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Insights into forsythia honeysuckle (Lianhuaqingwen) capsules: A Chinese herbal medicine repurposed for COVID-19 pandemic

Authors :
Hui Nan
Xiaodong Ren
Pengcheng Yu
Hong Liu
Qiao Guaiping
Wenqiang Cao
Liu Yuzhi
Ju Xingke
Li Han
Jia Minyi
Lei Tian
Li Juan
Liang Chengyuan
Source :
Phytomedicine Plus, Phytomedicine Plus, Vol 1, Iss 2, Pp 100027-(2021)
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

Highlights • The present review summarizes the plausible molecular mechanism of specific LH capsules in the control of SARS-COV-2 infection and the inhibition of cytokine storms caused by IL-6. • Preclinical and clinical trials of LH capsules in COVID-19 conducted in and outside China are elaborated. • A promising antiviral mechanism of LH capsules is defined, and the mechanism involving the suppression of inflammatory cytokine storms is explained. • Active substances in LH capsules that dock in ACE2 to prevent S protein binding are highlighted.<br />Background In December 2019, a novel coronavirus, SARS-CoV-2 caused a series of acute atypical respiratory diseases worldwide. However, there is still a lack of drugs with clear curative effects, and the clinical trial research of vaccines has not been completely finished. Purpose LH capsules are approved TCM patent medicine that are widely used for the treatment of respiratory tract infectious diseases caused by colds and flu. On April 12, 2020, LH capsules and granules were officially repurposed by the China Food and Drug Administration (CFDA) for patients with mild COVID-19 based on their safety and efficacy demonstrated through multicentre, randomized, controlled clinical trials. We hope to conduct a comprehensive review of it through modern pharmacy methods, and try to explain its possible mechanism. Methods Using the full names of LH capsules Lianhuaqingwen, Lianhua Qingwen andSARS-COV-2, COVID-19 as the keywords of the search terms, systemically search for existing related papers in various databases such as Web of Science and PubMed. And completed the collection of clinical data in ClinicalTrials.gov and Chinese Clinical Trial Registry. Last but not least, we have sorted out the anti-inflammatory and antiviral mechanisms of LH capsules through literature and Selleck. Results This review systematically sorted out the active ingredients in LH capsules. Furthermore, the related pharmacological and clinical trials of LH capsule on SARS-CoV-2, IAV and IBV were discussed in detail. Moreover, the present review provides the first summary of the potential molecular mechanism of specific substances in LH capsules involved in resistance to SARS-COV-2 infection and the inhibition of cytokine storm syndrome (CSS) caused by IL-6. Conclusion This review summarizes the available reports and evidence that support the use of LH capsules as potential drug candidates for the prevention and treatment of COVID-19. However, TCM exerts its effects through multiple targets and multiple pathways, and LH capsules are not an exception. Therefore, the relevant mechanisms need to be further improved and experimentally verified.<br />Graphical abstract Image, graphical abstract

Subjects

Subjects :
Vero E6, African Green Monkey Kidney Epithelial-6
Huh-7, Human Hepatocellular Carcinoma-7
3CLpro, 3C-like protease
HPLC, High-performance liquid chromatography
MOI, Multiplicity of infection
MERS, Middle east respiratory syndrome
AECOPD, Acute exacerbation of chronic obstructive pulmonary disease
Pharmacology
Other systems of medicine
IP-10, Interferon-inducible protein-10
Medicine
CCL-2/MCP-1, C-C motif ligand 2/monocyte chemoattractant protein-1
gp-130, Glycoprotein 130
HSV-1, Herpes simplex virus type 1
General Pharmacology, Toxicology and Pharmaceutics
qPCR, Quantitative PCR
media_common
MTT, Methyl Thiazolyl Tetrazolium
ERK, Extracellular signal-regulated kinase
CC50, 50% Cytotoxic concentration
IAV, Influenza A virus
HIV, Human immunodeficiency virus
mIL-6R, Membrane-bound form IL-6 Receptor
RSV, Respiratory syncytial virus
IL-8, Interleukin-8
Drug
media_common.quotation_subject
TCID50, 50% Tissue culture infective dose
COPD, Chronic obstructive pulmonary disease
Pharmacy
Article
DMSO, Dimethyl sulfoxide
mTOR, Mammalian target of rapamycin
HVJ, Hemagglutinating virus of Japan
medicine.disease
IBV, Influenza B virus
Clinical trial
CSS, Cytokine storm syndrome
Complementary and alternative medicine
RZ201-999
MIP-1β, Macrophage Inflammatory Protein-1β
IL-6R, IL-6 Receptor
MAPK, Mitogen-activated protein kinase
MOF, Multifunctional organ damage
AQP3, Aquaporins 3
PKA/p-CREB, Protein kinase A /phosphorylated cAMP response element-binding protein
nsps, Non-structural proteins
CXCL-10/IP-10, C-X-C Motif Chemokine Ligand 10/ Interferon Gamma-induced Protein 10
IFN-λ1, Interferon-λ1
Pandemic
PKB, Akt, Protein kinase B
ORFs, Open reading frames
CAT, COPD assessment test
COVID-19, Coronavirus disease 2019
Grb2, Growth factor receptor-bound protein 2
biology
LD50, 50% Lethal dose
TD50, Half-toxic dose
Cytokine storm syndrome (CSS)
MLD50, 50% Minimum lethal dose
Hep-2, Human epithelial type 2
FBS, Fatal bovine serum
LH capsules, Forsythia honeysuckle (Lianhuaqingwen) capsules
CT, Computed tomography
NF-kB, Nuclear transcription factor kappa-B
M protein, Membrane protein
RT-PCR, Reverse transcription PCR
PLpro, Papain-like proteases
PI3K, Phosphoinositide 3-kinases
MDCK, Madin-darby canine kidney
Coronavirus disease 2019 (COVID-19)
MCP-1, Monocyte chemotactic protein 1
PBS, Phosphate buffered saline
E protein, Envelope protein
RANTES, Regulated on activation normal T cell expressed and secreted
CPE, Cytopathic effect
PRC, People's Republic of China
Forsythia
MEK, Mitogen-activated protein kinase kinase
ACE2, Angiotensin-converting enzyme 2
ARDS, Acute respiratory distress syndrome
PHN, Phillyrin
IL-6, Interleukin-6
AIDS, Acquired immune deficiency syndrome
JAK/STAT, Janus kinase/signal transducers and activators of transcription
IC50, 50% Inhibition concentration
QC, Quality control
SARS-CoV-2
business.industry
Lianhuaqingwen
COVID-19
Forsythia honeysuckle (Lianhuaqingwen,LH) capsules
biology.organism_classification
CFDA, China Food and Drug Administration
JAK1/2, Janus kinase1/2
3C-like protease (3CLpro)
Ras, Ras GTPase
business
Cytokine storm
NHC, National Health Commission
TD0, Non-toxic Dose

Details

ISSN :
26670313
Volume :
1
Database :
OpenAIRE
Journal :
Phytomedicine Plus
Accession number :
edsair.doi.dedup.....8ed6ee319ef2e397034c14aa22649908