Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2020

01-12-2020 | Multiple Sclerosis | Research article

Phyllanthus amarus prevents LPS-mediated BV2 microglial activation via MyD88 and NF-κB signaling pathways

Authors: Elysha Nur Ismail, Ibrahim Jantan, Sharmili Vidyadaran, Jamia Azdina Jamal, Norazrina Azmi

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

Login to get access

Abstract

Background

Phyllanthus amarus has been shown to attenuate lipopolysaccharide (LPS)-induced peripheral inflammation but similar studies in the central nervous system are scarce. The aim of the present study was to investigate the neuroprotective effects of 80% ethanol extract of P. amarus (EPA) in LPS-activated BV2 microglial cells.

Methods

BV2 microglial cells c for 24 h, pre-treated with EPA for 24 h prior to LPS induction for another 24 h. Surface expression of CD11b and CD40 on BV2 cells was analyzed by flow cytometry. ELISA was employed to measure the production of pro-inflammatory mediators i.e. nitric oxide (NO) and tumor necrosis factor (TNF)-α. Western blotting technique was used to determine the expression of inducible nitric oxide synthase (iNOS), myeloid differentiation protein 88 (MYD88), nuclear factor kappa B (NF-κB), caspase-1, and mitogen activated protein kinase (MAPK).

Results

Qualitative and quantitative analyses of the EPA using a validated ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method indicated the presence of phyllanthin, hypophyllanthin, niranthin, ellagic acid, corilagin, gallic acid, phyltetralin, isolintetralin and geraniin. EPA suppressed the production of NO and TNFα in LPS-activated BV2 microglial cells. Moreover, EPA attenuated the expression of MyD88, NF-κB and MAPK (p-P38, p-JNK and p-ERK1/2). It also inhibited the expression of CD11b and CD40. EPA protected against LPS-induced microglial activation via MyD88 and NF-κB signaling in BV2 microglial cells.

Conclusions

EPA demonstrated neuroprotective effects against LPS-induced microglial cells activation through the inhibition of TNFα secretion, iNOS protein expression and subsequent NO production, inhibition of NF-κB and MAPKs mediated by adapter protein MyD88 and inhibition of microglial activation markers CD11b and CD40.
Literature
1.
go back to reference Wang X, Hu D, Zhang L, Lian G, Zhao S, Wang C, et al. Gomisin A inhibits lipopolysaccharide-induced inflammatory responses in N9 microglia via blocking the NF-κB/MAPKs pathway. Food Chem Toxicol. 2014;63:119–27.PubMed Wang X, Hu D, Zhang L, Lian G, Zhao S, Wang C, et al. Gomisin A inhibits lipopolysaccharide-induced inflammatory responses in N9 microglia via blocking the NF-κB/MAPKs pathway. Food Chem Toxicol. 2014;63:119–27.PubMed
2.
go back to reference Kofler J, Wiley CA. Microglia. Toxicol Pathol. 2011;39(1):103–14.PubMed Kofler J, Wiley CA. Microglia. Toxicol Pathol. 2011;39(1):103–14.PubMed
3.
go back to reference Labzin LI, Heneka MT, Latz E. Innate Immunity and Neurodegeneration. Annu Rev Med. 2018;69(1):437–49.PubMed Labzin LI, Heneka MT, Latz E. Innate Immunity and Neurodegeneration. Annu Rev Med. 2018;69(1):437–49.PubMed
4.
go back to reference Kettenmann H, Hanisch U, Noda M, Verkhratsky A. Physiology of Microglia. Physiol Rev. 2011;91:461–553.PubMed Kettenmann H, Hanisch U, Noda M, Verkhratsky A. Physiology of Microglia. Physiol Rev. 2011;91:461–553.PubMed
5.
go back to reference Amor S, Peferoen LAN, Vogel DYS, Breur M, van der Valk P, Baker D, et al. Inflammation in neurodegenerative diseases - an update. Immunology. 2014;142(2):151–66.PubMedPubMedCentral Amor S, Peferoen LAN, Vogel DYS, Breur M, van der Valk P, Baker D, et al. Inflammation in neurodegenerative diseases - an update. Immunology. 2014;142(2):151–66.PubMedPubMedCentral
6.
go back to reference Jeong H-K, Ji K, Min K, Joe E-H. Brain inflammation and microglia: facts and misconceptions. Exp Neurobiol. 2013;22(2):59–67.PubMedPubMedCentral Jeong H-K, Ji K, Min K, Joe E-H. Brain inflammation and microglia: facts and misconceptions. Exp Neurobiol. 2013;22(2):59–67.PubMedPubMedCentral
7.
go back to reference Kurkowska-Jastrzȩbska I, Litwin T, Joniec I, Ciesielska A, Przybyłkowski A, Członkowski A, et al. Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson’s disease. Int Immunopharmacol. 2004;4(10–11):1307–18.PubMed Kurkowska-Jastrzȩbska I, Litwin T, Joniec I, Ciesielska A, Przybyłkowski A, Członkowski A, et al. Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson’s disease. Int Immunopharmacol. 2004;4(10–11):1307–18.PubMed
8.
go back to reference Sun WH, He F, Zhang NN, Zhao ZA, Chen HS. Time dependent neuroprotection of dexamethasone in experimental focal cerebral ischemia: The involvement of NF-κB pathways. Brain Res. 1701;2018:237–45. Sun WH, He F, Zhang NN, Zhao ZA, Chen HS. Time dependent neuroprotection of dexamethasone in experimental focal cerebral ischemia: The involvement of NF-κB pathways. Brain Res. 1701;2018:237–45.
9.
go back to reference Murray CL, Skelly DT, Cunningham C. Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6. J Neuroinflammation. 2011;8:50.PubMedPubMedCentral Murray CL, Skelly DT, Cunningham C. Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6. J Neuroinflammation. 2011;8:50.PubMedPubMedCentral
10.
go back to reference Figueiredo RT, Fernandez PL, Mourao-Sa DS, Porto BN, Dutra FF, Alves LS, et al. Characterization of heme as activator of toll-like receptor 4. J Biol Chem. 2007;282(28):20221–9.PubMed Figueiredo RT, Fernandez PL, Mourao-Sa DS, Porto BN, Dutra FF, Alves LS, et al. Characterization of heme as activator of toll-like receptor 4. J Biol Chem. 2007;282(28):20221–9.PubMed
11.
go back to reference Fang H, Wang P-F, Zhou Y, Wang Y-C, Yang Q-W. Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury. J Neuroinflammation. 2013;10(1):27.PubMedPubMedCentral Fang H, Wang P-F, Zhou Y, Wang Y-C, Yang Q-W. Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury. J Neuroinflammation. 2013;10(1):27.PubMedPubMedCentral
12.
go back to reference Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Sig Transduct Target Ther. 2017;2:17023. Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Sig Transduct Target Ther. 2017;2:17023.
13.
go back to reference Qin H, Wilson CA, Lee SJ, Zhao X, Benveniste EN. LPS induces CD40 gene expression through the activation of NF-kappaB and STAT-1alpha in macrophages and microglia. Blood. 2005;106(9):3114–22.PubMedPubMedCentral Qin H, Wilson CA, Lee SJ, Zhao X, Benveniste EN. LPS induces CD40 gene expression through the activation of NF-kappaB and STAT-1alpha in macrophages and microglia. Blood. 2005;106(9):3114–22.PubMedPubMedCentral
14.
go back to reference Huang M-Y, Tu C-E, Wang S-C, Hung Y-L, Su C-C, Fang S-H, et al. Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia. BMC Complement Altern Med. 2018;18(1):221.PubMedPubMedCentral Huang M-Y, Tu C-E, Wang S-C, Hung Y-L, Su C-C, Fang S-H, et al. Corylin inhibits LPS-induced inflammatory response and attenuates the activation of NLRP3 inflammasome in microglia. BMC Complement Altern Med. 2018;18(1):221.PubMedPubMedCentral
15.
go back to reference Dai XJ, Li N, Yu L, Chen ZY, Hua R, Qin X, Zhang YM. Activation of BV2 microglia by lipopolysaccharide triggers an inflammatory reaction in PC12 cell apoptosis through a toll-like receptor 4-dependent pathway. Cell Stress Chaperones. 2015;20(2):321–31.PubMed Dai XJ, Li N, Yu L, Chen ZY, Hua R, Qin X, Zhang YM. Activation of BV2 microglia by lipopolysaccharide triggers an inflammatory reaction in PC12 cell apoptosis through a toll-like receptor 4-dependent pathway. Cell Stress Chaperones. 2015;20(2):321–31.PubMed
16.
go back to reference Joshi H, Parle M. Pharmacological Evidences for the Antiamnesic Effects of Phyllanthus amarus in mice. Afr J Biomed Res. 2007;10:165–73. Joshi H, Parle M. Pharmacological Evidences for the Antiamnesic Effects of Phyllanthus amarus in mice. Afr J Biomed Res. 2007;10:165–73.
17.
go back to reference Patel JR, Tripathi P, Sharma V, Chauhan NS, Dixit VK. Phyllanthus amarus: Ethnomedicinal uses, phytochemistry and pharmacology: A review. J Ethnopharmacol. 2011;138(2):286–313.PubMed Patel JR, Tripathi P, Sharma V, Chauhan NS, Dixit VK. Phyllanthus amarus: Ethnomedicinal uses, phytochemistry and pharmacology: A review. J Ethnopharmacol. 2011;138(2):286–313.PubMed
18.
go back to reference Mohamed SIA, Jantan I, Nafiah MA, Seyed MA, Chan KM. Dendritic cells pulsed with generated tumor cell lysate from Phyllanthus amarus immune response. BMC Complement Altern Med. 2018;18:1–14. Mohamed SIA, Jantan I, Nafiah MA, Seyed MA, Chan KM. Dendritic cells pulsed with generated tumor cell lysate from Phyllanthus amarus immune response. BMC Complement Altern Med. 2018;18:1–14.
19.
go back to reference Lim YY, Murtijaya J. Antioxidant properties of Phyllanthus amarus extracts as affected by different drying methods. LWT Food Sci Technol. 2007;40(9):1664–9. Lim YY, Murtijaya J. Antioxidant properties of Phyllanthus amarus extracts as affected by different drying methods. LWT Food Sci Technol. 2007;40(9):1664–9.
20.
go back to reference Joshi H, Parle M. Evaluation of the antiamnesic effects of Phyllanthus amarus in mice. Colombia Médica. 2007;38:132–9. Joshi H, Parle M. Evaluation of the antiamnesic effects of Phyllanthus amarus in mice. Colombia Médica. 2007;38:132–9.
21.
go back to reference Schröder S, Beckmann K, Franconi G, Meyer-Hamme G, Friedemann T, Greten HJ, et al. Can medical herbs stimulate regeneration or neuroprotection and treat neuropathic pain in chemotherapy-induced peripheral neuropathy? Evid Based Complement Alternat Med. 2013;2013:423713.PubMedPubMedCentral Schröder S, Beckmann K, Franconi G, Meyer-Hamme G, Friedemann T, Greten HJ, et al. Can medical herbs stimulate regeneration or neuroprotection and treat neuropathic pain in chemotherapy-induced peripheral neuropathy? Evid Based Complement Alternat Med. 2013;2013:423713.PubMedPubMedCentral
22.
go back to reference Shokunbi O, Odetola A. Gastroprotective and antioxidant activities of Phyllanthus amarus extracts on absolute ethanol-induced ulcer in albino rats. J Med Plant Res. 2008;2:261–7. Shokunbi O, Odetola A. Gastroprotective and antioxidant activities of Phyllanthus amarus extracts on absolute ethanol-induced ulcer in albino rats. J Med Plant Res. 2008;2:261–7.
23.
go back to reference Adeneye AA, Amole OO, Adeneye AK. Hypoglycemic and hypocholesterolemic activities of the aqueous leaf and seed extract of Phyllanthus amarus in mice. Fitoterapia. 2006;77(7–8):511–4.PubMed Adeneye AA, Amole OO, Adeneye AK. Hypoglycemic and hypocholesterolemic activities of the aqueous leaf and seed extract of Phyllanthus amarus in mice. Fitoterapia. 2006;77(7–8):511–4.PubMed
24.
go back to reference Moshi MJ, Lutale JJK, Rimoy GH, Abbas ZG, Josiah RM, Swai ABM. The Effect of Phyllanthus amarus Aqueous Extract on Blood Glucose in Non-insulin Dependent Diabetic Patients. Phytother Res. 2001;15:577–80.PubMed Moshi MJ, Lutale JJK, Rimoy GH, Abbas ZG, Josiah RM, Swai ABM. The Effect of Phyllanthus amarus Aqueous Extract on Blood Glucose in Non-insulin Dependent Diabetic Patients. Phytother Res. 2001;15:577–80.PubMed
25.
go back to reference Kumaran A, Karunakaran RJ. In vitro antioxidant activities of methanol extracts of five Phyllanthus species from India. LWT Food Sci Technol. 2007;40(2):344–52. Kumaran A, Karunakaran RJ. In vitro antioxidant activities of methanol extracts of five Phyllanthus species from India. LWT Food Sci Technol. 2007;40(2):344–52.
26.
go back to reference Yuandani IM, Jantan I, Mohamad HF, Husain K, Abdul Razak AF. Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils. Evid Based Complement Alternat Med. 2013;2013:1–9. Yuandani IM, Jantan I, Mohamad HF, Husain K, Abdul Razak AF. Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils. Evid Based Complement Alternat Med. 2013;2013:1–9.
27.
go back to reference Syed AB, Iqbal MM, Kiranmai M, Ibrahim M. Hepatoprotective Activity of Phyllanthus Amarus. Glob J Med Res. 2012;12(6):38–48. Syed AB, Iqbal MM, Kiranmai M, Ibrahim M. Hepatoprotective Activity of Phyllanthus Amarus. Glob J Med Res. 2012;12(6):38–48.
28.
go back to reference Ahmad MS, Bano S, Anwar S. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in vitro studies against Aflatoxin B1 toxicity. Egypt J Med Hum Genet. 2015;16(4):343–53. Ahmad MS, Bano S, Anwar S. Cancer ameliorating potential of Phyllanthus amarus: In vivo and in vitro studies against Aflatoxin B1 toxicity. Egypt J Med Hum Genet. 2015;16(4):343–53.
29.
go back to reference Wannannond P, Wattanathorn J, Muchimapura S, Thipkaew C, Kaen K. Phyllanthus Amarus Facilitates the Recovery of Peripheral Nerve after Injury. Am J Appl Sci. 2012;9(7):1000–7. Wannannond P, Wattanathorn J, Muchimapura S, Thipkaew C, Kaen K. Phyllanthus Amarus Facilitates the Recovery of Peripheral Nerve after Injury. Am J Appl Sci. 2012;9(7):1000–7.
30.
go back to reference Alagan A, Jantan I, Kumolosasi E, Ogawa S, Abdullah MA, Azmi N. Protective Effects of Phyllanthus amarus Against Lipopolysaccharide-Induced Neuroinflammation and Cognitive Impairment in Rats. Front Pharmacol. 2019;10:632.PubMedPubMedCentral Alagan A, Jantan I, Kumolosasi E, Ogawa S, Abdullah MA, Azmi N. Protective Effects of Phyllanthus amarus Against Lipopolysaccharide-Induced Neuroinflammation and Cognitive Impairment in Rats. Front Pharmacol. 2019;10:632.PubMedPubMedCentral
31.
go back to reference Illangkovan M, Jantan I, Mesaik MA, Abbas BS. Immunosuppressive effects of the standardized extract of Phyllanthus amarus on cellular immune responses in Wistar-Kyoto rats. Drug Des Devel Ther. 2015:4917–30. Illangkovan M, Jantan I, Mesaik MA, Abbas BS. Immunosuppressive effects of the standardized extract of Phyllanthus amarus on cellular immune responses in Wistar-Kyoto rats. Drug Des Devel Ther. 2015:4917–30.
32.
go back to reference Tong F, Zhang J, Liu L, Gao X, Cai Q, Wei C, et al. Corilagin Attenuates Radiation-Induced Brain Injury in Mice. Mol Neurobiol. 2016;53(10):6982–96.PubMed Tong F, Zhang J, Liu L, Gao X, Cai Q, Wei C, et al. Corilagin Attenuates Radiation-Induced Brain Injury in Mice. Mol Neurobiol. 2016;53(10):6982–96.PubMed
33.
go back to reference Nathiya VC, Vanisree AJ. Investigations on light –induced stress model and on the role of phyllanthus amarus in attenuation of stress related depression-with focus on 5ht2a m-rna expression. Ann Neurosci. 2010;17(4):167–75.PubMedPubMedCentral Nathiya VC, Vanisree AJ. Investigations on light –induced stress model and on the role of phyllanthus amarus in attenuation of stress related depression-with focus on 5ht2a m-rna expression. Ann Neurosci. 2010;17(4):167–75.PubMedPubMedCentral
34.
go back to reference Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology. 2016;233(9):1637–50.PubMedPubMedCentral Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology. 2016;233(9):1637–50.PubMedPubMedCentral
35.
go back to reference Kassuya CAL, Silvestre A, Menezes-de-Lima O, Marotta DM, Rehder VLG, Calixto JB. Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from Phyllanthus amarus. Evidence for interaction with platelet activating factor receptor. Eur J Pharmacol. 2006;546(1–3):182–8.PubMed Kassuya CAL, Silvestre A, Menezes-de-Lima O, Marotta DM, Rehder VLG, Calixto JB. Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from Phyllanthus amarus. Evidence for interaction with platelet activating factor receptor. Eur J Pharmacol. 2006;546(1–3):182–8.PubMed
36.
go back to reference Harikrishnan H, Jantan I, Haque MA, Kumolosasi E. Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. Through inhibition of NF-ΚB, MAPK, and PI3K-Akt signaling pathways in LPSinduced human macrophages. BMC Complement Altern Med. 2018;18(1):1–13. Harikrishnan H, Jantan I, Haque MA, Kumolosasi E. Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. Through inhibition of NF-ΚB, MAPK, and PI3K-Akt signaling pathways in LPSinduced human macrophages. BMC Complement Altern Med. 2018;18(1):1–13.
37.
go back to reference Kiemer AK, Hartung T, Huber C, Vollmar AM. Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-κB pathway. J Hepatol. 2003;38:289–97.PubMed Kiemer AK, Hartung T, Huber C, Vollmar AM. Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-κB pathway. J Hepatol. 2003;38:289–97.PubMed
38.
go back to reference Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75(6):639–53.PubMed Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci. 2004;75(6):639–53.PubMed
39.
go back to reference Kumar S, Chandra P, Bajpai V, Singh A, Srivastava M, Mishra DK, et al. Rapid qualitative and quantitative analysis of bioactive compounds from Phyllanthus amarus using LC/MS/MS techniques. Ind Crop Prod. 2015;69:143–52. Kumar S, Chandra P, Bajpai V, Singh A, Srivastava M, Mishra DK, et al. Rapid qualitative and quantitative analysis of bioactive compounds from Phyllanthus amarus using LC/MS/MS techniques. Ind Crop Prod. 2015;69:143–52.
40.
go back to reference Kumar S, Singh A, Bajpai V, Singh B, Kumar B. Development of a UHPLC–MS/MS method for the quantitation of bioactive compounds in Phyllanthus species and its herbal formulations. J Sep Sci. 2017;40:3422–9.PubMed Kumar S, Singh A, Bajpai V, Singh B, Kumar B. Development of a UHPLC–MS/MS method for the quantitation of bioactive compounds in Phyllanthus species and its herbal formulations. J Sep Sci. 2017;40:3422–9.PubMed
41.
go back to reference Dang Y, Xu Y, Wu W, Li W, Sun Y, Yang J, et al. Tetrandrine Suppresses Lipopolysaccharide-Induced Microglial Activation by Inhibiting NF-κB and ERK Signaling Pathways in BV2 Cells. Gressens P, editor. PLoS One. 2014;9(8):e102522.PubMedPubMedCentral Dang Y, Xu Y, Wu W, Li W, Sun Y, Yang J, et al. Tetrandrine Suppresses Lipopolysaccharide-Induced Microglial Activation by Inhibiting NF-κB and ERK Signaling Pathways in BV2 Cells. Gressens P, editor. PLoS One. 2014;9(8):e102522.PubMedPubMedCentral
42.
go back to reference Verma S, Sharma H, Garg M. Phyllanthus Amarus: A Review. J Pharmacogn Phytochem. 2014;3(2):18–22. Verma S, Sharma H, Garg M. Phyllanthus Amarus: A Review. J Pharmacogn Phytochem. 2014;3(2):18–22.
43.
go back to reference Jantan I, Ilangkovan M, Yuandani, Mohamad H. Correlation between the major components of Phyllanthus amarus and Phyllanthus urinaria and their inhibitory effects on phagocytic activity of human neutrophils. BMC Complement Altern Med. 2014;14(1):429.PubMedCentral Jantan I, Ilangkovan M, Yuandani, Mohamad H. Correlation between the major components of Phyllanthus amarus and Phyllanthus urinaria and their inhibitory effects on phagocytic activity of human neutrophils. BMC Complement Altern Med. 2014;14(1):429.PubMedCentral
44.
go back to reference Harun A, Vidyadaran S, Lim SM, Cole ALJ, Ramasamy K. Malaysian endophytic fungal extracts-induced anti-inflammation in Lipopolysaccharide-activated BV-2 microglia is associated with attenuation of NO production and, IL-6 and TNF-α expression. BMC Complement Altern Med. 2015;15:166.PubMedPubMedCentral Harun A, Vidyadaran S, Lim SM, Cole ALJ, Ramasamy K. Malaysian endophytic fungal extracts-induced anti-inflammation in Lipopolysaccharide-activated BV-2 microglia is associated with attenuation of NO production and, IL-6 and TNF-α expression. BMC Complement Altern Med. 2015;15:166.PubMedPubMedCentral
45.
go back to reference Zhang F, Wang Y-Y, Yang J, Lu Y-F, Liu J, Shi J-S. Tetrahydroxystilbene glucoside attenuates neuroinflammation through the inhibition of microglia activation. Oxidative Med Cell Longev. 2013;2013:680545. Zhang F, Wang Y-Y, Yang J, Lu Y-F, Liu J, Shi J-S. Tetrahydroxystilbene glucoside attenuates neuroinflammation through the inhibition of microglia activation. Oxidative Med Cell Longev. 2013;2013:680545.
46.
go back to reference Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism. Prog Neurobiol. 2005;76:77–98.PubMed Block ML, Hong JS. Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism. Prog Neurobiol. 2005;76:77–98.PubMed
47.
go back to reference Sierra A, Navascués J, Cuadros MA, Calvente R, Martín-Oliva D, Ferrer-Martín RM, et al. Expression of Inducible Nitric Oxide Synthase (iNOS) in Microglia of the Developing Quail Retina. PLoS One. 2014;9(8):e106048.PubMedPubMedCentral Sierra A, Navascués J, Cuadros MA, Calvente R, Martín-Oliva D, Ferrer-Martín RM, et al. Expression of Inducible Nitric Oxide Synthase (iNOS) in Microglia of the Developing Quail Retina. PLoS One. 2014;9(8):e106048.PubMedPubMedCentral
48.
go back to reference Panthi S, Manandhar S, Gautam K. Hydrogen sulfide, nitric oxide, and neurodegenerative disorders. Transl Neurodegener. 2018;7(1):3.PubMedPubMedCentral Panthi S, Manandhar S, Gautam K. Hydrogen sulfide, nitric oxide, and neurodegenerative disorders. Transl Neurodegener. 2018;7(1):3.PubMedPubMedCentral
49.
go back to reference Andreasson K. Emerging roles of PGE2 receptors in models of neurological disease. Prostaglandins Other Lipid Mediat. 2010;91(3–4):104–12.PubMed Andreasson K. Emerging roles of PGE2 receptors in models of neurological disease. Prostaglandins Other Lipid Mediat. 2010;91(3–4):104–12.PubMed
50.
go back to reference Ryan JC, Cross CA, Van Dolah FM. Effects of COX inhibitors on neurodegeneration and survival in mice exposed to the marine neurotoxin domoic acid. Neurosci Lett. 2011;487(1):83–7.PubMed Ryan JC, Cross CA, Van Dolah FM. Effects of COX inhibitors on neurodegeneration and survival in mice exposed to the marine neurotoxin domoic acid. Neurosci Lett. 2011;487(1):83–7.PubMed
51.
go back to reference Consonni A, Morara S, Codazzi F, Grohovaz F, Zacchetti D. Inhibition of lipopolysaccharide-induced microglia activation by calcitonin gene related peptide and adrenomedullin. Mol Cell Neurosci. 2011;48(2):151–60.PubMedPubMedCentral Consonni A, Morara S, Codazzi F, Grohovaz F, Zacchetti D. Inhibition of lipopolysaccharide-induced microglia activation by calcitonin gene related peptide and adrenomedullin. Mol Cell Neurosci. 2011;48(2):151–60.PubMedPubMedCentral
52.
go back to reference Kim S-J, Ha M-S, Choi E-Y, Choi J-I, Choi I-S. Nitric oxide production and inducible nitric oxide synthase expression induced by Prevotella nigrescens lipopolysaccharide. FEMS Immunol Med Microbiol. 2005;43(1):51–8.PubMed Kim S-J, Ha M-S, Choi E-Y, Choi J-I, Choi I-S. Nitric oxide production and inducible nitric oxide synthase expression induced by Prevotella nigrescens lipopolysaccharide. FEMS Immunol Med Microbiol. 2005;43(1):51–8.PubMed
53.
go back to reference McAdam E, Haboubi HN, Forrester G, Eltahir Z, Spencer-Harty S, Davies C, et al. Inducible Nitric Oxide Synthase (iNOS) and Nitric Oxide (NO) are Important Mediators of Reflux-induced Cell Signalling in Esophageal Cells. Carcinogenesis. 2012;33(11):2035–43.PubMed McAdam E, Haboubi HN, Forrester G, Eltahir Z, Spencer-Harty S, Davies C, et al. Inducible Nitric Oxide Synthase (iNOS) and Nitric Oxide (NO) are Important Mediators of Reflux-induced Cell Signalling in Esophageal Cells. Carcinogenesis. 2012;33(11):2035–43.PubMed
54.
go back to reference Alagan A. Phyllanthus amarus protects against spatial memory impairment induced by lipopolysaccharide in mice. Bioinformation. 2019;15(8):535–41.PubMedPubMedCentral Alagan A. Phyllanthus amarus protects against spatial memory impairment induced by lipopolysaccharide in mice. Bioinformation. 2019;15(8):535–41.PubMedPubMedCentral
55.
go back to reference Horvath RJ, Nutile-McMenemy N, Alkaitis MS, Deleo JA. Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures. J Neurochem. 2008;107(2):557–69.PubMedPubMedCentral Horvath RJ, Nutile-McMenemy N, Alkaitis MS, Deleo JA. Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures. J Neurochem. 2008;107(2):557–69.PubMedPubMedCentral
56.
go back to reference Bussi C, Ramos JMP, Arroyo DS, Gaviglio EA, Gallea JI, Wang JM, et al. Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death. Sci Rep. 2017;7:1–14. Bussi C, Ramos JMP, Arroyo DS, Gaviglio EA, Gallea JI, Wang JM, et al. Autophagy down regulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha-synuclein induced neuronal cell death. Sci Rep. 2017;7:1–14.
57.
go back to reference Tanaka T, Kai S, Matsuyama T, Adachi T, Fukuda K, Hirota K. General Anesthetics Inhibit LPS-Induced IL-1β Expression in Glial Cells. PLoS One. 2013;8(12):e82930.PubMedPubMedCentral Tanaka T, Kai S, Matsuyama T, Adachi T, Fukuda K, Hirota K. General Anesthetics Inhibit LPS-Induced IL-1β Expression in Glial Cells. PLoS One. 2013;8(12):e82930.PubMedPubMedCentral
58.
go back to reference Diomede F, Zingariello M, Cavalcanti MFXB, Merciaro I, De Isla N, Caputi S, et al. MyD88/ERK/NFkB pathways and pro-inflammatory cytokines release in periodontal ligament stem cells stimulated by Porphyromonas gingivalis. Eur J Histochem. 2017;61(2):2791.PubMedPubMedCentral Diomede F, Zingariello M, Cavalcanti MFXB, Merciaro I, De Isla N, Caputi S, et al. MyD88/ERK/NFkB pathways and pro-inflammatory cytokines release in periodontal ligament stem cells stimulated by Porphyromonas gingivalis. Eur J Histochem. 2017;61(2):2791.PubMedPubMedCentral
59.
go back to reference Horng T, Medzhitov R. Drosophila MyD88 is an adapter in the Toll signaling pathway. Proc Natl Acad Sci U S A. 2001;98(22):12654–8.PubMedPubMedCentral Horng T, Medzhitov R. Drosophila MyD88 is an adapter in the Toll signaling pathway. Proc Natl Acad Sci U S A. 2001;98(22):12654–8.PubMedPubMedCentral
60.
go back to reference Roy A, Srivastava M, Saqib U, Liu D, Faisal SM, Sugathan S, et al. Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways. Int Immunopharmacol. 2016;40:79–89.PubMed Roy A, Srivastava M, Saqib U, Liu D, Faisal SM, Sugathan S, et al. Potential therapeutic targets for inflammation in toll-like receptor 4 (TLR4)-mediated signaling pathways. Int Immunopharmacol. 2016;40:79–89.PubMed
61.
go back to reference Kim EK, Choi E-J. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta Mol Basis Dis. 2010;1802(4):396–405. Kim EK, Choi E-J. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta Mol Basis Dis. 2010;1802(4):396–405.
62.
go back to reference Chuang TY, Cheng AJ, Chen IT, Lan TY, Huang IH, Shiau CW, et al. Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone. Oncotarget. 2017;8(30):49735–48.PubMedPubMedCentral Chuang TY, Cheng AJ, Chen IT, Lan TY, Huang IH, Shiau CW, et al. Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone. Oncotarget. 2017;8(30):49735–48.PubMedPubMedCentral
Metadata
Title
Phyllanthus amarus prevents LPS-mediated BV2 microglial activation via MyD88 and NF-κB signaling pathways
Authors
Elysha Nur Ismail
Ibrahim Jantan
Sharmili Vidyadaran
Jamia Azdina Jamal
Norazrina Azmi
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-020-02961-0

Other articles of this Issue 1/2020

BMC Complementary Medicine and Therapies 1/2020 Go to the issue