Bioactive compounds, and bio-activities common to three natural products expected to boost the treatment of the comorbidities of COVID-19: A review

Abstract

COVID-19, with many variants of its causative virus, has been and is still causing ravages and claiming many lives all over the globe. Currently, there are no therapeutic agents against the disease except for a few already existing ones that are used to manage the symptoms and comorbidities associated with the disease. Even some currently developed vaccines cannot efficiently handle various variants of the causative agent for COVID-19. This review is aimed at utilizing the possible synergy that might exist in the combination therapy of Nigella sativa , Curcuma longa , and honey for better management of COVID-19 and the associated comorbidities. The literature search was performed by inputting some relevant keywords into important search engines and websites such as Google, Google Advanced Search, PubMed, and so on. In vitro studies on some bioactive compounds isolated from N. sativa and C. longa have demonstrated activity against SARS-CoV-2. The three natural products, N. sativa , C. longa , and honey have exhibited wonderful activities against some of the health conditions associated with COVID-19; such include; antiviral, immunomodulatory, antioxidant, anti-inflammatory, bronchodilatory, antihistamine, antitussive, antimicrobial and other activities. Some of the major active compounds responsible for the bioactivities of these products and their mechanisms of action have been highlighted. The products individually have exhibited strong biological activities against conditions associated with COVID-19 and so are expected to exert a synergistic effect when combined in the treatment of the disease even with many variants of the causative organism.

Keywords

References

1. Abbas, A. S., Ghozy, S., Minh, L. H. N., Hashan, M. R., Soliman, A. L., Van, N. T., Hirayama, K., & Huy, N. T. (2019). Honey in bronchial asthma: from folk tales to scientific facts. Journal of Medicinal Food, 22(6), 543-550.
2. Abdel-Moneim, A., Morsy, B. M., Mahmoud, A. M., Abo-Seif, M. A., & Zanaty, M. I. (2013). Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egypt. EXCLI Journal, 12, 943-955.
3. Abedi, F., Ghasemi, S., Farkhondeh, T., Azimi-Nezhad, M., Shakibaei, M., & Samarghandian, S. (2021). Possible potential effects of honey and its main components against Covid-19 infection. Dose-Response, 19(1), 1559325820982423.
4. Acner (2020). Retrieved from http://acner.org/avian-influenza/. Accessed on 13th August 2021.
5. Ahmad, M. F., Ahmad, F. A., Ashraf, S. A., Saad, H. H., Wahab, S., Khan, M. I., Ali, M., Mohan, S., Hakeem, K. R., et al. (2021). An updated knowledge of Black seed (Nigella sativa Linn.): Review of phytochemical constituents and pharmacological properties. Journal of Herbal Medicine, 25, 100404.
6. Al-Ameedy, T. H., & Omran, R. (2019). Antimicrobial Activity of Nigella sativa Extract Against some Bacterial and Fungal Species. Journal of University of Babylon for Pure and Applied Sciences, 27(1), 277-286.
7. Al-Hatamleh, M. A., Hatmal, M. M., Sattar, K., Ahmad, S., Mustafa, M. Z., Bittencourt, M. D. C., & Mohamud, R. (2020). Antiviral and immunomodulatory effects of phytochemicals from honey against COVID-19: Potential mechanisms of action and future directions. Molecules, 25(21), 5017.
8. Aleebrahim-Dehkordi, E., Soveyzi, F., Deravi, N., Rabbani, Z., Saghazadeh, A., & Rezaei, N. (2021). Human coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 in children. Journal of Pediatric Nursing, 56, 70-79.
9. Ali, A. M., & Kunugi, H. (2021). Propolis, bee honey, and their components protect against coronavirus disease 2019 (COVID-19): A review of in silico, in vitro, and clinical studies. Molecules, 26(5), 1232.
10. Almasaudi, S. (2020). The antibacterial activities of honey; 2020. Retrieved from https://doi.org/10.1016/jsjbs.2020.10.017/. Accessed on 15th June 2022.
11. Álvarez-Díaz, D. A., Franco-Muñoz, C., Laiton-Donato, K., Usme-Ciro, J. A., Franco-Sierra, N. D., Flórez-Sánchez, A. C., Gómez-Rangel, S., Rodríguez-Calderon, L. D., Barbosa-Ramirez, J., et al. (2020). Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia. Infection, Genetics and Evolution, 84, 104390.
12. Arawwawala, M., & Hewageegana, S. (2017). Health benefits and traditional uses of honey: A review. Journal of Apitherapy, 2(1), 9-14.
13. Badary, O. A., Hamza, M. S., & Tikamdas, R. (2021). Thymoquinone: A promising natural compound with potential benefits for COVID-19 prevention and cure. Drug Design, Development and Therapy, 1819-1833.
14. Bhatt, N. A., Singh, A., & Sharma, R. (2021). Pharmacological activities of Curcuma longa: A review. European Journal of Clinical Medicine, 8(4), 1232-1239.
15. Bormann, M., Alt, M., Schipper, L., van de Sand, L., Le-Trilling, V. T. K., Rink, L., Heinen, N., Madel, R. J., Otte, M., et al. (2021). Turmeric root and its bioactive ingredient curcumin effectively neutralize SARS-CoV-2 in vitro. Viruses, 13(10), 1914.
16. Boskabady, M., Mohsenpoor, N., & Takaloo, L. (2010). Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine, 17(10), 707-713.
17. Cheng, K., Yang, A., Hu, X., Zhu, D., & Liu, K. (2018). Curcumin attenuates pulmonary inflammation in lipopolysaccharide induced acute lung injury in neonatal rat model by activating peroxisome proliferator-activated receptor γ (PPARγ) pathway. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 24, 1178-1184.
18. Cui, J., Li, F., & Shi, Z. L. (2019). Origin and evolution of pathogenic coronaviruses. Nature Reviews Microbiology, 17(3), 181-192.
19. Fukuda, M., Kobayashi, K., Hirono, Y., Miyagawa, M., Ishida, T., Ejiogu, E. C., Sawai, M., Pinkerton, K. E., & Takeuchi, M. (2011). Jungle honey enhances immune function and antitumor activity. Evidence-Based Complementary and Alternative Medicine, 2011, 908743.
20. Galhardo, D., Garcia, R. C., Schneider, C. R., Braga, G. C., Chambo, E. D., França, D. L. B. D., & Ströher, S. M. (2020). Physicochemical, bioactive properties and antioxidant of Apis mellifera L. honey from western Paraná, Southern Brazil. Food Science and Technology, 41(1), 247-253.
21. Gowramma, B., Shueb, M., Manjunath, R., Priyanka, K. B., & Suresh, R. (2021). Honey as a natural antibiotic adjuvant. International Journal of Creative Research Thoughts, 9(3), 1978-1982.
22. Grinbaum, R. S., & Kiffer, C. R. V. (2021). Bacterial infections in COVID-19 patients: a review. Revista da Associação Médica Brasileira, 67(12), 1863-1868.
23. Hannan, M. A., Rahman, M. A., Sohag, A. A. M., Uddin, M. J., Dash, R., Sikder, M. H., Rahman, M. S., Timalsina, B., Munni, Y. A., et al. (2021). Black cumin (Nigella sativa L.): A comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients, 13(6), 1784.
24. Hossain, K. S., Hossain, M. G., Moni, A., Rahman, M., Rahman, U., Alam, M., Kundu, S., Rahman, M., Hannan, M., et al. (2020). Honey as a potential natural remedy against COVID-19: pharmacological insights and therapeutic promises. Heliyon, 6, e05798.
25. Hussain, A., Kausar, T., Din, A., Murtaza, M. A., Jamil, M. A., Noreen, S., Rehman, H. U., Shabbir, H., & Ramzan, M. A. (2021). Determination of total phenolic, flavonoid, carotenoid, and mineral contents in peel, flesh, and seeds of pumpkin (Cucurbita maxima). Journal of Food Processing and Preservation, 45(6), e15542.
26. Hussain, A., Kausar, T., Majeed, M. A., Aslam, J., Imtiaz, M., Haroon, H., Abbas, N., & Ali, A. (2023a). Development of nutritional biscuits for children, rich in Fe and Zn, by incorporation of pumpkin (Cucurbita maxima) seeds powder; a healthy pharma food in current post COVID 19 period. Pure and Applied Biology (PAB), 12(1), 392-403.
27. Hussain, A., Kausar, T., Sehar, S., Sarwar, A., Quddoos, M. Y., Aslam, J., Liaqat, A., Siddique, T., An, Q. U., et al. (2023b). A review on biochemical constituents of pumpkin and their role as pharma foods; a key strategy to improve health in post COVID 19 period. Food Production, Processing and Nutrition, 5(1), 1-14.
28. Ikhsan, M., Hiedayati, N., Maeyama, K., & Nurwidya, F. (2018). Nigella sativa as an anti-inflammatory agent in asthma. BMC Research Notes, 11(1), 1-5.
29. Koshak, A. E., Yousif, N. M., Fiebich, B. L., Koshak, E. A., & Heinrich, M. (2018). Comparative immunomodulatory activity of Nigella sativa L. preparations on proinflammatory mediators: A focus on asthma. Frontiers in Pharmacology, 9, 1075.
30. Lau, S. K., Lung, D. C., Wong, E. Y., Aw-Yong, K. L., Wong, A. C., Luk, H. K., Li, K. S., Fung, J., Chan, T. T., et al. (2021). Molecular evolution of human coronavirus 229E in Hong Kong and a fatal COVID-19 case involving coinfection with a novel human coronavirus 229E genogroup. MSphere, 6(1), e00819-00820.
31. Lauring, A. S., & Malani, P. N. (2021). Variants of Sars-Cov-2. JAMA, 326(9), 880-880.
32. Lee, H. K., Park, S. B., Chang, S. Y., & Jung, S. J. (2018). Antipruritic effect of curcumin on histamine-induced itching in mice. The Korean Journal of Physiology & Pharmacology, 22(5), 547-554.
33. Li, X., & Ma, X. (2020). Acute respiratory failure in COVID-19: is it “typical” ARDS? Critical Care, 24(1), 198.
34. Machado De-Melo, A. A., Almeida-Muradian, L. B. D., Sancho, M. T., & Pascual-Maté, A. (2018). Composition and properties of Apis mellifera honey: A review. Journal of Apicultural Research, 57(1), 5-37.
35. Mahase, E. (2021). Covid-19: Where are we on vaccines and variants? British Medical Journal, 372, n597.
36. Mahboubi, M. (2018). Natural therapeutic approach of Nigella sativa (Black seed) fixed oil in management of Sinusitis. Integrative Medicine Research, 7(1), 27-32.
37. Mahmoud, Y. K., & Abdelrazek, H. M. (2019). Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy. Biomedicine & Pharmacotherapy, 115, 108783.
38. Maideen, N. M. P. (2020). Prophetic medicine-Nigella sativa (Black cumin seeds)–potential herb for COVID-19? Journal of Pharmacopuncture, 23(2), 62-70.
39. Mammad, Z., Mammad, K., Aqeil, T., Kribii, A., & Ounine, K. (2017). Antibacterial and Antioxidant activity of Nigella sativa. International Journal of Innovation and Scientific Research, 31(1), 167-172.
40. Masad, R. J., Haneefa, S. M., Mohamed, Y. A., Al-Sbiei, A., Bashir, G., Fernandez-Cabezudo, M. J., & Al-Ramadi, B. K. (2021). The immunomodulatory effects of honey and associated flavonoids in cancer. Nutrients, 13(4), 1269.
41. Maurya, V. K., Kumar, S., Prasad, A. K., Bhatt, M. L., & Saxena, S. K. (2020). Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor. Virusdisease, 31, 179-193.
42. Mohammed, S. J., Amin, H. H., Aziz, S. B., Sha, A. M., Hassan, S., Abdul Aziz, J. M., & Rahman, H. S. (2019). Structural characterization, antimicrobial activity, and in vitro cytotoxicity effect of black seed oil. Evidence-Based Complementary and Alternative Medicine, 2019, 6515671.
43. Noor, H., Ikram, A., Rathinavel, T., Kumarasamy, S., Nasir Iqbal, M., & Bashir, Z. (2022). Immunomodulatory and anti-cytokine therapeutic potential of curcumin and its derivatives for treating COVID-19–a computational modeling. Journal of Biomolecular Structure and Dynamics, 40(13), 5769-5784.
44. Onifade, A. A., Jewell, A. P., & Adedeji, W. A. (2013). Nigella sativa concoction induced sustained seroreversion in HIV patient. African Journal of Traditional, Complementary and Alternative Medicines, 10(5), 332-335.
45. Paul, I. M., Beiler, J., McMonagle, A., Shaffer, M. L., Duda, L., & Berlin, C. M. (2007). Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Archives of Pediatrics & Adolescent Medicine, 161(12), 1140-1146.
46. Pena Júnior, D. S., Almeida, C. A., Santos, M. C. F., Fonseca, P. H. V., Menezes, E. V., de Melo Junior, A. F., Brandão, M. M., de Oliveira, D. A., Souza, L. F. d., et al. (2022). Antioxidant activities of some monofloral honey types produced across Minas Gerais (Brazil). Plos One, 17(1), e0262038.
47. Petersen, E., Ntoumi, F., Hui, D. S., Abubakar, A., Kramer, L. D., Obiero, C., Tambyah, P. A., Blumberg, L., Yapi, R., et al. (2022). Emergence of new SARS-CoV-2 Variant of Concern Omicron (B. 1.1. 529)-highlights Africa's research capabilities, but exposes major knowledge gaps, inequities of vaccine distribution, inadequacies in global COVID-19 response and control efforts. International Journal of Infectious Diseases, 114, 268-272.
48. Pop, R. M., Sabin, O., Suciu, Ș., Vesa, S. C., Socaci, S. A., Chedea, V. S., Bocsan, I. C., & Buzoianu, A. D. (2020). Nigella sativa’s anti-inflammatory and antioxidative effects in experimental inflammation. Antioxidants, 9(10), 921.
49. Pourrajab, F., Zare-Khormizi, M. R., & Sheikhha, M. H. (2020). Molecular basis for pathogenicity of human coronaviruses. Infection and Drug Resistance, 2385-2405.
50. Rattis, B. A., Ramos, S. G., & Celes, M. (2021). Curcumin as a Potential Treatment for COVID-19. Frontiers in Pharmacology, 12, 675287.
51. Romero, C. N. S., Colín, H. I., Goddy, R. M. E., Hermández, H. M., García, V. A., Paredes-Solís, S., & Reyes, F. S. (2022). Clinical signs and symptoms associated with COVID-19: A cross sectional study. International Journal of Odontostomatology, 16(1), 112-119.
52. Salehi, B., Quispe, C., Imran, M., Ul-Haq, I., Živković, J., Abu-Reidah, I. M., Sen, S., Taheri, Y., Acharya, K., et al. (2021). Nigella plants–Traditional uses, bioactive phytoconstituents, preclinical and clinical studies. Frontiers in Pharmacology, 12, 625386.
53. Salem, M. L., & Hossain, M. S. (2000). Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection. International Journal of Immunopharmacology, 22(9), 729-740.
54. Shaterzadeh-Yazdi, H., Noorbakhsh, M. F., Hayati, F., Samarghandian, S., & Farkhondeh, T. (2018). Immunomodulatory and anti-inflammatory effects of thymoquinone. Cardiovascular & Haematological Disorders-Drug Targets (Formerly Current Drug Targets-Cardiovascular & Hematological Disorders), 18(1), 52-60.
55. Sohail, M., & Umar, S. (2017). Patho-biological studies of PPR virus in experimentally infected goats with reference to immunomodulatory activity of Nigella sativa seeds. Journal of Animal and Plant Sciences, 27(6), 2017.
56. Sopo, S. M., Greco, M., Monaco, S., Varrasi, G., Di Lorenzo, G., & Simeone, G. (2015). Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review. Allergologia et Immunopathologia, 43(5), 449-455.
57. Stagos, D., Soulitsiotis, N., Tsadila, C., Papaeconomou, S., Arvanitis, C., Ntontos, A., Karkanta, F., Adamou‑Androulaki, S., Petrotos, K., et al. (2018). Antibacterial and antioxidant activity of different types of honey derived from Mount Olympus in Greece. International Journal of Molecular Medicine, 42(2), 726-734.
58. Tung, B. T., Nham, D. T., Hai, N. T., & Thu, D. K. (2019). Curcuma longa, the polyphenolic curcumin compound and pharmacological effects on liver. In R. S. Watson & V. R. Preedy (Eds.), Dietary Interventions in Liver Disease (pp. 125-134): Academic Press.
59. Umar, S., Munir, M. T., Subhan, S., Azam, T., Nisa, Q., Khan, M. I., Umar, W., Rehman, Z., Saqib, A. S., et al. (2016). Protective and antiviral activities of Nigella sativa against avian influenza (H9N2) in turkeys. Journal of the Saudi Society of Agricultural Sciences, 10, 1-7.
60. Vadivelan, S., Sarojini, T., Kirubhakaran, S., & Mathukumar, S. (2021). The Bronchodilating herbs used in the treatment of COVID-19: A Review. International Journal of Ayurvedic Medicine, 12(3), 477-481.
61. Wang, X., An, X., Wang, X., Bao, C., Li, J., Yang, D., & Bai, C. (2018). Curcumin ameliorated ventilator-induced lung injury in rats. Biomedicine & Pharmacotherapy, 98, 754-761.
62. Weerakoon, W. A. S. S., Perera, P. K., Gunasekera, D., & Suresh, T. S. (2014). Antihistamine effect of bee honey in Wistar rats. Retrieved from http://ir.kdu.ac.lk/handle/345/1567/. Accessed on 14th June, 2022.
63. Wiersinga, W. J., Rhodes, A., Cheng, A. C., Peacock, S. J., & Prescott, H. C. (2020). Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA, 324(8), 782-793.
64. Xie, X., Han, J. B., Ma, G., Feng, X. L., Li, X., Zou, Q. C., Deng, Z. H., & Zeng, J. (2021). Emerging SARS-CoV-2 B. 1.621/Mu variant is prominently resistant to inactivated vaccine-elicited antibodies. Zoological Research, 42(6), 789-791.
65. Zheng, D., Huang, C., Huang, H., Zhao, Y., Khan, M. R. U., Zhao, H., & Huang, L. (2020). Antibacterial mechanism of curcumin: A review. Chemistry & Biodiversity, 17(8), e2000171.

License

Copyright (c) 2023 Emmanuel Chigozie Aham, Ethel Ndidi Nkwoemeka, Nicodemus Emeka Nwankwo