Efficacy of a Persian herbal medicine compound on coronavirus disease 2019 (COVID-19): A randomized controlled trial
Mohammad Setayesh, Mehrdad Karimi, Arman Zargaran, Hamid Abousaidi, Armita Shahesmaeili, Fatemeh Amiri, Fatemeh Sadat Hasheminasab
Integrative Medicine Research, doi:10.1016/j.imr.2022.100869
Background: The global attention to the capacities of traditional medicine for alleviating the clinical manifestations of COVID-19 has been growing. The present trial aimed to evaluate the efficacy and safety of a Persian herbal medicine formula among patients with COVID-19. Methods: The present trial was conducted in Afzalipour hospital, Kerman, Iran, from June to September 2020. Hospitalized COVID-19 patients were randomly divided into intervention (Persian herbal medicine formula + routine treatment) or control (only routine treatment) groups. The intervention group received both capsule number 1 and 2 every 8 hours for 7 days. Capsule number 1 contained extract of the Glycyrrhiza glabra, Punica granatum , and Rheum palmatum , and the second capsule was filled by Nigella sativa powder. Participants were followed up to 7 days. The primary outcome was the number of hospitalization days, while cough, fever, and respiratory rate, days on oxygen (O 2 ) therapy, and mortality rate were considered as the secondary outcomes. Results: Eighty-two patients were enrolled to the study, while 79 cases completed the trial and their data were analyzed (mean age: 59.1 ± 17.1 years). Based on the results, the Persian medicine formula decreased the mean hospitalization days, so that the mean difference of length of hospitalization as primary outcome was 2.95 ± 0.43 days. A significant clinical improvement was observed regarding dyspnea, need for O 2 ) therapy, and respiratory rate in the intervention group. No adverse effects were reported.
Conclusion: The present study supported the use of the Persian medicine formula as an adjuvant therapy for hospitalized COVID-19 patients. Study registration: Iranian Registry of Clinical Trials (www.irct.ir): IRCT2020 0330 046899N1. Study registration: Iranian Registry of Clinical Trials (www.irct.ir): IRCT2020 0330 046899N1.
Conflict of interest There was no conflict of interest in this study.
CRediT authorship contribution statement
References
Azimi, Hashemi-Nasab, Mokaberinejad, Qaraaty, Mojahedi, The prevention and complementary therapy in Acute distress syndrome of COVID-19 in the viewpoint of Persian medicine: A narrative review, J Babol Univ Medical Sci,
doi:10.22088/jbums.23.1.177Azimi, Hasheminasab, Evaluating the efficacy and safety of the myrtle (Myrtus communis) in treatment and prognosis of patients suspected to novel coronavirus disease (COVID-19): study protocol for a randomized controlled trial, Trials,
doi:10.1186/s13063-020-04915-wAzimi, Mojahedi, Mokaberinejad, Hasheminasab, Ethnomedicine knowledge of Iranian traditional healers and the novel coronavirus disease 2019 (COVID-19), J Adv Med Med Res,
doi:10.30699/jambs.29.135.238Bensaad, Kim, Quah, Kim, Shahimi, Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum, BMC Complement Altern Med,
doi:10.1186/s12906-017-1555-0Chandrasekaran, Deepak, Thiyagarajan, Kathiresan, Sangli et al., Dual inhibitory effect of Glycyrrhiza glabra (GutGardTM) on COX and LOX products, Phytomedicine,
doi:10.1016/j.phymed.2010.08.001Cinatl, Morgenstern, Bauer, Chandra, Rabenau et al., Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus, The Lancet,
doi:10.1016/S0140-6736(03)13615-XCornélio Favarin, De Oliveira, Freire De Oliveira, De, Rogerio, Potential effects of medicinal plants and secondary metabolites on acute lung injury, Biomed Res Int,
doi:10.1155/2013/576479Forouzanfar, Bazzaz, Hosseinzadeh, Black cumin (Nigella sativa) and its constituent (thymoquinone): a review on antimicrobial effects, Iran J Basic Med Sci,
doi:10.22038/IJBMS.2015.3849Franceschelli, Pesce, Vinciguerra, Ferrone, Riccioni et al., Licocalchone-C extracted from Glycyrrhiza glabra inhibits lipopolysaccharideinterferon-γ inflammation by improving antioxidant conditions and regulating inducible nitric oxide synthase expression, Molecules,
doi:10.3390/molecules16075720Frattaruolo, Carullo, Brindisi, Mazzotta, Bellissimo et al., Antioxidant and anti-inflammatory activities of flavanones from Glycyrrhiza glabra L.(licorice) leaf phytocomplexes: Identification of licoflavanone as a modulator of NF-kB/MAPK pathway, Antioxidants,
doi:10.3390/antiox8060186Ghannad, Mohammadi, Safiallahy, Faradmal, Azizi et al., The effect of aqueous extract of Glycyrrhiza glabra on herpes simplex virus 1, Jundishapur J Microbiol,
doi:10.5812/jjm.11616Guarner, Three emerging coronaviruses in two decades: the story of SARS, MERS, and now COVID-19, Am J Clin Pathol,
doi:10.1093/ajcp/aqaa029Haidari, Ali, Casscells, Sw, Madjid, Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir, Phytomedicine,
doi:10.1016/j.phymed.2009.06.002Hoever, Baltina, Michaelis, Kondratenko, Baltina et al., Antiviral activity of glycyrrhizic acid derivatives against SARS − coronavirus, J Med Chem,
doi:10.1021/jm0493008Hosseinzadeh, Bazzaz, Haghi, Antibacterial activity of total extracts and essential oil of Nigella sativa L. seeds in mice, Pharmacologyonline
Hosseinzadeh, Eskandari, Ziaee, Antitussive effect of thymoquinone, a constituent of Nigella sativa seeds, in guinea pigs, Pharmacologyonline
Iranzadasl, Karimi, Moadeli, Pasalar, Persian medicine recommendations for the prevention of pandemics related to the respiratory system: a narrative literature review, Integr Med Res,
doi:10.1016/j.imr.2020.100483Jin, Cai, Cheng, Cheng, Deng et al., A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version), Mil Med Res,
doi:10.1186/s40779-020-0233-6Johnson, Harris, Cain, Hummer, Goyal et al., Pulmonary and extra-pulmonary clinical manifestations of COVID-19, Front Med,
doi:10.3389/fmed.2020.00526Khorasani, Research Institute for Islamic and Complementary Medicine
Liu, Gao, Yuan, Yang, Shi et al., Efficacy and safety of integrated traditional Chinese and western medicine for corona virus disease 2019 (COVID-19): a systematic review and meta-analysis, Pharmacol Res,
doi:10.1016/j.phrs.2020.104896Luo, Su, Gong, Qin, Liu et al., Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. extracts, Biosci Trends
Marinova, Ribarova, Atanassova, Total phenolics and total flavonoids in Bulgarian fruits and vegetables, J Chem Technol Metal
Marsik, Kokoska, Landa, Nepovim, Soudek et al., In vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1-and-2-catalyzed prostaglandin E2 biosyntheses, Planta Med,
doi:10.1055/s-2005-871288Miyake, Tango, Ota, Mitamura, Yoshiba et al., Efficacy of Stronger Neo-Minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis, J Gastroenterol Hepatol,
doi:10.1046/j.1440-1746.2002.02876.xMohit, Farrokhzad, Faraji, Heidarzadeh-Esfahani, Kafeshani, Effect of Nigella sativa L. supplementation on inflammatory and oxidative stress indicators: a systematic review and meta-analysis of controlled clinical trials, Complement Ther Med,
doi:10.1016/j.ctim.2020.102535Pal, Berhanu, Desalegn, Kandi, Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2): An update, Cureus,
doi:10.7759/cureus.7423Qiu, Wei, Zhao, Zhong, Zhao et al., Outcome reporting from protocols of clinical trials of coronavirus disease 2019 (COVID-19): a review, medRxiv,
doi:10.1101/2020.03.04.20031401Salem, Hossain, Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection, Int J Immunopharmacol,
doi:10.1016/S0192-0561(00)00036-9Schubert, Lansky, Neeman, Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids, J Ethnopharmacol,
doi:10.1016/s0378-8741(98)00222-0Sekhavati, Jafari, Seyedalinaghi, Jamalimoghadamsiahkali, Sadr et al., Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2020.106143Shakeri, Hashempur, Beigomi, Khiveh, Nejatbakhsh et al., Strategies in traditional Persian medicine to maintain a healthy life in the elderly, J Complement Integr Med,
doi:10.1515/jcim-2019-0273Shakeri, Hashempur, Mojibian, Aliasl, Bioos et al., A comparative study of ranitidine and quince (Cydonia oblonga mill) sauce on gastroesophageal reflux disease (GERD) in pregnancy: a randomised, open-label, active-controlled clinical trial, J Obstet Gynaecol,
doi:10.1080/01443615.2018.1431210Shaygannia, Bahmani, Zamanzad, Rafieian-Kopaei, A review study on Punica granatum L, J Evid Based Complementary Altern Med,
doi:10.1177/2156587215598039Siahpoosh, How can Persian medicine (traditional Iranian medicine) be effective to control COVID-19?, Trad Integr Med,
doi:10.18502/tim.v5i2.3624Soleymani, Zargaran, A historical report on preparing sustained release dosage forms for addicts in medieval Persia, 16th Century AD. Subst Use Misuse,
doi:10.1080/10826084.2018.1432648Song, Li, Wu, -X, Shen, Liu et al., Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model, Acta Pharmacol Sin,
doi:10.1038/aps.2017.147Song, Wang, Zhang, Investigation of urinary interleukin-6 level in chronic renal failure patients and the influence of Rheum palmatum in treating it, Zhongguo Zhong Xi Yi Jie He Za Zhi
Tajmiri, Farhangi, Dehghan, Nigella Sativa treatment and serum concentrations of thyroid hormones, transforming growth factor β (TGF-β) and interleukin 23 (IL-23) in patients with Hashimoto's thyroiditis, Eur J Integr Med,
doi:10.1016/j.eujim.2016.03.003Thiyagarajan, Chandrasekaran, Deepak, Agarwal, Modulation of lipopolysaccharide-induced pro-inflammatory mediators by an extract of Glycyrrhiza glabra and its phytoconstituents, Inflammopharmacology,
doi:10.1007/s10787-011-0080-xVardanjani, Heydari, Dowran, Pasalar, A cross-sectional study of Persian medicine and the COVID-19 pandemic in Iran: Rumors and recommendations, Integr Med Res,
doi:10.1016/j.imr.2020.100482Walsh, Effectiveness of Chinese herbal medicine and Persian medicine against viral infections: A systematic review, Syst Rev Pharm,
doi:10.31838/srp.2021.2.6Zhang, Qiu, Wang, Long, Mao, Effect of Rheum palmatum L. on NF-κB signaling pathway of mice with acute liver failure, Asian Pac J Trop Med,
doi:10.1016/j.apjtm.2015.09.011Zhang, Zhan, Yao, Gao, Shong, Antiviral activity of tannin from the pericarp of Punica granatum L. against genital Herpes virus in vitro, China J Chin Mater Med
