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Protection by rhynchophylline against MPTP/MPP+-induced neurotoxicity via regulating PI3K/Akt pathway.
J Ethnopharmacol. 2021 Mar 25; 268:113568.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Isolated from Uncaria rhynchophylla (U. rhynchophylla), rhynchophylline (Rhy) has been applied for treating diseases related to central nervous system such as Parkinson's disease. Nevertheless, the molecular mechanism of the neuroprotective effect has not been well interpreted.

AIM OF THE STUDY

To investigate the effects of Rhy on MPTP/MPP + -induced neurotoxicity in C57BL/6 mice or PC12 cells and study the mechanisms involved.

MATERIALS AND METHODS

The neuroprotective effect of Rhy on MPTP-induced neurotoxicity was evaluated by spontaneous motor activity test, as well as a test of rota-rod on a rat model of Parkinson's disease. The numbers of TH-positive neurons in the substantia nigra pars compacta (SNpc) was assessed by immunohistological. CCK-8, lactate dehydrogenase (LDH), reactive oxygen species (ROS), the concentration of intracellular calcium ([Ca2+]i) and flow cytometry analysis were performed to evaluate the pharmacological property of Rhy on 1-methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in PC12 cells. Besides, LY294002, a PI3K inhibitor was employed to determine the underlying molecular signaling pathway revealing the effect of Rhy by western-blot analysis.

RESULTS

The results showed that Rhy exhibited a protective effect against the MPTP-induced decrease in tyrosine hydroxylase (TH)-positive fibers in the substantia nigra at 30 mg/kg, demonstrated by the immunohistological and behavioral outcomes. Furthermore, it has been indicated that cell viability was improved and the MPP+-induced apoptosis was inhibited after the treatment of Rhy at 20 μM, which were severally analyzed by the CCK-8 and the Annexin V/propidium iodide staining method. In addition, Rhy treatment attenuated MPP+-induced up-regulation of LDH, ([Ca2+]i), and the levels of ROS. Besides, it can be revealed from the Western blot assay that LY294002, as a selective Phosphatidylinositol 3-Kinase (PI3K) inhibitor, effectively inhibited the Akt phosphorylation caused by Rhy, which suggested that Rhy showed its protective property through the activated the PI3K/Akt signaling pathway. Moreover, the Rhy-induced decreases of Bax and caspase-3 as the proapoptotic markers and the increase of Bcl-2 as the antiapoptotic marker, were blocked by LY294002 in the MPP+-treated PC12 cells.

CONCLUSIONS

Rhy exerts a neuroprotective effect is partly mediated by activating the PI3K/Akt signaling pathway.

Authors+Show Affiliations

The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: meizhuzheng@mail.cncnc.edu.cn.College of Life Science, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: minghuichen@mail.cncnc.edu.cn.College of Life Science, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: wenliwang@mail.cncnc.edu.cn.College of Life Science, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: mizhou@mail.cncnc.edu.cn.The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: zhengmz605@mail.cncnc.edu.cn.College of Life Science, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: yajunfan@mail.cncnc.edu.cn.The Central Laboratory, Changchun Normal University, Changchun, Jilin, PR China. Electronic address: dongfangshi@mail.cncnc.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33188898

Citation

Zheng, Meizhu, et al. "Protection By Rhynchophylline Against MPTP/MPP+-induced Neurotoxicity Via Regulating PI3K/Akt Pathway." Journal of Ethnopharmacology, vol. 268, 2021, p. 113568.
Zheng M, Chen M, Wang W, et al. Protection by rhynchophylline against MPTP/MPP+-induced neurotoxicity via regulating PI3K/Akt pathway. J Ethnopharmacol. 2021;268:113568.
Zheng, M., Chen, M., Wang, W., Zhou, M., Liu, C., Fan, Y., & Shi, D. (2021). Protection by rhynchophylline against MPTP/MPP+-induced neurotoxicity via regulating PI3K/Akt pathway. Journal of Ethnopharmacology, 268, 113568. https://doi.org/10.1016/j.jep.2020.113568
Zheng M, et al. Protection By Rhynchophylline Against MPTP/MPP+-induced Neurotoxicity Via Regulating PI3K/Akt Pathway. J Ethnopharmacol. 2021 Mar 25;268:113568. PubMed PMID: 33188898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection by rhynchophylline against MPTP/MPP+-induced neurotoxicity via regulating PI3K/Akt pathway. AU - Zheng,Meizhu, AU - Chen,Minghui, AU - Wang,Wenli, AU - Zhou,Mi, AU - Liu,Chunming, AU - Fan,Yajun, AU - Shi,Dongfang, Y1 - 2020/11/11/ PY - 2020/10/09/received PY - 2020/11/03/revised PY - 2020/11/03/accepted PY - 2020/11/15/pubmed PY - 2021/3/11/medline PY - 2020/11/14/entrez KW - MPP(+) KW - MPTP KW - Parkinson's disease KW - Phosphoinositide 3-kinase/Akt signaling pathway KW - Rhynchophylline SP - 113568 EP - 113568 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 268 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Isolated from Uncaria rhynchophylla (U. rhynchophylla), rhynchophylline (Rhy) has been applied for treating diseases related to central nervous system such as Parkinson's disease. Nevertheless, the molecular mechanism of the neuroprotective effect has not been well interpreted. AIM OF THE STUDY: To investigate the effects of Rhy on MPTP/MPP + -induced neurotoxicity in C57BL/6 mice or PC12 cells and study the mechanisms involved. MATERIALS AND METHODS: The neuroprotective effect of Rhy on MPTP-induced neurotoxicity was evaluated by spontaneous motor activity test, as well as a test of rota-rod on a rat model of Parkinson's disease. The numbers of TH-positive neurons in the substantia nigra pars compacta (SNpc) was assessed by immunohistological. CCK-8, lactate dehydrogenase (LDH), reactive oxygen species (ROS), the concentration of intracellular calcium ([Ca2+]i) and flow cytometry analysis were performed to evaluate the pharmacological property of Rhy on 1-methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in PC12 cells. Besides, LY294002, a PI3K inhibitor was employed to determine the underlying molecular signaling pathway revealing the effect of Rhy by western-blot analysis. RESULTS: The results showed that Rhy exhibited a protective effect against the MPTP-induced decrease in tyrosine hydroxylase (TH)-positive fibers in the substantia nigra at 30 mg/kg, demonstrated by the immunohistological and behavioral outcomes. Furthermore, it has been indicated that cell viability was improved and the MPP+-induced apoptosis was inhibited after the treatment of Rhy at 20 μM, which were severally analyzed by the CCK-8 and the Annexin V/propidium iodide staining method. In addition, Rhy treatment attenuated MPP+-induced up-regulation of LDH, ([Ca2+]i), and the levels of ROS. Besides, it can be revealed from the Western blot assay that LY294002, as a selective Phosphatidylinositol 3-Kinase (PI3K) inhibitor, effectively inhibited the Akt phosphorylation caused by Rhy, which suggested that Rhy showed its protective property through the activated the PI3K/Akt signaling pathway. Moreover, the Rhy-induced decreases of Bax and caspase-3 as the proapoptotic markers and the increase of Bcl-2 as the antiapoptotic marker, were blocked by LY294002 in the MPP+-treated PC12 cells. CONCLUSIONS: Rhy exerts a neuroprotective effect is partly mediated by activating the PI3K/Akt signaling pathway. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/33188898/Protection_by_rhynchophylline_against_MPTP/MPP+_induced_neurotoxicity_via_regulating_PI3K/Akt_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(20)33456-5 DB - PRIME DP - Unbound Medicine ER -