The COVID-19 pandemic is a highly challenging situation and affects people's lives severely. Nowadays, the original coronavirus gets mutated into different variants and infects all age groups. Elderly people with comorbidities like diabetes are highly susceptible to coronavirus infection due to poor glycemic control, and immunity. The mechanism of COVID-19 infection is not fully understood. However, the scenario of current infection is similar to the history of pandemics that the world faced earlier (i.e.) the persisted hyperglycemia is considered as the major root cause of severe viral infections. The uncontrolled hyperglycemia can produce low-grade inflammation and impaired immunity mediated cytokine storm that can cause multiple organs failure and sudden death in diabetic patients with COVID-19 infection. The available hypoglycemic and antiviral drugs and vaccines are not sufficiently efficient against COVID-19 and also cause several side effects. As the traditional medicines are considered life-saving drugs for various human diseases, the present review has analyzed the herbs-spices with antiviral, antidiabetic, antioxidant, anti-inflammatory, and immunomodulatory properties. The intake of this herbal-spices formulation could exert both therapeutic and prophylactic effects against the COVID-19. However, the proper scientific studies are necessary for the validation of its efficacy and mode of action against COVID-19.
The authors wish to thank the All India Council for Technical Education (AICTE), New Delhi, India, for utilizing the research facility established under the Research Promotion Scheme (Ref. No: 8-164/RIFD/RPS/POLICY-4/2013-140.
The authors declare no competing of interest.
Aara, A., Chappidi, V., Ramadas, M., 2020. Antioxidant activity of eugenol in Piper betel leaf extract. Journal of Family Medicine and Primary Care. 9, 327–331.
Abdelhady, M.I.S., Shaheen, U., Bader, A., Youns, M.A., 2016. A new sucrase enzyme inhibitor from Azadirachta indica. Pharmacog- nosy Magazine. 12, 293–296.
Acevedo-Murillo, J.A., León, M.L.G., Firo-Reyes, V., Santiago- Cordova, J.L., Gonzalez-Rodriguez, A.P., Wong-Chew, R.M., 2019. Zinc supplementation promotes a Th1 response and improves clinical symptoms in fewer hours in children with pneumonia younger than 5 years old. A randomized controlled clinical trial. Frontiers in Pediatrics. 7, 431.
Acharya, S.B., Ghosh, Saradindu, Yadav, G., Sharma, K., Ghosh, Sirsendu, Joshi, S., 2018. Formulation, evaluation and antibacterial efficiency of water-based herbal hand sanitizer gel. bioRxiv, 373928. https://
Ajaya Kumar, R., Sridevi, K., Vijaya Kumar, N., Nanduri, S., Rajagopal, S., 2004. Anticancer and immunostimulatory compounds from Andrographis paniculata. Journal of Ethnopharmacology. 92, 291–295.
Akram, M., Tahir, I.M., Shah, S.M.A., Mahmood, Z., Altaf, A., Ahmad, K., Munir, N., Daniyal, M., Nasir, S., Mehboob, H., 2018. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review. Phytotherapy Research. 32, 811–822.
AlaguLakshmi, S., Shafreen, R.M.B., Priya, A., Shunmugiah, K.P., K., 2020. Ethnomedicines of Indian origin for combating COVID- 19 infection by hampering the viral replication: using structure- based drug discovery approach. Journal of Biomolecular Structure and Dynamics. 2, 1–16.
Alipourfard, I., Datukishvili, N., Mikeladze, D., 2019. TNF-α downregulation modifies insulin receptor substrate 1 (IRS-1) in metabolic signaling of diabetic insulin-resistant hepatocytes. Media- tors of Inflammation. 2019, 3560819.
Arablou, T., Aryaeian, N., 2018. The effect of ginger (Zingiber officinale) as an ancient medicinal plant on improving blood lipids. Journal of Herbal Medicine. 12, 11–15.
Arulselvan, P., Fard, M.T., Tan, W.S., Gothai, S., Fakurazi, S., Norhaizan, M.E., Kumar, S.S., 2016. Role of antioxidants and natural products in inflammation. Oxidative Medicine and Cellular Longevity. 2016, 5276130.
Asada, Y., Li, W., Yoshikawa, T., 2000. Biosynthesis of the dimethylallyl moiety of glabrol in Glycyrrhiza glabra hairy root cultures via a non-mevalonate pathway. Phytochemistry. 55, 323–326. 10.1016/s0031-9422(00)00327-7.
Ashfaq, U.A., Jalil, A., Qamar, M.T., 2016. Antiviral phytochemicals identification from Azadirachta indica leaves against HCV NS3 protease: an in silico approach. Natural Product Research. 30, 1866– 1869.
Azeez, T.B., Lunghar, J., 2021. Anti-inflammatory effects of turmeric (Curcuma longa) and ginger (Zingiber officinale). Inflammation and Natural Products, 127–146.
Baell, J.B., 2016. Feeling Nature’s PAINS: Natural products, natural product drugs, and pan assay interference compounds (PAINS). Journal of Natural Products. 79(3), 616–628.
Balakrishnan, R., Vijayraja, D., Jo, S.H., Ganesan, P., Su-Kim, I., Choi, D.K., 2020. Antioxidants medicinal profile, phytochemistry, and pharmacological activities of Murraya koenigii and its primary bioactive compounds. Antioxidants. 9(2), 101.
Bangash, M.N., Patel, J., Parekh, D., 2020. COVID-19 and the liver: little cause for concern. The Lancet Gastroenterology and Hepatology. 5(6), 529–530.
Beidokhti, M.N., Jäger, A.K., 2017. Review of antidiabetic fruits, vegetables, beverages, oils and spices commonly consumed in the diet. Journal of Ethnopharmacology. 201, 26–41. j.jep.2017.02.031.
Berbudi, A., Rahmadika, N., Tjahjadi, A.I., Ruslami, R., 2019. Type 2 Diabetes and its impact on the immune system. Cur- rent Diabetes Reviews. 16, 442–449.
Bhagyasri, Y., Priyanka, S., Vadithya, S., Subramanian, S., 2018. Formulation and evaluation of polyherbal syrup for antidiabetic syrup. International Journal of Pharmacy and Pharmaceutical Sciences. 3, 223–227.
Bi, X., Lim, J., Henry, C.J., 2017. Spices in the management of diabetes mellitus. Food Chemistry. 217, 281–293. j.foodchem.2016.08.111.
Biswas, D., Nandy, S., Mukherjee, A., Pandey, D.K., Dey, A., 2020. Moringa oleifera Lam. and derived phytochemicals as promising antiviral agents: A review. South African Journal of Botany. 129, 272– 282.
Bonaventura, P., Benedetti, G., Albarède, F., Miossec, P., 2005. Zinc and its role in immunity and inflammation. Autoimmunity Reviews. 14(4), 277–285.
Bornstein, S.R., Rubino, F., Khunti, K., Mingrone, G., Hopkins, D., Birkenfeld, A.L., Boehm, B., Amiel, S., Holt, R.I., Skyler, J.S.,. Devries, J.H., Renard, E., Eckel, R.H., Zimmet, P., Alberti, K.G., Vidal, J., Geloneze, B., Chan, J.C., Ji, L., Ludwig, B., 2020. Practical recommendations for the management of diabetes in patients with COVID-19. The Lancet Diabetes and Endocrinology. 8, 546–550.
Bozan, B., Temelli, F., 2008. Chemical composition and oxidative stability of flax, safflower and poppy seed and seed oils. Bioresource Technology. 99, 6354–6359. j.biortech.2007.12.009.
Bui, T.T., Fan, Y., Piao, C.H., Nguyen, T.V., Shin, D.U., Jung, S.Y.,.Hyeon, E., Song, C.H., Lee, S.Y., Shin, H.S., Chai, O.H., 2020. Piper Nigrum extract improves OVA-induced nasal epithelial barrier dysfunction via activating Nrf2/HO-1 signaling. Cellular Immunology. 351.
Callaway, J.C., 2004. Hempseed as a nutritional resource: An overview. Euphytica. 140, 65–72.
Carboni, E., Carta, A.R., Carboni, E., 2020. Can pioglitazone be potentially useful therapeutically in treating patients with COVID- 19? Medical Hypotheses. 140, 109776. j.mehy.2020.109776.
Carr, A.C., Maggini, S., 2017. Vitamin C and immune function. Nutrients. 9(11), 1211–1211.
Chaachouay, N., Douira, A., Zidane, L., 2021. COVID-19, prevention and treatment with herbal medicine in the herbal markets of salé prefecture. European Journal of Integrative Medicine. 42, 101285.
Chamberlain, J.J., Rhinehart, A.S., Shaefer, C., Neuman, A., 2016. Diagnosis and management of diabetes: synopsis of the 2016 American diabetes association standards of medical care in diabetes. Annals of Internal Medicine. 164(8).
Chambial, S., Dwivedi, S., Shukla, K.K., John, P.J., Sharma, P., 2013. Vitamin C in disease prevention and cure: An overview. Indian Journal of Clinical Biochemistry. 28(4), 314–328. 10.1007/s12291-013-0375-3.
Chang, G.H., Lin, Y.S., Hsu, K.H., Cheng, Y.C., Yang, P.R., Tsai, M.S.,Tsai, Y.T., Hsu, C.M., Chang, P.J., Shi, C.S., Yang, Y.H., Wu, C.Y., 2021. Nasal irrigation with Glycyrrhiza glabra extract for treatment of allergic rhinitis - A study of in vitro. Journal of Ethnopharmacology. 275, 114116.
Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X., Zhang, L., 2020. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 395, 30211–30218. s0140-6736(20)30211-7.
Chen, Y., Yang, D., Cheng, B., Chen, J., Peng, A., Yang, C., Liu, C.,Xiong, M., Deng, A., Zhang, Y., Zheng, L., Huang, K., 2020. Clinical characteristics and outcomes of patients with diabetes and COVID-19 in associating with glucose-lowering medication. Diabetes Care. 43, 1399–1407.
Cho, N.H., Shaw, J.E., Karuranga, S., Huang, Y., Fernandes, J.D.D.R., Ohlrogge, A.W., Malanda, B., 2018. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Research and Clinical Practice. 138, 271–281.
Churiyah, P., Rofaani, O.B., Tarwadi, E., 2015. Antiviral and immunostimulant Activities of Andrographis paniculata. HAYATI Journal of Biosciences. 22(2), 67–72.
Cruz, K.J.C., Oliveira, A.R.S.D., Morais, J.B.S., Severo, J.S.,.Mendes, P.M.V., Melo, S.R.D.S., Sousa, G.S.D., Marreiro, D.D.N., 2018. Zinc and Insulin Resistance: Biochemical and Molecular Aspects. Biological Trace Element Research. 186(2), 407–412.
Dai, Y., Chen, S.R., Chai, L., Zhao, J., Wang, Y., Wang, Y., 2019. Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide. Critical Reviews in Food Science and Nutrition. 59, 17–29. 10408398.2018.1501657.
Das, D., 2020. Lemon juice mediated efficient and eco-friendly organic transformations. Tetrahedron Letters. 61, 152298. 10.1016/j.tetlet.2020.152298.
de Frel, D.L., Atsma, D.E., Pijl, H., Seidell, J.C., Leenen, P.J.M., Dik, W.A., Rossum, E.F.C.V., 2020. The impact of obesity and lifestyle on the immune system and susceptibility to infections such as COVID-19. Frontiers in Nutrition. 7, 597600.
Defronzo, R.A., 2009. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 58(4), 773–95.
Ding, S., Jiang, H., Fang, J., 2018. Regulation of immune function by polyphenols. Journal of Immunology Research. 2018, 1264074.
Driggin, E., Madhavan, M.V., Bikdeli, B., Chuich, T., Laracy, J., Biondi-Zoccai, G., Brown, T.S., Nigoghossian, C.D., Zidar, D.A., Haythe, J., Brodie, D., Beckman, J.A., Kirtane, A.J., Stone, G.W., Krumholz, H.M., Parikh, S.A., 2020. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. Journal of the American College of Cardiology. 75(18), 2352–2371.
Eckel, R.H., Grundy, S.M., Zimmet, P.Z., 2005. The metabolic syndrome. Lancet. 365, 1415–1428.
Falowo, A.B., Mukumbo, F.E., Idamokoro, E.M., Lorenzo, J.M., Afolayan, A.J., Muchenje, V., 2018. Multi-functional application of Moringa oleifera Lam. in nutrition and animal food products: A review. Food Research International. 106, 317–334. 10.1016/j.foodres.2017.12.079.
Fan, Y., Zhao, K., Shi, Z.L., Zhou, P., 2019. Bat Coronaviruses in China. Viruses. 11(3), 210.
Fiore, C., Eisenhut, M., Krausse, R., Ragazzi, E., Pellati, D., Armanini, D., Bielenberg, J., 2008. Antiviral effects of Glycyrrhiza species. Phy- totherapy Research. 22(2), 141–148.
Frykberg, R.G., Banks, J., 2015. Challenges in the treatment of chronic wounds. Advances in Wound Care. 4, 560–582.
Ganesan, P., Phaiphan, A., Murugan, Y., Baharin, B.S., 2013. Comparative study of bioactive compounds in curry and coriander leaves: An update. Journal of Chemical and Pharmaceutical Research. 5, 590–594.
Geerlings, S.E., Hoepelman, A.I.M., 1999. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunology and Medical Microbiology. 26(3-4), 259–265. j.1574-695x.1999.tb01397.x.
Ghorbani, A., 2013. Best herbs for managing diabetes: A review of clinical studies. Brazilian Journal of Pharmaceutical Sciences. 49(3), 413–422.
Gorbalenya, A.E., Baker, S.C., Baric, R.S., Groot, R.J.D., Drosten, C., Gulyaeva, A.A., Haagmans, B.L., Lauber, C., Leontovich, A.M., Neu- man, B.W., Penzar, D., Perlman, S., Poon, L.L., Samborskiy, D.V., Sidorov, I.A., Sola, I., Ziebuhr, J., 2020. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology. 5(4), 536–544.
Guan, W., Liang, W., Zhao, Y., 2020. Comorbidity and its impact on 1590 patients with Covid-19 in China: a national wide analysis. European Respiratory Journal. 55, 2000547. 10.1183/13993003.00547-2020.
Gunville, C., Mourani, P., Ginde, A., 2013. The role of vitamin in prevention and treatment of infection. Inflammation and Allergy Drug Targets. 12, 239–245. 18715281113129990046.
Guo, W., Li, M., Dong, Y., Zhou, H., Zhang, Z., Tian, C., Qin, R.,.Wang, H., Shen, Y., Du, K., Zhao, L., Fan, H., Luo, S., Hu, D., 2020. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes/Metabolism Research and Reviews. e3319, e3319.
Gupta, Ghosh, A., Singh, A.K., Misra, A., 2020. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes and Metabolic Syndrome. 14(3), 211–212. j.dsx.2020.03.002.
Gupta, M., 2010. Pharmacological properties and traditional therapeutic uses of important Indian spices: A review. International Journal of Food Properties. 13, 1092–1116.
Gupta, S.C., Sung, B., Kim, J.H., Prasad, S., Li, S., Aggarwal, B.B., 2013. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Molecular Nutrition and Food Research. 57, 1510–1528.
Hanhineva, K., Törrönen, R., Bondia-Pons, I., Pekkinen, J., Kolehmainen, M., Mykkänen, H., Poutanen, K., 2010. Impact of dietary polyphenols on carbohydrate metabolism. International Journal of Molecular Sciences. 11(4), 1365–1402.
Haridas, M., Sasidhar, V., Nath, P., Abhithaj, J., Sabu, A., Ram- manohar, P., 2021. Compounds of Citrus medica and Zingiber officinale for COVID-19 inhibition: In silico evidence for cues from Ayurveda. Future Journal of Pharmaceutical Sciences. 7(1), 13.
Hotamisligil, G.S., Shargill, N.S., Spiegelman, B.M., 1993. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 259(5091), 87–91.
Hu, X.Y., Wu, R.H., Logue, M., Blondel, C., Lai, L., Stuart, B., Flower, A.,Fei, Y.T., Moore, M., Shepherd, J., Liu, J.P., Lewith, G., 2017. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. PLOS One. 12(8), e0181780.
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., … Cao, B., 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China. Lancet. 395, 30183–30188.
Huang, H.Z., Qiu, M., Lin, J.Z., Li, M.Q., Ma, X.T., Ran, F., Luo, C.H.,Wei, X.C., Xu, R.C., Tan, P., Fan, S.H., Yang, M., Han, L.,.Zhang, D.K., 2021. Potential effect of tropical fruits Phyllanthus emblica L. for the prevention and management of type 2 diabetic complications: a systematic review of recent advances. European Journal of Nutrition. 60(7), 3525–3542. s00394-020-02471-2.
Huang, Z., Liu, Y., Qi, G., Brand, D., Zheng, S.G., 2018. Role of vitamin A in the immune system. Journal of Clinical Medicine. 7(9), 258.
Hussein, R.A., El-Anssary, A.A., 2018. The key drivers of the pharmacological actions of medicinal plants , Builders P. H., (Eds.), Plants secondary metabolites. . 10.5772/intechopen.76139.
Iacobellis, G., Penaherrera, C.A., Bermudez, L.E., Mizrachi, E.B., 2020. Admission hyperglycemia and radiological findings of SARS- CoV2 in patients with and without diabetes. Diabetes Research and Clinical Practice. 164, 108185.
Irshad, M., Chaudhuri, P.S., 2002. Oxidant-antioxidant system: role and significance in human body. Indian Journal of Experimental Biology. 40(11), 1233–1239.
Jalali, A., Dabaghian, F., Akbrialiabad, H., Foroughinia, F., Zarshenas, M.M., 2021. A pharmacology-based comprehensive review on medicinal plants and phytoactive constituents possibly effective in the management of COVID-19. Phytotherapy Research. 35(4), 1925–1938.
Jantan, I., Haque, M.A., Ilangkovan, M., Arshad, L., 2019. An insight into the modulatory effects and mechanisms of action of Phyllanthus Species and their bioactive metabolites on the immune system. Frontiers in Pharmacology. 10, 878.
Jiang, M., Sheng, F., Zhang, Z., Ma, X., Gao, T., Fu, C., Li, P., 2021. Andrographis paniculata (Burm.f.) Nees and its major constituent andrographolide as potential antiviral agents. Journal of Ethnopharmacology. 272, 113954. Joshi, M.B., Lad, A., Prasad, A.S.B., Balakrishnan, A., Ramachandra, L., Satyamoorthy, K., 2013. High glucose modulates IL-6 mediated immune homeostasis through impeding neutrophil extracellular trap formation. FEBS Letters. 587(14), 2241–2246.
Kar, P., Kumar, V., Vellingiri, B., Sen, A., Jaishee, N., Anandraj, A., Malhotra, H., Bhattacharyya, S., Mukhopadhyay, S., Kinoshita, M., Govindasamy, V., Roy, A., Naidoo, D., Subramaniam, M.D., 2020. Anisotine and amarogentin as promising inhibitory candidates against SARS-CoV-2 proteins: a computational investigation. Journal of Biomolecular Structure and Dynamics, 1–11.
Kaushik, S., Dar, L., Kaushik, S., Yadav, J.P., 2021. Identification and characterization of new potent inhibitors of dengue virus NS5 proteinase from Andrographis paniculata supercritical extracts on in animal cell culture and in silico approaches. Journal of Ethnopharmacology. 267, 113541.
Kazi, S., 2014. Use of traditional plants in diabetes mellitus: A review. International Journal of Pharmacy. 4(4), 283–289.
Keel, S.B., Doty, R.T., Yang, Z., Quigley, J.G., Chen, J., Knoblaugh, S., Kingsley, P.D., Domenico, I.D., Vaughn, M.B., Kaplan, J., Palis, J., Abkowitz, J.L., 2008. A heme export protein is required for red blood cell differentiation and iron homeostasis. Science. 319(5864), 825– 828.
Khedikar, S.G., Erande, M.P., 2018. Effect of poly-herbal formulation in management of type-II diabetes mellitus. International Journal of Medical Science and Innovative Research. 3(5), 235–240.
Kim, H.Y., Okubo, T., Juneja, L.R., Yokozawa, T., 2010. The protective role of amla (Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome in a rat model. The British Journal of Nutrition. 103(4), 502–512.
Klimek-Szczykutowicz, M., Szopa, A., Ekiert, H., 2020. Citrus limon (Lemon) phenomenon-a review of the chemistry, pharmacological properties, applications in the modern pharmaceutical, food, and cosmetics industries, and biotechnological studies. Plants. 9(1), 119.
Krishnaiah, D., Sarbatly, R., Nithyanandam, R., 2011. A review of the antioxidant potential of medicinal plant species. Food and Bioproducts Processing. 89, 217–233.
Kroslak, E., Maliar, T., Nemecek, P., Viskupicova, J., Maliarova, M., Havrlentova, M., Kraic, J., 2017. Antioxidant and proteinase inhibitory activities of selected Poppy (Papaver somniferum L.) genotypes. Chemistry and Biodiversity. 14(9).
Kurokawa, M., Wadhwani, A., Kai, H., Hidaka, M., Yoshida, H., Sugita, C., Watanabe, W., Matsuno, K., Hagiwara, A., 2016. Activation of cellular immunity in herpes simplex virus type 1-infected mice by the oral administration of aqueous extract of Moringa oleifera Lam. leaves. Phytotherapy Research. 30(5), 797–804.
Kwon, Y.J., Son, D.H., Chung, T.H., Lee, Y.J., 2020. A Review of the pharmacological efficacy and safety of licorice root from corroborative clinical trial findings. Journal of Medicinal Food. 23(1), 12–20.
Lachman, J., Hejtmankova, A., Miholova, D., Kolihova, D., Tluka, P., 2006. Relations among alkaloids, cadmium and zinc contents in opium poppy. Plant, Soil and Environment. 52(6), 282–288. https://
Lakshmi, S.S., Kumari, H.V.M., Mohan, S., Meenakumari, R., 2020. Therapeutic effectiveness of the siddha immunomodulatory polyherbal. World Journal of Pharmaceutical Research. 9(7), 712– 731.
Lee, G.Y., Han, S.N., 2018. The role of vitamin E in immunity. Nutrients.10(11), 1614–1614.
Leone, A., Spada, A., Battezzati, A., Schiraldi, A., Aristil, J., Bertoli, S., 2015. Cultivation, genetic, ethnopharmacology, phytochemistry and pharmacology of Moringa oleifera leaves: An overview. International Journal of Molecular Sciences. 16(6), 12791–12835.
Li, B., Yang, J., Zhao, F., Zhi, L., Wang, Xiqian, Liu, L., Bi, Z., Zhao, Y., 2020. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clinical Research in Cardiology. 109, 531–538.
Li, C., Li, Y., Ding, C., 2019. Molecular sciences the role of copper homeostasis at the host-pathogen axis: from bacteria to fungi. International Journal of Molecular Sciences. 20(1), 175–175.
Liang, R., Wu, W., Huang, J., Jiang, S., Lin, Y., 2012. Magnesium affects the cytokine secretion of CD4+ T lymphocytes in acute asthma. Journal of Asthma. 49, 1012–1015.
Liu, F., Zhu, Y., Zhang, J., Li, Y., Peng, Z., 2020. Intravenous high-dose vitamin C for the treatment of severe COVID-19: Study protocol for a multicentre randomised controlled trial. BMJ Open. 10(7), e039519.
Liu, H., Ye, F., Sun, Q., Liang, H., Li, C., Lu, R., Huang, B., Tan, W.,.Lai, L., 2021. Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro. Journal of Enzyme Inhibition and Medicinal Chemistry. 36(1), 497–503.
Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H.,Huang, B., Zhu, N., Bi, Y., 2020. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 395, 30251–30259. https://
Lu, S.Y., Chu, Y.L., Sridhar, K., Tsai, P.J., 2021. Effect of ultrasound, high-pressure processing, and enzymatic hydrolysis on carbohydrate hydrolyzing enzymes and antioxidant activity of lemon (Citrus limon) flavedo. LWT. 138, 110511.
Ma, Y., Kosińska-Cagnazzo, A., Kerr, W.L., Amarowicz, R., Swan- son, R.B., Pegg, R.B., 2014. Separation and characterization of soluble esterified and glycoside-bound phenolic compounds in dry-blanched peanut skins by liquid chromatography-electrospray ionization mass spectrometry. Journal of Agricultural and Food Chemistry. 62, 11488–11504.
Malagi, K., 2018. Impact of herbs on immunomodulation in diabetes mellitus. Journal of Diabetes, Metabolic Disorders and Control. 5(2), 74–76.
Maret, W., 2017. Zinc in pancreatic islet biology, insulin sensitivity, and diabetes. Preventive Nutrition and Food Science. 22, 1–8. 10.3746/pnf.2017.22.1.1.
Mohiuddin, A.K., 2019. A brief review of traditional plants as sources of pharmacological interests. Open Journal of Plant Science. 4(1), 1– 008.
Morvaridzadeh, M., Fazelian, S., Agah, S., Khazdouz, M., Rahimlou, M., Agh, F., Potter, E., Heshmati, S., Heshmati, J., 2020. Effect of ginger (Zingiber officinale) on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Cytokine. 135, 155224.
Murugan, N.A., Pandian, C.J., Jeyakanthan, J., 2021. Computational investigation on Andrographis paniculata phytochemicals to evaluate their potency against SARS-CoV-2 in comparison to known antiviral compounds in drug trials. Journal of Biomolecular Structure and Dynamics. 39(12), 4415–4426.
Mussard, E., Cesaro, A., Lespessailles, E., Legrain, B., Berteina-Raboin, S., Toumi, H., 2019. Andrographolide, a natural antioxidant: an update. Antioxidants. 8(12), 571.
Nieman, D.C., Wentz, L.M., 2019. The compelling link between physical activity and the body’s defense system. Journal of Sport and Health Science. 8(3), 201–217.
Ogurtsova, K., Fernandes, J.D.D.R., Huang, Y., Linnenkamp, U., Guariguata, L., Cho, N.H., Cavan, D., Shaw, J.E., Makaroff, L.E., 2017. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Research and Clinical Practice. 128, 40–50.
Omar, E.A., Kam, A., Alqahtani, A., Li, K.M., Razmovski-Naumovski, V., Nammi, S., Chan, K., Roufogalis, B.D., Li, G.Q., 2010. Herbal medicines and nutraceuticals for diabetic vascular complications: mechanisms of action and bioactive phytochemicals. Current Phar- maceutical Design. 16(34), 3776–3807.
Padayachee, B., Baijnath, H., 2020. An updated comprehensive review of the medicinal, phytochemical and pharmacological properties of Moringa oleifera. South African Journal of Botany. 129, 304–316.
Parasuraman, S., Thing, G.S., Dhanaraj, S.A., 2014. Polyherbal formulation: Concept of ayurveda. Pharmacognosy Reviews. 8(16), 73–80.
Patel, R.R., 2020. Tulsi: The queen of medicinal herbs. Journal of Bioequivalence and Bioavailability. 12, 407–407.
Pereira, A., Banegas-Luna, A.J., Peña-García, J., Pérez-Sánchez, H., Apostolides, Z., 2019. Evaluation of the anti-diabetic activity of some common herbs and spices: providing new insights with inverse virtual screening. Molecules. 24(22), 4030–4030. molecules24224030.
Pingali, U., Ali, M.A., Gundagani, S., Nutalapati, C., 2020. Evaluation of the effect of an aqueous extract of Azadirachta indica (Neem) leaves and twigs on glycemic control, endothelial dysfunction and systemic inflammation in subjects with type 2 diabetes mellitus - a randomized, double-blind, placebo-controlled clinical study. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 13, 4401–4412. https://
Poudel, R.R., Bhusal, Y., Tharu, B., Kafle, N.K., 2017. Role of zinc in insulin regulation and diabetes. Journal of Social Health and Diabetes. 5, 83–87.
Pundarikakshudu, K., Kanaki, N.S., 2019. Analysis and regulation of Traditional Indian Medicines (TIM). Journal of AOAC International. 102(4), 977–978.
Punthakee, Z., Goldenberg, R., Katz, P., 2018. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Canadian Journal of Diabetes. 42(1), 10–15.
Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., Xie, C., Ma, K., Shang, K., Wang, W., Tian, D.S., 2020. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clinical Infectious Diseases. 71, 762–768. 10.1093/cid/ciaa248.
Qiu, D., Li, X.N., 2015. Pioglitazone inhibits the secretion of proinflammatory cytokines and chemokines in astrocytes stimulated with lipopolysaccharide. International Journal of Clinical Pharma- cology and Therapeutics. 53(9), 746–752. cp202339.
Rabie, A.M., 2021a. Cyanorona-20: The first potent anti-SARS-CoV- 2 agent. International Immunopharmacology. 98, 107831. https://
Rabie, A.M., 2021b. Discovery of (E)- N-(4-cyanobenzylidene)- 6-fluoro- 3-hydroxypyrazine-2 -carboxamide (cyanorona-20): the first potent and specific anti-COVID-19 drug. Chemical Papers, 1–17. https://
Rachmawati, I., 2014. In Vitro immunomodulatory activity of aqueous extract of Moringa oleifera Lam. leaf to the CD4+, CD8+ and B220+ cells in Mus musculus. Journal of Experimental Life Science. 4(1), 15–20.
Ragab, D., Eldin, H.S., Taeimah, M., Khattab, R., Salem, R., 2020. The COVID-19 cytokine storm; what we know so far. Frontiers in Immunology. 11, 1446.
Rains, J.L., Jain, S.K., 2011. Oxidative stress, insulin signaling, and diabetes. Free Radical Biology and Medicine. 50, 567–575. https://
Rambod, M., Rakhshan, M., Tohidinik, S., Nikoo, M.H., 2020. The effect of lemon inhalation aromatherapy on blood pressure, electrocardiogram changes, and anxiety in acute myocardial infarction patients: A clinical, multi-centered, assessor-blinded trial design. Complementary Therapies in Clinical Practice. 39, 101155. https://
Read, S.A., Obeid, S., Ahlenstiel, C., Ahlenstiel, G., 2019. The role of zinc in antiviral immunity. Advances in Nutrition. 10, 696–710.
Rink, L., Gabriel, P., 2000. Zinc and the immune system. The Proceedings of the Nutrition Society. 59, 541–552.
Roncon, L., Zuin, M., Rigatelli, G., Zuliani, G., 2020. Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome. Journal of Clinical Virology. 127, 104354.
Rupp, J.C., Locatelli, M., Grieser, A., Ramos, A., Campbell, P.J., Yi, H., Steel, J., Burkhead, J.L., Bortz, E., 2017. Host cell copper transporters CTR1 and ATP7A are important for Influenza A virus replication. Virology Journal. 14(1), 11.
Sanlier, N., Gencer, F., 2020. Role of spices in the treatment of diabetes mellitus: A minireview. Trends in Food Science and Technology. 99, 441–449.
Sen, D., Bhaumik, S., Debnath, P., Debnath, S., 2021. Potentiality of Moringa oleifera against SARS-CoV-2: identified by a rational computer aided drug design method. Journal of Biomolecular Structure and Dynamics, 1–18.
Sengupta, P.S., 2020. Use of piper betel to combat COVID19. Prepare@u_general. 1, 1–10. 10.36375/prepare_u.a92.
Shaji, D., Yamamoto, S., Saito, R., Suzuki, R., Nakamura, S., Kurita, N., 2021. Proposal of novel natural inhibitors of severe acute respiratory syndrome coronavirus 2 main protease: Molecular docking and ab initio fragment molecular orbital calculations. Biophysical Chemistry. 275, 106608.
Sharma, S., Ray, A., Sadasivam, B., 2020. Metformin in COVID-19: A possible role beyond diabetes. Diabetes Research and Clinical Practice. 164, 108183.
Singh, A.K., Singh, A., Singh, R., Misra, A., 2020. Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies. Diabetes and Metabolic Syndrome. 14(4), 641–648.
Singh, B.N., Singh, B.R., Singh, R.L., Prakash, D., Dhakarey, R., Upadhyay, G., Singh, H.B., 2009. Oxidative DNA damage protective activity, antioxidant and anti-quorum sensing potentials of Moringa oleifera. Food and Chemical Toxicology. 47(6), 1109–1116. https://
Singh, M.K., Yadav, S.S., Yadav, R.S., Chauhan, A., Katiyar, D., Khat- tri, S., 2015. Protective effect of Emblica-officinalis in arsenic induced biochemical alteration and inflammation in mice. SpringerPlus. 4, 438.
Song, Z., Xu, Y., Bao, L., Zhang, L., Yu, P., Qu, Y., Zhu, H.,Zhao, W., Han, Y., Qin, C., 2019. From SARS to MERS, Thrusting Coronaviruses into the Spotlight. Viruses. 11(1), 59.
Srivastava, V., Yadav, A., Sarkar, P., 2020. Molecular Docking and ADMET study of bioactive compounds of glycyrrhiza glabra against main protease of SARS-CoV2. Materials today.
Sudhakar, K., Mishra, V., Hemani, V., Verma, A., Jain, A., Jain, S., Charyulu, R.N., 2021. Reverse pharmacology of phytoconstituents of food and plant in the management of diabetes: Current status and perspectives. Trends in Food Science and Technology. 110, 594–610.
Suja, R.S., Nair, A.M.C., Sujith, S., Preethy, J., Deepa, A.K., 2009. Evaluation of immunomodulatory potential of Embolica officinalis fruit pulp extract in mice. Journal of Animal Research. 43, 103–106. Sun, Z.G., Zhao, T.T., Lu, N., Yang, Y.A., Zhu, H.L., 2019. Research progress of glycyrrhizic acid on antiviral activity. Mini Reviews in Medicinal Chemistry. 19(10), 826–832.
Suresh, K., Vasudevan, D.M., 1994. Augmentation of murine natural killer cell and antibody dependent cellular cytotoxicity activities by Phyllanthus emblica, a new immunomodulator. Journal of Ethnopharmacology. 44(1), 55–60.
Takooree, H., Aumeeruddy, M.Z., Rengasamy, K., Venugopala, K.N., Jeewon, R., Zengin, G., Mahomoodally, M.F., 2019. A systematic review on black pepper (Piper nigrum L.): from folk uses to pharmacological applications. Critical Reviews in Food Science and Nutrition. 59(sup1), 210–243.
Tan, K.S., Lee, K.O., Low, K.C., Gamage, A.M., Liu, Y., Tan, G.Y.,Koh, H.Q., Alonso, S., Gan, Y.H., 2012. Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria. The Journal of Clinical Investigation. 122(6), 2289–2300.
Tessaro, F., Ayala, T.S., Nolasco, E.L., Bella, L.M., Martins, J.O., 2017. Insulin influences LPS-induced TNF-α and IL-6 release through distinct pathways in mouse macrophages from different compartments. Cellular Physiology and Biochemistry. 42(5), 2093– 2104.
Tie, H.T., Tan, Q., Luo, M.Z., Li, Q., Yu, J.L., Wu, Q.C., 2016. Zincas an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials. The British Journal of Nutrition. 115(5), 807–816.
Trinh, T.A., Park, J., Oh, J.H., Park, J.S., Lee, D., Kim, C.E., Choi, H.S.,Kim, S.B., Hwang, G.S., Koo, B.A., Kang, K.S., 2020. Effect of herbal formulation on immune response enhancement in RAW.7 macrophages. Biomolecules. 10(3), 424.
Ullah, M., Wahab, A., Saeed, S., Khan, S.U., Ali, H., Humayun, S.,.Abbasi, B.A., Saud, S., Naveed, K., Khan, S.A., Fahad, S., 2021. Coronavirus and its terrifying inning around the globe: The pharmaceutical cares at the main frontline. Chemosphere. 275, 129968–129968.
Umar, H.I., Josiah, S.S., Saliu, T.P., Jimoh, T.O., Ajayi, A., Danjuma, J.B., 2021. In-silico analysis of the inhibition of the SARS-CoV-2 main protease by some active compounds from selected African plants. Journal of Taibah University Medical Sciences. 16(2), 162–176.
Variya, B.C., Bakrania, A.K., Patel, S.S., 2016. Emblica officinalis (Amla): A review for its phytochemistry, ethnomedicinal uses and medicinal potentials with respect to molecular mechanisms. Pharmacological Research. 111, 180–200. j.phrs.2016.06.013.
Walter, T.M., Justinraj, S., Justinraj, C.S., Nandini, V.S., 2020. Effect of nilavembu kudineer in the prevention and management of COVID- 19 by inhibiting ACE2 Receptor. Siddha Papers. 15(2).
Wang, L., Liang, J., Leung, P.S., 2015. The ACE2/Ang-(1-7)/Mas axis regulates the development of pancreatic endocrine cells in mouse embryos. PLOS One. 10(6), e0128216. journal.pone.0128216.
Wink, M., 2015. Modes of action of herbal medicines and plant secondary metabolites. Medicines (Basel). 2(3), 251–286.
Wittschier, N., Faller, G., Hensel, A., 2009. Aqueous extracts and polysaccharides from liquorice roots (Glycyrrhiza glabra L.) inhibit adhesion of Helicobacter pylori to human gastric mucosa. Journal of Ethnopharmacology. 125(2), 218–223. j.jep.2009.07.009.
Yadav, S.S., Singh, M.K., Singh, P.K., Kumar, V., 2017. Traditional knowledge to clinical trials: A review on therapeutic actions of Emblica officinalis. Biomedicine and Pharmacotherapy. 93, 1292– 1302.
Yarnell, E., 2017. Herbs for viral respiratory infections. Alternative and Complementary Therapies. 24, 35–43.
Yi, Y.D., Chang, I.M., 2004. An overview of traditional Chinese herbal formulae and a proposal of a new code system for expressing the formula titles. Evidence-based Complementary and Alternative Medicine. 1(2), 125–132.
Yoon, J., JM, C., SS, H., HK, K., MS, K., JW, J., HP, S., 2019. Fermented milk containing Lactobacillus paracasei and Glycyrrhiza glabra has a beneficial effect in patients with Helicobacter pylori infection: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 98(35), e16601.
Zhang, J.J., Dong, X., Cao, Y.Y., Yuan, Y.D., Yang, Y.B., Yan, Y.Q.,Akdis, C.A., Gao, Y.D., 2020. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 75(7), 1730– 1741.
Zhang, Y., Li, H., Zhang, J., Cao, Y., Zhao, X., Yu, N., Gao, Y., Ma, J., Zhang, H., Zhang, J., Guo, X., Liu, X., 2020. The clinical characteristics and outcomes of patients with diabetes and secondary hyperglycaemia with coronavirus disease 2019: A single-centre, retrospective, observational study in Wuhan. Diabetes, Obesity and Metabolism. 22(8), 1443–1454.