition test was performed to assess their recognition memory. At the end of the test period, an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution were used to euthanize all rats. Then Aβ1–42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) were investigated in the cerebral cortex and hippocampus. Results Pretreatment with CHRE at all doses could attenuate short- and long-term impairments in recognition memory. Additionally, CHRE also inhibited the increase of Aβ1–42 protein levels and the expression of inflammatory markers in both brain regions as well as receiving Celebrex. Conclusions This suggests that preventive treatment of CHRE might be a potential therapy against cognitive impairments via reducing Aβ1–42 protein levels and neuroinflammation caused by Aβ1–42. |
| first_indexed | 2024-12-11T12:34:48Z |
| format | Article |
| id | doaj.art-4bbc8ba257a7477f932b486efd208f42 |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-12-11T12:34:48Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-4bbc8ba257a7477f932b486efd208f422022-12-22T01:07:09ZengBMCBMC Complementary Medicine and Therapies2662-76712022-04-0122111210.1186/s12906-022-03591-4Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced ratsNutchareeporn Nillert0Chantana Boonyarat1Jariya Umka Welbat2Komsun Bunreungthong3Ploenthip Puthongking4Wanassanun Pannangrong5Department of Anatomy, Faculty of Medicine, Khon Kaen UniversityFaculty of Pharmaceutical Sciences, Khon Kaen UniversityDepartment of Anatomy, Faculty of Medicine, Khon Kaen UniversityDepartment of Anatomy, Faculty of Medicine, Khon Kaen UniversityFaculty of Pharmaceutical Sciences, Khon Kaen UniversityDepartment of Anatomy, Faculty of Medicine, Khon Kaen UniversityAbstract Background Alzheimer’s disease (AD) pathogenesis is associated with amyloid-β (Aβ)-induced neuroinflammation. In AD, the activation of microglia caused by Aβ accumulation is followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), and ultimately leads to cognitive impairments. Clausena harmandiana (CH) is a medicinal plant in the Rutaceae family and has been used in folk medicine to relieve illnesses such as stomachache and headache, and as a health tonic. Interestingly, CH root extract (CHRE) has several anti-inflammatory and other pharmacological activities, but there are no studies in AD-like animal models. Objectives This study aims to evaluate the effects of CHRE on cognitive impairments, increased Aβ1–42 protein levels, and neuroinflammation in Aβ1–42-induced rats. Methods Forty-eight adult male Sprague-Dawley rats (250–300 g) were randomly divided into 6 groups (n = 8) of the sham control, V + Aβ, CB + Aβ CHRE125 + Aβ, CHRE250 + Aβ, and CHRE500 + Aβ. Sodium carboxymethylcellulose, Celebrex (10 mg/kg BW) and CHRE (125, 250, and 500 mg/kg BW) were given orally or without any treatment for 35 days. On day 21, aggregated Aβ1–42 at a concentration of 1 μg/μl were injected into both lateral ventricles (1 μl/side) of all treated rats, while sterilized normal saline were injected to untreated rats. Ten days later, the novel object recognition test was performed to assess their recognition memory. At the end of the test period, an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution were used to euthanize all rats. Then Aβ1–42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) were investigated in the cerebral cortex and hippocampus. Results Pretreatment with CHRE at all doses could attenuate short- and long-term impairments in recognition memory. Additionally, CHRE also inhibited the increase of Aβ1–42 protein levels and the expression of inflammatory markers in both brain regions as well as receiving Celebrex. Conclusions This suggests that preventive treatment of CHRE might be a potential therapy against cognitive impairments via reducing Aβ1–42 protein levels and neuroinflammation caused by Aβ1–42.https://doi.org/10.1186/s12906-022-03591-4Clausena harmandianaAlzheimer’s diseaseAmyloid-βNeuroinflammationRecognition memory |
| spellingShingle | Nutchareeporn Nillert Chantana Boonyarat Jariya Umka Welbat Komsun Bunreungthong Ploenthip Puthongking Wanassanun Pannangrong Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats BMC Complementary Medicine and Therapies Clausena harmandiana Alzheimer’s disease Amyloid-β Neuroinflammation Recognition memory |
| title | Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats |
| title_full | Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats |
| title_fullStr | Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats |
| title_full_unstemmed | Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats |
| title_short | Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats |
| title_sort | clausena harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in aβ1 42 induced rats |
| topic | Clausena harmandiana Alzheimer’s disease Amyloid-β Neuroinflammation Recognition memory |
| url | https://doi.org/10.1186/s12906-022-03591-4 |
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