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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

Cytotoxicity and Anti-Inflammatory Effects of Polyherbal Formulations, Joint Pain Spl and Rumalaya Forte on Lipopolysaccharide Induced Inflammation in IC-21 Macrophages

Author(s): Arunagirinathan Koodalingam*, Arumugam Rajalakshmi and Ezhumalai Parthiban

Volume 20, Issue 3, 2021

Published on: 04 January, 2021

Page: [290 - 301] Pages: 12

DOI: 10.2174/1871523019999210104203252

Price: $65

Abstract

Aim: To test the effectiveness of marketed polyherbal formulations on lipopolysaccharide-induced inflammatory conditions in macrophages.

Background: Usage of herbal compounds among patients suffering from arthritis and cancer is increasing every year. Many anti-inflammatory herbal products available in the market should be screened thoroughly for their possible mechanism of action.

Objective: Joint Pain Spl (JPS) is a polyherbal dietary food supplement composed of 13 herbal plants, and Rumalaya Forte (RF) is a polyherbal formulation comprising of 6 herbal plants. These were tested for their cytotoxicity, as well as antioxidant and anti-inflammatory activities in LPS treated IC-21 peritoneal macrophages.

Methods: Commercially available JPS and RF powder was used to prepare the extract. The aqueous and methanol extracts were quantified for the presence of phenolic and flavonoid compounds and confirmed with HPLC. In vitro DPPH free scavenging activity was performed. Cytotoxicity was tested by MTT assay. Anti-inflammatory activity was tested using lipopolysaccharide-stimulated IC-21 peritoneal macrophage cells.

Results: The phytochemical screening showed the presence of phenolic and flavonoid compounds in JPS and RF. The aqueous and methanol extracts of JPS and RF possesses significant DPPH free radical scavenging activity. MTT assay revealed that 90.64% (aqueous extract) and 92.21% (methanol extract) of exposed macrophages are viable even after 24h exposure of maximal tested concentrations of herbal formulations. Pre-treatment of JPS and RF on LPS induced IC-21 macrophages showed a reduction in nitric oxide production (maximal 79.95%) and a high level of superoxide anion scavenging activity (maximal 82.5%) over control.

Conclusion: The two tested polyherbal formulations, such as JPS and RF possess anti-inflammatory activity by modulating free radical generation in IC-21 macrophages. Thus the presence of the phenolic and flavonoid compounds may contribute to the antioxidant activity.

Keywords: Inflammation, herbal formulation, macrophages, free radicals, plant extracts, nitric oxide.

Graphical Abstract
[1]
Glaros, T.; Larsen, M.; Li, L. Macrophages and fibroblasts during inflammation, tissue damage and organ injury. Front. Biosci., 2009, 14, 3988-3993.
[http://dx.doi.org/10.2741/3506] [PMID: 19273328]
[2]
Mccain, J. The disease burden of the most common autoimmune diseases. Manag. Care, 2016, 25(7), 28-32.
[PMID: 28121529]
[3]
Heneka, M.T. Inflammation in Alzheimer disease. Clin. Neurosci. Res., 2006, 6, 247-260.
[http://dx.doi.org/10.1016/j.cnr.2006.09.005]
[4]
Tönnies, E.; Trushina, E. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J. Alzheimers Dis., 2017, 57(4), 1105-1121.
[http://dx.doi.org/10.3233/JAD-161088] [PMID: 28059794]
[5]
Flauaus, C.; Schmidtko, A. Gastrointestinal and cardiovascular side effects of NSAIDs. Pharmakon, 2017, 5, 61-68.
[6]
Selvam, C.; Jachak, S.M. A cyclooxygenase (COX) inhibitory biflavonoid from the seeds of Semecarpus anacardium. J. Ethnopharmacol., 2004, 95(2-3), 209-212.
[http://dx.doi.org/10.1016/j.jep.2004.07.026] [PMID: 15507338]
[7]
Jung, H.W.; Mahesh, R.; Park, J.H.; Boo, Y.C.; Park, K.M.; Park, Y.K. Bisabolangelone isolated from Ostericum koreanum inhibits the production of inflammatory mediators by down-regulation of NF-kappaB and ERK MAP kinase activity in LPS-stimulated RAW264.7 cells. Int. Immunopharmacol., 2010, 10(2), 155-162.
[http://dx.doi.org/10.1016/j.intimp.2009.10.010] [PMID: 19879381]
[8]
Koodalingam, A.; Manikandan, R.; Indhumathi, M.; Kaviya, E.S. Cytoprotective and anti-inflammatory effects of kernel extract from Adenanthera pavonina on lipopolysaccharide-stimulated rat peritoneal macrophages. Asian Pac. J. Trop. Med., 2015, 8(2), 112-119.
[http://dx.doi.org/10.1016/S1995-7645(14)60300-X] [PMID: 25902024]
[9]
Singh, S.; Kumar, R.; Jain, H.; Gupta, Y.K. Anti-inflammatory and antiarthritic activity of UNIM-301 (a polyherbal unani formulation) in Wistar rats. Pharmacognosy Res., 2015, 7(2), 188-192.
[http://dx.doi.org/10.4103/0974-8490.150515] [PMID: 25829793]
[10]
Lai, N.S.; Livneh, H.; Fan, Y.H.; Lu, M.C.; Liao, H.H.; Tsai, T.Y. Use of Chinese herbal medicines by rheumatoid arthritis patients was associated with lower risk of stroke: A retrospective cohort study. Complement. Ther. Med., 2019, 45, 124-129.
[http://dx.doi.org/10.1016/j.ctim.2019.05.029] [PMID: 31331548]
[11]
Yang, R.; Yuan, B.C.; Ma, Y.S.; Zhou, S.; Liu, Y. The anti-inflammatory activity of licorice, a widely used Chinese herb. Pharm. Biol., 2017, 55(1), 5-18.
[http://dx.doi.org/10.1080/13880209.2016.1225775] [PMID: 27650551]
[12]
Parasuraman, S.; Thing, G.S.; Dhanaraj, S.A. Polyherbal formulation: Concept of ayurveda. Pharmacogn. Rev., 2014, 8(16), 73-80.
[http://dx.doi.org/10.4103/0973-7847.134229] [PMID: 25125878]
[13]
Tripathi, Y.B.; Reddy, M.M.; Pandey, R.S.; Subhashini, J.; Tiwari, O.P.; Singh, B.K.; Reddanna, P. Anti-inflammatory properties of BHUx, a polyherbal formulation to prevent atherosclerosis. Inflammopharmacology, 2004, 12(2), 131-152.
[http://dx.doi.org/10.1163/1568560041352301] [PMID: 15265316]
[14]
Kumar, E.; Rajan, V.R.; Kumar, A.D.; Parasuraman, S.; Emerson, S.F. Hepatoprotective activity of Clearliv a polyherbal formulation in Wistar rats. Arch. Med. Health Sci., 2013, 1, 120.
[http://dx.doi.org/10.4103/2321-4848.123023]
[15]
Chopade, A.R.; Naikwade, N.S.; Mulla, W.A.; Sayyed, F.J. Evaluation of marketed herbal formulations on chronic inflammatory muscle hyperalgesia. Int. J. Pharm. Tech. Res., 2011, 3, 349-355.
[16]
Kang, H.J.; Hong, S.H.; Kang, K.H.; Park, C.; Choi, Y.H. Anti-inflammatory effects of Hwang-Heuk-San, a traditional Korean herbal formulation, on lipopolysaccharide-stimulated murine macrophages. BMC Complement. Altern. Med., 2015, 15, 447.
[http://dx.doi.org/10.1186/s12906-015-0971-2] [PMID: 26698114]
[17]
Subash, K.R.; Somasundaram, G.; Rao, N.J.; Bhaarati, G.M.; Cheriyan, B.V.; Kumar, K.S. Studies on the in vitro anti-oxidant properties of a polyherbal formulation: Rumalaya Forte. J. Clin. Diagn. Res., 2012, 6, 1254-1257.
[18]
Santhrani, T.; Vineela, S. Ameliorative effects of Rumalaya Forte in sciatic nerve transection induced neuropathy in rats. Asian J. Pharm. Biol. Res., 2011, 1, 136-144.
[19]
Chaithra, D.; Yasodamma, N.; Alekhya, C. Anti-inflammatory activity of Curcuma neilgherrensis wt. rhizome extracts. World J. Pharm. Pharm. Sci., 2016, 4, 1040-1053.
[20]
Scott, D.L.; Wolfe, F.; Huizinga, T.W. Rheumatoid arthritis. Lancet, 2010, 376(9746), 1094-1108.
[http://dx.doi.org/10.1016/S0140-6736(10)60826-4] [PMID: 20870100]
[21]
Ulusoy, H.; Güçer, T.K.; Murat, A.K.S.U.; Arslan, Ş.; Habiboglu, A.; Akgöl, G.; Bilgici, A.; Ömer, K.U.R.U.; Cetin, I.; Kamanli, A.; Özgöçmen, S. The use of complementary and alternative medicine in Turkish patients with rheumatic diseases. Arch. Rheumatol., 2012, 27, 031-037.
[22]
Li, X.Z.; Zhang, S.N. Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction. Phytother. Res., 2020, 34(1), 51-66.
[http://dx.doi.org/10.1002/ptr.6509] [PMID: 31515874]
[23]
Saeed, N.; Khan, M.R.; Shabbir, M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement. Altern. Med., 2012, 12, 221.
[http://dx.doi.org/10.1186/1472-6882-12-221] [PMID: 23153304]
[24]
A Handbook of Practical and Clinical Immunology; Talwar, G.P.; Gupta, S.K., Eds.; CBS Publishers & Distributors.: New Delhi, India., 2009.
[25]
Wang, J.; Mazza, G. Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/IFN-γ-activated RAW 264.7 macrophages. J. Agric. Food Chem., 2002, 50(4), 850-857.
[http://dx.doi.org/10.1021/jf010976a] [PMID: 11829656]
[26]
Jung, K.K.; Lee, H.S.; Cho, J.Y.; Shin, W.C.; Rhee, M.H.; Kim, T.G.; Kang, J.H.; Kim, S.H.; Hong, S.; Kang, S.Y. Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia. Life Sci., 2006, 79(21), 2022-2031.
[http://dx.doi.org/10.1016/j.lfs.2006.06.048] [PMID: 16934299]
[27]
Patil, S.K.; Salunkhe, V.R.; Ghumte, D.S.; Mohite, S.K.; Magdum, C.S. Comparative studies on anti-inflammatory activity of hydrogels containing herbal extracts. Int. J. Pharm. Chem. Biol. Sci., 2012, 2, 612-616.
[28]
Aggarwal, B.B.; Prasad, S.; Reuter, S.; Kannappan, R.; Yadev, V.R.; Park, B.; Kim, J.H.; Gupta, S.C.; Phromnoi, K.; Sundaram, C.; Prasad, S.; Chaturvedi, M.M.; Sung, B. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: “reverse pharmacology” and “bedside to bench” approach. Curr. Drug Targets, 2011, 12(11), 1595-1653.
[http://dx.doi.org/10.2174/138945011798109464] [PMID: 21561421]
[29]
Lättig, J.; Böhl, M.; Fischer, P.; Tischer, S.; Tietböhl, C.; Menschikowski, M.; Gutzeit, H.O.; Metz, P.; Pisabarro, M.T. Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design. J. Comput. Aided Mol. Des., 2007, 21(8), 473-483.
[http://dx.doi.org/10.1007/s10822-007-9129-8] [PMID: 17701137]
[30]
Maroon, J.C.; Bost, J.W.; Maroon, A. Natural anti-inflammatory agents for pain relief. Surg. Neurol. Int., 2010, 1, 80.
[http://dx.doi.org/10.4103/2152-7806.73804] [PMID: 21206541]
[31]
Stote, K.S.; Clevidence, B.A.; Novotny, J.A.; Henderson, T.; Radecki, S.V.; Baer, D.J. Effect of cocoa and green tea on biomarkers of glucose regulation, oxidative stress, inflammation and hemostasis in obese adults at risk for insulin resistance. Eur. J. Clin. Nutr., 2012, 66(10), 1153-1159.
[http://dx.doi.org/10.1038/ejcn.2012.101] [PMID: 22854880]
[32]
Olanow, C.W. An introduction to the free radical hypothesis in Parkinson’s disease. Ann. Neurol., 1992, 32(Suppl.), S2-S9.
[http://dx.doi.org/10.1002/ana.410320703] [PMID: 1510376]
[33]
Hegazy, M.F.; Abdelfatah, S.; Hamed, A.R.; Mohamed, T.A.; Elshamy, A.A.; Saleh, I.A.; Reda, E.H.; Abdel-Azim, N.S.; Shams, K.A.; Sakr, M.; Sugimoto, Y.; Paré, P.W.; Efferth, T. Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells. Phytomedicine, 2019, 59, 152771.
[http://dx.doi.org/10.1016/j.phymed.2018.11.031] [PMID: 31055230]
[34]
Jeong, K.; Shin, Y.C.; Park, S.; Park, J.S.; Kim, N.; Um, J.Y.; Go, H.; Sun, S.; Lee, S.; Park, W.; Choi, Y.; Song, Y.; Kim, G.; Jeon, C.; Park, J.; Lee, K.; Bang, O.; Ko, S.G. Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice. J. Biomed. Sci., 2011, 18, 14.
[http://dx.doi.org/10.1186/1423-0127-18-14] [PMID: 21299906]
[35]
Jang, D.; Murrell, G.A.C. Nitric oxide in arthritis. Free Radic. Biol. Med., 1998, 24(9), 1511-1519.
[http://dx.doi.org/10.1016/S0891-5849(97)00459-0] [PMID: 9641270]
[36]
Vane, J.R.; Mitchell, J.A.; Appleton, I.; Tomlinson, A.; Bishop-Bailey, D.; Croxtall, J.; Willoughby, D.A. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Proc. Natl. Acad. Sci., 1994, 91, 2046-2050.
[http://dx.doi.org/10.1073/pnas.91.6.2046]
[37]
Sharma, J.N.; Al-Omran, A.; Parvathy, S.S. Role of nitric oxide in inflammatory diseases. Inflammopharmacology, 2007, 15(6), 252-259.
[http://dx.doi.org/10.1007/s10787-007-0013-x] [PMID: 18236016]
[38]
Ritchie, R.H.; Drummond, G.R.; Sobey, C.G.; De Silva, T.M.; Kemp-Harper, B.K. The opposing roles of NO and oxidative stress in cardiovascular disease. Pharmacol. Res., 2017, 116, 57-69.
[http://dx.doi.org/10.1016/j.phrs.2016.12.017] [PMID: 27988384]
[39]
Dong, B.; An, L.; Yang, X.; Zhang, X.; Zhang, J.; Tuerhong, M.; Jin, D.Q.; Ohizumi, Y.; Lee, D.; Xu, J.; Guo, Y. Withanolides from Physalis peruviana showing nitric oxide inhibitory effects and affinities with iNOS. Bioorg. Chem., 2019, 87, 585-593.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.051] [PMID: 30928880]
[40]
Inaba, R.; Mirbod, S.M.; Sugiura, H. Effects of Maharishi Amrit Kalash 5 as an Ayurvedic herbal food supplement on immune functions in aged mice. BMC Complement. Altern. Med., 2005, 5, 8.
[http://dx.doi.org/10.1186/1472-6882-5-8] [PMID: 15790423]
[41]
Peng, L.H.; Ko, C.H.; Siu, S.W.; Koon, C.M.; Yue, G.L.; Cheng, W.H.; Lau, T.W.; Han, Q.B.; Ng, K.M.; Fung, K.P.; Lau, C.B.S.; Leung, P.C. In vitro & in vivo assessment of a herbal formula used topically for bone fracture treatment. J. Ethnopharmacol., 2010, 131(2), 282-289.
[http://dx.doi.org/10.1016/j.jep.2010.06.039] [PMID: 20600749]
[42]
Stowe, D.F.; Camara, A.K. Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function. Antioxid. Redox Signal., 2009, 11(6), 1373-1414.
[http://dx.doi.org/10.1089/ars.2008.2331] [PMID: 19187004]
[43]
Schulz, E.; Gori, T.; Münzel, T. Oxidative stress and endothelial dysfunction in hypertension. Hypertens. Res., 2011, 34(6), 665-673.
[http://dx.doi.org/10.1038/hr.2011.39] [PMID: 21512515]
[44]
Emerit, J.; Edeas, M.; Bricaire, F. Neurodegenerative diseases and oxidative stress. Biomed. Pharmacother., 2004, 58(1), 39-46.
[http://dx.doi.org/10.1016/j.biopha.2003.11.004] [PMID: 14739060]
[45]
Afonso, V.; Champy, R.; Mitrovic, D.; Collin, P.; Lomri, A. Reactive oxygen species and superoxide dismutases: Role in joint diseases. Joint Bone Spine, 2007, 74(4), 324-329.
[http://dx.doi.org/10.1016/j.jbspin.2007.02.002] [PMID: 17590367]
[46]
Hecht, F.; Pessoa, C.F.; Gentile, L.B.; Rosenthal, D.; Carvalho, D.P.; Fortunato, R.S. The role of oxidative stress on breast cancer development and therapy. Tumour Biol., 2016, 37(4), 4281-4291.
[http://dx.doi.org/10.1007/s13277-016-4873-9] [PMID: 26815507]
[47]
Chakraborty, M.; Karmakar, I.; Haldar, S.; Das, A.; Bala, A.; Haldar, P.K. Amelioration of oxidative DNA damage in mouse peritoneal macrophages by Hippophae salicifolia due to its proton (H(+)) donation capability: Ex vivo and in vivo studies. J. Pharm. Bioallied Sci., 2016, 8(3), 210-216.
[http://dx.doi.org/10.4103/0975-7406.172663] [PMID: 27413349]
[48]
Gökbulut, A.; Orhan, N.; Orhan, D.D. Phenolic compounds characterization, carbohydrate digestive enzyme inhibitory and antioxidant activities of Hieracium pannosum Boiss. S. Afr. J. Bot., 2017, 108, 387-392.
[http://dx.doi.org/10.1016/j.sajb.2016.08.021]
[49]
Bhatt, M.; Reddy, M.N. Antimetastatic, superoxide anion and nitric oxide reduction potential of Solanum xanthocarpum on human lung cancer cell line A549. Indian J. Tradit. Knowl., 2018, 17, 468-473.
[50]
Karami, A.; Kavoosi, G.; Maggi, F. The emulsion made with essential oil and aromatic water from Oliveria decumbens protects murine macrophages from LPS-induced oxidation and exerts relevant radical scavenging activities. Biocatal. Agric. Biotechnol., 2019, 17, 538-544.
[http://dx.doi.org/10.1016/j.bcab.2019.01.015]
[51]
Marques, F.M.; Figueira, M.M.; Schmitt, E.F.P.; Kondratyuk, T.P.; Endringer, D.C.; Scherer, R.; Fronza, M. In vitro anti-inflammatory activity of terpenes via suppression of superoxide and nitric oxide generation and the NF-κB signalling pathway. Inflammopharmacology, 2019, 27(2), 281-289.
[http://dx.doi.org/10.1007/s10787-018-0483-z] [PMID: 29675712]
[52]
Mary, N.K.; Babu, B.H.; Padikkala, J. Antiatherogenic effect of Caps HT2, a herbal Ayurvedic medicine formulation. Phytomedicine, 2003, 10(6-7), 474-482.
[http://dx.doi.org/10.1078/094471103322331412] [PMID: 13678230]

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