The use of Ephedra herbs in the treatment of COVID-19

Document Type : Mini Review Article

Authors

1 Department of Microbiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran

2 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

3 Department of Psychology, Faculty of Literature and Human Science, University of Malayer, Malayer, Iran

4 Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

5 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Objective: Ephedra herbs are the only extant genus in its family, Ephedraceae, and order, Ephedrales. It has been prescribed in traditional medicine for improving headaches and respiratory infections. On the other hand, because the coronavirus disease 2019 (COVID-19) causes respiratory problems and COVID-19 pandemic is the most widespread outbreak that has affected humanity in the last century, the current review aims using literature search to investigate the effects of the Ephedra herbs compounds on COVID-19 to supply a reference for its clinical application in the inhibition and remedy of COVID-19.
Materials and Methods: This review was performed using articles published in various databases, including Web of Science, PubMed, Scopus, and Google Scholar, without a time limit. For this paper, the following keywords were used: "Ephedra", "coronavirus disease 2019", "COVID-19", "Severe acute respiratory syndrome coronavirus 2" or "SARS CoV 2".
Results: The results of this review show that the Ephedra herbs have effectiveness on COVID-19 and its compounds can bind to angiotensin-converting enzyme 2 (ACE2) with a high affinity and act as a blocker and prevent the binding of the virus.
Conclusion: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.

Keywords


Alimohamadi Y, Sepandi M, Taghdir M,
Hosamirudsari H. 2020. Determine the
most common clinical symptoms in
COVID-19 patients: a systematic review
and meta-analysis. J Prev Med Hyg, 61:
e304-e312.
Al-Snafi AE. 2017. Nutritional and
pharmacological importance of Ficus
carica-A review. IOSR J Pharm, 7: 33-48.
Arokiaraj S, Vincent S, Vannam DK. 2020.
Touting traditional knowledge and herbal
medicine to combat and prevent COVID19. Curr Pharm Biotechnol, 21: 1280-
1281.
Askew RR, Nieves-Aldrey JL. 2017.
Eupelmidae (Hymenoptera, Chalcidoidea)
of Iberia and the Canary Islands: an
annotated checklist with descriptions of
some previously unrecognised males and
a new species of Calosota Curtis, 1836.
Graellsia, 73: 1-17.
Atique S, Bautista JR, Block LJ, Lee JJ,
Lozada-Perezmitre E, Nibber R,
Ephedra herbs in the treatment of COVID-19
AJP, Vol. 13, No. 3, May-Jun 2023 237
O'Connor S, Peltonen LM, Ronquillo C,
Tayaben J. 2020. A nursing informatics
response to COVID-19: Perspectives
from five regions of the world. J Adv
Nurs, 76: 2462-2468.
Barkat MA, Goyal A, Barkat HA, Salauddin
M, Pottoo FH, Anwer ET. 2021. Herbal
medicine: clinical perspective and
regulatory status. comb chem high
throughput screen, 24: 1573-1582.
Basit A, Saeed S, Ahmed A, Baloch N, Ali
AZ. 2021. Genetic structuring of Ephedra
an important medicinal plant from low to
high altitudinal zones of Balochistan,
Pakistan. Biodiversitas, 22: 713-718.
Benabderrahim MA, Yahia Y, Bettaieb I,
Elfalleh W, Nagaz K. 2019. Antioxidant
activity and phenolic profile of a
collection of medicinal plants from
Tunisian arid and Saharan regions. Ind
Crops Prod, 138: 111427.
Besharati MR, Izadi M, Talebpour, A. 2022.
Some natural hypomethylating agents in
food, water and environment are against
distribution and risks of COVID-19
pandemic: Results of a bigdata research.
Avicenna J Phytomed, 12: 309-324.
Caveney S, Charlet DA, Freitag H, Maier‑
Stolte M, Starratt, AN. 2001. New
observations on the secondary chemistry
of world Ephedra (Ephedraceae). Am J
Bot, 88: 1199-1208.
Chaitanya B, Sagi SR, Shashikanth P,
Karunakar K. 2014. Evaluation of antiasthmatic activity of ethanolic extract of
Ephedra gerardiana wall in mice by
ovalbumin induced method. AJPCR, 1:
166-169.
Chan JF, Yuan S, Kok KH, To KK, Chu H,
Yang J, Xing F, Liu J, Yip CC, Poon,
RW. 2020. A familial cluster of
pneumonia associated with the 2019
novel coronavirus indicating person-toperson transmission: a study of a family
cluster. Lancet, 395: 514-523.
Cheng Y, Chen X, Wu Y, Sun D, Yu X, Li S.
2020. Analysis on rules of TCM
prescriptions in treating and preventing
COVID-19 based on data mining. J Tradit
Chin Med, 54: 32-39.
DiPietro MA, Mondie C. 2021. Toxicity of
herbal medications suggested as treatment
for COVID‑19: A narrative review. J Am
Coll Emerg Physicians Open, 2: e12411.
Dousari AS, Satarzadeh N, Amirheidari B,
Forootanfar H. 2022. Medicinal and
therapeutic properties of Ephedra. Rev
Bras Farmacogn, 32: 883-899.
Dousari AS, Moghadam MT, Satarzadeh N.
2020. COVID-19 (Coronavirus disease
2019): a new coronavirus disease. Infect
Drug Resist, 13: 2819-2828.
Elhadef K, Smaoui S, Fourati M, Ben Hlima
H, Chakchouk Mtibaa A, Sellem I,
Ennouri K, Mellouli L. 2020. A review on
worldwide Ephedra history and story:
from fossils to natural products mass
spectroscopy characterization and
biopharmacotherapy potential. Evid
Based Complement Alternat Med, 2020:
1540638.
Eng YS, Lee CH, Lee WC, Huang CC, Chang
JS. 2019. Unraveling the molecular
mechanism of traditional chinese
medicine: formulas against acute airway
viral infections as examples. Molecules,
24: 3505.
Gao K, Song YP, Song A. 2020. Exploring
active ingredients and function
mechanisms of Ephedra-bitter almond for
prevention and treatment of Corona virus
disease 2019 (COVID-19) based on
network pharmacology. BioData min, 13:
19.
González-Juárez DE, Escobedo-Moratilla A,
Flores J, Hidalgo-Figueroa S, MartínezTagüeña N, Morales-Jiménez J, MuñizRamírez A, Pastor-Palacios G, PérezMiranda S, Ramírez-Hernández A. 2020.
A review of the Ephedra genus:
distribution, ecology, ethnobotany,
phytochemistry and pharmacological
properties. Molecules, 25: 3283.
Gorbalenya AE, Baker SC, Baric RS, de Groot
RJ, Drosten C, Gulyaeva AA, Haagmans
B, Lauber C, Leontovich A, Neuman B.
2020. Coronaviridae study group of the
international committee on taxonomy of
viruses: the species severe acute
respiratory syndrome-related coronavirus:
classifying 2019-nCoV and naming it
SARS-CoV-2. Nat Microbiol, 5: 536-544.
Guo YR, Cao QD, Hong ZS, Tan YY, Chen
SD, Jin HJ, Tan KS, Wang DY, Yan Y.
2020. The origin, transmission and
clinical therapies on coronavirus disease
2019 (COVID-19) outbreak–an update on
the status. Mil Med Res, 7: 11.
Gurley B, Wang P, Gardner S. 1998.
Ephedrine‑type alkaloid content of
Sadeghi Dousari et al.
AJP, Vol. 13, No. 3, May-Jun 2023 238
nutritional supplements containing
Ephedra sinica (ma‑huang) as determined
by high performance liquid
chromatography. J Pharm Sci, 87: 1547-
1553.
Hashem-Dabaghian F, Azimi SA, Bahram M,
Latifi SA, Enayati A, Qaraaty M. 2022.
Effect of lavender (Lavandula
angustifolia L.) syrup on olfactory
dysfunction in COVID-19 infection: a
pilot controlled clinical trial. Avicenna J
Phytomed, 12: 1-7.
Hu K, Guan WJ, Bi Y, Zhang W, Li L, Zhang
B, Liu Q, Song Y, Li X, Duan Z. 2019.
Efficacy and safety of Lianhuaqingwen
capsules, a repurposed Chinese Herb.
Patients with Coronavirus disease.
Phytomedicine, 85: 153242.
Jin YH, Cai L, Cheng ZS, Cheng H, Deng T,
Fan YP, Fang C, Huang D, Huang LQ,
Huang Q. 2020. A rapid advice guideline
for the diagnosis and treatment of 2019
novel coronavirus (2019-nCoV) infected
pneumonia (standard version). Mil Med
Res, 7: 4.
Kahn JS, McIntosh K. 2005. History and
recent advances in coronavirus discovery.
Pediatr Infect Dis J, 24: S223-S227.
Bent S, Tiedt TN, Shlipak MG. 2003. The
relative safety of ephedra compared with
other herbal products. Ann Intern Med,
139: 386-387.
Lee DY, Li QY, Liu J, Efferth T. 2021.
Traditional Chinese herbal medicine at
the forefront battle against COVID-19:
clinical experience and scientific basis.
Phytomedicine, 80: 153337.
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong
Y, Ren R, Leung KS, Lau EH, Wong JY.
2020. Early transmission dynamics in
Wuhan, China, of novel coronavirus–
infected pneumonia. N Engl J Med, 382:
1199-1207.
Li M, Fan X, Zhou L, Jiang M, Shang E. 2022.
The effect of Ma-Xin-Gan-Shi decoction
on asthma exacerbated by respiratory
syncytial virus through regulating TRPV1
channel. J Ethnopharmacol, 291: 115157.
Li X, Qiu Q, Li M, Lin H, Cao S, Wang Q,
Chen Z, Jiang W, Zhang W, Huang Y.
2021. Chemical composition and
pharmacological mechanism of ephedraglycyrrhiza drug pair against coronavirus
disease 2019 (COVID-19). Aging
(Albany NY), 13: 4811-4830.
Liu SH, Chuang WC, Lam W, Jiang Z, Cheng
YC. 2015. Safety surveillance of
traditional Chinese medicine: current and
future. Drug Saf, 38: 117-128.
Liu Z, Li X, Gou C, Li L, Luo X, Zhang C,
Zhang Y, Zhang J, Jin A, Li H. 2020.
Effect of Jinhua Qinggan granules on
novel coronavirus pneumonia in patients.
J Tradit Chin Med, 40: 467-472.
Lv Y, Wang S, Liang P, Wang Y, Zhang X,
Jia Q, Fu J, Han S, He L. 2021. Screening
and evaluation of anti-SARS-CoV-2
components from Ephedra sinica by
ACE2/CMC-HPLC-IT-TOF-MS
approach. Anal Bioanal Chem, 413: 2995-
3004.
Mei J, Zhou Y, Yang X, Zhang F, Liu X, Yu
B. 2021. Active components in Ephedra
sinica Stapf disrupt the interaction
between ACE2 and SARS-CoV-2 RBD:
potent COVID-19 therapeutic agents. J
Ethnopharmacol, 278: 114303.
Moghadam MT, Taati B, Paydar Ardakani
SM, Suzuki K. 2021. Ramadan fasting
during the COVID-19 pandemic;
observance of health, nutrition and
exercise criteria for improving the
immune system. Front nutr, 7: 570235.
Nomura T, Fukushi M, Oda K, Higashiura A,
Irie T, Sakaguchi T. 2019. Effects of
traditional Kampo drugs and their
constituent crude drugs on Influenza virus
replication in vitro: suppression of viral
protein synthesis by Glycyrrhizae Radix.
Evid Based Complement Alternat Med,
2019: 3230906.
World Health Organization. 2020. Laboratory
testing for coronavirus disease ( COVID19) in suspected human cases: interim
guidance. WHO, 2020: 1-10.
Panaampon J, Kudo E, Kariya R, Okada S.
2019. Ephedrine enhances HIV-1
reactivation from latency through
elevating tumor necrosis factor receptor II
(TNFRII) expression. Heliyon, 5: e02490.
Qamar W, Khan R, Khan AQ, Rehman MU,
Lateef A, Tahir M, Ali F, Sultana S. 2012.
Alleviation of lung injury by glycyrrhizic
acid in benzo (a) pyrene exposed rats:
probable role of soluble epoxide
hydrolase and thioredoxin reductase.
Toxicology, 291: 25-31.
Ren Jl, Zhang AH, Wang XJ. 2020.
Traditional Chinese medicine for
COVID-19 treatment. Pharmacol Res,
Ephedra herbs in the treatment of COVID-19
AJP, Vol. 13, No. 3, May-Jun 2023 239
155: 104743.
Sadeghi Dosari A, Norouzi A, Taati
Moghadam M, Satarzadeh N. 2016.
Antimicrobial activity of Ephedra
pachyclada methanol extract on some
enteric gram-negative bacteria which
causes nosocomial infections by agar
dilution method. ZJRMS, 18: e4015.
Sahin AR, Erdogan A, Agaoglu PM, Dineri Y,
Cakirci AY, Senel ME, Okyay RA,
Tasdogan AM. 2020. 2019 novel
coronavirus (COVID-19) outbreak: a
review of the current literature. Eurasian
J Med Oncol, 4: 1-7.
Shakibnia P, Ahmadi RH, Fallah F,
Ebrahimzadeh F, Dosari AS, Mojtahedi
A, Hajipour N, Luyeh MS, Moghadam
MT. 2021. Iran as the center of challenges
in the Middle East for the outbreak of
COVID-19 delta variant. Iran Red
Crescent Med J, 23: e1394.
Sõukand R, Pieroni A, Biró M, Dénes A,
Dogan Y, Hajdari A, Kalle R, Reade B,
Mustafa B, Nedelcheva A. 2015. An
ethnobotanical perspective on traditional
fermented plant foods and beverages in
Eastern Europe. J Ethnopharmacol, 170:
284-296.
Taati Moghadam M, Babakhani S, Rajabi S,
Bagheri Baravati F, Raeisi M, Sadeghi
Dousari A. 2021. Does stress and anxiety
contribute to COVID-19? Iran J
Psychiatry Behav Sci, 15: e106041.
Thakur A, Pathak SR. 2018. Introduction to
medicinally important constituent from
Chinese medicinal plants. In: Ashish T,
Supriya T (Eds), Synthesis of Medicinal
Agents from Plants, pp. 333-349,
Amsterdam, Elsevier.
Wang C, Ming H, Jia W, Su W, Zhan LR, Luo
D, Yang JY. 2020. Analysis of
medication regularity and
pharmacodynamic characteristics of
traditional Chinese medicine treatment in
444 severe cases of COVID-19. China J
Chin Materia Medica, 45: 3007-3012.
Wang Q, Yang Y, Zhao X, Zhu B, Nan P,
Zhao J, Wang L, Chen F, Liu Z, Zhong Y.
2006. Chemical variation in the essential
oil of Ephedra sinica from Northeastern
China. Food Chem, 98: 52-58.
Wang S, Hu Y, Tan W, Wu X, Chen R, Cao J,
Chen M, Wang Y. 2012. Compatibility art
of traditional Chinese medicine: from the
perspective of herb pairs. J
Ethnopharmacol, 143: 412-423.
Wei W, Du H, Shao C, Zhou H, Lu Y, Yu L,
Wan H, He Y. 2019. Screening of
antiviral components of Ma Huang Tang
and investigation on the Ephedra
alkaloids efficacy on influenza virus type
A. Front pharmacol, 10: 961.
Xiao M, Tian J, Zhou Y, Xu X, Min X, Lv Y,
Peng M, Zhang Y, Yan D, Lang S. 2020.
Efficacy of Huoxiang Zhengqi dropping
pills and Lianhua Qingwen granules in
treatment of COVID-19: a randomized
controlled trial. Pharmacol Res, 161:
105126.
Xin S, Cheng X, Zhu B, Liao X, Yang F, Song
L, Shi Y, Guan X, Su R, Wang J. 2020.
Clinical retrospective study on the
efficacy of Qingfei Paidu decoction
combined with Western medicine for
COVID-19 treatment. Biomed
Pharmacother, 129: 110500.
Yang Y, Lin L, Ferguson DK, Wang Y. 2018.
Macrofossil evidence unveiling evolution
of male cones in Ephedraceae (Gnetidae).
BMC Evol Biol, 18: 125.
Zhang BM, Wang ZB, Xin P, Wang QH, Bu
H, Kuang HX. 2018. Phytochemistry and
pharmacology of genus Ephedra. Chin J
Nat Med, 16: 811-828.
Zhao JY, Yan JY, Qu JM. 2020.
Interpretations of “diagnosis and
treatment protocol for novel coronavirus
pneumonia (trial version 7)”. Chin Med J,
133: 1347-1349.
Zhou Z, Zhu C, Zhang B. 2020. Study on
medication regularity of traditional
Chinese medicine in treatment of novel
coronavirus pneumonia based on data
mining. Zhongguo Zhong Yao Za Zhi, 45:
1248-1252.
Zhu DH, Zhang JK, Jia JF, Liu JJ, Wei JJ,
Yang M, Yang Y, Li M, Hao ZY, Zheng
XK, Feng WS. 2022. Alkaloids from the
stem of Ephedra equisetina. J Asian Nat
Prod Res, 12: 1-7.
Zu Z, Jiang M. 2020. Coronavirus Disease
2019 (COVID-19): a perspective from
China. Radiology, 296: e15-e25