Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Anti-inflammatory Activity of Mollugo cerviana Methanolic Extract in LPS-induced Acute Inflammatory RAW 264.7 Macrophages

Author(s): Robina Antony, Jijin Raveendran and Prabath Gopalakrishnan Biju*

Volume 25, Issue 10, 2022

Published on: 02 March, 2021

Page: [1661 - 1671] Pages: 11

DOI: 10.2174/1386207324666210302101204

Price: $65

Abstract

Background: The management of acute inflammation, which arises from complex biological responses to harmful stimuli, is an important determinant in the recovery from an otherwise detrimental outcome such as septicemia. However, the side effects and limitations of current therapeutics necessitate the development of newer and safer alternatives. Mollugo cerviana is a common medicinal herb of the Indian subcontinent and has been traditionally used for its fever mitigating anti-microbial and hepatoprotective action. We have already reported the rich presence of radical scavenging phytochemicals in the plant extracts and their strong antioxidant properties.

Objective: In the present study, we have evaluated the anti-inflammatory effects of methanolic extract (ME) of the areal parts of M. cerviana in a lipopolysaccharide (LPS)-induced acute inflammatory cell culture model.

Methods: RAW 264.7 mouse macrophage cells were stimulated by the bacterial endotoxin LPS at a concentration of 1 μg/mL. Cytotoxicity and anti-inflammatory potential of ME were carried out.

Results: The concentration of M. cerviana extract up to 150 μg/ml was found to be non-toxic to cells (MTT and NRU assay). LPS induces acute inflammation by binding to TLR-4 receptors, initiating a downstream signalling cascade that results in pro-inflammatory cytokine secretion. Extract treatment at 100 μg/ml suppressed LPS-induced gene expression (qPCR) and secretion (ELISA) of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, and the chemokine CCL2, leading to dampening of the acute inflammatory cascade. LPS-induced elevation of ROS level (DCFDA method) was significantly reduced by extract treatment. Nitric oxide production, as indicated by nitrite level, was significantly reduced post extract treatment.

Conclusion: This study demonstrated that M. cerviana methanolic extract has a potent antiinflammatory effect in the in vitro acute inflammation model of LPS-stimulated RAW 264.7 cells. There is no reported study so far on the anti-inflammatory properties of M. cerviana in an LPSinduced acute inflammatory model, which closely mimics a human bacteremia response. Hence, this study highlights the therapeutic potential of this extract as a source of anti-inflammatory lead molecules.

Keywords: Acute inflammation, anti-inflammatory, lipopolysaccharide, macrophage, ROS, pro-inflammatory cytokines.

« Previous Next »
Graphical Abstract

[1]
Yang, G.; Lee, K.; Lee, M.; Ham, I.; Choi, H.Y. Inhibition of lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by chloroform fraction of Cudrania tricuspidata in RAW 264.7 macrophages. BMC Complement. Altern. Med., 2012, 12, 250.
[http://dx.doi.org/10.1186/1472-6882-12-250] [PMID: 23228109]
[2]
Shao, J.; Li, Y.; Wang, Z.; Xiao, M.; Yin, P.; Lu, Y.; Qian, X.; Xu, Y.; Liu, J. 7b, a novel naphthalimide derivative, exhibited anti-inflammatory effects via targeted-inhibiting TAK1 following down-regulation of ERK1/2- and p38 MAPK-mediated activation of NF-κB in LPS-stimulated RAW264.7 macrophages. Int. Immunopharmacol., 2013, 17(2), 216-228.
[http://dx.doi.org/10.1016/j.intimp.2013.06.008] [PMID: 23810444]
[3]
Hotchkiss, R.S.; Moldawer, L.L.; Opal, S.M.; Reinhart, K.; Turnbull, I.R.; Vincent, J.L. Sepsis and septic shock. Nat. Rev. Dis. Primers, 2016, 2, 16045.
[http://dx.doi.org/10.1038/nrdp.2016.45] [PMID: 28117397]
[4]
Demoruelle, M.K.; Deane, K.D.; Holers, V.M. When and where does inflammation begin in rheumatoid arthritis? Curr. Opin. Rheumatol., 2014, 26(1), 64-71.
[http://dx.doi.org/10.1097/BOR.0000000000000017] [PMID: 24247116]
[5]
Tsukamoto, H.; Takeuchi, S.; Kubota, K.; Kobayashi, Y.; Kozakai, S.; Ukai, I.; Shichiku, A.; Okubo, M.; Numasaki, M.; Kanemitsu, Y.; Matsumoto, Y.; Nochi, T.; Watanabe, K.; Aso, H.; Tomioka, Y. Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation. J. Biol. Chem., 2018, 293(26), 10186-10201.
[http://dx.doi.org/10.1074/jbc.M117.796631] [PMID: 29760187]
[6]
Van den Bossche, J.; O’Neill, L.A.; Menon, D. Macrophage immunometabolism: Where are we (Going)? Trends Immunol., 2017, 38(6), 395-406.
[http://dx.doi.org/10.1016/j.it.2017.03.001] [PMID: 28396078]
[7]
Jeon, H.L.; Yoo, J.M.; Lee, B.D.; Lee, S.J.; Sohn, E.J.; Kim, M.R. Anti-inflammatory and antioxidant actions of n-arachidonoyl serotonin in RAW264.7 cells. Pharmacology, 2016, 97(3-4), 195-206.
[http://dx.doi.org/10.1159/000443739] [PMID: 26859139]
[8]
Baranowski, D.C.; Buchanan, B.; Dwyer, H.C.; Gabriele, J.P.; Kelly, S.; Araujo, J.A. Penetration and efficacy of transdermal NSAIDs in a model of acute joint inflammation. J. Pain Res., 2018, 11, 2809-2819.
[http://dx.doi.org/10.2147/JPR.S177967] [PMID: 30519083]
[9]
Yokota, J.; Kyotani, S. Influence of nanoparticle size on the skin penetration, skin retention and anti-inflammatory activity of non-steroidal anti-inflammatory drugs. J. Chin. Med. Assoc., 2018, 81(6), 511-519.
[http://dx.doi.org/10.1016/j.jcma.2018.01.008] [PMID: 29555445]
[10]
Wu, Y.; Yang, Y.; Zhao, W.; Xu, Z.P.; Little, P.J.; Whittaker, A.K.; Zhang, R.; Ta, H.T. Novel iron oxide-cerium oxide core-shell nanoparticles as a potential theranostic material for ROS related inflammatory diseases. J. Mater. Chem. B Mater. Biol. Med., 2018, 6(30), 4937-4951.
[http://dx.doi.org/10.1039/C8TB00022K] [PMID: 32255067]
[11]
Su, L.; Tu, Y.; Kong, D.P.; Chen, D.G.; Zhang, C.X.; Zhang, W.N.; Zhuang, C.L.; Wang, Z.B. Drug repurposing of anti-infective clinical drugs: Discovery of two potential anti-cytokine storm agents. Biomed. Pharmacother., 2020, 131, 110643.
[http://dx.doi.org/10.1016/j.biopha.2020.110643] [PMID: 32846329]
[12]
Sadique, J.; Chandra, T.; Thenmozhi, V.; Elango, V. The anti-inflammatory activity of Enicostemma littorale and Mollugo cerviana. Biochem. Med. Metab. Biol., 1987, 37(2), 167-176.
[http://dx.doi.org/10.1016/0885-4505(87)90023-5] [PMID: 2885019]
[13]
Parvathamma, S.; Shanthamma, C. Antimicrobial activity of mollugo cerviana ser. (Molluginaceae). Anc. Sci. Life, 2000, 20(1-2), 11-13.
[PMID: 22556991]
[14]
Joshi, A.; Prasad, S.K.; Joshi, V.K.; Hemalatha, S. Phytochemical standardization, antioxidant, and antibacterial evaluations of Leea macrophylla: A wild edible plant. Yao Wu Shi Pin Fen Xi, 2016, 24(2), 324-331.
[http://dx.doi.org/10.1016/j.jfda.2015.10.010] [PMID: 28911586]
[15]
Luo, Y.; Jiang, Q.; Zhu, Z.; Sattar, H.; Wu, J.; Huang, W.; Su, S.; Liang, Y.; Wang, P.; Meng, X. Phosphoproteomics and proteomics reveal metabolism as a key node in LPS-induced acute inflammation in RAW264.7. Inflammation, 2020, 43(5), 1667-1679.
[http://dx.doi.org/10.1007/s10753-020-01240-x] [PMID: 32488682]
[16]
Park, N.Y.; Kim, S.G.; Park, H.H.; Jeong, K.T.; Lee, Y.J.; Lee, E. Anti-inflammatory effects of Juncus effusus extract (JEE) on LPS-stimulated RAW 264.7 cells and edema models. Pharm. Biol., 2016, 54(2), 243-250.
[http://dx.doi.org/10.3109/13880209.2015.1029053] [PMID: 25885933]
[17]
Gutierrez, R.M.P.; Hoyo-Vadillo, C. Anti-inflammatory potential of Petiveria alliacea on activated RAW264.7 murine macrop-hages. Pharmacogn. Mag., 2017, 13(Suppl. 2), S174-S178.
[http://dx.doi.org/10.4103/pm.pm_479_16] [PMID: 28808377]
[18]
Hsu, C.C.; Lien, J.C.; Chang, C.W.; Chang, C.H.; Kuo, S.C.; Huang, T.F. Yuwen02f1 suppresses LPS-induced endotoxemia and adjuvant-induced arthritis primarily through blockade of ROS formation, NFkB and MAPK activation. Biochem. Pharmacol., 2013, 85(3), 385-395.
[http://dx.doi.org/10.1016/j.bcp.2012.11.002] [PMID: 23142712]
[19]
Kim, S.K.; Ko, Y.H.; Lee, Y.; Lee, S.Y.; Jang, C.G. Antineuroinflammatory effects of 7,3′,4′-trihydroxyisoflavone in lipopolysaccharide-stimulated BV2 microglial cells through MAPK and NF-κB signaling suppression. Biomol. Ther. (Seoul), 2020.
[http://dx.doi.org/10.4062/biomolther.2020.093] [PMID: 32812529]
[20]
Napagoda, M.T.; Malkanthi, B.M.; Abayawardana, S.A.; Qader, M.M.; Jayasinghe, L. Photoprotective potential in some medicinal plants used to treat skin diseases in Sri Lanka. BMC Complement. Altern. Med., 2016, 16(1), 479.
[http://dx.doi.org/10.1186/s12906-016-1455-8] [PMID: 27881112]
[21]
Ahmed, N.; Mahmood, A.; Tahir, S.S.; Bano, A.; Malik, R.N.; Hassan, S.; Ashraf, A. Ethnomedicinal knowledge and relative importance of indigenous medicinal plants of Cholistan desert, Punjab Province, Pakistan. J. Ethnopharmacol., 2014, 155(2), 1263-1275.
[http://dx.doi.org/10.1016/j.jep.2014.07.007] [PMID: 25066204]
[22]
Devanathadesikan Seshadri, V.; Vijayaraghavan, P.; Kim, Y.O.; Kim, H.J.; Ahmed Al-Ghamdi, A.; Elshikh, M.S.; Al-Dosary, M.A.; Alsubaie, Q.D. In vitro antioxidant and cytotoxic activities of polyherbal extracts from Vetiveria zizanioides, Trichosanthes cucumerina, and Mollugo cerviana on HeLa and MCF-7 cell lines. Saudi J. Biol. Sci., 2020, 27(6), 1475-1481.
[http://dx.doi.org/10.1016/j.sjbs.2020.04.005] [PMID: 32489283]
[23]
Ormazabal, P.; Cifuentes, M.; Vari, R.; Scazzocchio, B.; Masella, R.; Pacheco, I.; Vega, W.; Paredes, A.; Morales, G. Hydroethanolic extract of lampaya medicinalis phil. (Verbenaceae) decreases proinflammatory marker expression in palmitic acid-exposed macrophages. Endocr. Metab. Immune Disord. Drug Targets, 2020.
[24]
Wang, L.; Xu, M.L.; Liu, J.; Wang, Y.; Hu, J.H.; Wang, M.H. Sonchus asper extract inhibits LPS-induced oxidative stress and pro-inflammatory cytokine production in RAW264.7 macrophages. Nutr. Res. Pract., 2015, 9(6), 579-585.
[http://dx.doi.org/10.4162/nrp.2015.9.6.579] [PMID: 26634045]
[25]
Nunes, R.; Broering, M.F.; De Faveri, R.; Goldoni, F.C.; Mariano, L.N.B.; Mafessoli, P.C.M.; Delle Monache, F.; Cechinel Filho, V.; Niero, R.; Santin, J.R.; Quintão, N.L.M. Effect of the metanolic extract from the leaves of Garcinia humilis Vahl (Clusiaceae) on acute inflammation. Inflammopharmacology, 2019.
[http://dx.doi.org/10.1007/s10787-019-00645-x] [PMID: 31552547]
[26]
Srisook, K.; Mankhong, S.; Chiranthanut, N.; Kongsamak, K.; Kitwiwat, N.T.; Tongjurai, P.; Aramsangtienchai, P. Anti-inflammatory effect of trans-4-methoxycinnamaldehyde from Etlingera pavieana in LPS-stimulated macrophages mediated through inactivation of NF-κB and JNK/c-Jun signaling pathways and in rat models of acute inflammation. Toxicol. Appl. Pharmacol., 2019, 371, 3-11.
[http://dx.doi.org/10.1016/j.taap.2019.03.026] [PMID: 30943385]
[27]
Hong, Y.H.; Weng, L.W.; Chang, C.C.; Hsu, H.F.; Wang, C.P.; Wang, S.W.; Houng, J.Y. Anti-inflammatory effects of Siegesbeckia orientalis ethanol extract in in vitro and in vivo models. BioMed Res. Int., 2014, 2014, 329712.
[http://dx.doi.org/10.1155/2014/329712] [PMID: 25328884]

Rights & Permissions Print Cite
Article Metrics
63
1
© 2024 Bentham Science Publishers | Privacy Policy