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Systematic review of anti-viral & immunomodulatory potential of Ashwagandha (Withania Somnifera. Linn) in light of covid-19 pandemic

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Background: Traditional medicinal system like the TCM (Traditional Chinese Medicine) has successfully contribution against COVID-19. Now, the ancient science of Ayurveda is being looked upon. Ayurveda holds a treasure of valuable herbs that might help in this situation. Ashwagandha (Withaniasomnifera.Linn) is one such wonder herb. It holds a prominent place among Rasayana herbs of Ayurveda. Many systematic reviews of Ashwagandha considering its adaptogen, anti-cancer, cognition enhancer etc. activities are available. However, none could be found to exclusively review its anti-viral and immunomodulator activities. Aim: Hence, these two aspects were chosen especially bearing current COVID-19 situation in mind. Conclusion: The current systematic review study indicates that the use of Ashwagandha for immunomodulatory, anti-viral and especially against COVID-19 has a logical and scientific basis.
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International Journal of Botany Studies
494
International Journal of Botany Studies
ISSN: 2455-541X; Impact Factor: RJIF 5.12
Received: 27-09-2020; Accepted: 13-10-2020: Published: 28-10-2020
www.botanyjournals.com
Volume 5; Issue 5; 2020; Page No. 494-497
Systematic review of anti-viral & immunomodulatory potential of Ashwagandha (Withania
Somnifera. Linn) in light of covid-19 pandemic
Vivek Varma1, Shweta Parwe2*, Milind Nisargandha3
1 PG Scholar, Department of Panchakarma, MGACH and RC, Salod, Wardha, Maharashtra, India
2 Professor and Head, Department of Panchakarma, MGACH and RC, Datta Meghe Institute of Medical Sciences, Wardha,
Nagpur, Maharashtra, India
3 Department of Physiology, Ashwini Rural Medical College, Hospital and Research Centre Kumbhari, University of Health
Sciences, Nashik, Maharashtra, India
Abstract
Background: Traditional medicinal system like the TCM (Traditional Chinese Medicine) has successfully contribution
against COVID-19. Now, the ancient science of Ayurveda is being looked upon. Ayurveda holds a treasure of valuable herbs
that might help in this situation. Ashwagandha (Withaniasomnifera.Linn) is one such wonder herb. It holds a prominent place
among Rasayana herbs of Ayurveda. Many systematic reviews of Ashwagandha considering its adaptogen, anti-cancer,
cognition enhancer etc. activities are available. However, none could be found to exclusively review its anti-viral and
immunomodulator activities.
Aim: Hence, these two aspects were chosen especially bearing current COVID-19 situation in mind.
Conclusion: The current systematic review study indicates that the use of Ashwagandha for immunomodulatory, anti-viral
and especially against COVID-19 has a logical and scientific basis.
Keywords: Novel coronavirus, Ashwagandha, Traditional medicine, Withaniasomnifera, Immunity
Introduction
In December 2019, several patients with pneumonia of
unknown cause were identified in Wuhan, China.
Coronavirus disease 2019 (COVID-19) is a newly
recognized infectious disorder that has to unfold hastily all
through Wuhan, Hubei, China, to other provinces in China
and numerous countries around the sector. The variety of
fatalities day by day due to COVID-19 is escalating [1]. The
COVID-19 pandemic has changed the world in many ways.
Lack of conclusive treatment in modern medicine has been a
key feature of this pandemic. Traditional medicinal system
like the TCM (Traditional Chinese Medicine) has
successfully contribution against COVID-19 [2]. According
to WHO, management of COVID-19 has mainly focused on
infection prevention, case detection and monitoring and
supportive care [3].
Now, the ancient science of Ayurveda is being looked upon.
Ayurveda holds a treasure of valuable herbs that might help
in this situation.
Ashwagandha (Withaniasomnifera.Linn) is one such
wonder herb. It belongs to family Solanaceae and is
commonly known as “Indian Winter cherry” or “Indian
Ginseng”. A variety of therapeutic uses of Ashwagandha
have been enlisted in different Ayurveda treatises. It holds a
prominent place among Rasayana herbs of Ayurveda. It is
mentioned as tonic, aphrodisiac, narcotic, diuretic,
anthelmintic, and astringent, thermo genic and stimulant [4,
5]. Many studies have been published regarding its
immunomodulatory activity. It has also been studied for its
anti-viral potential by many scholars.
Many systematic reviews of Ashwagandha considering its
adaptogen, anti-cancer, cognition enhancer etc. activities are
available. However, none could be found to exclusively
review its anti-viral and immunomodulator activities. These
two aspects were chosen especially bearing current COVID-
19 situation in mind, where Ashwagandha is considered as a
potential medicine.
Materials and Methods
Articles published in AYUSH research portal and DHARA
(Digital Helpline for Ayurveda Research Articles) were
analyzed for this study. The key words used for the purpose
of database search included “Ashwagandha and Withania
somnifera.” The articles published in English language only
were included. No other exclusion criteria were applied as
regards journal, year, authors etc. A comprehensive list of
all articles published until July 2020 was prepared.
In the next stage, all the articles obtained from searching the
databases were compiled and screened by reading their
“title” and then the “abstract.” Studies that satisfied the
inclusion criteria i.e. immunomodulator, anti-viral and
COVID-19 studies were only included at this stage and
others excluded.
The selected articles were screened finally by reading the full-text
or abstract as per availability and were analyzed further. This
search process for systematic review was done as per Preferred
Reporting Items for Systematic review and Mata Analysis
(PRISMA) guidelines [6]. (Diagram. 1)
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Fig 1: Flow of information through different phases of systematic review, according to PRISMA guideline
Results
The ayush research portal search for keyword
Ashwagandha’ yielded 153 articles; while keyword
Withania somnifera’ yielded 229 articles. The DHARA
online database search for keyword Ashwagandha’ yielded
101 articles; while keyword ‘Withania somnifera’ yielded
194 articles. However, 17 articles were retrieved on basis of
aforementioned inclusion and exclusion parameters. The
seventeen articles were further categorized as mentioned in
Table 1: Showing categorization of selected articles
Parameter
Full Text
Only Abstract
Immunomodulatory Activity
02
06
Anti-viral Activity
02
01
COVID-19 related studies
06
--
Total
10
07
1. Immunomodulatory Activity
Total eight studies were found concerned with
immunomodulator activity of Ashwagandha. One study was
based on review of Ayurveda principles as basis for
combating infections through increase in immunity [7]. It
enlisted Ashwagandha for this purpose based on review of
Ayurvedic literature. Rest seven studies included of four
pre-clinical studies and three clinical studies.
A) Pre-clinical studies
In a pre-clinical study, Ashwagandha (Withania somnifera)
and Brahmi (Bacopa monnieri) were concentrated to
upgrade insusceptible capacity and contrasted their
belongings with that of Echinacea, noted for its capacity to
improve safe function [8]. It was discovered that they could
upgrade safe capacity by expanding immunoglobulin
creation. It was additionally felt that, these natural
medications may manage immunizer creation by expanding
both Th1 and Th2 cytokine creation.
In an in-silico study, assessment of the immunomodulatory
impact of Ashwagandha was clarified utilizing system
ethnopharmacology technique [9]. It recognized five
bioactive that were equipped for directing fifteen resistant
framework pathways through sixteen objective proteins by
bioactive-target and protein-protein associations. The
examination additionally uncovered the capability of
withanolide-phytosterol mix to accomplish powerful
immunomodulation and seven novel bioactive-invulnerable
objective mixes.
The immunomodulatory exercises of Ashwagandha
separates were concentrated in mice model in another study
[10]. Immunomodulatory impact was evaluated in If IgE-
intervened hypersensitivity in as decrease of ovalbumin-
actuated paw oedema, in creatures treated with WS2 at
dosages of 150 and 300 mg/kg, and the outcomes were
contrasted and the standard medication disodium
chromoglycate. A noteworthy increment in white platelet
checks and platelet includes was seen in creatures treated
with Ashwagandha extract. Cyclophosphamide-incited
immune suppression was neutralized by treatment with
Ashwagandha extricates uncovering huge increment in hem
agglutinating immunizer reactions and haemolytic counter
acting agent reactions towards sheep red platelets.
In a comparative report, the immunomodulatory movement
of Ashwagandha was concentrated in mice with
myelosuppression instigated by at least one of the
accompanying three mixes viz, cyclophosphamide,
azathioprin, or prednisolone [11]. The evaluation of
immunomodulatory movement was completed by
hematological and serological tests. A huge regulation of
invulnerable reactivity was seen in all the three creature
models. It was discovered that, Ashwagandha forestalled
myelosuppression in mice treated with every one of the
three immunosuppressive medications tried.
B) Clinical Studies
In a clinical study, a group of 37 underweight patients
suffering frequently from seasonal diseases was treated with
Ashwagandhafor one month [12]. It significantly improved
the physical strength, functions of the lungs and heart,
immediate memory and weight of them. It also significantly
increased the immunity of the persons as it increased their
serum IgA, IgG and IgM. Immuno enhancing effect of an
herbal tea fortified with Ashwagandha along with
Glycyrrhziaglabra, Zingiberofficinale, Ocimumsanctum and
Elettariacardamomum was studied on innate immunity of
healthy volunteers in another double-blind study [13]. It was
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observed that, NK cell activity of the volunteers in study
group was significantly improved, which is an important
aspect of the early innate immune response to infections.
In a clinical study, assessment of Rasayana or
immunomodulator activities of wild and cultivated varieties
of Ashwagandha were studied in healthy volunteers [14]. It
was observed that, both varieties brought about significant
improvement in various subjective and objective parameters
related to immunity as per Ayurveda and modern medicine.
2. Anti-viral Activit
Three studies were focused on anti-viral activity of
Ashwagandha other than COVID-19 infection. There were
two pre-clinical studies and one clinical study.
A) Pre-clinical studies
In -vitro study, Ashwagandha and Ocimum sanctum Linn,
Tinosporacordifolia (Willd.) Miers. ex Hook.f. &Thoms,
Avicennia officinalis Linn. Also, Rhizophoramucronata
Lam. were screened for against HIV activity [15]. The
impacts of various concentrates on gp120/CD4
communication were inspected in the current investigation,
utilizing a gp120 catch ELISA unit. It was discovered that,
these spices applied their enemy of HIV movement by
means of various instruments of activity, viz. impedance
with the gp120/CD4 communication and hindrance of viral
RT. Consequently, their customary use for the treatment of
irresistible infections of viral root was advocated.
As an extension to this study, aqueous extracts of
Ashwagandha and Ocimumsanctum Linn.,
Tinosporacordifolia (Willd.) Miers ex Hook. f. & Thoms,
Avicenniaofficinalis Linn., Rhizophoramucronata Lam.
were studied to evaluate inhibitory activity of HIV-protease
[16]. Pepsin was used as a substitute for HIV-protease in this
study. These extracts showed potent inhibitory activity
against pepsin enzyme.
B) Clinical Study
In a clinical study on patients of acute viral hepatitis, a
polyherbal formulation, Livwin’ containing extracts of
seven medicinal plants including Ashwagandha, was studied
[17]. It was found to be effective in uncomplicated patients of
acute viral hepatitis with good biochemical recovery.
3. Covid-19 Related Studies
None of the studies related to COVID-19 were of clinical
nature. Total six studies were reviewed in this regard. Out of
them, one study compiled literary reviews of
immunomodulator drugs in Ayurveda and their probable
efficacy against COVID-19 [18]. Rests five were laboratory-
based studies.
In an in-silico study, the immunomodulatory and hostile to
SARS-CoV-2 capability of key phyto constituents from
Ayurveda based Rasayana drugs, viz., Ashwagandha,
Guduchi and Shatavari were investigated utilizing
approaches like system pharmacology, and sub-atomic
docking [19]. Among these three spices, Ashwagandha was
seen as the most potent immunomodulator through its
capability to adjust T cell separation, NK cell cytotoxicity
just as T cell, B cell and NOD like receptor flagging
pathways. The investigation gave prompts clinical use of
these spices in prophylaxis as a result of their potentialin
repressing the replication of SARS-CoV2.In another study
with molecular docking approach, exploration of beneficial
roles of phytochemicals and active pharmacological agents
present in Ashwagandha and Tulsi, Haldi, Giloy, Black
pepper, Ginger, Clove, Cardamom, lemon were done [20].
The study revealed their potential to inhibit different stages
of SARS-CoV-2 infection as well as other Corona virus
target proteins.
Likewise, in another examination screening of
photochemical from thirty restorative plants focusing on the
proteins of SARS-CoV2 for recognizable proof of antiviral
therapeutics was done [21]. Withaferin A from Ashwagandha
additionally demonstrated noteworthy authoritative to the
objective's proteins. This atomic docking study gave a
premise to the utilization of traditional therapeutic plants as
elective lines of treatment for COVID-19 contamination. In
an in silico molecular docking procedure, Ashwagandha
along with Harsingar (Nyctanthesarbor-tristis), Giloy
(Tinosporacordifolia), Aloe vera (Aloe barbadensis miller),
Turmeric (Curcuma longa), Neem (Azadirachtaindica),
Ginger (Zingiberofficinale), Red onion (Allium cepa), Tulsi
(Ocimum sanctum), Cannabis (Cannabis sativa), Black
pepper (Piper nigrum); was studied [22]. The inhibition
potentials of these herbs were assessed by comparing with
the binding affinity of hydroxychloroquine. Ashwagandha
was found to show promising results.
Antiviral capability of Ashwagandha against COVID-19 by
surveyed methods for computational techniques in another
study [23]. The phytocompounds from Ashwagandha
demonstrated promising activity that could square or
hamper viral section into the host cells, by upsetting
cooperation’s between viral S-protein receptor restricting
area and host ACE2 receptor.
4. Discussion and Conclusion
The global acceptance of Ayurveda largely depends on
evidence-based efforts. Providing backing up of systematic
reviews is one such requisite. The ministry of AYUSH has
proclaimed Ashwagandha as a potential drug against
COVID-19 [24]. A number of clinical studies are being
conducted due to the proactive measures of Ministry of
AYUSH.
The systematic review of articles available from AYUSH
research portal and DHARA shows a promising side of
situation. Both these databases are credible sources for
understanding condition of Ayurveda research. The present
review was limited to these two databases and it can be
further expanded by taking into account other databases too.
Also, only abstracts were available for many articles. A
detailed review of their full text may add some more
insights in future studies.
Ashwagandha is a celebrated herb from science of
Ayurveda. Though much deliberation has been done on its
adaptogen effects. Still, it holds a lot of potential in terms of
immunomodulator activities. Also, its anti-viral activity on
viral hepatitis and HIV is promising.
The antiviral therapies like Lopinavir/Ritonavir and Other
Antiretrovirals are found to be effective in some cases.
Ribavirin is an antiviral inhabits viral RNA-dependent RNA
polymerase. Its activity is found beneficial against COVID-
19 [25].
It was seen that, numbers of studies for assessing action
against COVID-19 were more as compared to other studies.
This is a welcome gesture towards government efforts to
bring Ashwagandha as prophylactic treatment of COVID-
19. Though none of the studies were of clinical nature,
International Journal of Botany Studies www.botanyjournals.com
497
laboratory studies show a hopeful scenario. It can be
assumed that clinical studies will be carried out and
published soon in this regard.
Thus, the above findings clearly indicate that the use of
Ashwagandha for activities such as immunomodulatory,
anti-viral and especially against COVID-19 has a logical
and scientific basis.
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2806
... The chemical structure of curcumin is responsible for its high lipid-soluble nature, because of which it can position itself well within the cell membrane and positively modify the signalling pathways, such as the NF-kB (Nuclear factor kappa B) and MAPK (Mitogenactivated protein kinase), which allows the curcuminoid extract to assist the immune response and inhibit any aberrant cell cycle [16]. Withania somnifera, commonly called Ashwagandha belongs to the Solanaceae family [17]. It is a well-known herb for steroidal lactones, which are antibacterial, anti-inflammatory, and anti-fungal in nature [18]. ...
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The spread of COVID-19 across continents has led to a global health emergency. COVID-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected nearly all the continents with around 1.52 million confirmed cases worldwide. Currently only a few regimes have been suggested to fight the infection and no specific antiviral agent or vaccine is available. Repurposing of the existing drugs or use of natural products are the fastest options available for the treatment. The present study is aimed at employing computational approaches to screen phytochemicals from the medicinal plants targeting the proteins of SARS-CoV2 for identification of antiviral therapeutics. The study focuses on three target proteins important in the life cycle of SARS-CoV-2 namely Spike (S) glycoprotein, main protease (Mpro) and RNA-dependent RNA-polymerase (RdRp). Molecular docking was performed to screen phytochemicals in medicinal plants to determine their feasibility as potential inhibitors of these target viral proteins. Of the 30 plant phytochemicals screened, Silybin, an active constituent found in Silybum marianum exhibited higher binding affinity with targets in SARS-CoV-2 in comparison to currently used repurposed drugs against SARS-CoV-2. Withaferin A from Withania somnifera also showed significant binding to the targets proteins. In addition, phytochemicals from Tinospora cordiofolia and Aloe barbadensis displayed good binding energetics with the target proteins in SARS-CoV-2. These results provide a basis for the use of traditional medicinal plants as alternative lines of treatment for COVID-19 infection.
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Background Newly emerged COVID-19 has been shown to engage the host cell ACE2 through its spike protein receptor binding domain (RBD). Here we show that natural phytochemical from a medicinal herb, Withania somnifera, have distinct effects on viral RBD and host ACE2 receptor complex. Methods We employed molecular docking to screen thousands of phytochemicals against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy, along with the computation of salt bridge electrostatics. Results We report that W. somnifera compound, Withanone, docked very well in the binding interface of AEC2-RBD complex, and was found to move slightly towards the interface centre on simulation. Withanone significantly decreased electrostatic component of binding free energies of ACE2-RBD complex. Two salt bridges were also identified at the interface; incorporation of Withanone destabilized these salt bridges and decreased their occupancies. We postulate, such an interruption of electrostatic interactions between the RBD and ACE2 would block or weaken COVID-19 entry and its subsequent infectivity. Conclusion Our data, for the first time, show that natural phytochemicals could well be the viable options for controlling COVID-19 entry into host cells, and W. somnifera may be the first choice of herbs in these directions to curb the COVID-19 infectivity.
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Medicinal plants namely Ocimum sanctum Linn., Withania somnifera Dunal, Tinospora cordifolia (Willd.) Miers. ex Hook.f. & Thoms., Avicennia officinalis Linn. and Rhizophora mucronata Lam. were screened for anti-HIV activity in the present study. O. sanctum, T. cordifolia, A. officinalis and R. mucronata showed anti-HIV potential by inhibiting the virus by 2 different mechanisms. Interference with the gp120/CD4 interaction and inhibition of viral Reverse Transcriptase (RT) contributed to the overall anti-viral activity in vitro. Among these plants A. officinalis and R. mucronata are mangrove plants and their medicinal properties are rarely reported.
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The study was planned to evaluate the efficacy and safety of Livwin (polyherbal formulation) in acute viral hepatitis. In this study, there were 29 patients in each group, receiving either Livwin (containing Ashwagandha, Arjuna, Bhumyamalaki, Daruharidra, Guduchi, Kutki and Punarnava) or placebo capsules containing lactose powder (500 mg). Both drugs were given orally two capsules two times a day for eight weeks followed by treatment free period of four weeks. Recovery of patients was assessed by noting symptomatic recovery and by measuring levels of serum bilirubin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), alkaline phosphatase at baseline, 2, 4, 8 and 12 weeks. Significant earlier recovery of weakness was observed with Livwin as compared to placebo at 2, 4 and 8 weeks. Serum bilirubin and ALT was observed in normal range in significantly more number of patients with Livwin treatment as compared to placebo at 2, 4 and 8 weeks. AST was observed in normal range in significantly more number of patients with Livwin treatment as compared to placebo at 2 and 4 weeks. Livwin is found effective in uncomplicated patients of acute viral hepatitis. Epigastric pain and diarrhea were reported with Livwin treatment.
Article
Aqueous extracts of Ocimum sanctum Linn., Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thoms, Withania somnifera Dunal, Avicennia officinalis Linn. and Rhizophora mucronata Lam. were included for the present in vitro study. Pepsin was used as a substitute for HIV-protease to evaluate inhibitory activity of these extracts, as pepsin has close resemblance with HIV-protease in proteolytic activity. O. sanctum revealed the highest inhibitory activity followed by R. mucronata. In our earlier study, O. sanctum and R. mucronata exerted anti-HIV activity via multiple mechanisms of action; viz., interference with the gp120 / CD4 interaction and inhibition of HIV-reverse transcriptase. In the present study, they also showed potent inhibitory activity against pepsin enzyme (indirectly against HIV-protease) which may be due their flavonoids content.
Ashwagandha an immunomodulator drug
  • Rajeev Dr
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Dr. Rajeev Kushwah, Sharma MC, Ashwagandha an immunomodulator drug, Journal of Ayurveda. 2008; 2(4):56-67.
Immunomodulatory herbs of Ayurveda and covid-19: a review article
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Maurya, Dharmendra Kumar, Sharma, Deepak. Evaluation of Traditional Ayurvedic Preparation for Prevention and Management of the Novel Coronavirus (SARS-CoV-2) UsingMolecular Docking Approach.