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The Natural Products Journal

Author(s): Ketut Agus Adrianta* and I Gede Bayu Somantara

DOI: 10.2174/2210315511666211119123421

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The Curcumin and Gingerol Combination as an Immune Regulator and Anti-Inflammatory Agent of SARS-CoV Infection According to a Nutrigenomic Approach: A Mini-Review

Article ID: e191121198138 Pages: 10

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Abstract

Introduction: The COVID-19 pathophysiology caused by SARS-Cov-2 is closely related to immunoregulation and the process of inflammation. There are therapeutic targets in both, which are ideal for the healing process of infected patients. Phytonutrients are closely related to nutrigenomics. Curcumin and gingerol are two types of phytonutrients that have been studied, researched, and developed as therapeutic agents for diseases.

Objective: This study aimed to examine the potential of curcumin and gingerol as immune regulators and anti-inflammatory agents in SARS-CoV-2 infections using a nutrigenomic approach.

Methods: The literature review method was used in this study. Relevant information was gathered from scientific engines and databases (Google Scholar, Elsevier, Science Direct, Scopus, Wiley Online Library, PubMed) published during 2010-2021, and the data were analyzed by deductive qualitative descriptive technique.

Results and Discussion: Curcumin in turmeric and gingerol in ginger have the potential to be used as a therapy for COVID-19 as they could be immune regulators and anti-inflammatory agents for SARS-CoV-2 infection. Curcumin and gingerol can act as primary and secondary antioxidants that can activate endogenous antioxidant enzymes, regulate cell signaling related to immunity such as interferons, nuclear factor-kappa beta, nitric oxide, and tumor necrosis factor-alpha, as well as stimulate anti-inflammatory and pro-inflammatory cytokine homeostasis, especially interleukins (IL-1β, IL-6, IL-17, IL-8). In silico, these two compounds were also proven to have potential as SARS-CoV-2 antivirals by acting as viral protease inhibitors.

Conclusion: The combination of curcumin and gingerol showed synergistic activity with increasing antioxidant and anti-inflammatory capacities. Thus, it has great potential for use in COVID-19 therapy.

Keywords: SARS-CoV-2, COVID-19, nutrigenomic, curcumin, gingerol, coronavirus.

Graphical Abstract

[1]
Ferruzzi, M.G.; Tanprasertsuk, J.; Kris-Etherton, P.; Weaver, C.M.; Johnson, E.J. Perspective: The role of beverages as a source of nutrients and phytonutrients. Adv. Nutr., 2020, 11(3), 507-523.
[http://dx.doi.org/10.1093/advances/nmz115] [PMID: 31755901]
[2]
Thakur, N.; Raigond, P.; Singh, Y.; Mishra, T.; Singh, B.; Lal, M.K.; Dutt, S. Recent updates on bioaccessibility of phytonutrients. Trends Food Sci. Technol., 2019, 2020(97), 366-380.
[http://dx.doi.org/10.1016/j.tifs.2020.01.019]
[3]
Bule, M.; Issa, I.A.; Fazlullah, K.; Shah, M.A.; Niaz, K. Development of new food products based on phytonutrients. Woodhead Publishing: UK. 2020.
[http://dx.doi.org/10.1016/B978-0-12-815354-3.00008-3]
[4]
Den Hartogh, D.J.; Gabriel, A.; Tsiani, E. Antidiabetic properties of curcumin i: Evidence from in vitro studies. Nutrients, 2020, 12(1), E118.
[http://dx.doi.org/10.3390/nu12010118] [PMID: 31906278]
[5]
Rohman, A.; Widodo, H.; Lukitaningsih, E.; Windarsih, A.; Rafi, M.; Nurrulhidayah, A.F. Review on in vitro antioxidant activities of curcuma species commonly used as herbal components in Indonesia. Food Res., 2020, 4(2), 286-293.
[http://dx.doi.org/10.26656/fr.2017.4(2).163]
[6]
Guimarãesa, A.F.; Vinhasa, A.C.A.; Angélica Ferraz Gomesa, L.H.S.; Krepsky, P.B. Rhizomes chemical composition, yield variation and stability. Quim. Nov., 2020, 43(7), 909-913.
[http://dx.doi.org/10.21577/0100-4042.20170547]
[7]
Serpa Guerra, A.M.; Gómez Hoyos, C.; Velásquez-Cock, J.A.; Vélez Acosta, L.; Gañán Rojo, P.; Velásquez Giraldo, A.M.; Zuluaga Gallego, R. The nanotech potential of turmeric (Curcuma longa L.) in food technology: A review. Crit. Rev. Food Sci. Nutr., 2020, 60(11), 1842-1854.
[http://dx.doi.org/10.1080/10408398.2019.1604490] [PMID: 31017458]
[8]
Indriani, U.; Idiawati, N.; Wibowo, M.A. Uji aktivitas antiinflamasi dan toksisitas infus. Kim. Khatulistiwa, 2018, 7(2), 107-112.
[9]
Lee, S.Y.; Cho, S.S.; Li, Y.C.; Bae, C.S.; Park, K.M.; Park, D.H. Anti-inflammatory effect of Curcuma Longa and Allium Hookeri co-treatment via NF-KB and COX-2 pathways. Sci. Rep., 2020, 10(1), 1-11.
[http://dx.doi.org/10.1038/s41598-020-62749-7] [PMID: 31913322]
[10]
Shereen, M.A.; Khan, S.; Kazmi, A.; Bashir, N.; Siddique, R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J. Adv. Res., 2020, 24, 91-98.
[http://dx.doi.org/10.1016/j.jare.2020.03.005] [PMID: 32257431]
[11]
Zumla, A.; Chan, J.F.W.; Azhar, E.I.; Hui, D.S.C.; Yuen, K.Y. Coronaviruses - drug discovery and therapeutic options. Nat. Rev. Drug Discov., 2016, 15(5), 327-347.
[http://dx.doi.org/10.1038/nrd.2015.37] [PMID: 26868298]
[12]
Fernandez-Gutierrez, B. COVID-19 with pulmonary involvement. an autoimmune disease of known cause. Reumatol. Clínica (English Ed.), 2020, 16(4), 253-254.
[http://dx.doi.org/10.1016/j.reumae.2020.04.001]
[13]
Channappanavar, R.; Fehr, A.R.; Vijay, R.; Mack, M.; Zhao, J.; Meyerholz, D.K.; Perlman, S. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe, 2016, 19(2), 181-193.
[http://dx.doi.org/10.1016/j.chom.2016.01.007] [PMID: 26867177]
[14]
Killip, M.J.; Fodor, E.; Randall, R.E. Influenza virus activation of the interferon system. Virus Res., 2015, 209, 11-22.
[http://dx.doi.org/10.1016/j.virusres.2015.02.003] [PMID: 25678267]
[15]
Zheng, J.; Perlman, S. Immune responses in influenza a virus and human coronavirus infections: An ongoing battle between the virus and host. Curent Opin. Virol., 2020, 28(January), 43-52.
[http://dx.doi.org/10.1016/j.coviro.2017.11.002]
[16]
Shokri, S.; Mahmoudvand, S.; Taherkhani, R.; Farshadpour, F. Modulation of the immune response by Middle East respiratory syndrome coronavirus. J. Cell. Physiol., 2019, 234(3), 2143-2151.
[http://dx.doi.org/10.1002/jcp.27155] [PMID: 30146782]
[17]
Channappanavar, R.; Perlman, S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol., 2017, 39(5), 529-539.
[http://dx.doi.org/10.1007/s00281-017-0629-x] [PMID: 28466096]
[18]
Kindrachuk, J.; Ork, B.; Hart, B.J.; Mazur, S.; Holbrook, M.R.; Frieman, M.B.; Traynor, D.; Johnson, R.F.; Dyall, J.; Kuhn, J.H.; Olinger, G.G.; Hensley, L.E.; Jahrling, P.B. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for middle east respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob. Agents Chemother., 2015, 59(2), 1088-1099.
[http://dx.doi.org/10.1128/AAC.03659-14] [PMID: 25487801]
[19]
DeDiego, M.L.; Nieto-Torres, J.L.; Regla-Nava, J.A.; Jimenez- Guardeño, J.M.; Fernandez-Delgado, R.; Fett, C.; Castaño-Rodriguez, C.; Perlman, S.; Enjuanes, L. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J. Virol., 2014, 88(2), 913-924.
[http://dx.doi.org/10.1128/JVI.02576-13] [PMID: 24198408]
[20]
Khan, M.S.; Muhammad, T.; Ikram, M.; Kim, M.O. Dietary supplementation of the antioxidant curcumin halts systemic LPS-induced neuroinflammation-associated neurodegeneration and memory/synaptic impairment via the JNK/NF-KB/AKT signaling pathway in adult rats. Oxid. Med. Cell. Longev., 2019, 2019, 7860650.
[http://dx.doi.org/10.1155/2019/7860650] [PMID: 31827700]
[21]
Maithilikarpagaselvi, N.; Sridhar, M.G.; Sripradha, R. Evaluation of free radical scavenging activities and phytochemical screening of curcuma longa extracts. J. Young Pharm., 2020, 12(2), 113-117.
[http://dx.doi.org/10.5530/jyp.2020.12.23]
[22]
Singh, L.M.; Chakraborty, B.; Pal, R.; Nath, A.; Pal, S.; Rahman, D.S.; Ghosh, S.K.; Sengupta, M. A comparative study on the antioxidant and immunomodulatory properties of curcumin conjugated gold nanospheres and free curcumin. J. Appl. Pharm. Sci., 2017, 7(11), 56-63.
[http://dx.doi.org/10.7324/JAPS.2017.71108]
[23]
Ferreira, V.H.; Nazli, A.; Dizzell, S.E.; Mueller, K.; Kaushic, C. The anti-inflammatory activity of curcumin protects the genital mucosal epithelial barrier from disruption and blocks replication of HIV-1 and HSV-2. PLoS One, 2015, 10(4), e0124903.
[http://dx.doi.org/10.1371/journal.pone.0124903] [PMID: 25856395]
[24]
Zahedipour, F.; Hosseini, S.A.; Sathyapalan, T.; Majeed, M.; Jamialahmadi, T.; Al-Rasadi, K.; Banach, M.; Sahebkar, A. Potential effects of curcumin in the treatment of COVID-19 infection. Phytother. Res., 2020, 34(11), 2911-2920.
[http://dx.doi.org/10.1002/ptr.6738] [PMID: 32430996]
[25]
Avasarala, S.; Zhang, F.; Liu, G.; Wang, R.; London, S.D.; London, L. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome. PLoS One, 2013, 8(2), e57285.
[http://dx.doi.org/10.1371/journal.pone.0057285] [PMID: 23437361]
[26]
Obata, K.; Kojima, T.; Masaki, T.; Okabayashi, T.; Yokota, S.; Hirakawa, S.; Nomura, K.; Takasawa, A.; Murata, M.; Tanaka, S.; Fuchimoto, J.; Fujii, N.; Tsutsumi, H.; Himi, T.; Sawada, N. Curcumin prevents replication of respiratory syncytial virus and the epithelial responses to it in human nasal epithelial cells. PLoS One, 2013, 8(9), e70225.
[http://dx.doi.org/10.1371/journal.pone.0070225] [PMID: 24058438]
[27]
Tian, S.; Hu, W.; Niu, L.; Liu, H.; Xu, H.; Xiao, S.Y. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J. Thorac. Oncol., 2020, 15(5), 700-704.
[http://dx.doi.org/10.1016/j.jtho.2020.02.010] [PMID: 32114094]
[28]
Sarada, T.M. Attenuation of NFkB activation augments alveolar transport proteins expression and activity under hypoxia. Int. J. Sci. Res., 2015, 4(3), 2230-2237.
[29]
Titto, M.; Ankit, T.; Saumya, B.; Gaural, A.K; Sarada, S.K.S. Curcumin prophylaxis refurbishes alveolar epithelial barrier integrity and alveolar fluid clearance under hypoxia. Respir. Physiol. Neurobiol., 2019, 2020(274), 103336.
[http://dx.doi.org/10.1016/j.resp.2019.103336]
[30]
Babaei, F.; Nassiri-Asl, M.; Hosseinzadeh, H. Curcumin (a constituent of turmeric): New treatment option against COVID-19. Food Sci. Nutr., 2020, 8(10), 5215-5227.
[http://dx.doi.org/10.1002/fsn3.1858] [PMID: 33133525]
[31]
Gouda, M.M.; Shaikh, S.B.; Bhandary, Y.P. Inflammatory and fibrinolytic system in acute respiratory distress syndrome. Lung, 2018, 196(5), 609-616.
[http://dx.doi.org/10.1007/s00408-018-0150-6] [PMID: 30121847]
[32]
Kumaki, Y.; Salazar, A.M.; Wandersee, M.K.; Barnard, D.L. Prophylactic and therapeutic intranasal administration with an immunomodulator, Hiltonol® (Poly IC:LC), in a lethal SARS-CoV- infected BALB/c mouse model. Diabetes Metab. Syndr., 2020, 14(4), 337-339.
[PMID: 32305024]
[33]
Jasso-Miranda, C.; Herrera-Camacho, I.; Flores-Mendoza, L.K.; Dominguez, F.; Vallejo-Ruiz, V.; Sanchez-Burgos, G.G.; Pando-Robles, V.; Santos-Lopez, G.; Reyes-Leyva, J. Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies. Infect. Drug Resist., 2019, 12, 1833-1852.
[http://dx.doi.org/10.2147/IDR.S210890] [PMID: 31303775]
[34]
Ting, D.; Dong, N.; Fang, L.; Lu, J.; Bi, J.; Xiao, S.; Han, H. Multisite inhibitors for enteric coronavirus: Antiviral cationic carbon dots based on curcumin. ACS Appl. Nano Mater., 2018, 1(10), 5451-5459.
[http://dx.doi.org/10.1021/acsanm.8b00779]
[35]
Yadav, R.; Mishra, S. A study on development of nutrigenomics premix powder. Int. J. Sci. Res., 2017, 6(12), 1224-1226.
[http://dx.doi.org/10.21275/ART20178538]
[36]
Ghasemzadeh, A.; Jaafar, H.Z.E.; Rahmat, A. Optimization protocol for the extraction of 6-gingerol and 6-shogaol from Zingiber officinale var. rubrum Theilade and improving antioxidant and anticancer activity using response surface methodology. BMC Complement. Altern. Med., 2015, 15(1), 258.
[http://dx.doi.org/10.1186/s12906-015-0718-0] [PMID: 26223685]
[37]
Ghasemzadeh, A.; Jaafar, H.Z.E.; Baghdadi, A.; Tayebi-Meigooni, A. Formation of 6-, 8- and 10-shogaol in ginger through application of different drying methods: altered antioxidant and antimicrobial activity. Molecules, 2018, 23(7), E1646.
[http://dx.doi.org/10.3390/molecules23071646] [PMID: 29976903]
[38]
Mukkavilli, R.; Yang, C.; Singh Tanwar, R.; Ghareeb, A.; Luthra, L.; Aneja, R. Absorption, metabolic stability, and pharmacokinetics of ginger phytochemicals. Molecules, 2017, 22(4), E553.
[http://dx.doi.org/10.3390/molecules22040553] [PMID: 28358331]
[39]
Mao, Q.Q.; Xu, X.Y.; Cao, S.Y.; Gan, R.Y.; Corke, H.; Beta, T.; Li, H.B. Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods, 2019, 8(6), 1-21.
[http://dx.doi.org/10.3390/foods8060185] [PMID: 31151279]
[40]
Zhang, M.; Viennois, E.; Prasad, M.; Zhang, Y.; Wang, L.; Zhang, Z.; Han, K. Edible Ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Physiol. Behav., 2019, 176(3), 139-148.
[http://dx.doi.org/10.1016/j.biomaterials.2016.06.018.Edible]
[41]
Chang, J.S.; Wang, K.C.; Yeh, C.F.; Shieh, D.E.; Chiang, L.C. Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J. Ethnopharmacol., 2013, 145(1), 146-151.
[http://dx.doi.org/10.1016/j.jep.2012.10.043] [PMID: 23123794]
[42]
Bare, Y. Virtual screening: Prediksi potensi 8-shogaol terhadap c-jun n-terminal kinase (jnk). J. Penelit. dan Pengkaj. Ilmu Pendidik. e-Saintika, 2020, 4(1), 1.
[http://dx.doi.org/10.36312/e-saintika.v4i1.157]
[43]
Chen, L.; Hu, C.; Hood, M.; Zhang, X.; Zhang, L.; Kan, J.; Du, J. A novel combination of vitamin C, curcumin and glycyrrhizic acid potentially regulates immune and inflammatory response associated with coronavirus infections: A perspective from system biology analysis. Nutrients, 2020, 12(4), 1-17.
[http://dx.doi.org/10.3390/nu12041193] [PMID: 32344708]
[44]
Felgenhauer, U.; Schoen, A.; Gad, H.H.; Hartmann, R.; Schaubmar, A.R.; Failing, K.; Drosten, C.; Weber, F. Inhibition of SARS-CoV-2 by type I and type III interferons. J. Biol. Chem., 2020, 295(41), 13958-13964.
[http://dx.doi.org/10.1074/jbc.AC120.013788] [PMID: 32587093]
[45]
Soufli, I.; Toumi, R.; Rafa, H.; Touil-Boukoffa, C. Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases. World J. Gastrointest. Pharmacol. Ther., 2016, 7(3), 353-360.
[http://dx.doi.org/10.4292/wjgpt.v7.i3.353] [PMID: 27602236]
[46]
Famurewa, A.C.; Ekeleme-Egedigwe, C.A.; Onwe, C.S.; Egedigwe, U.O.; Okoro, C.O.; Egedigwe, U.J.; Asogwa, N.T. Ginger juice prevents cisplatin-induced oxidative stress, endocrine imbalance and NO/iNOS/NF-κB signalling via modulating testicular redox-inflammatory mechanism in rats. Andrologia, 2020, 52(10), e13786.
[http://dx.doi.org/10.1111/and.13786] [PMID: 32777091]
[47]
Gamage, K.; Dissanayake, C.; Angoda, W.; Chandrasiri Waliwita, L.; Liyanage, R.P. A review on medicinal uses of Zingiber Officinale (Ginger). Int. J. Health Sci. Res., 2020, 10(6), 142.
[48]
Pan, M.H.; Hsieh, M.C.; Hsu, P.C.; Ho, S.Y.; Lai, C.S.; Wu, H.; Sang, S.; Ho, C.T. 6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Mol. Nutr. Food Res., 2008, 52(12), 1467-1477.
[http://dx.doi.org/10.1002/mnfr.200700515] [PMID: 18683823]
[49]
Butt, M.S.; Naz, A.; Sultan, M.T.; Qayyum, M.M.N. Anti-oncogenic perspectives of spices/herbs: A comprehensive review. EXCLI J., 2013, 12, 1043-1065.
[http://dx.doi.org/10.17877/DE290R-7360] [PMID: 27092039]
[50]
Abolaji, A.O.; Ojo, M.; Afolabi, T.T.; Arowoogun, M.D.; Nwawolor, D.; Farombi, E.O. Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Chem. Biol. Interact., 2017, 270, 15-23.
[http://dx.doi.org/10.1016/j.cbi.2017.03.017] [PMID: 28373059]
[51]
Yeh, H.; Chuang, C.H.; Chen, H.C.; Wan, C.J.; Chen, T.L.; Lin, L.Y. Bioactive components analysis of two various gingers (zingiber officinale roscoe) and antioxidant effect of ginger extracts. Lebensm. Wiss. Technol., 2014, 55(1), 329-334.
[http://dx.doi.org/10.1016/j.lwt.2013.08.003]
[52]
Ueno, N.; Hasebe, T.; Kaneko, A.; Yamamoto, M.; Fujiya, M.; Kohgo, Y.; Kono, T.; Wang, C.Z.; Yuan, C.S.; Bissonnette, M.; Chang, E.B.; Musch, M.W. TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-κB suppression. PLoS One, 2014, 9(5), e97456.
[http://dx.doi.org/10.1371/journal.pone.0097456] [PMID: 24857966]
[53]
Zhang, Z.; Du, G.J.; Wang, C.Z.; Wen, X.D.; Calway, T.; Li, Z.; He, T.C.; Du, W.; Bissonnette, M.; Musch, M.W.; Chang, E.B.; Yuan, C.S. Compound K, a Ginsenoside metabolite, inhibits colon cancer growth via multiple pathways including p53-p21 interactions. Int. J. Mol. Sci., 2013, 14(2), 2980-2995.
[http://dx.doi.org/10.3390/ijms14022980] [PMID: 23434653]
[54]
Guerin, E.; Shkoporov, A.; Stockdale, S.R.; Clooney, A.G.; Ryan, F.J.; Sutton, T.D.S.; Draper, L.A.; Gonzalez-Tortuero, E.; Ross, R.P.; Hill, C. Biology and taxonomy of crass-like bacteriophages, the most abundant virus in the human gut. Cell Host Microbe, 2018, 24(5), 653-664.e6.
[http://dx.doi.org/10.1016/j.chom.2018.10.002] [PMID: 30449316]
[55]
Rathinavel, T.; Palanisamy, M.; Palanisamy, S.; Subramanian, A.; Thangaswamy, S. Phytochemical 6-Gingerol – A promising drug of choice for COVID-19. Int. J. Adv. Sci. Eng., 2020, 06(04), 1482-1489.
[http://dx.doi.org/10.29294/IJASE.6.4.2020.1482-1489]
[56]
Townsend, E.A.; Zhang, Y.; Xu, C.; Wakita, R.; Emala, C.W. Active components of ginger potentiate β-agonist-induced relaxation of airway smooth muscle by modulating cytoskeletal regulatory proteins. Am. J. Respir. Cell Mol. Biol., 2014, 50(1), 115-124.
[http://dx.doi.org/10.1165/rcmb.2013-0133OC] [PMID: 23962082]
[57]
Mangprayool, T.; Kupittayanant, S.; Chudapongse, N. Participation of citral in the bronchodilatory effect of ginger oil and possible mechanism of action. Fitoterapia, 2013, 89(1), 68-73.
[http://dx.doi.org/10.1016/j.fitote.2013.05.012] [PMID: 23685048]
[58]
Khan, A.M.; Shahzad, M.; Raza Asim, M.B.; Imran, M.; Shabbir, A. Zingiber officinale ameliorates allergic asthma via suppression of Th2-mediated immune response. Pharm. Biol., 2015, 53(3), 359-367.
[http://dx.doi.org/10.3109/13880209.2014.920396] [PMID: 25420680]
[59]
Vahdat Shariatpanahi, Z.; Mokhtari, M.; Taleban, F.A.; Alavi, F.; Salehi Surmaghi, M.H.; Mehrabi, Y.; Shahbazi, S. Effect of enteral feeding with ginger extract in acute respiratory distress syndrome. J. Crit. Care, 2013, 28(2), 217.e1-217.e6.
[http://dx.doi.org/10.1016/j.jcrc.2012.04.017] [PMID: 22884532]
[60]
Mushtaq, Z.; Tahir Nadeem, M.; Arshad, M.U.; Saeed, F.; Ahmed, M.H.; Bader Ul Ain, H.; Javed, A.; Anjum, F.M.; Hussain, S. Exploring the biochemical and antioxidant potential of ginger (adric) and turmeric (haldi). Int. J. Food Prop., 2019, 22(1), 1642-1651.
[http://dx.doi.org/10.1080/10942912.2019.1666138]
[61]
Poh, K.H.; Muhammad, N.; Abdullah, N.; Talip, A. The evaluation of antioxidant activity of individual and mixture of lemongrass, curry leaves, turmeric and ginger extracts. J. Sci. Technol., 2018, 10(2), 66-70.
[http://dx.doi.org/10.30880/jst.2018.10.02.011]
[62]
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[63]
Singh, R.; Mehta, A.; Mehta, P.; Petel, J.R. In vivo evaluation for anti-inflammatory activities of hyro alcoholic combined extracts of Curcuma Longa and Zingiber Officinale Rhizomes. J. Nov. Res. Pharm. Technol., 2014, 1(2), 13-19.
[64]
Ramadan, G.; El-Menshawy, O. Protective effects of ginger- turmeric rhizomes mixture on joint inflammation, atherogenesis, kidney dysfunction and other complications in a rat model of human rheumatoid arthritis. Int. J. Rheum. Dis., 2013, 16(2), 219-229.
[http://dx.doi.org/10.1111/1756-185X.12054] [PMID: 23773648]
[65]
Heidari-Beni, M.; Moravejolahkami, A.R.; Gorgian, P.; Askari, G.; Tarrahi, M.J.; Bahreini-Esfahani, N. Herbal formulation “turmeric extract, black pepper, and ginger” versus Naproxen for chronic knee osteoarthritis: A randomized, double-blind, controlled clinical trial. Phytother. Res., 2020, 34(8), 2067-2073.
[http://dx.doi.org/10.1002/ptr.6671] [PMID: 32180294]
[66]
Kravchenko, I.; Eberle, L.; Nesterkina, M.; Kobernik, A. Anti-inflammatory and analgesic activity of ointment based on dense ginger extract (Zingiber Officinale). J. HerbMed Pharmacol., 2019, 8(2), 126-132.
[http://dx.doi.org/10.15171/jhp.2019.20]
[67]
Panahi, Y.; Rahimnia, A.R.; Sharafi, M.; Alishiri, G.; Saburi, A.; Sahebkar, A. curcuminoid treatment for knee osteoarthritis: A randomized double-blind placebo-controlled trial. Phytother. Res., 2014, 28(11), 1625-1631.
[http://dx.doi.org/10.1002/ptr.5174] [PMID: 24853120]
[68]
Clutterbuck, A.L.; Allaway, D.; Harris, P.; Mobasheri, A. Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage. F1000 Res., 2013, 2, 147.
[http://dx.doi.org/10.12688/f1000research.2-147.v1] [PMID: 24555068]
[69]
Madkor, H.R.; Mansour, S.W.; Ramadan, G. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats. Br. J. Nutr., 2011, 105(8), 1210-1217.
[http://dx.doi.org/10.1017/S0007114510004927] [PMID: 21144104]
[70]
Patwardhan, M.; Morgan, M.T.; Dia, V.; D’Souza, D.H. Heat sensitization of hepatitis A virus and Tulane virus using grape seed extract, gingerol and curcumin. Food Microbiol., 2020, 90(90), 103461.
[http://dx.doi.org/10.1016/j.fm.2020.103461] [PMID: 32336357]
[71]
Akinyemi, A.J.; Thomé, G.R.; Morsch, V.M.; Bottari, N.B.; Baldissarelli, J.; de Oliveira, L.S.; Goularte, J.F.; Belló-Klein, A.; Duarte, T.; Duarte, M.; Boligon, A.A.; Athayde, M.L.; Akindahunsi, A.A.; Oboh, G.; Schetinger, M.R. Effect of ginger and turmeric rhizomes on inflammatory cytokines levels and enzyme activities of cholinergic and purinergic systems in hypertensive rats. Planta Med., 2016, 82(7), 612-620.
[http://dx.doi.org/10.1055/s-0042-102062] [PMID: 27002391]
[72]
Oso, B.J.; Adeoye, A.O.; Olaoye, I.F. Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases. J. Biomol. Struct. Dyn., 2020, 1(1), 1-12.
[http://dx.doi.org/10.1080/07391102.2020.1813630] [PMID: 32876538]
[73]
AyanfeOluwa. The potential of organically cultivated ginger, turmeric and garlic to improve body immune system in combating COVID-19. Af rican Org. Agric. NOARA, 2021. (January).
[http://dx.doi.org/10.13140/RG.2.2.20582.24643]
[74]
Wen, C.C.; Kuo, Y.H.; Jan, J.T.; Liang, P.H.; Wang, S.Y.; Liu, H.G.; Lee, C.K.; Chang, S.T.; Kuo, C.J.; Lee, S.S.; Hou, C.C.; Hsiao, P.W.; Chien, S.C.; Shyur, L.F.; Yang, N.S. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J. Med. Chem., 2007, 50(17), 4087-4095.
[http://dx.doi.org/10.1021/jm070295s] [PMID: 17663539]
[75]
 , Anggakusuma; Colpitts, C.C.; Schang, L.M.; Rachmawati, H.; Frentzen, A.; Pfaender, S.; Behrendt, P.; Brown, R.J.P.; Bankwitz, D.; Steinmann, J. Turmeric curcumin inhibits entry of all hepatitis c virus genotypes into human liver cells. Gut, 2014, 63(7), 1137-1149.
[http://dx.doi.org/10.1136/gutjnl-2012-304299]
[76]
Marbawati, D.; Umniyati, S.R. Uji Anti virus senyawa kurkumin dan pgv-0 pada virus dengue-2 Dengan RT-PCR antiviral test of curcumin and PGV-0 on Dengue-2 virus by RT-PCR. BALABA, 2016, 45(1), 15-22.
[77]
Edwards, R.L.; Luis, P.B.; Nakashima, F.; Kunihiro, A.G.; Presley, S.H.; Funk, J.L.; Schneider, C. Mechanistic differences in the inhibition of NF-ΚB by turmeric and its curcuminoid constituents. J. Agric. Food Chem., 2020, 68(22), 6154-6160.
[http://dx.doi.org/10.1021/acs.jafc.0c02607] [PMID: 32378408]
[78]
Gorabi, A.M.; Razi, B.; Aslani, S.; Abbasifard, M.; Imani, D.; Sathyapalan, T.; Sahebkar, A. Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials. Cytokine, 2021, 143(143), 155541.
[http://dx.doi.org/10.1016/j.cyto.2021.155541] [PMID: 33934954]
[79]
Gan, L.; Li, C.; Wang, J.; Guo, X. Curcumin modulates the effect of histone modification on the expression of chemokines by type II alveolar epithelial cells in a rat COPD model. Int. J. Chron. Obstruct. Pulmon. Dis., 2016, 11(11), 2765-2773.
[http://dx.doi.org/10.2147/COPD.S113978] [PMID: 27853364]
[80]
Toda, K.; Tsukayama, I.; Nagasaki, Y.; Konoike, Y.; Tamenobu, A.; Ganeko, N.; Ito, H.; Kawakami, Y.; Takahashi, Y.; Miki, Y.; Yamamoto, K.; Murakami, M.; Suzuki-Yamamoto, T. Red-kerneled rice proanthocyanidin inhibits arachidonate 5-lipoxygenase and decreases psoriasis-like skin inflammation. Arch. Biochem. Biophys., 2020, 689(689), 108307.
[http://dx.doi.org/10.1016/j.abb.2020.108307] [PMID: 32112739]
[81]
Boozari, M.; Butler, A.E.; Sahebkar, A. Impact of curcumin on toll-like receptors. J. Cell. Physiol., 2019, 234(8), 12471-12482.
[http://dx.doi.org/10.1002/jcp.28103] [PMID: 30623441]
[82]
Khaerunnisa, S.; Kurniawan, H.; Awaluddin, R.; Suhartati, S. Potential inhibitor of COVID-19 main protease (m pro) from several medicinal plant compounds by molecular docking study. Preprints., 2020.
[http://dx.doi.org/10.20944/preprints202003.0226.v1]
[83]
Abdel-Moneim, A.; Morsy, B.M.; Mahmoud, A.M.; Abo-Seif, M.A.; Zanaty, M.I. Original article : Beneficial therapeutic effects of nigella sativa. EXCLI J., 2013, 12(Lc), 943-955.
[84]
El-adawi, H.; El-demellawy, M.; El-wahab, A.A. Some Medicinal Plant Extracts Exhibit Potency Against Viral Hepatitis C. J. Biosci. Technol., 2011, 2(1), 223-231.
[85]
Sahoo, M.; Jena, L.; Rath, S.N.; Kumar, S. Identification of suitable natural inhibitor against influenza A (H1N1) neuraminidase protein by molecular docking. Genomics Inf., 2016, 14(3), 96-103.
[http://dx.doi.org/10.5808/GI.2016.14.3.96]
[86]
Astani, A.; Reichling, J.; Schnitzler, P. Screening for antiviral activities of isolated compounds from essential oils. Evid. Based Complement. Alternat. Med., 2011, 2011, 253643.
[http://dx.doi.org/10.1093/ecam/nep187] [PMID: 20008902]
[87]
Kim, Y.; Kim, D.M.; Kim, J.Y. Ginger extract suppresses inflammatory response and maintains barrier function in human colonic epithelial CACO-2 cells exposed to inflammatory mediators. J. Food Sci., 2017, 82(5), 1264-1270.
[http://dx.doi.org/10.1111/1750-3841.13695] [PMID: 28369951]
[88]
Lee, H.Y.; Park, S.H.; Lee, M.; Kim, H.J.; Ryu, S.Y.; Kim, N.D.; Hwang, B.Y.; Hong, J.T.; Han, S.B.; Kim, Y. 1-Dehydro-[10]-gingerdione from ginger inhibits IKKβ activity for NF-κB activation and suppresses NF-κB-regulated expression of inflammatory genes. Br. J. Pharmacol., 2012, 167(1), 128-140.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01980.x] [PMID: 22489648]
[89]
Deol, P.K.; Khare, P.; Bishnoi, M.; Kondepudi, K.K.; Kaur, I.P. Coadministration of ginger extract-Lactobacillus acidophilus (cobiotic) reduces gut inflammation and oxidative stress via downregulation of COX-2, i-NOS, and c-Myc. Phytother. Res., 2018, 32(10), 1950-1956.
[http://dx.doi.org/10.1002/ptr.6121] [PMID: 29876980]
[90]
Elsayed, N.M.; Allehyani, N.M.M.; Elzahar, K.M.; Mostafa, A.A.Z.M. Ginger as a possible treatment for COVID-19. Biosci. Res., 2020, 17(4), 4112-4117.
[91]
Jafarzadeh, A.; Ahangar-Parvin, R.; Nemat, M.; Taghipour, Z.; Shamsizadeh, A.; Ayoobi, F.; Hassan, Z.M. Ginger extract modulates the expression of IL-12 and TGF-β in the central nervous system and serum of mice with experimental autoimmune encephalomyelitis. Avicenna J. Phytomed., 2017, 7(1), 54-65.
[http://dx.doi.org/10.22038/ajp.2016.7002] [PMID: 28265547]
[92]
Aryaeian, N.; Shahram, F.; Mahmoudi, M.; Tavakoli, H.; Yousefi, B.; Arablou, T.; Jafari Karegar, S. The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis. Gene, 2019, 698(March), 179-185.
[http://dx.doi.org/10.1016/j.gene.2019.01.048] [PMID: 30844477]
[93]
Maizura, M.; Aminah, A.; Aida, W.M.W. Total phenolic content and antioxidant activity of kesum (Polygonum Minus), ginger (Zingiber Officinale) and turmeric (Curcuma Longa) extract. Int. Food Res. J., 2011, 18(2), 526-531.
[94]
Sahoo, N.; Mishra, S.K.; Swain, R.K.; Acharya, A.P.; Pattnaik, S.; Sethy, K.; Sahoo, L. Effect of turmeric and ginger supplementation on immunity, antioxidant, liver enzyme activity, gut bacterial load and histopathology of broilers. Indian J. Anim. Sci., 2019, 89(7), 774-779.
[95]
Ramadan, G.; Al-Kahtani, M.A.; El-Sayed, W.M. Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation, 2011, 34(4), 291-301.
[http://dx.doi.org/10.1007/s10753-010-9278-0] [PMID: 21120596]
[96]
Moosavi, L.; Mazloom, Z.; Mokhtari, M.; Sartang, M.M.; Mahmoodi, M. Comparison of the effects of combination of turmeric, ginger and cinnamon hydroalcoholic extracts with metformin on body weight, glycemic control, inflammation, oxidative stress and pancreatic histopatalogical changes in diabetic rat. Int. J. Nurs. Sci., 2020, 5(2), 61-68.
[http://dx.doi.org/10.30476/IJNS.2020.86516.1069.Int]