Article Type : Review Article
Authors : Ghaffari M
Keywords : COVID-19; Myocarditis; Herbal medicine; Inflammation
Novel
Coronavirus (COVID-19), which first appeared in late 2019, is a pandemic that
has spread over the world. This virus quickly spread over the world due to its
great transmissibility, creating serious health problems. COVID-19 is easily
transmitted from person to person. When an infected individual coughs or
sneezes, it spreads through their respiratory secretions, such as fluid
droplets. This virus not only harms the lungs, but it also harms the heart. The
virus causes inflammatory cells to infiltrate the body, causing significant
edema. All of these factors can have a negative impact on heart function,
leading to the development of HF. Myocarditis can be caused by a virus-induced
cell-mediated autoimmune response. Edema of the cardiac interstitium, as well
as necrosis of the myocardium and interstitial connective tissue, are symptoms
of this form of virus-induced myocarditis. There are currently no specific
medications that can effectively block the virus. In-silico, in-vitro, and
in-vivo techniques were used to explore several natural treatments and
chemicals, including alkaloids, terpenes, flavonoids, and benzoquinones, but
there was insufficient data. Natural antiviral compounds having a broad
antiviral range could provide a safe, effective, and low-cost platform for
discovering new SARS-CoV-2 treatments. This article summarizes the epidemiology
and pathophysiology of COVID-19, as well as herbal therapies that can target
inflammation, inflammatory cells, and the respiratory and cardiac consequences
that come with them.
The World Health
Organization (WHO) declared the COVID-19 outbreak a pandemic on March 11, 2020,
after it was first reported on December 8, 2019 in China's Hubei region. Dr.
Zhang Jixian of Hubei Provincia Hospital of Integrated Chinese and Western
Medicine identified this condition as an infection with a novel beta
coronavirus [1]. Coronaviruses are single-stranded RNA viruses that belong to
the Coronaviridae family of viruses. Within the coronavirus family, there are
four different genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and
Deltacoronavirus. Middle East respiratory sickness (MERS-CoV), SARS CoV,
SARS-like bat CoV, and now SARS-CoV-2 are all members of the Betacoronavirus
lineage within the Coronaviridae subfamily [2]. Despite the fact that it has a
preference for the lungs, where it produces interstitial pneumonitis, in the
most severe instances, multiorgan failure ensues. COVID-19 appears to have
intricate interactions with the cardiovascular (CV) system. Understanding the
underlying pathobiology of coronavirus infection is critical for better
understanding the relationships between cardiovascular disease (CVD) and
COVID-19 [1]. SARS-CoV-2 infects the host cell by triggering cell membrane
receptors, notably the ACE2 receptor, to recognize the virus's spike proteins.
Lung, kidney, heart, and gastrointestinal cells all have ACE2 receptors. The
viral envelope merges with the host's cell membrane after this interaction and
a conformational shift in the spike protein, releasing the viral RNA into the
host cell. The viral RNA replicates its genetic material and synthesizes new
proteins once inside the host cell [2]. Integrins may also be used by
SARS-CoV-2 to enter the host cell. Integrins are a class of cell-surface
receptors made up of non-covalently linked subunits that identify and bind to
ECM proteins and regulate cell survival, proliferation, differentiation, and
migration [2]. COVID-19 infection is linked to systemic inflammation, a pro-inflammatory
cytokine storm, and sepsis, which can lead to multiorgan failure and death.
There is a time lag between the onset of symptoms and the occurrence of cardiac
injury. COVID-19 binds to the transmembrane ACE2 to gain access to host cells
such as type 2 pneumocytes, macrophages, endothelial cells, pericytes, and
cardiac myocytes, causing inflammation and multiorgan failure. Infection of
endothelial cells or pericytes, in particular, could cause significant
microvascular and macrovascular dysfunction. It can also destabilize
atherosclerotic plaques and explain the development of acute coronary syndromes
when combined with immunological over-reactivity [1]. Despite the fact that the
virus's primary organ of harm is the lung, COVID-19 is now considered a
systemic disease that affects a wide range of other critical organs, including
the heart, liver, and kidney. However, it's still unclear whether organ and
tissue damage in COVID-19 individuals is a direct or indirect result of the
viral infection [3]. The virus could target organs and tissues that have ACE2
expression. ACE2, a major regulator of blood pressure and cardiac
contractility, is known to be highly expressed in cardiovascular cells [4].
Patients with COVID-19 have been reported to have changes in cardiac-specific
biomarkers in their peripheral blood. As previously indicated, hs-cTnI is a
specific biomarker for myocardial damage. Other non- or less-specific cardiac
biomarkers, such as creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB),
and lactate dehydrogenase, may also rise in COVID-19 cardiovascular problems
(LDH). The biomarkers, on the other hand, may not always change in the same way
[5]. Recent autopsy findings revealed significant levels of inflammatory
infiltrates in the lung and heart tissues, demonstrating the inflammatory
character of tissue damage caused by SARS-CoV-2 infection. SARS-CoV-2 has the
potential to directly infect cardiomyocytes, resulting in viral myocarditis and
damage. However, the precise cellular process by which SARS-CoV-2 infects and
damages cardiomyocytes has yet to be identified. COVID-19 treatment has largely
been limited to supportive measures because of the lack of a specific therapy
for this condition to date. Pre-existing health problems raise the likelihood
of cardiovascular comorbidity, which leads to a worse prognosis.
COVID-19-induced myocardial damage is more common in patients over 60 and those
with diabetes [6].
Myocarditis and/or
pericarditis can be caused by the coronavirus, which may or may not be
accompanied with pneumonia. Heart failure, arrhythmias, diffuse ST-segment
abnormalities, and substantial production of myocardial enzymes such as
natriuretic peptides and troponin are all symptoms of this myocarditis.
COVID-19 patients have been documented to experience a variety of
cardiovascular problems. Acute myocardial damage, myocarditis, arrhythmia,
pericarditis, heart failure, and shock are all common consequences [7-10]. The
etiologic agent of COVID-19, severe acute respiratory syndrome-coronavirus 2
(SARS-CoV-2), can infect the heart, vascular tissues, and circulating cells via
ACE2, the host cell receptor for the viral spike protein. Acute cardiac damage
is a common extra pulmonary symptom of COVID-19, and it can have long-term
repercussions. Myocarditis is difficult to diagnose because of its diverse
clinical presentation, which can range from asymptomatic left ventricular
systolic dysfunction to mimicking the symptoms of acute myocardial infarction.
Myocarditis is characterized by inflammation brought on by immune system cells'
activity. Natural killer cells come first, within 5 days of viral infection,
according to animal studies, followed by CD4 and CD8 T cells 5 to 7 days later.
T cell invasion is accompanied by neutrophil and macrophage infiltration, which
contributes significantly to the pathophysiology of myocarditis. When there is
a long enough period of inflammation, Th17 T cells have been found to enter the
myocardium [11].
COVID-19 is a disease that
affects the cardiovascular system. Patients with acute myocardial infarction
were older, with a higher prevalence of previous CVD, according to a new
statistic. COVID-19 patients with acute heart damage accounted for 12% of the
total. Furthermore, a rent review article found that cardiac Troponin, a
biomarker of myocardial damage, was elevated in roughly 5–25 percent of
hospitalized COVID-19 cases [12]. In 3470 COVID-19 patients, a systematic
analysis of 72 papers from different countries found a pooled prevalence of
cardiovascular disease and hypertension of 8.3% and 13.3%, respectively [13].
COVID-19 can damage
cardiomyocytes by recognizing ACE2 receptor infections and generating numerous
inflammatory responses, according to the pathophysiology of COVID-19 patients.
ARDS can generate an inflammatory storm and/or an oxygen supply imbalance by
directly damaging infected cardiac cells via ACE2 receptors on these cells.
Cardiovascular symptoms are common in COVID-19 individuals as a result of
systemic inflammatory reactions and immune system dysfunction. COVID-19
infection has been linked to myocardial injury due to a cytokine storm
triggered by an unbalanced response including Th1 and Th2 cells, which can
result in respiratory failure, hypoxemia, shock, or hypotension. Myocardial
damage occurs during an infection, especially in people with chronic CVD, since
the burden on the heart is increased and there is an imbalance in the oxygen
supply and demand. Angiotensinogen, renin, angiotensin II (Ang II), Ang II
receptors, such as AT1 and AT2 receptors, and angiotensin converting enzyme
(ACE) make up the renin-angiotensin system (RAS). ACE2 is found in venous and
arterial smooth muscle cells, as well as endothelial cells, and is involved in
the immunological response and cardiovascular mechanisms that lead to
myocardial injury. COVID-19 infection is caused by the viral spike protein
binding to ACE2, according to several studies. One major proteinase is encoded
by all coronaviruses. This major proteinase is known as a 3C-like proteinase.
As a result, the coronavirus enzyme is known as one major proteinase is encoded
by all coronaviruses. This major proteinase is known as a 3C-like proteinase.
Coronavirus 3C-like proteinase, or 3CLpro, is the name given to the coronavirus
enzyme. The 3CLpro is similar to the 3Cpro, which is the major picornaviral
protease. Coronaviruses also contain one (group 3) or two (groups 1 and 2)
papain-like proteases, known as PLP1pro and PLP2p, respectively. The
coronavirus replication complex is controlled by the primary viral proteinase
(3CLpro). It may be an appealing therapeutic target. PLpro might also be
regarded an important target for antiviral medicines because to its significant
role. For the SARS coronavirus (SARS-CoV) and SARS-CoV-2 to reach the host
target cells, ACE2 is a functional receptor. As a result, ACE2 inhibition could
be evaluated for antiviral research against SARS- CoV and SARS-CoV-2 [13]. As a
result, these three proteins are promising targets for therapeutic development.
Inflammatory reactions triggered by COVID-19 infection are classified as
primary or secondary. Prior to the formation of neutralizing antibodies, the
major inflammatory response usually occurs after viral infections. Adaptive
immunity and antibody neutralization are the first steps in the secondary
inflammatory response. Myocardial damage is observed to be worsened in patients
with increased inflammatory activity, platelet activation, increased
thromboxane production, and reduced fibrinolytic function after an acute
infection. The early inflammatory and immunological response has caused a
significant cytokine storm [IL-6, IL-7, IL-22, IL-17] during COVID-19's rapid
proliferation. C-reactive protein (CRP) levels that are elevated in COVID-19
patients indicate the presence of inflammation. In addition, patients with CAD
had higher levels of inflammatory cytokine expression in epicardial adipose
tissue (EAT). COVID-19 infection can cause a variety of heart symptoms,
including myocardial damage, arrhythmia, and even cardiac collapse. Increased
high-sensitivity cardiac troponin I (cTnI) levels have been found to indicate
myocardial damage due to COVID-19 infection in some patients. Heart failure has
been proposed as one of the most common COVID-19 consequences, which could be
caused by worsening preexisting cardiac dysfunctions as well as newly formed
cardiomyopathy and myocarditis [14,15]. Patients with COVID-19 in the early
stages may have a normal or low total white blood cell count, as well as a low
lymphocyte count. As a result of the higher ratio of neutrophils to lymphocytes
that occurs with lymphopenia, the higher ratio of neutrophils to lymphocytes is
considered a negative prognostic factor. LDH, muscle enzymes, and C-reactive
protein levels may be elevated in patients. In critically ill patients, the
thrombogenic biomarker D-dimer may rise, blood lymphocyte counts fall steadily,
and laboratory changes in multiorgan damage biomarkers become noticeable. The
lung and heart tissues contain significant levels of inflammatory infiltrates,
demonstrating the inflammatory character of tissue damage caused by SARS-CoV-2
infection [12].
COVID-19 is primarily
treated with supportive care. Support is frequently necessary for
myocarditis-related diseases such as arrhythmia and heart failure. There is
currently no specific treatment for this condition. SARS-Cov-2 RNA
transcription was reduced when broad-spectrum antiviral medicines like
Remdesivir were used. These medications are still being studied in clinical
trials. ACE inhibitors and angiotensin receptor blockers, neutralizing
antiviral plasma, stem cell transplantation, anti-ischemic therapy, and
traditional herbal medicines are among the other treatment options. Blocking
the angiotensin-converting enzyme (ACE), which is required for SARS-CoV-2 cell
adhesion, is one of the most intriguing mechanisms. As a result, two proteins,
3C-like protease (3CLpro) and angiotensin-converting enzyme 2 (ACE2), have been
proposed as potential targets for screening medicines for their capacity to
suppress SARS-CoV-2 replication and proliferation. The ability of herbal
therapies developed from traditional medicines to cure myocarditis is now being
researched. These medicines might be made up of extracts from a single plant
species or extracts from numerous sources. The sections that follow provide an
overview of complementary and herbal medicine.
The term complementary
medicine refers to a wide range of health-care techniques that aren't part of a
country's traditional or conventional medicine and aren't fully incorporated
into the dominant health-care system. In certain countries, they are used
interchangeably with traditional medicine. The purpose of this review is to
summarize the effects of a few herbal treatments on the cardiovascular and
immune systems. Herbal medicines include herbs, herbal materials, herbal
preparations, and completed herbal products that contain active substances,
plant parts, other plant materials, or combinations thereof as a supplemental
medical method. Herbal products, botanical goods, and phytomedicines are items
manufactured from botanicals or plants that are used to treat ailments or
maintain health. Taking herbal supplements has been around for thousands of
years [7]. Herbal supplements are considered foods by the FDA, not medicines.
As a result, they are exempt from the same testing, manufacturing, and labeling
requirements as pharmaceuticals. Complementary and alternative medicine (CAM)
has exploded in popularity in the United States in recent years. The Institute
of Medicine claimed in their book, Complementary and Alternative Medicine in the
United States, that more than one-third of American adults use some type of
CAM, and that annual visits to CAM providers outnumber visits to primary care
physicians. Herbal drugs are regulated by the FDA as dietary supplements in the
United States. The approval and marketing of herbal remedies in the European
Union is governed by national legislation. If a product has been used in the
European Union for at least 15 years (traditional use registration), no
clinical testing or efficacy trials are required [11]. Herbal items have labels
that explain how herbs might affect various bodily functions. Herbal supplement
labeling, on the other hand, cannot relate to the treatment of specific medical
diseases. This is due to the fact that herbal supplements are not subjected to
the same clinical research or manufacturing regulations as prescription or
over-the-counter pharmaceuticals [8]. Herbal drugs, unlike conventional drugs,
do not require clinical trials or formal regulatory permission before being
marketed, and as a result, their efficacy and safety are rarely demonstrated.
Although herbs have been shown to have an influence on biological mechanisms
associated to the cardiovascular system, there is a dearth of data on clinical
effects. Physicians should always evaluate their patients' use of herbal drugs
and discuss the potential advantages and adverse effects with them. Herbs have
been utilized for medical purposes for thousands of years in the past. Herbal
drugs have been more popular in cardiovascular medicine than in other medical
professions. Digoxin and digitoxin, which are derived from Digitalis lanata and
Digitalis purpurea, respectively; reserpine, which is derived from Rauwolfia
serpentina and was originally used to treat psychosis; and acetylsalicylic acid
(aspirin), which is obtained from willow bark. Efficacy of herbal treatments in
treating myocarditis is being studied in a number of clinical trials. One of
the problems with employing these medicines is that the contents of these
mixtures are mostly unknown, as well as the heterogeneity of herbal medicines.
Based on the pathophysiology of COVID-19 and its multisystem effects, herbal
treatments with antiviral activity, immune system enhancement, and
anti-inflammatory effects are some of the therapeutic methods that can be used.
The following section will go over these topics.
Medicinal herbs and extracts
have been utilized for decades in ethnobotany, traditional Chinese medicine
(TCM), and Ayurvedic medicine because they appear to have favorable effects on
health. A recent study in Wuhan, China, found a link between the TCM notion of
"invigorating spleen and removing moisture" and an improvement in new
coronavirus pneumonia (NCP), highlighting the relevance of intestinal function
and microenvironmental balance. The treatment comprised TCM ingredients such
quercetin, luteolin, and kaempferol [16-18].
1,8-Cineole: (Eucalyptol)-is a natural chemical found in a
variety of plants, including cardamom and bay leaf. It's a monoterpene oxide
and cyclic ether. It possesses anti-inflammatory and bronchodilatory
properties, and it has a high pharmacological effect against respiratory
disorders. It's used to treat a wide range of respiratory and inflammatory
conditions. Furthermore, it has been demonstrated that it inhibits the
expression of NF-B in humans [19-23].
6-gingerol: Turmeric contains a bioactive compound called
6-gingerol. It contains anti-inflammatory, antiviral, antibacterial,
anti-diabetic, anti-oxidant, and anti-cancer properties, according to studies.
TNF-, IL-2, and IL-8 expression in infected cells were all regulated by
6-gingerol. It inhibits the cell's production of pro-inflammatory cytokines
[23].
Anethole: It is a phenlypropanoid (natural aromatic
chemical) generated from essential oils. It's found in fennel seed and star
anise. Anethole decreased TNF-, IL-6, and IL-1 expression in infected mice,
according to a study. Anti-inflammatory cytokine (IL-10) expression rose at the
same time.
Apigenin: It is a flavonoid that can be found in large
concentrations in parsley, celery, onions, oranges, and plants. Apigenin has
been shown to have antioxidant, antihyperglycemic, anti-inflammatory, and
antiapoptotic effects (in myocardial ischemia). Biological effects, such as
cytostatic and cytotoxic activity against various cancer cells, antiatherogenic
and protective actions in hypertension, cardiac hypertrophy, and autoimmune
myocarditis, have been detailed in a recent review, indicating additional
potential health advantages. The mechanism of action of apigenin is based on
its modulatory actions on dendritic cells, which are responsible for
immunological homeostasis [18].
Astragaloside IV (ASIV): It is a pharmacologically active component of
Astragalus membranaceus, a traditional Chinese medicine with anti-inflammatory,
antifibrotic, antioxidant, antiasthma, and immune-regulatory properties [14].
Several studies have showed that using ASIV can help in the treatment of
cardiovascular disorders such hypertension, myocardial infarction, and
cardiomyopathy. ASIV increased cardiac function and reduced cardiac hypertrophy
in studies by upregulating Nrf2, which was largely done via boosting the
Nrf2/HO-1 signaling pathway [21].
Capsaicin: A phytochemical found in chili peppers. In cells,
capsaicin reduces the expression of NO, TNF-, and IL-1. Furthermore, it
stimulates IB expression while preventing NF-B p65 from translocating from the
cytoplasm to the nucleus. It also stopped NOS and COX-2 from working in cells.
It stopped NF-B from activating. As a result, it inhibited pro-inflammatory
signaling in infected cells [23].
Carvone: Peppermint oil contains carvone, a bioactive
molecule (essential oil). Because of its pharmacological and biological
qualities, it is widely used as an antiviral, antibacterial, anti-inflammatory,
anti-cancer, and anti-oxidant. Carvone has the potential to suppress
neuraminidase (NA). Carvone linked to the influenza virus's neuraminidase
active site successfully [23].
Cinnamaldehyde: A naturally occurring phenylpropanoid component of
cinnamon essential oil. It has anti-inflammatory, anti-viral, anti-oxidant,
anti-immunomodulatory, anti-bacterial, anti-cancer, and anti-cholesterol
properties, among others. In lung-damaged tissues, it reduced viral generation
and inflammation [23].
Coconut oil: Consumption has been linked to a variety of health
advantages, including improved antibacterial, antifungal, antiviral,
antiparasitic, antidermatophytic, antioxidant, and immunostimulant activity.
The medium-chain fatty acids (MCFA), particularly lauric acid, which is the
most abundant in coconut oil, are responsible for the wide range of
antimicrobial properties. In the human body, lauric acid is transformed to
monolaurin, which has the antibacterial and antiviral properties stated
previously [18].
Curcumin (Curcuma longa): Turmeric is made from the dried rhizome of Curcuma
longa, a widely used spice in meals and Ayurvedic medicine. It has a number of
pharmacologic qualities, including antioxidant, anti-inflammatory, and
antifibrotic effects. Curcumin, a polyphenol produced from turmeric, has been
studied for its antiviral properties against SARS-CoV-2. The possible mechanism
of action relies on the Ang II type 1 (AT1) receptor protein level being
reduced and the Ang II type 2 (AT2) receptor being upregulated. Even at high
oral quantities, curcumin is not hazardous, and it is already licensed and
widely utilized in the food business. Curcumin inhibited the expression of
pro-inflammatory cytokines such as IL-6, IL-10, IFNc, and MCP-1 via reducing
NFB p65 phosphorylation [18].
Diallyl trisulfide: The organosulphur compound diallyl trisulfide was
obtained from garlic. It has a number of medicinal qualities, including
antiviral, anti-inflammation, antibacterial, anti-cholesterol, and anti-oxidant
effects. Asthma, cancer, heart disease, osteoarthritis, and acute or chronic
liver injury have all been treated with it [23]. Diosgenin-is a
phytocompound derived from fenugreek seed extract that is a steroidal
sapogenin. It has been found to have antiviral, antioxidant, anti-inflammatory,
anti-diabetic, anti-viral, anti-oxidant, anti-inflammatory, anti-diabetic, and
anti-diabetic properties, as well as in hypercholesterolemia and
gastrointestinal ailments. Diosgenin inhibited viral mRNA expression and, as a
result, viral replication via inhibiting STAT3 expression [23].
Eugenol: The phenolic component obtained from essential oil
is eugenol (allyl chain-substituted guaiacol). Eugenol is found in clove,
cinnamon, nutmeg, basil, bay leaf, and black pepper, among other things. In
cells, it suppresses the activity of COX-2 and TNF-. It also prevents NF-B from
becoming activated. It also inhibits the expression of pro-inflammatory
cytokines in macrophages. Its anti-inflammatory mechanism mode is active due to
its inhibitory effect on prostaglandin generation and neutrophil/macrophage chemotaxis
[23].
Garlic: Newer research suggests that garlic essential oil
may be a helpful natural antivirus option for preventing CoV attacks on the
human body, while additional research is needed. The inhibitory effect of the
organosulfur compounds found in garlic essential oil on the host receptor ACE2
protein in the human body has been confirmed using a molecular docking
technique. This is a significant discovery about individual garlic compounds'
coronavirus resistance on the SARS-CoV-2 main protease (PDB6LU7) protein;
seventeen organosulfur compounds, accounting for 99.4% of the garlic essential
oil constituents, had remarkable interactions with the amino acids of the ACE2
protein and the main protease PDB6LU7.
Glycyrrhizin: (a saponin made up of triterpenes)-Due to its
beneficial pharmacological effects, such as downregulating pro-inflammatory
cytokines, binding ACE2, obstructing intracellular reactive oxygen species
(ROS) accumulation, thrombin inhibition, provoking endogenous interferon, and
inhibiting the extra formation of airway exudates, it may be a potential
therapeutic option for COVID19.
Jinhua Qinggan: Honeysuckle, gypsum, ephedra (honey), bitter almond,
baicalin, forsythia, fritillaria, burdock seed, artemisia annua, mint, and
licorice are all found in Jinhua Qinggan granules. In clinical practice, Jinhua
Qinggan has been utilized as an adjuvant therapy for COVID-19. Fever, cough,
weariness, sputum, and anxiety were greatly reduced when Jinhua Qinggan was
added [19].
Kaempferol: Kaempferol is a flavonoid found in foods including
spinach, cabbage, kale, beans, tea, and broccoli that has been shown to have
antioxidant and anti-inflammatory properties. Several research have looked into
how effective these flavanols are at blocking the 3a ion channel created by ORF
3a-coded proteins, reducing viral generation and release from host cells. This
capacity allows the body's immune system to change in order to combat the viral
infection. Because the benefits of kaempferol can be limited by the autoxidation
process, the dosage must be large and modified according to the circumstance
[18].
Lianhua Qingwen granules: contain forsythia, honeysuckle, ephedra, bitter
almond, gypsum, isatis, mianma guanzhong, houttuynia cordata patchouli,
rhubarb, rhodiola rosea, menthol, and licorice, and is a TCM compound
preparation based on the principle of plague prevention and cure. It can
prevent inflammation-induced lung tissue damage by inhibiting the release of
inflammatory mediators.
Linalool-is a monoterpene that can be extracted from
coriander leaves. Cinnamon, rosemary, basil, cardamom, and thyme all contain
it. Infected mice's IL-1, IL-18, TNF-, and IFN- expression levels were reduced
[23].
Monolaurin- Piperine: An amide alkaloid obtained from
black, white, and long pepper extracts' fruits. It has been found to have
anti-inflammatory, anti-viral, analgesic, anti-convulsant, and anti-cancer
biological and pharmaceutical therapeutic properties. Inflammatory disorders
such as asthma, Alzheimer's disease (AD), Parkinson's disease, arthritis,
gastritis, and endometritis are also treated with it. Piperine's
anti-inflammatory activities inhibit inflammatory signaling in chronic diseases
via NF-B, MAPK, AP-1, COX-2, NOS-2, IL-1, TNF-, PGE2, and STAT3 [23].
Quercetin: A flavonoid present in a variety of foods,
including onions, grapes, shallots, tea, tomatoes, and a variety of seeds,
nuts, flowers, barks, and medicinal botanicals such as Ginkgo biloba, Hypericum
perforatum, and Sambucus canadensis. It has antioxidant, anti-inflammatory, and
antiviral properties, with some preliminary evidence of anticancer benefits.
These effects are related to lipid peroxidation inhibition, platelet
aggregation inhibition, lipopolysaccharide-induced tumor necrosis factor
production in macrophages, and lipopolysaccharide-induced IL-8 production in
lung cells [18].
Reduning: Honeysuckle, gardenia, and artemisia annua are used
to make Reduning. Pharmacological effects of the injection include antipyretic,
anti-inflammatory, and antiviral properties. Anti-inflammatory, antiviral, and
immunomodulatory properties of reduning injection The method of action could
involve IL-17, C-type lectin receptor, HIF-1, and other pathways operating on
IL-6, CASP3, MAPK1, CCL2, and other targets via the IL-17, C-type lectin
receptor, HIF-1, and other pathways. Reduning has been shown to be effective in
the treatment of lung damage and cardiovascular disease [19].
Shenfu: Red ginseng and black monkshood are used to make
Shenfu, which is extensively used to treat cardiovascular and cerebrovascular
illnesses. It can also be used alone or in combination with other medications
to treat severe pneumonia, sepsis, multiple organ failure, and malignancies.
Shenfu reduces the levels of pro-inflammatory cytokines TNF-, IL-6, IL-8,
procalcitonin, and hypersensitivity CRP in the serum of sepsis patients,
improving therapeutic benefits. Shenfu can lower IL-6 levels, raise the amount
of CD3 +, CD4 +, and CD8 + -T cells in the peripheral blood, and maintain the
pro-inflammatory/anti-inflammatory balance, all of which improve sepsis therapy
efficacy [19].
Shengmai: Red ginseng, ophiopogon japonicas, and schisandra
chinensis make up Shengmai. Clinically, Shengmai has been utilized to treat
cardiovascular and cerebrovascular illnesses.
Shenmai: Red ginseng and ophiopogon japonicus make up
Shenmai. It's used to treat conditions like coronary artery disease, viral
myocarditis, chronic pulmonary artery disease, and neutropenia. Saponins,
sugars, amino acids, flavonoids, lignans, organic acids, and other chemicals
are the major components of Shenmai injection. When administered as an adjuvant
treatment for severe pneumonia, Shenmai can lower inflammatory factors, raise
anti-inflammatory factors, and lower the quantity of white blood cells, C -
reactive protein, and procalcitonin [19].
Shufeng Jiedu granules: To treat acute upper respiratory tract infections.
Polygonum cuspidatum, forsythia, radix isatidis, bupleurum, radix, verbena,
reed root, and licorice are among the granules. Shufeng Jiedu's
anti-inflammatory properties are linked to the down-regulation of NF-kB mRNA
expression and suppression of the MAPK/NF-kB signaling pathway [19].
Sulforaphane: The active anti-inflammatory ingredient in mustard
leaf extract is sulforaphane. Isothiocyanate is a kind of isothiocyanate (group
of sulfur-containing organic compounds). Sulforaphane inhibited the human
immunodeficiency virus (HIV) infection in macrophages via regulating the
transcription of the regulator Nrf2. In HIV-infected cells, sulforaphane
inhibited infection before the development of long terminal repeat (2-LTR)
viral DNA rings [23].
Tanreqing: Scutellaria baicalensis, bear bile powder, goat
horn, honeysuckle, and forsythia make up Tanreqing. Tanreqing contains
quercetin and luteolin, which have anti-influenza a virus action in vitro.
Quercetin has been shown in studies to lower TGF-1, -SMA, and TNF- expression,
block rat alveolar cell death, and diminish inflammation and fibrosis
destruction in rat lung tissue. Baicalin inhibits the expression of TNF- and
IL-1, which can minimize inflammatory damage to lung tissue [19].
Thymoquinone: The monoterpene substance thymoquinone is present
in the seeds of black cumin. It has anti-oxidant, anti-inflammatory,
anti-cancer, immunomodulatory, anti-viral, and anti-bacterial properties, among
other things.
Xingnaojing: Musk, turmeric, borneol, gardenia, and other
components make up Xingnaojing. Acute poisoning, viral encephalitis,
craniocerebral damage, acute cerebrovascular disease, pulmonary encephalopathy,
pneumonia, respiratory failure, and sepsis are all common clinical uses. During
the adjuvant therapy of ventilator-associated pneumonia, Xingnaojing can
suppress the overexpression of serum CRP, IL-6, and TNF-. It can also lower the
risk of an inflammatory reaction and harm to several organ functions [19].
Xin-Ji-Er-Kang (XJEK): Is a traditional Chinese herbal medicinal
combination made up of fourteen different herbs, including Panax ginseng C.A.
Mey., Astragalus Mongolic Bunge, Ophiopogon japonicus (Thunb). Ker Gawl., and
Polygonatum odoratisms (Mill). Clinical trials and laboratory studies have
revealed that it protects against “Xiong-Bi” disease, viral myocarditis, and
toxic myocarditis. XJEK efficiently lowers blood pressure and may diminish
vascular oxidative stress, as well as ACh-induced relaxation and endothelial
dysfunction [20].
Xiyanping: The major ingredient of Xiyanping is an
andrographolide substance. In COVID-19 patients, Xiyanping can reduce
inflammation and relieve symptoms like cough, fever, and rales in the lungs.
Reducing viral replication and infection, inhibiting concurrent bacterial
infections, increasing body immunity, and enhancing liver function and
cardiovascular damage are some of the other advantages [19].
Xuebijing: Safflower, red peony, chuanxiong, salvia
miltiorrhiza, and angelica make up Xuebijing. Sepsis, systemic inflammatory
response syndrome, and multiple organ dysfunction syndromes are among the
conditions for which it is prescribed (MODS). In China, Xuebijing is commonly
used to treat severe pneumonia, chronic obstructive pulmonary disease, acute
respiratory distress syndrome, and other life-threatening illnesses [19].
The novel Coronavirus
(COVID-19), which arose in late 2019, has become a global threat. This virus
quickly spread over the world due to its great transmissibility, creating
serious health problems. There are currently no specific treatments that
effectively block the virus, and developing new medications takes about ten
years of research. In-silico, in-vitro, and in-vivo techniques were used to
explore a variety of natural cures and chemicals, including alkaloids,
terpenes, flavonoids, and benzoquinones. Despite the vast amount of data
obtained by a computational approach, experimental proof is rarely available.
As a result, naturally occurring compounds with a broad antiviral range could
provide a safe, effective, and low-cost platform for discovering new SARS-CoV-2
treatments. However, before moving further with human clinical trials, further
well-designed animal studies investigating the mechanism of action,
pharmacokinetics, and safety profile of plant complexes and their separated
bioactive components are required. Many experimental attempts to treat COVID-19
inflammatory and cardiac alterations with natural treatments have yielded
positive outcomes. However, because of the low methodological quality, small
sample size, and small number of trials on particular herbs, these findings
should be interpreted with caution. Concerns about coronavirus illness 2019
(COVID-19) have sparked interest in dietary supplements and complementary and
alternative therapy. These treatments and therapies are advertised as having
the ability to boost or promote the body's natural immune function. Consumers
may be made to believe that these products or therapies assist the body fight
illnesses like COVID-19 by improving immune function. There is, however, no
proof that "immune boosters" or other supplements may prevent, treat,
or cure COVID-19 or other viral illnesses. The United States Food and Drug
Administration (FDA) continues to issue warning letters to companies marketing
fake COVID-19 prevention, treatment, mitigation, diagnosis, or cure products.
The following FDA website (https://www.fda.gov) has a list of companies who
have received such warning letters from the FDA. Finally, randomized controlled
trials must be conducted to determine the genuine therapeutic benefits and side
effects of herbal therapies in the treatment of myocarditis.