Xiao-Wen Jiang1, Wen-Wu Liu2, Yu-Ting Wu3, Qiong Wu3, Hong-Yuan Lu3, Zi-Hua Xu4, Hui-Yuan Gao5, Qing-Chun Zhao6. 1. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110840, People's Republic of China. 2. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. 3. School of Life Sciences, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. 4. Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110840, People's Republic of China. 5. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address: sypugaohy@163.com. 6. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; School of Life Sciences, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110840, People's Republic of China. Electronic address: zhaoqingchun1967@163.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a frequently occurring disease of the elderly, and "deficiency" is the root of AD. Most famous experts of traditional Chinese medicine believe that the disease is based on deficiency, and the deficiency of kidney essence is the basis. Notopterygium incisum (Qiang huo) is beneficial to bladder, liver, and kidneys. It is used to treat liver and kidney deficiency, language difficulties, and mental coma. Qiang huo yu feng tang has been used to treat liver and kidney deficiency, unclear language and mental paralysis in many traditional Chinese medicine books and records. In modern times, it has been used to treat AD and exhibited favourable efficacy. AIM OF THE STUDY: This study attempts to investigate the effects of furocoumarins from Notopterygium incisum (NRE) on the Aβ cascade, tau pathology and inflammatory pathology of AD. MATERIALS AND METHODS: In this study, we reported a detailed protocol for stabilizing HEK APPswe293T cells with lentivirus for the first time. This cell line can secrete high concentration of Aβ. In addition, we treated N2a cells with AKT/PKC specific inhibitors (wortmannin/GF-109203X) and established a tau pathological cell model (AKT/PKC N2a) by activating GSK3β and triggering hyperphosphorylation of tau. The Aβ levels and the expression of phosphorylated tau were detected by ELISA and Western blot. The cognitive ability of NRE on APP/PS1 mice was detected using a Morris water maze (MWM) assay and Aβ contents were also evaluated. RESULTS: In HEK APPswe293T cells, NRE (10, 20, 40 μg/mL) significantly inhibited the secretion and production of Aβ in dose dependent manner. In addition, NRE also suppressed the expression of phosphorylated tau in wortmannin/GF-109203X treated N2a cells. Furthermore, NRE ameliorated the cognitive impairment of APP/PS1 mice, and the contents of Aβ, IL-1β and TNF-α were significantly depressed in hippocampus and cortex. CONCLUSION: In conclusion, our results demonstrated that NRE has a potential anti-AD effect via the inhibition of the Aβ cascade, tau pathology and neuroinflammation in vitro and in vivo.
ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a frequently occurring disease of the elderly, and "deficiency" is the root of AD. Most famous experts of traditional Chinese medicine believe that the disease is based on deficiency, and the deficiency of kidney essence is the basis. Notopterygium incisum (Qiang huo) is beneficial to bladder, liver, and kidneys. It is used to treat liver and kidney deficiency, language difficulties, and mental coma. Qiang huo yu feng tang has been used to treat liver and kidney deficiency, unclear language and mental paralysis in many traditional Chinese medicine books and records. In modern times, it has been used to treat AD and exhibited favourable efficacy. AIM OF THE STUDY: This study attempts to investigate the effects of furocoumarins from Notopterygium incisum (NRE) on the Aβ cascade, tau pathology and inflammatory pathology of AD. MATERIALS AND METHODS: In this study, we reported a detailed protocol for stabilizing HEK APPswe293T cells with lentivirus for the first time. This cell line can secrete high concentration of Aβ. In addition, we treated N2a cells with AKT/PKC specific inhibitors (wortmannin/GF-109203X) and established a tau pathological cell model (AKT/PKC N2a) by activating GSK3β and triggering hyperphosphorylation of tau. The Aβ levels and the expression of phosphorylated tau were detected by ELISA and Western blot. The cognitive ability of NRE on APP/PS1mice was detected using a Morris water maze (MWM) assay and Aβ contents were also evaluated. RESULTS: In HEK APPswe293T cells, NRE (10, 20, 40 μg/mL) significantly inhibited the secretion and production of Aβ in dose dependent manner. In addition, NRE also suppressed the expression of phosphorylated tau in wortmannin/GF-109203X treated N2a cells. Furthermore, NRE ameliorated the cognitive impairment of APP/PS1mice, and the contents of Aβ, IL-1β and TNF-α were significantly depressed in hippocampus and cortex. CONCLUSION: In conclusion, our results demonstrated that NRE has a potential anti-AD effect via the inhibition of the Aβ cascade, tau pathology and neuroinflammation in vitro and in vivo.