Effects of Iranian herbal Zofa® syrup for the management of clinical symptoms in patients with COVID-19: A randomized clinical trial

Document Type : Original Research Article


1 Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

2 Trauma Research Center, Nursing Faculty, Baqiyatallah University of Medical Sciences, Tehran, Iran

3 Department of Anesthesiology and Critical Care, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

4 Pharmacotherapy Department, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran

5 Academic Diabetes, Endocrinology and Metabolism, Allam Diabetes Centre Hull Royal Infirmary Anlaby Road HU3 2JZ, Hull, UK

6 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Tehran, Iran. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Tehran, Iran


Objective: The objective of this study was to determine the role of Iranian herbal Zofa® syrup in improving the clinical symptoms of patients with COVID-19.
Materials and Methods: This randomized clinical trial was conducted on 105 patients with COVID-19. Patients were randomly assigned to the intervention (n=35) group (received 10 ml of Zofa® syrup every 8 hours/seven days plus standard treatment) or the control (n=70) group (received only standard treatment). Assessments were performed before and after treatment.
Results: The groups were comparable regarding age (p=0.980), gender (p=0.584), comorbidities (p=0.318), or drug history (p=0.771). There was no difference between patients' recovery status at the time of discharge (p=0.327) or two weeks post-discharge (p=0.165) in the intervention and control groups. No patient was hospitalized to the intensive care unit (ICU) for supplemental oxygen therapy and no patient died in the intervention group. However, in the control group, three (4.5%) patients were transferred to the ICU, and two (3.03%) patients died.
Conclusion: Considering the better recovery status of the patients at the time of discharge and the absence of patient deaths in the intervention group, more additional studies are needed to confirm these findings and elucidate the role of Zofa® in COVID-19.


Ahmadi R, Salari S, Sharifi MD, Reihani H,
Rostamiani MB, Behmadi M, Taherzadeh
Z, Eslami S, Rezayat SM, Jaafari MR,
Elyasi S. 2021. Oral nano-curcumin
formulation efficacy in the management of
mild to moderate outpatient COVID-19: a
randomized triple-blind placebo-controlled
clinical trial. Food Sci Nutr, 9: 4068-4075.
Babich O, Sukhikh S, Prosekov A, Asyakina
L, Ivanova S. 2020. Medicinal plants to
strengthen immunity during a pandemic.
Pharmaceuticals (Basel), 13: 12-18.
Banaee M, Soleimany V, Nematdoost Haghi
B. 2017. Therapeutic effects of
marshmallow (Althaea officinalis L.)
extract on plasma biochemical parameters
of common carp infected with Aeromonas
hydrophila. Vet Res Forum, 8: 145-153.
Bhattacharyya R, Iyer P, Phua GC, Lee JH.
2020. The interplay between coagulation
and inflammation pathways in COVID-19-
associated respiratory failure: a narrative
review. Pulm Ther, 6: 215-231.
Bohn MK, Hall A, Sepiashvili L, Jung B,
Steele S, Adeli K. 2020. Pathophysiology
of COVID-19: mechanisms underlying
disease severity and progression.
Physiology. Physiology (Bethesda), 35:
Bonaterra GA, Bronischewski K, Hunold, P,
Schwarzbach H, Heinrich EU, Fink C,
Aziz-Kalbhenn H, Müller J, Kinscherf R.
2020. Anti-inflammatory and anti-oxidative
effects of phytohustil(®) and root extract of
althaea officinalis L. on macrophages in
vitro. Front Pharmacol, 11: 290-295.
Borrelli F, Pagano E, Formisano C, Piccolella
S, Fiorentino A, Tenore, GC, Izzo AA,
Rigano D, Pacifico S. 2019. Hyssopus
officinalis subsp. aristatus: An unexploited
wild-growing crop for new disclosed
bioactives. Ind Crops Prod, 140: 11-15.
Champasuri S, Itharat A. 2016. Bioactivities of
ethanolic extracts of three parts (wood,
nutmeg and mace) from myristica fragrans
houtt. J Med Assoc Thai, 99 Suppl 4: S124-
Choopani R, Sadr S, Kaveh S, Kaveh, N,
Dehghan S. 2015. Pharmacological
treatment of catarrh in Iranian traditional
medicine. J Tradit Complement Med, 5: 71-
Costela-Ruiz VJ, Illescas-Montes R, PuertaPuerta JM, Ruiz C, Melguizo-Rodríguez L.
2020. SARS-CoV-2 infection: the role of
cytokines in COVID-19 disease. Cytokine
Growth Factor Rev, 54: 62-75.
Cuschieri S. 2019. The CONSORT statement.
Saudi J Anaesth, 13: S27-S30.
Effects of Zofa®
syrup on COVID-19
AJP, Vol. 13, No. 5, Sep-Oct 2023 511
Fiore C, Eisenhut M, Krausse R, Ragazzi, E,
Pellati D, Armanini, D, Bielenberg J. 2008.
Antiviral effects of Glycyrrhiza species.
Phytother Res, 22: 141-148.
Hansell DM, Bankier AA, Macmahon H,
Mcloud TC, Muller NL, Remy J. 2008.
Fleischner Society: glossary of terms for
thoracic imaging. Radiology, 246: 697-722.
Harvey WT, Carabelli AM, Jackson B, Gupta
RK, Thomson EC, Harrison EM, Ludden
C, Reeve R, Rambaut, A, Peacock SJ,
Robertson DL, Consortium CGU. 2021.
SARS-CoV-2 variants, spike mutations and
immune escape. Nat Rev Microbiol, 19:
Helsinki. 2013. Ethical principles for medical
research involving human subjects. JAMA,
310: 2191-2194.
Hosseini SA, Zahedipour F, Sathyapalan T,
Jamialahmadi T, Sahebkar A. 2021.
Pulmonary fibrosis: therapeutic and
mechanistic insights into the role of
phytochemicals. BioFactors, 47: 250-269.
Iranzadasl M, Karimi Y, Moadeli F, Pasalar
M. 2021. Persian medicine
recommendations for the prevention of
pandemics related to the respiratory
system: a narrative literature review. Integr
Med Res, 10: 10048-10053.
Irwin RS, Dudiki N, French CL. 2020. Lifethreatening and non-life-threatening
complications associated with coughing: a
scoping review. Chest, 158: 2058-2073.
Jacobs SS. 2020. Complications of chronic
cough: another call for treatment strategies.
Chest, 158: 1818-1819.
Karsch-Völk M, Barrett B, Kiefer D, Bauer R,
Ardjomand-Woelkart K, Linde K. 2014.
Echinacea for preventing and treating the
common cold. Cochrane Database Syst
Rev, 2: 530-532.
Letessier MP, Svoboda KP, Walters DR.
2001. Antifungal activity of the essential
oil of hyssop (Hyssopus officinalis). J
Phytopathol, 149: 673-678.
Martins CF, Campos ML, Irioda AC, Stremel
DP, Trindade A, Pontarolo R. 2017. Antiinflammatory effect of malva sylvestris,
sida cordifolia, and pelargonium graveolens
is related to inhibition of prostanoid
production. Molecules, 22: 14-16.
Mesaik AM, Poh HW, Bin OY, Elawad I,
Alsayed B. 2018. In vivo antiInflammatory, anti-bacterial and antidiarrhoeal activity of ziziphus jujuba fruit
extract. Open Access Maced J Med Sci, 6:
Monavari H, Hamkar R, Babaei NZ, Adibi, L,
Noroozi M, Ziaei A. 2007. Antiviral effect
assay of twenty five species of various
medicinal plants families in Iran. IJM, 1:
Otto SP, Day T, Arino J, Colijn C, Dushoff J,
Li M, Mechai S, Van-Domselaar G, Wu J,
Earn-D JD, Ogden NH. 2021. The origins
and potential future of SARS-CoV-2
variants of concern in the evolving
COVID-19 pandemic. Current Biology, 31:
Pandey V, Verma RS, Chauhan A, Tiwari R.
2014. Compositional variation in the leaf,
flower and stem essential oils of Hyssop
(Hyssopus officinalis L.) from WesternHimalaya. J Herb Med, 4: 89-95.
Paudyal V, Sun S, Hussain R, Abutaleb MH,
Hedima EW. 2022. Complementary and
alternative medicines use in COVID-19: a
global perspective on practice, policy and
research. Res Social Adm Pharm, 18: 2524-
Pawar KS, Mastud RN, Pawar SK, Pawar, SS,
Bhoite RR, Bhoite RR, Kulkarni MV,
Deshpande AR. 2021. Oral curcumin with
piperine as adjuvant therapy for the
treatment of COVID-19: a randomized
clinical trial. Front Pharmacol, 12: 6693-
Perotin JM, Launois C, Dewolf M, Dumazet
A, Dury S, Lebargy F, Dormoy V, Deslee
G. 2018. Managing patients with chronic
cough: challenges and solutions. Ther Clin
Risk Manag, 14: 1041-1051.
Proal AD, Vanelzakker MB. 2021. Long
COVID or post-acute sequelae of COVID19 (PASC): an overview of biological
factors that may contribute to persistent
symptoms. Front Microbiol, 12: 6981-
Rahmanzade R, Rahmanzadeh R, Hashemian
SM, Tabarsi P. 2020. Iran's approach to
COVID-19: evolving treatment protocols
and ongoing clinical trials. Front Public
Health, 8: 5518-5519.
Rajaei A, Salarbashi D, Asrari N, Fazly
Bazzaz BS, Aboutorabzade, SM, Shaddel
R. 2021. Antioxidant, antimicrobial, and
cytotoxic activities of extracts from the
seed and pulp of Jujube (Ziziphus jujuba)
grown in Iran. Food Sci Nutr, 9: 682-691.
Ghazvini et al.
AJP, Vol. 13, No. 5, Sep-Oct 2023 512
Schoen K, Horvat N, Guerreiro NFC, De
Castro I, De Giassi KS. 2019. Spectrum of
clinical and radiographic findings in
patients with diagnosis of H1N1 and
correlation with clinical severity. BMC
Infect Dis, 19: 964-968.
Sokmen A, Gulluce M, Askin Akpulat H,
Daferera D, Tepe B, Polissiou M, Sokmen
M, Sahin F. 2004. The in vitro
antimicrobial and antioxidant activities of
the essential oils and methanol extracts of
endemic Thymus spathulifolius. Food
Control, 15: 627-634.
Song WJ, Hui CKM, Hull JH, Birring SS,
Mcgarvey L, Mazzone SB, Chung, KF.
2021. Confronting COVID-19-associated
cough and the post-COVID syndrome: role
of viral neurotropism, neuroinflammation,
and neuroimmune responses. Lancet Respir
Med, 9: 533-544.
Süleyman K, Nesrin H, Veysel T, Ersin K,
Hakan K. 2010. Chemical composition,
antimicrobial and antioxidant activities of
Hyssop (Hyssopus officinalis L.) essential
oil. Notulae Botanicae Horti Agrobotanici
Cluj-Napoca, 38: 33-39.
Vahedian-Azimi A, Abbasifard M, RahimiBashar F, Guest PC, Majeed M,
Mohammadi A, Banach M, Jamialahmadi
T, Sahebkar A. 2022. Effectiveness of
curcumin on outcomes of hospitalized
COVID-19 patients: A systematic review
of clinical trials. Nutrients, 14: 256-260.
Vlase L, Benedec D, Hanganu D, Damian G,
Csillag I, Sevastre B, Mot AC, SilaghiDumitrescu R, Tilea I. 2014. Evaluation of
antioxidant and antimicrobial activities and
phenolic profile for Hyssopus officinalis,
ocimum basilicum and teucrium
chamaedrys. Molecules, 19: 5490-5507.
Wiersinga WJ, Rhodes A, Cheng AC,
Peacock SJ, Prescott HC. 2020.
Pathophysiology, transmission, diagnosis,
and treatment of coronavirus disease 2019
(COVID-19): a review. JAMA, 324: 782-
Yang Y, Islam MS, Wang J, Li Y, Chen X.
2020. Traditional chinese medicine in the
treatment of patients infected with 2019-
new coronavirus (SARS-CoV-2): a review
and perspective. Int J Biol Sci, 16: 1708-
Zahedipour F, Hosseini SA, Sathyapalan T,
Majeed M, Jamialahmadi T, Al-Rasadi K,
Banach M, Sahebkar A. 2020. Potential
effects of curcumin in the treatment of
COVID-19 infection. Phytother Res, 34: