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Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function

  • Authors:
    • Wenbo Fan
    • Jianwu Zhou
  • View Affiliations / Copyright

    Affiliations: Pharmaceutical Technology Department, Chemical Engineering School, Jiuquan Vocational Technical College, Jiuquan, Gansu 735000, P.R. China, Medical Laboratory of Qinghai Provincial People's Hospital, Xining, Qinghai 810000, P.R. China
    Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 40
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    Published online on: November 28, 2023
       https://doi.org/10.3892/etm.2023.12328
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Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Icariside II (ICS II) is known to confer notable therapeutic effects against a variety of neurodegenerative diseases, such as AD. Therefore, the present study aimed to evaluate the possible effects of ICS II on 1‑methyl‑4‑phenylpyridinium (MPP+)‑induced SK‑N‑SH cell injury, in addition to understanding the underlying mechanism of action. The MPP+‑induced SK‑N‑SH cell model was used to simulate PD in vitro. The viability and mitochondrial membrane potential of SK‑N‑SH cells were detected by MTT assay and JC‑1 staining, respectively. Lactate dehydrogenase (LDH) release, ATP levels and complex I activity in treated SK‑N‑SH cells were measured using LDH activity, ATP and Complex I assay kits, respectively. The protein expression levels of histone deacetylase 2 (HDAC2) and γ‑H2A histone family member X and the copy number of mitochondrial DNA were measured by western blotting or reverse transcription‑quantitative PCR, respectively. Autodock 4.2 was used to predict the molecular docking site of ICS II on HDAC2. The results of the present study demonstrated that ICS II mitigated SK‑N‑SH cytotoxicity induced by MPP+. Specifically, ICS II alleviated DNA damage and restored mitochondrial function in SK‑N‑SH cells treated with MPP+. In addition, ICS II reduced the HDAC2 protein expression levels in MPP+‑induced SK‑N‑SH cells. However, overexpression of HDAC2 reversed the protective effects of ICS II on DNA damage and mitochondrial dysfunction in MPP+‑induced SK‑N‑SH cells. In conclusion, the results of the present study suggest that ICS II can protect dopaminergic neurons from MPP+‑induced neurotoxicity by downregulating HDAC2 expression to restore mitochondrial function.
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1 

Sharma S, Awasthi A and Singh S: Altered gut microbiota and intestinal permeability in Parkinson's disease: Pathological highlight to management. Neurosci Lett. 712(134516)2019.PubMed/NCBI View Article : Google Scholar

2 

Nair AT, Ramachandran V, Joghee NM, Antony S and Ramalingam G: Gut microbiota dysfunction as reliable non-invasive early diagnostic biomarkers in the pathophysiology of Parkinson's disease: A critical review. J Neurogastroenterol Motil. 24:30–42. 2018.PubMed/NCBI View Article : Google Scholar

3 

Xu X, Wang R, Hao Z, Wang G, Mu C, Ding J, Sun W and Ren H: DJ-1 regulates tyrosine hydroxylase expression through CaMKKβ/CaMKIV/CREB1 pathway in vitro and in vivo. J Cell Physiol. 235:869–879. 2020.PubMed/NCBI View Article : Google Scholar

4 

Yin C, Deng Y, Liu Y, Gao J, Yan L and Gong Q: Icariside II ameliorates cognitive impairments induced by chronic cerebral hypoperfusion by inhibiting the amyloidogenic pathway: Involvement of BDNF/TrkB/CREB signaling and up-regulation of PPARα and PPARγ in rats. Front Pharmacol. 9(1211)2018.PubMed/NCBI View Article : Google Scholar

5 

Deng Y, Xiong D, Yin C, Liu B, Shi J and Gong Q: Icariside II protects against cerebral ischemia-reperfusion injury in rats via nuclear factor-κB inhibition and peroxisome proliferator-activated receptor up-regulation. Neurochem Int. 96:56–61. 2016.PubMed/NCBI View Article : Google Scholar

6 

Yan BY, Pan CS, Mao XW, Yang L, Liu YY, Yan L, Mu HN, Wang CS, Sun K, Liao FL, et al: Icariside II improves cerebral microcirculatory disturbance and alleviates hippocampal injury in gerbils after ischemia-reperfusion. Brain Res. 1573:63–73. 2014.PubMed/NCBI View Article : Google Scholar

7 

Yin C, Deng Y, Gao J, Li X, Liu Y and Gong Q: Icariside II, a novel phosphodiesterase-5 inhibitor, attenuates streptozotocin-induced cognitive deficits in rats. Neuroscience. 328:69–79. 2016.PubMed/NCBI View Article : Google Scholar

8 

Deng Y, Long L, Wang K, Zhou J, Zeng L, He L and Gong Q: Icariside II, a broad-spectrum anti-cancer agent, reverses beta-amyloid-induced cognitive impairment through reducing inflammation and apoptosis in rats. Front Pharmacol. 8(39)2017.PubMed/NCBI View Article : Google Scholar

9 

Xiao HH, Chen JC, Li H, Li RH, Wang HB, Song HP, Li HY, Shan GS, Tian Y, Zhao YM, et al: Icarisid II rescues cognitive dysfunction via activation of Wnt/β-catenin signaling pathway promoting hippocampal neurogenesis in APP/PS1 transgenic mice. Phytother Res. 36:2095–2108. 2022.PubMed/NCBI View Article : Google Scholar

10 

Yan L, Deng Y, Gao J, Liu Y, Li F, Shi J and Gong Q: Icariside II effectively reduces spatial learning and memory impairments in Alzheimer's disease model mice targeting beta-amyloid production. Front Pharmacol. 8(106)2017.PubMed/NCBI View Article : Google Scholar

11 

Li Y, Gu Z, Lin S, Chen L, Dzreyan V, Eid M, Demyanenko S and He B: Histone deacetylases as epigenetic targets for treating Parkinson's disease. Brain Sci. 12(672)2022.PubMed/NCBI View Article : Google Scholar

12 

Ma P and Schultz RM: HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation. Cell Death Differ. 23:1119–1127. 2016.PubMed/NCBI View Article : Google Scholar

13 

Stoddard SV, May XA, Rivas F, Dodson K, Vijayan S, Adhika S, Parker K and Watkins DL: Design of potent panobinostat histone deacetylase inhibitor derivatives: Molecular considerations for enhanced isozyme selectivity between HDAC2 and HDAC8. Mol Inform. 38(e1800080)2019.PubMed/NCBI View Article : Google Scholar

14 

Chen J, Li N, Liu B, Ling J, Yang W, Pang X and Li T: Pracinostat (SB939), a histone deacetylase inhibitor, suppresses breast cancer metastasis and growth by inactivating the IL-6/STAT3 signalling pathways. Life Sci. 248(117469)2020.PubMed/NCBI View Article : Google Scholar

15 

Tan Y, Delvaux E, Nolz J, Coleman PD, Chen S and Mastroeni D: Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease. Neurobiol Aging. 68:134–141. 2018.PubMed/NCBI View Article : Google Scholar

16 

Choong CJ, Sasaki T, Hayakawa H, Yasuda T, Baba K, Hirata Y, Uesato S and Mochizuki H: A novel histone deacetylase 1 and 2 isoform-specific inhibitor alleviates experimental Parkinson's disease. Neurobiol Aging. 37:103–116. 2016.PubMed/NCBI View Article : Google Scholar

17 

Singer TP and Ramsay RR: Mechanism of the neurotoxicity of MPTP. An update. FEBS Lett. 274:1–8. 1990.PubMed/NCBI View Article : Google Scholar

18 

Yuan X, Wu Y, Lu L and Feng J: Long noncoding RNA SNHG14 knockdown exerts a neuroprotective role in MPP+-induced Parkinson's disease cell model through mediating miR-135b-5p/KPNA4 axis. Metab Brain Dis. 37:2363–2373. 2022.PubMed/NCBI View Article : Google Scholar

19 

Xu F, Lv C, Deng Y, Liu Y, Gong Q, Shi J and Gao J: Icariside II, a PDE5 inhibitor, suppresses oxygen-glucose deprivation/reperfusion-induced primary hippocampal neuronal death through activating the PKG/CREB/BDNF/TrkB signaling pathway. Front Pharmacol. 11(523)2020.PubMed/NCBI View Article : Google Scholar

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

21 

Halczuk KM, Boguszewska K, Urbaniak SK, Szewczuk M and Karwowski BT: 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a cause of autoimmune thyroid diseases (AITD) during pregnancy? Yale J Biol Med. 93:501–515. 2020.PubMed/NCBI

22 

Perelman A, Wachtel C, Cohen M, Haupt S, Shapiro H and Tzur A: JC-1: Alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis. 3(e430)2012.PubMed/NCBI View Article : Google Scholar

23 

Jiang DQ, Ma YJ, Wang Y, Lu HX, Mao SH and Zhao SH: Microglia activation induces oxidative injury and decreases SIRT3 expression in dopaminergic neuronal cells. J Neural Transm (Vienna). 126:559–568. 2019.PubMed/NCBI View Article : Google Scholar

24 

Harrington JS, Ryter SW, Plataki M, Price DR and Choi AMK: Mitochondria in health, disease, and aging. Physiol Rev. 103:2349–2422. 2023.PubMed/NCBI View Article : Google Scholar

25 

Golpich M, Amini E, Mohamed Z, Azman Ali R, Mohamed Ibrahim N and Ahmadiani A: Mitochondrial dysfunction and biogenesis in neurodegenerative diseases: Pathogenesis and treatment. CNS Neurosci Ther. 23:5–22. 2017.PubMed/NCBI View Article : Google Scholar

26 

Grimm A and Eckert A: Brain aging and neurodegeneration: From a mitochondrial point of view. J Neurochem. 143:418–431. 2017.PubMed/NCBI View Article : Google Scholar

27 

Park JS, Davis RL and Sue CM: Mitochondrial dysfunction in Parkinson's disease: New mechanistic insights and therapeutic perspectives. Curr Neurol Neurosci Rep. 18(21)2018.PubMed/NCBI View Article : Google Scholar

28 

Kim HY, Bae CH, Kim J, Lee Y, Jeon H, Kim H and Kim S: Rumex japonicus houtt. protects dopaminergic neurons by regulating mitochondrial function and gut-brain axis in in vitro and in vivo models of Parkinson's disease. Antioxidants (Basel). 11(141)2022.PubMed/NCBI View Article : Google Scholar

29 

Wu LK, Agarwal S, Kuo CH, Kung YL, Day CH, Lin PY, Lin SZ, Hsieh DJ, Huang CY and Chiang CY: Artemisia leaf extract protects against neuron toxicity by TRPML1 activation and promoting autophagy/mitophagy clearance in both in vitro and in vivo models of MPP+/MPTP-induced Parkinson's disease. Phytomedicine. 104(154250)2022.PubMed/NCBI View Article : Google Scholar

30 

Liu Y, Wang Y, Chen Q, Jiao F, Wang L and Gong Z: HDAC2 inhibitor CAY10683 reduces intestinal epithelial cell apoptosis by inhibiting mitochondrial apoptosis pathway in acute liver failure. Histol Histopathol. 34:1173–1184. 2019.PubMed/NCBI View Article : Google Scholar

31 

Frankowski H, Yeboah F, Berry BJ, Kinoshita C, Lee M, Evitts K, Davis J, Kinoshita Y, Morrison RS and Young JE: Knock-down of HDAC2 in human induced pluripotent stem cell derived neurons improves neuronal mitochondrial dynamics, neuronal maturation and reduces amyloid beta peptides. Int J Mol Sci. 22(2526)2021.PubMed/NCBI View Article : Google Scholar

32 

Li Y, Feng L, Xie D, Lin M, Li Y, Chen N, Yang D, Gao J, Zhu Y and Gong Q: Icariside II, a naturally occurring SIRT3 agonist, protects against myocardial infarction through the AMPK/PGC-1α/apoptosis signaling pathway. Antioxidants (Basel). 11(1465)2022.PubMed/NCBI View Article : Google Scholar

33 

Feng L, Gao J, Liu Y, Shi J and Gong Q: Icariside II alleviates oxygen-glucose deprivation and reoxygenation-induced PC12 cell oxidative injury by activating Nrf2/SIRT3 signaling pathway. Biomed Pharmacother. 103:9–17. 2018.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Fan W and Zhou J: Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function. Exp Ther Med 27: 40, 2024.
APA
Fan, W., & Zhou, J. (2024). Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function. Experimental and Therapeutic Medicine, 27, 40. https://doi.org/10.3892/etm.2023.12328
MLA
Fan, W., Zhou, J."Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function". Experimental and Therapeutic Medicine 27.1 (2024): 40.
Chicago
Fan, W., Zhou, J."Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function". Experimental and Therapeutic Medicine 27, no. 1 (2024): 40. https://doi.org/10.3892/etm.2023.12328
Copy and paste a formatted citation
x
Spandidos Publications style
Fan W and Zhou J: Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function. Exp Ther Med 27: 40, 2024.
APA
Fan, W., & Zhou, J. (2024). Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function. Experimental and Therapeutic Medicine, 27, 40. https://doi.org/10.3892/etm.2023.12328
MLA
Fan, W., Zhou, J."Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function". Experimental and Therapeutic Medicine 27.1 (2024): 40.
Chicago
Fan, W., Zhou, J."Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function". Experimental and Therapeutic Medicine 27, no. 1 (2024): 40. https://doi.org/10.3892/etm.2023.12328
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