Neuroprotective Effect of Bacopa Monnieri Extract on Oxidized Low Density Lipoprotein-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells

Main Article Content

Panit Yamchuen
Narttaya Chaiwiang
Phakhamon Lapphanichayakool
Kornkanok Ingkaninan
Nanteetip Limpeanchob


Oxidized low density lipoprotein (LDL)-mediates neurotoxicity and possibly plays some roles in the pathological process of Alzheimer’s disease (AD). Neuroprotection of Bacapa monerri (L.) Wettst (BM) has been studied in various cells and animal models but not in oxidized LDL-induced toxicity. This study aimed to investigate the neuroprotective effects of BM extract and fourcomponents including three bacoside A; bacopaside I (BA-I), II (Ba-II), and bacoside A3 (Ba-A3), and one flavonoid; luteolin (Lut) in SH-SY5Y neuroblastoma cells. The results demonstrated that BM extract diminished the neurotoxicity of oxidized LDL in a dose dependent manner, potentially by suppression of cellular oxidative stress. Among four tested compounds, Lut exhibited the most effect on preventing the cell injury mediated by oxidized LDL. These compounds also suppressed the increment of cellular acetylcholinesterase (AChE) activity mediated by oxidized LDL, possibly as the consequence of oxidation suppression. These data support the beneficial effect of BM as a neuroprotective agent and this effect is possibly a combined result of its constituents.

Article Details

Research Articles


Reitz C, Mayeux R. Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014;88(4):640-51.

Imtiaz B, Tolppanen AM, Kivipelto M, Soininen H. Future directions in Alzheimer's disease from risk factors to prevention. Biochem Pharmacol. 2014;88(4):661-70.

Dias IHK, Mistry J, Fell S, Reis A, Spickett CM, Polidori MC, et al. Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation. Free Radic Biol Med. 2014;75:48-59.

Marwarha G, Ghribi O. Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease–Parkinson's disease overlap? Exp Gerontol. 2015;68:13-8.

Schippling S, Kontush A, Arlt S, Buhmann C, Stürenburg H-J, Mann U, et al. Increased lipoprotein oxidation in alzheimer’s disease. Free Radic Biol Med. 2000;28(3):351-60.

Papassotiropoulos A, Lütjohann D, Bagli M, Locatelli S, Jessen F, Buschfort R, et al. 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia. J Psychiatr Res. 2002;36(1):27-32.

Kankaanpää J, Turunen SP, Moilanen V, Hörkkö S, Remes AM. Cerebrospinal fluid antibodies to oxidized LDL are increased in Alzheimer's disease. Neurobiol Dis. 2009;33(3):467-72.

Yamchuen P, Aimjongjun S, Limpeanchob N. Oxidized low density lipoprotein increases acetylcholinesterase activity correlating with reactive oxygen species production. Neurochem Int. 2014;78:1-6.

Keller JN, Hanni KB, Markesbery WR. Oxidized low-density lipoprotein induces neuronal death: implications for calcium, reactive oxygen species, and caspases. J Neurochem. 1999;72(6):2601-9.

Nowicki M, Muller K, Serke H, Kosacka J, Vilser C, Ricken A, et al. Oxidized low-density lipoprotein (oxLDL)-induced cell death in dorsal root ganglion cell cultures depends not on the lectin-like oxLDL receptor-1 but on the toll-like receptor-4. J Neurosci Res. 2010;88(2):403-12.

Aguiar S, Borowski T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res. 2013;16(4):313-26.

Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine. 2005;12(4):305-17.

Holcomb LA, Dhanasekaran M, Hitt AR, Young KA, Riggs M, Manyam BV. Bacopa monniera extract reduces amyloid levels in PSAPP mice. J Alzheimers Dis. 2006;9(3):243-51.

Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K. Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol. 2008;120(1):112-7.

Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Norman Scholfield C. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-35.

Deepak M, Sangli GK, Arun PC, Amit A. Quantitative determination of the major saponin mixture bacoside A in Bacopa monnieri by HPLC. Phytochem Anal. 2005;16(1):24-9.

Singh HK, Rastogi RP, Srimal RC, Dhawan BN. Effect of bacosides A and B on avoidance responses in rats. Phytother Res. 1988;2(2):70-5.

Mathew J, Paul J, Nandhu MS, Paulose CS. Bacopa monnieri and Bacoside-A for ameliorating epilepsy associated behavioral deficits. Fitoterapia. 2010;81(5):315-22.

Singh R, Ramakrishna R, Bhateria M, Bhatta RS. In vitro evaluation of Bacopa monniera extract and individual constituents on human recombinant monoamine oxidase enzymes. Phytother Res. 2014;28(9):1419-22.

Sumathi T, Nathiya VC, Sakthikumar M. Protective effect of bacoside-A against morphine-induced oxidative stress in rats. Indian J Pharm Sci. 2011;73(4):409-15.

Thomas RB, Joy S, Ajayan MS, Paulose CS. Neuroprotective potential of Bacopa monnieri and bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats. Cell Mol Neurobiol. 2013;33(8):1065-74.

Anand T, Pandareesh MD, Bhat PV, Venkataramana M. Anti-apoptotic mechanism of Bacoside rich extract against reactive nitrogen species induced activation of iNOS/Bax/caspase 3 mediated apoptosis in L132 cell line. Cytotechnology. 2014;66(5):823-38.

Anbarasi K, Vani G, Balakrishna K, Devi CSS. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats. Life Sci. 2006;78(12):1378-84.

Cheng HY, Hsieh MT, Tsai FS, Wu CR, Chiu CS, Lee MM, et al. Neuroprotective effect of luteolin on amyloid beta protein (25-35)-induced toxicity in cultured rat cortical neurons. Phytother Res. 2010;24 Suppl 1:S102-8.

Phrompittayarat W, Wittaya-areekul S, Jetiyanon K, Putalun W, Tanaka H, Ingkaninan K. Determination of saponin glycosides in Bacopa monnieri by reversed phase high performance liquid chromatography. Thai Pharm Health Sci J. 2007;2(1):26-32.

Ingkaninan K, Temkitthawon P, Chuenchom K, Yuyaem T, Thongnoi W. Screening for acetylcholinesterase inhibitory activity in plants used in Thai traditional rejuvenating and neurotonic remedies. J Ethnopharmacol. 2003;89(2–3):261-4.

Shinomol GK, Mythri RB, Srinivas Bharath MM, Muralidhara. Bacopa monnieri extract offsets rotenone-induced cytotoxicity in dopaminergic cells and oxidative impairments in mice brain. Cell Mol Neurobiol. 2012;32(3):455-65.

Le XT, Pham HT, Do PT, Fujiwara H, Tanaka K, Li F, et al. Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice: possible involvement of glutamatergic and cholinergic systems. Neurochem Res. 2013;38(10):2201-15.

Sumathi T, Nathiya VC, Sakthikumar M. Protective Effect of Bacoside-A against Morphine-Induced Oxidative Stress in Rats. Indian J Pharm Sci. 2011;73(4):409-15.

Singh M, Murthy V, Ramassamy C. Modulation of hydrogen peroxide and acrolein-induced oxidative stress, mitochondrial dysfunctions and redox regulated pathways by the Bacopa monniera extract: potential implication in Alzheimer's disease. J Alzheimers Dis. 2010;21(1):229-47.

Liu R, Meng F, Zhang L, Liu A, Qin H, Lan X, et al. Luteolin isolated from the medicinal plant Elsholtzia rugulosa (Labiatae) prevents copper-mediated toxicity in beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells. Molecules. 2011;16(3):2084-96.

Wruck CJ, Claussen M, Fuhrmann G, Romer L, Schulz A, Pufe T, et al. Luteolin protects rat PC12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway. J Neural Transm Suppl. 2007(72):57-67.

Zhao G, Yao-Yue C, Qin GW, Guo LH. Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons. Neurobiol Aging. 2012;33(1):176-86.

Zhu L, Bi W, Lu D, Zhang C, Shu X. Luteolin inhibits SH-SY5Y cell apoptosis through suppression of the nuclear transcription factor-kappaB, mitogen-activated protein kinase and protein kinase B pathways in lipopolysaccharide-stimulated cocultured BV2 cells. Exp Ther Med. 2014;7(5):1065-70.

Lin TY, Lu CW, Wang SJ. Luteolin protects the hippocampus against neuron impairments induced by kainic acid in rats. Neurotoxicology. 2016;55:48-57.

Xu J, Wang H, Ding K, Zhang L, Wang C, Li T, et al. Luteolin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE pathway. Free Radic Biol Med. 2014;71:186-95.

Yu TX, Zhang P, Guan Y, Wang M, Zhen MQ. Protective effects of luteolin against cognitive impairment induced by infusion of Abeta peptide in rats. Int J Clin Exp Pathol. 2015;8(6):6740-7.