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Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells

Author(s): Elaine Wan Ling Chan*, Emilia Tze Ying Yeo, Kelly Wang Ling Wong, Mun Ling See, Ka Yan Wong and Sook Yee Gan

Volume 16, Issue 3, 2019

Page: [251 - 260] Pages: 10

DOI: 10.2174/1567205016666190228124630

Price: $65

Abstract

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments.

Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators.

Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay.

Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators.

Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).

Keywords: Piper sarmentosum, Alzheimer's disease, inflammation, microglia, neuroprotection, cytokines.

« Previous Next »
[1]
Zhang F, Jiang L. Neuroinflammation in Alzheimer’s disease. Neuropsychiatr Dis Treat 11: 243-56. (2015)
[2]
Spires-Jones TL, Hyman BT. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 82: 756-71. (2014)
[3]
Krause DL, Muller N. Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer’s disease. Int J Alzheimers Dis 732806. (2010).
[4]
Mandrekar S, Landreth GE. Microglia and inflammation in Alzheimer’s disease. CN. Neurol Disord Drug Targets 9: 156-67. (2010)
[5]
Minter MR, Taylor JM, Crack PJ. The contribution of neuroinflammation to amyloid toxicity in Alzheimer’s disease. J Neurochem 136: 457-74. (2016)
[6]
Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 3: 136. (2015)
[7]
Zakaria Z, Patahuddin H, Mohamad A, Israf D, Sulaiman M. In vivo anti-nociceptive and anti-inflammatory activities of the aqueous extract of the leaves of Piper sarmentosum. J Ethnopharmacol 128: 42-8. (2010)
[8]
Khan M, Elhussein S, Khan MM, Khan N. Anti-acetylcholinesterase activity of Piper sarmentosum by a continuous immobilised-enzyme assay. APCBEE Procedia 2: 199-204. (2012)
[9]
Hussain K, Hashmi FK, Latif A, Ismail Z, Sadikun A. A review of the literature and latest advances in research of Piper sarmentosum. Pharm Biol 20: 1045-52. (2012)
[10]
Li Q, Qu FL, Gao Y, Jiang YP, Rahman K, Lee KH, et al. Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity. J Ethnopharmacol 199: 9-19. (2017)
[11]
Ugusman A, Zakaria Z, Hui CK, Nordin NAMM. Piper sarmentosum increases nitric oxide production in oxidative stress: A study on human umbilical vein endothelial cells. Clinics 65: 709-14. (2010)
[12]
Hafizah A, Zaiton Z, Zulkhairi A, Ilham MA, Anita M, Zaleha A. Piper sarmentosum as an antioxidant on oxidative stress in human umbilical vein endothecial cells induced by hydrogen peroxide. J Zhejiang Univ Sci B 11: 357-65. (2010)
[13]
Stohr JR, Xiao PG, Bauer R. Constituents of Chinese Piper species and their inhibitory activity on prostaglandin and leukotriene biosynthesis in vitro. J Ethnopharmacol 75: 133-9. (2001)
[14]
Sireeratawong S, Vannasiri S, Sritiwong S, Itharat A, Jaijoy K. Anti-inflammatory, anti-nociceptive and antipyretic effects of the ethanol extract from root of Piper sarmentosum Roxb. J Med Assoc Thai 93(Supplement. 7): S1-6. (2010)
[15]
Chromy BA, Nowak RJ, Lambert MP, Viola KI, Chang I, Velasco PT, et al. Self-assembly of Aβ1-42 into globular neurotoxins. Biochemistry 42: 12749-60. (2003)
[16]
Lester GE, Lewers KS, Medina MB, Saftner RA. Comparative analysis of strawberry total phenolics via fast blue vs. folin-ciocalteu assay: Interference by ascorbic acid. J Food Compos Anal 27: 102-7. (2012)
[17]
Kamiloglu S, Pasli A, Ozcelik B, Van Camp J, Capanoglu E. Colout retention, anthocyanin stability and antioxidant capacity in black carrot (Daucus carota) jams and marmalades: effect of processing, storage conditions and in vitro gastrointestinal digestion. J Funct Foods 13: 1-10. (2015)
[18]
Bachstetter AD, Xing B, Almeida LD, Dimayuga ER, Watterson DM, Van Eldik LJ. Microglial p38α MAPK is a key regulator of proinflammatory cytokine up-regulation induced by toll-like receptor (TLR) ligands or beta amyloid (Aβ). J Neuroinflammation 8: 79. (2011)
[19]
Perry VH, James AR, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol 6: 193-201. (2010)
[20]
Asiimwe N, Yeo SG, Kim MS, Jung JY, Jeong NY. Nitric oxide: Exploring the contextual link with Alzheimer’s Disease. Oxid Med Cell Longev 7205747 (2016)
[http://dx.doi.org/10.1155/2016/7205747]
[21]
Sayre L, Perry G, Smith M. Oxidative stress and neurotoxicity. Chem Res Toxicol 21: 172-88. (2008)
[22]
Olmos G, Llado J. Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity. Mediators Inflamm (2014)
[http://dx.doi.org/10.1155/2014/861231]
[23]
Zheng C, Zhou X, Wang J. The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TNF-β and IFN-γ. Transl Neurodegener 5: 7. (2016)
[24]
He FQ, Qiu BY, Li TK, et al. Tetrandrine suppresses amyloid-β-induced inflammatory cytokines by inhibiting NF-κB pathway in murine BV2 microglial cells. Int Immunopharmacol 11: 1220-5. (2011)
[25]
Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev 22: 189-95. (2011)
[26]
Parajuli R, Sonobe Y, Horiuchi H, Takeuchi H, Mizuno T, Suzumura A. Oligomeric amyloid β induces IL-1β processing via production of ROS: implication in Alzheimer’s disease. Cell Death Dis 4: e975. (2013)
[27]
Bachstetter AD, Van Eldik LJ. The p38 MAP kinase family as regulators of proinflammatory cytokine production in degenerative diseases of the CNS. Aging Dis 3: 199-211. (2010)
[28]
Lee JK, Kim N. Recent advances in the inhibition of p38 MAPK as a potential strategy for the treatment of Alzheimer’s disease. Molecules 22: 1287. (2017)
[29]
Alam JJ. Selective brain-targeted antagonism of p38 MAPKα reduces hippocampal IL-1β levels and improves morris water maze performance in aged rats. J Alzheimers Dis 48: 219-7. (2015)
[30]
Awah FM, Verla AW. Antioxidant activity, nitric oxide scavenging activity and phenolic contents of Ocimum gratissimum leaf extract. J Med Plants Res 24: 2479-87. (2010)
[31]
Boora F, Chirisa E, Mukanganyama S. Evaluation of nitrite radical scavenging properties of selected Zimbabwean plant extracts and their phytoconstituents. J Food Process 918018 (2014)
[http://dx.doi.org/10.1155/2014/918018]
[32]
Nimse SB, Pal D. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv 5: 27986-8006. (2015)
[33]
Rukachaisirikul T, Siriwattanakit P, Sukcharoenphol K, Wongvein C, Ruttanaweang P, Wongwattanavuch P, et al. Chemical constituents and bioactivity of Piper sarmentosum. J Ethnopharmacol 93: 173-6. (2004)
[34]
Hussain K, Ismail Z, Sadikum A, Ibrahim P. Standardisation and in vivo antioxidant activity of ethanol extracts of fruit and leaf of Piper sarmentosum. Planta Med 76: 418-25. (2010)
[35]
Tuntiwachwuttikul P, Phansa P, Pootaeng-On Y, Taylor WC. Chemical constituents of the roots of Piper sarmentosum. Chem Pharm Bull 54: 149-51. (2006)
[36]
Aldini R, Micucci M, Cevenini M, Fato R, Bergamini B, Nanni C, et al. Antiinflammatory effect of phytosterols in experimental murine colitis model: Prevention, induction, remission study. Plos One 9: e108112. (2014)
[37]
Ugusman A, Zakaria Z, Hui CK, Nordin NAMM, Zaleha AM. Flavonoids of Piper sarmentosum and its cytoprotective effects against oxidative stress. EXCLI 11: 705-14. (2012)
[38]
Yeo ETY, Wong KWL, See ML, Wong K, Gan SY, Chan WLE. Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflamation and attenuates tau hyperphosphorylation in SH-SY5Y cells. J Ethnopharmacol 217: 187-94. (2018)

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