The protective mechanism of action of plantamajoside on a rat model of acute spinal cord injury

Hu,Hua; Jian,Xiaofei

doi:10.3892/etm.2021.9809

The protective mechanism of action of plantamajoside on a rat model of acute spinal cord injury

Authors:
- Hua Hu
- Xiaofei Jian
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Affiliations: Department of Orthopedics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Jiangan, Wuhan, Hubei 430014, P.R. China
Published online on: February 19, 2021 https://doi.org/10.3892/etm.2021.9809
Article Number: 378
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute spinal cord injury (ASCI) is a severe traumatic disease of the central nervous system, characterized by a high incidence and high morbidity, for which there are no effective drug therapies in the clinic. A rat model of ASCI was established to study the effects of plantamajoside (PMS) treatment on the expression of apoptotic factors, including caspase‑3, caspase‑9, poly (ADP‑ribose) polymerase (PARP), Bax and Bcl‑2. The Allen's weight hit rat ASCI model was used for the present study, and the rats were treated with various concentrations of PMS. The behavior of rats was assessed using the Basso‑Beattle‑Bresnahan locomotor rating scale (BBB), the histopathologic changes of spinal cord tissue were observed by hematoxylin and eosin staining, the survival of neurons was assessed by TUNEL staining and the expression levels of apoptotic proteins such as caspase‑3, caspase‑9, PARP, Bcl‑2 and Bax was measured using western blot assays and RT‑qPCR. It was observed that PMS could reverse the decrease in the BBB score after ASCI, improve the morphological characteristics of the spinal cord, reduce the degree apoptosis and affect the expression of caspase‑3, caspase‑9, PARP, Bax and Bcl‑2 in a concentration dependent manner. In conclusion, PMS protected ASCI rats by inhibiting apoptosis; therefore PMS may be a potential candidate for ASCI therapy.

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1	Guan B, Chen R, Zhong M, Liu N and Chen Q: Protective effect of Oxymatrine against acute spinal cord injury in rats via modulating oxidative stress, inflammation and apoptosis. Metab Brain Dis. 35:149–157. 2020.PubMed/NCBI View Article : Google Scholar
2	Witiw CD and Fehlings MG: Acute spinal cord injury. J Spinal Disord Tech. 28:202–210. 2015.PubMed/NCBI View Article : Google Scholar
3	Hu W, Wang H, Liu Z, Liu Y, Wang R, Luo X and Huang Y: Neuroprotective effects of lycopene in spinal cord injury in rats via antioxidative and anti-apoptotic pathway. Neurosci Lett. 642:107–112. 2017.PubMed/NCBI View Article : Google Scholar
4	Chamberlain JD, Meier S, Mader L, von Groote PM and Brinkhof MWG: Mortality and longevity after a spinal cord injury: Systematic review and meta-analysis. Neuroepidemiology. 44:182–198. 2015.PubMed/NCBI View Article : Google Scholar
5	Rouanet C, Reges D, Rocha E, Gagliardi V and Silva GS: Traumatic spinal cord injury: Current concepts and treatment update. Arq Neuropsiquiatr. 75:387–393. 2017.PubMed/NCBI View Article : Google Scholar
6	Zhong ZX, Feng SS, Chen SZ, Chen ZM and Chen XW: Inhibition of MSK1 promotes inflammation and apoptosis and inhibits functional recovery after spinal cord injury. J Mol Neurosci. 68:191–203. 2019.PubMed/NCBI View Article : Google Scholar
7	Varma AK, Das A, Wallace G IV, Barry J, Vertegel AA, Ray SK and Banik NL: Spinal cord injury: A review of current therapy, future treatments, and basic science frontiers. Neurochem Res. 38:895–905. 2013.PubMed/NCBI View Article : Google Scholar
8	Luo Y, Fu C, Wang Z, Zhang Z, Wang H and Liu Y: Mangiferin attenuates contusive spinal cord injury in rats through the regulation of oxidative stress, inflammation and the Bcl-2 and Bax pathway. Mol Med Rep. 12:7132–7138. 2015.PubMed/NCBI View Article : Google Scholar
9	Li Y, Gan L, Li GQ, Deng L, Zhang X and Deng Y: Pharmacokinetics of plantamajoside and acteoside from Plantago asiatica in rats by liquid chromatography-mass spectrometry. J Pharm Biomed Anal. 89:251–256. 2014.PubMed/NCBI View Article : Google Scholar
10	Son WR, Nam MH, Hong CO, Kim Y and Lee KW: Plantamajoside from Plantago asiatica modulates human umbilical vein endothelial cell dysfunction by glyceraldehyde-induced AGEs via MAPK/NF-κB. BMC Complement Altern Med. 17(66)2017.PubMed/NCBI View Article : Google Scholar
11	Wu H, Zhao G, Jiang K, Chen X, Zhu Z, Qiu C, Li C and Deng G: Plantamajoside ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation. Int Immunopharmacol. 35:315–322. 2016.PubMed/NCBI View Article : Google Scholar
12	Ma C and Ma W: Plantamajoside inhibits lipopolysaccharide-induced MUC5AC expression and inflammation through suppressing the PI3K/Akt and NF-κB signaling pathways in human airway epithelial cells. Inflammation. 41:795–802. 2018.PubMed/NCBI View Article : Google Scholar
13	Pei S, Yang X, Wang H, Zhang H, Zhou B, Zhang D and Lin D: Plantamajoside, a potential anti-tumor herbal medicine inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of matrix metalloproteinase-9 and -2. BMC Cancer. 15(965)2015.PubMed/NCBI View Article : Google Scholar
14	Liu F, Huang X, He JJ, Song C, Peng L, Chen T and Wu BL: Plantamajoside attenuates inflammatory response in LPS-stimulated human gingival fibroblasts by inhibiting PI3K/AKT signaling pathway. Microb Pathog. 127:208–211. 2019.PubMed/NCBI View Article : Google Scholar
15	Yin WZ, Xu J, Li C, Dai XK, Wu T and Wen JF: Plantamajoside inhibits the proliferation and epithelial-to-mesenchymal transition in hepatocellular carcinoma cells via modulating hypoxia-inducible factor-1α-dependent gene expression. Cell Biol Int. 44:1616–1627. 2020.PubMed/NCBI View Article : Google Scholar
16	Wang Y and Yan D: Plantamajoside exerts antifibrosis effects in the liver by inhibiting hepatic stellate cell activation. Exp Ther Med. 18:2421–2428. 2019.PubMed/NCBI View Article : Google Scholar
17	Li Y, Gu R, Zhu Q and Liu J: Changes of spinal edema and expression of aquaporin 4 in methylprednisolone-treated rats with spinal cord injury. Ann Clin Lab Sci. 48:453–459. 2018.PubMed/NCBI
18	Wang B, Dai W, Shi L, Teng H, Li X, Wang J and Geng W: Neuroprotection by Paeoniflorin against Nuclear Factor Kappa B-Induced Neuroinflammation on Spinal Cord Injury. BioMed Res Int. 2018(9865403)2018.PubMed/NCBI View Article : Google Scholar
19	Yune TY, Lee JY, Jung GY, Kim SJ, Jiang MH, Kim YC, Oh YJ, Markelonis GJ and Oh TH: Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. J Neurosci. 27:7751–7761. 2007.PubMed/NCBI View Article : Google Scholar
20	Basso DM, Beattie MS and Bresnahan JC: A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 12:1–21. 1995.PubMed/NCBI View Article : Google Scholar
21	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
22	Oyinbo CA: Secondary injury mechanisms in traumatic spinal cord injury: A nugget of this multiply cascade. Acta Neurobiol Exp (Wars). 71:281–299. 2011.PubMed/NCBI
23	Tator CH and Benzel EC (eds): Contemporary Management of Spinal Cord Injury: From Impact to Rehabilitation. Thieme for the American Association of Neurological Surgeons, Illinois, 2000.
24	Dumont RJ, Okonkwo DO, Verma S, Hurlbert RJ, Boulos PT, Ellegala DB and Dumont AS: Acute spinal cord injury, part I: Pathophysiologic mechanisms. Clin Neuropharmacol. 24:254–264. 2001.PubMed/NCBI View Article : Google Scholar
25	Jin X and Yamashita T: Microglia in central nervous system repair after injury. J Biochem. 159:491–496. 2016.PubMed/NCBI View Article : Google Scholar
26	Hall ED, Wang JA, Bosken JM and Singh IN: Lipid peroxidation in brain or spinal cord mitochondria after injury. J Bioenerg Biomembr. 48:169–174. 2016.PubMed/NCBI View Article : Google Scholar
27	Li G, Shen F, Fan Z, Wang Y, Kong X, Yu D, Zhi X, Lv G and Cao Y: Dynasore improves motor function recovery via inhibition of neuronal apoptosis and astrocytic proliferation after spinal cord injury in rats. Mol Neurobiol. 54:7471–7482. 2017.PubMed/NCBI View Article : Google Scholar
28	Schwartz M and Hauben E: T cell-based therapeutic vaccination for spinal cord injury. Prog Brain Res. 137:401–406. 2002.PubMed/NCBI View Article : Google Scholar
29	Young W: Spinal cord contusion models. Prog Brain Res. 137:231–255. 2002.PubMed/NCBI View Article : Google Scholar
30	Han AR, Nam MH and Lee KW: Plantamajoside inhibits UVB and advanced glycation end products-induced MMP-1 expression by suppressing the MAPK and NF-κB pathways in HaCaT cells. Photochem Photobiol. 92:708–719. 2016.PubMed/NCBI View Article : Google Scholar
31	Jung HY, Seo DW, Hong CO, Kim JY, Yang SY and Lee KW: Nephroprotection of plantamajoside in rats treated with cadmium. Environ Toxicol Pharmacol. 39:125–136. 2015.PubMed/NCBI View Article : Google Scholar
32	Ravn HW, Mondolot L, Kelly MT and Lykke AM: Plantamajoside-A current review. Phytochem Lett. 12:42–53. 2015.
33	Xiao D, Yang R, Gong L, Zhang Y, Xie Y and Ni S: Plantamajoside inhibits high glucose-induced oxidative stress, inflammation, and extracellular matrix accumulation in rat glomerular mesangial cells through the inactivation of Akt/NF-κB pathway. J Recept Signal Transduct Res: doi.org/10.1080/10799893.2020.1784939.
34	Wang C, Zhang L, Ndong JC, Hettinghouse A, Sun G, Chen C, Zhang C, Liu R and Liu CJ: Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice. J Neuroinflammation. 16(238)2019.PubMed/NCBI View Article : Google Scholar
35	Thompson CB: Apoptosis in the pathogenesis and treatment of disease. Science. 267:1456–1462. 1995.PubMed/NCBI View Article : Google Scholar
36	Lu X, Xue P, Fu L, Zhang J, Jiang J, Guo X, Bao G, Xu G, Sun Y, Chen J, et al: HAX1 is associated with neuronal apoptosis and astrocyte proliferation after spinal cord injury. Tissue Cell. 54:1–9. 2018.PubMed/NCBI View Article : Google Scholar
37	Zhang J, Cui Z, Shen A, Li W, Xu G, Bao G, Sun Y, Wang L, Gu H, Zhou Y, et al: Upregulation of myelin and lymphocyte protein (MAL) after traumatic spinal cord injury in rats. J Mol Histol. 44:125–134. 2013.PubMed/NCBI View Article : Google Scholar
38	Timmins JM, Ozcan L, Seimon TA, Li G, Malagelada C, Backs J, Backs T, Bassel-Duby R, Olson EN, Anderson ME, et al: Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J Clin Invest. 119:2925–2941. 2009.PubMed/NCBI View Article : Google Scholar
39	Lan WB, Lin JH, Chen XW, Wu CY, Zhong GX, Zhang LQ, Lin WP, Liu WN, Li X and Lin JL: Overexpressing neuroglobin improves functional recovery by inhibiting neuronal apoptosis after spinal cord injury. Brain Res. 1562:100–108. 2014.PubMed/NCBI View Article : Google Scholar
40	Edlich F: BCL-2 proteins and apoptosis: Recent insights and unknowns. Biochem Biophys Res Commun. 500:26–34. 2018.PubMed/NCBI View Article : Google Scholar
41	Tang P, Hou H and Zhang L, Lan X, Mao Z, Liu D, He C, Du H and Zhang L: Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats. Mol Neurobiol. 49:276–287. 2014.PubMed/NCBI View Article : Google Scholar
42	Hou Q, Cymbalyuk E, Hsu SC, Xu M and Hsu YT: Apoptosis modulatory activities of transiently expressed Bcl-2: Roles in cytochrome C release and Bax regulation. Apoptosis. 8:617–629. 2003.PubMed/NCBI View Article : Google Scholar
43	Ying X, Tu W, Li S, Wu Q, Chen X, Zhou Y, Hu J, Yang G and Jiang S: Hyperbaric oxygen therapy reduces apoptosis and dendritic/synaptic degeneration via the BDNF/TrkB signaling pathways in SCI rats. Life Sci. 229:187–199. 2019.PubMed/NCBI View Article : Google Scholar
44	Mueller THJ, Kienle K, Beham A, Geissler EK, Jauch KW and Rentsch M: Caspase 3 inhibition improves survival and reduces early graft injury after ischemia and reperfusion in rat liver transplantation. Transplantation. 78:1267–1273. 2004.PubMed/NCBI View Article : Google Scholar
45	Yuan B, Pan S and Zhang WW: Effects of gangliosides on expressions of caspase-3 and NGF in rats with acute spinal cord injury. Eur Rev Med Pharmacol Sci. 21:5843–5849. 2017.PubMed/NCBI View Article : Google Scholar
46	Yuan B, Pan S and Zhang WW: Effects of gangliosides on expressions of caspase-3 and NGF in rats with acute spinal cord injury. Eur Rev Med Pharmacol Sci. 21:5843–5849. 2017.PubMed/NCBI View Article : Google Scholar
47	Yamasaki K, Setoguchi T, Takenouchi T, Yone K and Komiya S: Stem cell factor prevents neuronal cell apoptosis after acute spinal cord injury. Spine. 34:323–327. 2009.PubMed/NCBI View Article : Google Scholar
48	Decker P and Muller S: Modulating poly (ADP-ribose) polymerase activity: Potential for the prevention and therapy of pathogenic situations involving DNA damage and oxidative stress. Curr Pharm Biotechnol. 3:275–283. 2002.PubMed/NCBI View Article : Google Scholar