Efficacy of a Persian herbal medicine compound on coronavirus disease 2019 (COVID-19): A randomized controlled trial

다국어 초록 (Multilingual Abstract)

Background: The global attention to the capacities of traditional medicine for alleviating the clinical man-ifestations 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 Gly-cyrrhiza 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 hospitaliza-tion days, while cough, fever, and respiratory rate, days on oxygen (O2) 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 pri-mary outcome was 2.95 ± 0.43 days. A significant clinical improvement was observed regarding dyspnea, need for O2) 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.

다국어 초록 (Multilingual Abstract)

Background: The global attention to the capacities of traditional medicine for alleviating the clinical man-ifestations 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 Gly-cyrrhiza 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 hospitaliza-tion days, while cough, fever, and respiratory rate, days on oxygen (O2) 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 pri-mary outcome was 2.95 ± 0.43 days. A significant clinical improvement was observed regarding dyspnea, need for O2) 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.

참고문헌 (Reference)

1 Marinova D, "Total phenolics and total flavonoids in Bulgarian fruits and vegetables" 40 (40): 255-260, 2005

2 Guarner Jeannette, "Three emerging coronaviruses in two decades : the story of SARS, MERS, and now COVID-19" 153 (153): 420-421, 2020

3 Azimi M, "The prevention and complementary therapy in Acute distress syndrome of COVID-19 in the viewpoint of Persian medicine : A narrative review" 23 (23): 177-188, 2022

4 Masoud Sabouri Ghannad, "The Effect of Aqueous Extract of Glycyrrhiza glabra on Herpes Simplex Virus 1" Briefland 7 (7): 2014

5 Shakeri A, "Strategies in traditional Persian medicine to maintain a healthy life in the elderly" 18 (18): 29-36, 2020

6 Mahendra Pal, "Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update" Cureus, Inc. 12 (12): e7423-, 2020

7 Ehsan Sekhavati, "Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial" Elsevier BV 56 (56): 106143-, 2020

8 Hashempur MH, "Rhazes—his life and contributions to the field of dermatology" 153 (153): 70-, 2017

9 Johnson KD, "Pulmonary and extra-pulmonary clinical manifestations of COVID-19" 7 : 526-, 2020

10 Salem ML, "Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection" 22 (22): 729-740, 2000

11 Daniely Cornélio Favarin, "Potential Effects of Medicinal Plants and Secondary Metabolites on Acute Lung Injury" Hindawi Limited 2013 : 1-12, 2013

12 Mehran Haidari, "Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir" Elsevier BV 16 (16): 1127-1136, 2009

13 Maryam Iranzadasl ; Yasin Karimi ; Fatemeh Moadeli ; Mehdi Pasalar, "Persian medicine recommendations for the prevention of pandemics related to the respiratory system: A narrative literature review" 한국한의학연구원 10 (10): 1-5, 2021

14 Qiu R, "Outcome reporting from protocols of clinical trials of coronavirus disease 2019 (COVID-19): a review"

15 Koshak AE, "Nigella sativa L. as a potential phytotherapy for covid19: a mini-review of in-silico studies" 93 : 100602-, 2020

16 Tajmiri S, "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" 8 (8): 576-580, 2016

17 P. Thiyagarajan, "Modulation of lipopolysaccharide-induced pro-inflammatory mediators by an extract of Glycyrrhiza glabra and its phytoconstituents" Springer Science and Business Media LLC 19 (19): 235-241, 2011

18 Lin J-C, "Mechanism of action of glycyrrhizic acid in inhibition of EpsteinBarr virus replication in vitro" 59 (59): 41-47, 2003

19 Khorasani MA, "Makhzan al Advieh" Bavardaran Press Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences 2001

20 Sara Franceschelli, "Licocalchone-C Extracted from Glycyrrhiza Glabra Inhibits Lipopolysaccharide-Interferon-γ Inflammation by Improving Antioxidant Conditions and Regulating Inducible Nitric Oxide Synthase Expression" MDPI AG 16 (16): 5720-5734, 2011

21 Song H, "Investigation of urinary interleukin-6 level in chronic renal failure patients and the influence of Rheum palmatum in treating it" 20 (20): 107-109, 2000

22 Marsik P, "In vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1-and-2-catalyzed prostaglandin E2 biosyntheses" 71 (71): 739-742, 2005

23 Beketov E, "Improved method of flavonoid extraction from bird cherry fruits" 39 (39): 316-318, 2005

24 M. Tauseef Sultan, "Immunity: Plants as Effective Mediators" Informa UK Limited 54 (54): 1298-1308, 2014

25 Marzieh Beygom Siahpoosh, "How Can Persian Medicine (Traditional Iranian Medicine) Be Effective to Control COVID-19?" Knowledge E 5 (5): 18502-, 2020

26 Cinatl J, "Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus" 361 (361): 2045-2046, 2003

27 Azimi M, "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" 21 (21): 1-5, 2020

28 Azimi M, "Ethnomedicine knowledge of Iranian traditional healers and the novel coronavirus disease 2019(COVID-19)" 29 (29): 238-245, 2021

29 T HO, "Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction" Elsevier BV 74 (74): 92-101, 2007

30 Song Y-d, "Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model" 39 (39): 1317-1325, 2018

31 Miyake K, "Efficacy of Stronger Neo-Minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis" 17 (17): 1198-1204, 2002

32 Liu M, "Efficacy and safety of integrated traditional Chinese and western medicine for corona virus disease 2019(COVID-19) : a systematic review and meta-analysis" 158 : 104896-, 2020

33 Walsh M, "Effectiveness of Chinese herbal medicine and Persian medicine against viral infections : A systematic review" 12 (12): 65-81, 2020

34 Rong-Zhen Zhang, "Effect of Rheum palmatum L. on NF-κB signaling pathway of mice with acute liver failure" Medknow 8 (8): 841-847, 2015

35 Mohsen Mohit, "Effect of Nigella sativa L. supplementation on inflammatory and oxidative stress indicators: A systematic review and meta-analysis of controlled clinical trials" Elsevier BV 54 : 102535-, 2020

36 Chandrasekaran C, "Dual inhibitory effect of Glycyrrhiza glabra(GutGardTM)on COX and LOX products" 18 (18): 278-284, 2011

37 Rahman A, "Defining a ‘Risk Group’and Ageism in the Era of COVID-19" 25 : 631-634, 2020

38 M. Akram Khan, "Chemical composition of Nigella sativa Linn: Part 2 Recent advances" Springer Science and Business Media LLC 24 (24): 67-79, 2016

39 Forouzanfar F, "Black cumin(Nigella sativa)and its constituent(thymoquinone) : a review on antimicrobial effects" 17 (17): 929-938, 2014

40 Zhang J, "Antiviral activity of tannin from the pericarp of Punica granatum L. against genital Herpes virus in vitro" 20 (20): 556-558, 1995

41 Hoever G, "Antiviral activity of glycyrrhizic acid derivatives against SARS− coronavirus" 48 (48): 1256-1259, 2005

42 Hosseinzadeh H, "Antitussive effect of thymoquinone, a constituent of Nigella sativa seeds, in guinea pigs" 2 : 480-484, 2008

43 Shay Yehoshua Schubert, "Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids" Elsevier BV 66 (66): 11-17, 1999

44 Luca Frattaruolo, "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" MDPI AG 8 (8): 186-, 2019

45 Hosseinzadeh H, "Antibacterial activity of total extracts and essential oil of Nigella sativa L. seeds in mice" 2 : 429-435, 2007

46 Lamees A. BenSaad, "Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum" Springer Science and Business Media LLC 17 (17): 2017

47 Luo W, "Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. extracts" 3 (3): 124-126, 2009

48 Parvaiz M, "A review:Medicinal importance of Glycyrrhiza glabra L.(fabaceae family)" 8 (8): 8-13, 2014

49 Jin Y-H, "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)" 7 (7): 4-, 2020

50 Soleymani S, "A historical report on preparing sustained release dosage forms for addicts in medieval Persia, 16th Century AD" 53 (53): 1726-1729, 2018

51 Hossein Molavi Vardanjani ; Seyed Taghi Heydari ; Behzad Dowran ; Mehdi Pasalar, "A cross-sectional study of Persian medicine and the COVID-19 pandemic in Iran: Rumors and recommendations" 한국한의학연구원 9 (9): 1-5, 2020

52 Shakeri A, "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" 38 (38): 899-905, 2018

53 Erfaneh Shaygannia, "A Review Study on Punica granatum L" SAGE Publications 21 (21): 221-227, 2015