G.

Siva Ram et al / Int. J. Res. Ayurveda Pharm. 12 (3), 2021

Review Article
www.ijrap.net (ISSN:2229–3566)

CONCEPTUAL REVIEW ON THE POTENTIAL OF PUNARNAVADYA GHRITA IN TACKLING

THE SYMPTOMS OF COVID-19
G. Siva Ram *
MD (Ayurveda), Registered Ayurvedic Private Practitioner, India
Received on: 13/05/21 Accepted on: 15/06/21

*Corresponding author
E-mail: parada99ram@gmail.com

DOI: 10.7897/2277-4343.120393

ABSTRACT

COVID-19 disease has created panic among all with respect to health and economy. On 11th March 2020 WHO (world health organisation) declared
novel corona virus outbreak as global pandemic. Confirmed effective remedy to prevent or treat COVID-19 is not yet established. Ayurveda, the Indian
system of medicine is the oldest medicinal literature known to mankind as old as 3000 BC and is recognised as medical system by WHO. There is a
need to investigate time tested potent classical Ayurvedic formulations backed by contemporary scientific studies in treating symptoms of COVID-19
disease. Vijaya (Cannabis sativa Linn.) in Ayurveda notable for its Vyavayi (quick absorption) and Yogavahi (synergetic action) properties said to be
originated from ambrosia as per Vedic mythology. Recent scientific research on the phytochemicals of Cannabis plant showed promising results in
decreasing the pro-inflammatory cytokine storm and to an extent halting the replication of SARS-CoV-2. We have put forward one such classical
Cannabis Ayurvedic formulation Punarnavadya Ghrita available in market which can be useful as an alternative remedy for prophylactic and curative
to the symptoms of novel corona virus disease whose individual herbal phytochemical compounds are studied through in silico, in vitro and in vivo
methods in treating COVID-19 with positive outcomes.

Keywords: Punarnavadya Ghrita, Cannabis, COVID-19, SARS-CoV-2, Main protease, Cytokine storm.

INTRODUCTION main focus in tackling the COVID-19 disease by AYUSH

personnel,3,4 we focused on certain attributes said in Ayurveda
The corona virus disease 2019 pandemic has caused havoc on which are required for the quick stimulation of both body and
every aspect of public health causing social and economic mind for improving immune system and fitness of the body to
disruption. Scientists across the globe are attempting to help tackle the COVID-19 disease. Vyavayi guna5 (fast diffusing
investigate anti-viral, immunity modulators and vaccines specific quality) is a specific property of few herbs in Ayurveda which
to COVID-19 with not much efficacy tailed by side effects like first spreads/ circulates quickly throughout the body to exert its
the steroid medications which are immune suppressants. Classical action and then undergoes paka (digestion). Sattva (goodness) is
medicines in Ayurveda are time tested formulations which are the purest quality among the three primary attributes of mind
being successfully revalidated through scientific studies by many which is said to be required for homeostasis in the neuronal
institutes across the world of AYUSH systems. In these impulses which triggers all the physiological functions in the
circumstances there is a need to encourage Ayurvedic body6. Medhya7 (intellect promoting) is also a unique quality
medications which are backed by scientific research as among certain herbs to help maintain the neuronal health and
prophylactic and symptomatic treatment measures in COVID-19. psychological balance. Vajikarana-Rasayana8 (aphrodisiac and
The COVID-19 disease caused by SARS-CoV-2 can be rejuvenative) herbs are the best in improving and maintaining
compared to Bhuta, Rakshasa, Graha, etc, a kind of microbes energy levels, stamina and immunity. All these qualities are
elucidated in Ayurveda which may cause Bhutabhishangaja present in one single herb called Vijaya (Cannabis sativa Linn.)9
Jwara (fever caused by invisible organisms), a kind of Agantu and recent scientific researches done on the phytocannabinoids of
Jwara (fever caused by external factors) negatively effecting Cannabis plant showed encouraging results in decreasing the pro-
Pranavaha srotas (the vessels carrying the vitals) related to inflammatory cytokine storm and to an extent halting the
Lungs, Heart and Brain1. The spread of COVID-19 pandemic is replication of SARS-CoV-2 which will be explained in brief.
compared to Janapadodhwamsa or Maraka, a broad term for There are more than 200 formulations10 of Vijaya (Cannabis
epidemic in Ayurveda which cause contagious diseases through sativa Linn.) in Ayurveda that are mostly unexplored. So, we
four important factors Viz. polluted air, water, land and season. It searched online journals for scientific research articles on
has been said that pandemic spreading by air can be easily treated Elsevier, Pub Med, Research Gate, Science Direct, Medline,
than other causative factors like water, land and seasons. Pancha- Google Scholar, Semantic Scholar, Ayush research portal, etc, for
karma (purification therapies) to detoxify, Rasayana Ayurvedic herbs useful in COVID-19 disease; in parallel also
(rejuvenative) therapies to improve the immune system, explored classical Vijaya (Cannabis sativa Linn.) based
symptomatic treatment and anti-viral medicines to control the Ayurvedic formulations available in the AYUSH medical shops
replication of virus or entry of virus into the body are the prime or online pharmaceutical markets having such combination of
focus in treating Covid-19 like pandemic in Ayurveda2. researched herbs on COVID-19.

Powerful medicines are required to quickly address the We found a classical Cannabis based Ayurvedic formulation
damage/infection caused by the Covid-19. Immune modulators, available in the market called Punarnavadya Ghrita from a GMP
anti-inflammatory drugs and symptomatic treatment being the certified Ayurvedic company Charaka Hanf Pvt. Ltd.11 taken

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from Shotha roga chikitsa prakarana (chapter related to the tiredness, aches, loss of appetite, nausea, diarrhoea, etc13,14 which
treatment of inflammations) of the classical book Bhaishajya can be managed by the researched herbs of Punarnavadya Ghrita
ratnavali12 listed in the first schedule of drugs and cosmetics act as per the properties of the individual herbs in Ayurvedic
(1940). This polyherbal infused Ghee is blended by a unique literature15. In silico, In vitro and In vivo research is available on
combination of five anti-inflammatory herbs indicated in Jwara the phytochemicals of these five herbal ingredients for
(fever), Kasa (cough), Shwasa (shortness of breath, asthma) and symptomatically treating COVID-19 and also inhibiting the
Daruna Shotha (severe inflammation) which are the major replication of SARS-CoV-2 with positive outcomes will be
symptoms of COVID-19. Other symptoms of COVID-19 are discussed below in brief.
headache, sore throat, chest pain, loss of taste and smell,

Table 1: The herbal ingredients of Punarnavadya Ghrita

S. No. Sanskrit name Scientific name Family Part used

1. Vijaya Cannabis sativa Linn. Cannabinaceae Leaf
2. Punarnava Boerhavia diffusa Linn. Nyctaginaceae Root
3. Bhunimba Andrographis paniculata (Burm. f.) Nees. Acanthaceae Whole plant
4. Shunthi Zingiber officinale Rosc. Zingiberaceae Rhizome
5. Devadaru Cedrus deodara (Roxb.) G. Don. Pinaceae Heart wood15

Table 2: The Ayurvedic pharmacological properties of the above researched herbs

S. No. Herbs Rasa (taste) Guna (qualities) Virya Vipaka (taste Dosha (fundamental
(potency) after digestion) bio-elements)
1. Vijaya Tikta (bitter), Laghu (light), Ushna (hot) Katu (pungent) alleviates Kapha-Vata
Katu (pungent) Tikshna (sharp)
2. Punarnava Madhura (sweet), Laghu (light), Ushna (hot) Katu (pungent) alleviates Kapha-pitta
Tikta (bitter) Ruksha (dry)
3. Bhunimba Tikta (bitter) Laghu (light), Ruksha Sita (cold) Katu (pungent) alleviates Kapha-pitta
(dry), Sara (mobility)
4. Shunthi Katu (pungent) Laghu (light), Ushna (hot) Madhura (sweet) alleviates Kapha-Vata
Snigdha (oily), Grahi
(absorbent)
5. Devadaru Tikta (bitter), Laghu (light), Ushna (hot) Katu (pungent) alleviates Kapha-Vata15
Katu (pungent) Snigdha (oily)

Scientific research on phytochemicals of the herbs of inflammation and the suppression of cytokine storm. This was
Punarnavadya Ghrita on SARS-CoV-2 associated with immune cell apoptosis involving the
mitochondrial pathway, as suggested by single-cell RNA
Vijaya (Cannabis sativa Linn.) sequencing. A transcriptomic analysis of immune cells from the
lungs revealed an increase in mitochondrial respiratory chain
The endocannabinoid system is found in multiple systems within enzymes following THC treatment. THC caused the
the human body, including the immune system. Its activation can downregulation of miR-185, which correlated with an increase in
lead to beneficial results such as decreased viral entry, decreased the pro-apoptotic gene targets. Interestingly, the gene expression
viral replication and a decrease in pro-inflammatory cytokines datasets from the bronchoalveolar lavage fluid (BALF) of human
such as IL-2, IL-4, IL-6, IL-12, TNF-α or TNF-γ. Moreover, COVID-19 patients showed some similarities between cytokine
endocannabinoid system activation can lead to an increase in anti- and apoptotic genes with SEB-induced ARDS. Collectively, this
inflammatory cytokines, mainly represented by IL-10. Overall, study suggests that the activation of cannabinoid receptors may
the cannabinoid system can potentially reduce pulmonary serve as a therapeutic modality to treat ARDS associated with
inflammation, increase the immunomodulatory effect, decrease COVID-1920.
PMN infiltration, reduce fibrosis, and decrease viral replication,
as well as decrease the cytokine storm16. Ghrelin, an endogenous ligand for the growth hormone
secretagogue receptor, is a peptide hormone secreted mainly by
In an in vitro study Cannabis compounds Viz. CBD, CBG and the stomach. Interestingly, ghrelin possesses promising
THCV exhibited anti-inflammatory activity in COVID-19- antioxidant, anti-and inflammatory effects, making it an attractive
related inflammation in lung epithelial cells and pro- agent to reduce the complications of the SARS-CoV-2. In
inflammatory activity in macrophages17. addition, ghrelin exerts a wide range of immunomodulatory and
anti-inflammatory effects and can mitigate the uncontrolled
In an experimental study CBD (Cannabidiol), the cytokine production responsible for acute lung injury by
Phytocannabinoid and its metabolite, 7-OH-CBD potently blocks upregulating PPARγ and down-regulating NF-κB expression.
SARS-CoV-2 replication in lung epithelial cells. CBD acts after Ghrelin has also been reported to enhance Nrf2 expression in
5 cellular infections, inhibiting viral gene expression and inflammatory conditions which led to the suppression of
reversing many effects of SARS-CoV-2 on host gene oxidative stress. The current opinion summarizes the evidence for
transcription. CBD (Cannabidiol) induces interferon expression the possible pharmacological benefits of ghrelin in the therapeutic
and up-regulates its antiviral signalling pathway18. CBD might management of SARS-CoV-2 infection. Delta-9
represent as a potential anti-inflammatory therapeutic approach Tetrahydrocannabinol (THC) compound of cannabis is
against SARS-CoV2-induced inflammation19. responsible for the stimulation and release of ghrelin21.

In an animal experimental study; the treatment of SEB-mediated High CBD (cannabidiol) Cannabis extracts are able to down‐
ARDS mice with Delta-9 Tetrahydrocannabinol (THC), the main regulate the expression of the two key receptors for SARS‐CoV2
Phytocannabinoid led to a 100% survival, decreased lung in several models of human epithelia. CBD (cannabidiol) exerts a

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wide range of immunomodulatory and anti‐inflammatory effects four key targets including three non-structural proteins 3CLpro
and it can mitigate the uncontrolled cytokine production (Mpro), papain-like protease (PLpro) and RNA-directed RNA
responsible for acute lung injury. CBD being a PPARγ agonist, it polymerase (RdRp) and a structural protein spike protein (S) of
can display a direct antiviral activity and PPARγ agonists are the virus which are responsible for replication, transcription and
regulators of fibroblast/myofibroblast activation and can inhibit host cell recognition. Results state phytochemical
the development of pulmonary fibrosis, thus ameliorating lung neoandrographolide has the stronger binding affinity than other
function in recovered patients22. compounds towards spike protein-ACE2 complex (-
7.8 kcal/mol), 3CLpro (-7.1 kcal/mol), PLpro (-7.3 kcal/mol) and
Punarnava (Boerhavia diffusa Linn.) RdRp (-7.4 kcal/mol). In this way Andrographis paniculata was
shown to have potency against the Covid-19 and have evidenced
Main protease (Mpro) of SARS-CoV-2 is a key enzyme of corona its microscopic mechanism through rational computational
viruses and has a pivotal role in mediating viral replication and modelling26.
transcription, making it an attractive drug targets to design anti-
viral meds. Many phytochemicals of Boerhavia diffusa were Experiments were done by plaque assay for viral output study
tested with molecular docking study and an article was published. using the legitimate model of human lung epithelial cells, Calu-
The ligands that showed the least binding energy were Biorobin 3, to determine anti-SARS-CoV–2 activity of Andrographis
8.17 kcal/mol, Bioquercetin 7.97 kcal/mol and Boerhavisterol paniculata extract and its major component andrographolide.
6.77 kcal/mol. These binding energies were found to be SARS-CoV-2 at 25TCID50 (Median Tissue Culture Infectious
favourable for an efficient docking and resultant inhibition of the Dose) was able to reach the maximal infectivity of 95% in Calu-
viral main protease23. 3 cells. Post-infection treatment of Andrographis paniculata and
andrographolide in SARS-CoV–2 infected Calu-3 cells
Bhunimba (Swertia chirata Buch. - Ham) significantly inhibited the production of infectious virions with
the IC50 of 0.036 μg/mL and 0.034 μM, respectively, as
SARS-CoV-2 proteins associated with host attachment and viral determined by plaque assay27.
replication namely, spike protein, main protease enzyme
(Mpro) and RNA-dependent RNA polymerase (RdRp) are Andrographolide from Andrographis paniculata and its
promising druggable targets for COVID-19 therapeutic research. fluorescent derivative, the nitrobenzoxadiazole-conjugated
Extensive molecular docking of the phytocompounds of Swertia andrographolide (Andro- NBD), suppressed the main protease
chirata at the binding pockets of the viral proteins revealed their (Mpro) activities of 2019-nCoV. Moreover, Andro-NBD was
promising inhibitory potential. Subsequent assessment of shown to covalently link its fluorescence to Mpro. Further mass
physicochemical features and potential toxicity of the compounds spectrometry (MS) analysis suggests that andrographolide
followed by robust molecular dynamics simulations and analysis formed a covalent bond with the active site Cys145 of SARS-
of MM-PBSA energy scoring function revealed amarogentin, a CoV–2 Mpro. Consistently, molecular modelling analysis
natural bitter terpenoids of Swertia chirata against SARS-CoV-2 supported the docking of andrographolide within the catalytic
RdRp as potential inhibitor and displayed significantly higher pockets of viral Mpro28.
binding energy score24.
Shunthi (Zingiber officinale Rosc.)
Bhunimba (Andrographis paniculata (Burm. f.) Nees.)
SARS-CoV-2 utilises its Spike protein as a significant part of its
The drug compound, Andrographolide extracted from the envelop that participate in the interaction with its cellular receptor
plant Andrographis paniculata was analysed by in angiotensin converting enzyme 2(ACE2). Consequently, the
silico computational docking tools it successfully docked against spike protein is cleaved by extracellular catalytic domain of
the inhibitor region of the main protease of SARS-CoV-2 virus Transmembrane protease Serine 2 (TMPRSS2) also called as
with docking score of -3.094357 Kcal/mol, the docking score Serine protease or Hepsin leading to entry of virus into the host
showed great binding when compared to synthetic compounds cell. Molecular docking study revealed that Gingerenone (-5.87
when they are docked against Mpro such as disulfiram, tideglusib kcal/mol) and Zingiberene (-5.77 kcal/mol) have shown effective
and shikonin which are -46.16 Kcal/mol, -61.79 Kcal/mol and - binding affinity towards ACE2. Shoagol (-5.72 kcal/mol),
17.35 Kcal/mol. And it also shows great binding score when Zingerone (-5.79 kcal/mol) and Zingiberene (-5.52 kcal/mol)
compared against recently proposed combination of three drugs have shown higher binding with extracellular domain of serine
namely, lopinavir, ostelmivir and ritonavir whose binding scores protease TMPRSS2. Zingiberene scored significant binding
are -4.1Kcal/mol, -4.65 Kcal/mol and -5.11 Kcal/mol. Even some energy (-6.23 kcal/mol) with Spike protein of SARS-CoV-229.
plant molecules which are studied to inhibit the main protease of
SARS-CoV-2 failed to prove their binding score when compared Studies against the viral receptors by using the molecular docking
with the Andrographolide such as kaempferol -9.41 Kcal/mol, technique revealed phytocompound 6-gingerol proves anti-viral
quercetin -8.58 Kcal/mol, demethoxycurcumin -8.17 Kcal/mol, efficiency against SARS CoV-2 by showing the highest binding
curcumin -7.31 Kcal/mol, catechin -7.05 Kcal/mol, epichatechin affinity ranging from -2.8764 KJ/mol to -15.7591 KJ/mol with
gallate- 7.24 Kcal/mol, zingerol -6.67 Kcal/mol and gingerol - various COVID-19 viral protein targets including Viral proteases,
5.40 Kcal/mol respectively. Even proposed inhibitor of RNA binding protein, Spike protein30. A molecular docking study
Mpro such as PRD_002214 has a docking score of - showed that the nine phytochemicals of Zingiber officinale are
10.466 Kcal/mol which proclaim that Andrographolide has better potential inhibitors against the main protease enzyme (6LU7) of
properties than other proposed inhibitors25. COVID-1931.

A molecular docking approach, and combined molecular Devadaru (Cedrus deodara (Roxb.) G. Don)
dynamics and MM-GBSA based free energy calculations
approach were used to study the potency of the four selected The bark of Cedrus deodara contains large amounts of
phytochemicals namely andrographolide, 14-deoxy 11, 12- taxifolin32,33, a flavonoid, also called dihydroquercetin was tested
didehydro andrographolide, neoandrographolide and 14-deoxy using molecular docking on main protease (Mpro) of SARS-
andrographolide from Andrographis paniculata plant against the CoV-2 in an in-silico study and binding affinity to Mpro was

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assessed. It was subjected to molecular dynamics simulation and of -7.2 could be a potential inhibitor of SARS-CoV-2 main
predicted activity (IC50) using 3D-QSAR analysis. Study suggests protease41.
taxifolin potential inhibitory activity against SARS-CoV-2
Mpro with IC50 value 9.63 μM34. DISCUSSION

Essential oil from pine needles of Cedrus deodara was Punarnavadya Ghrita is a potent anti-inflammatory classical
determined, and twenty‐three components, representing 95.79% medication mentioned in Shotha (anti-inflammatory) chapter in
of the oil, were identified by gas chromatography mass the book Bhaishajya Ratnavali indicated in Jwara (fever), Kasa
spectrometry. The main components include α‐terpineol (30.2%), (cough), Shwasa (shortness of breath, asthma) and Daruna
linalool (24.47%), limonene (17.01%), anethole (14.57%) and Shotha (severe inflammation) which are also the prime symptoms
caryophyllene (3.14%)35. observed in COVID-19 as per WHO. It is prepared from the
goodness of Bilona A2 Cow Ghee and infused with the Rasayana
Alpha‐terpineol, a monoterpenoid has the strongest inhibitory (rejuvenating) herb Vijaya (Cannabis sativa Linn.) which is
effects on the ACE2 protein in human body and PDB6LU7 Vyavayi (fast acting) and having Yogavahi (synergetic action).
protein in the SARS‐CoV‐2 in a molecular docking simulation Vijaya (Cannabis sativa Linn.) has Grahi (Absorbent), Dipana
study. Docking of α‐terpineol ‐ACE2 has DS (docking score (appetiser), Pachana (digestive) and Ruchya (improves taste)
energy) of −11.0 kcal.mol−1 and RMSD (root mean square properties9 which can quickly correct the metabolism of impaired
deviation) of 1.97 Å, while the site‐site bonding interaction digestion, the root cause leading to complications in most of the
exhibiting the length of the binding of compound with amino acid diseases (Rogah Sarve api mandagnou)42 said by Vagbhata. Ojas
between -OH of α‐terpineol and amino acids Asn 103 is 2.25 Å (immunity) is the Upadhatu43 of Sukra dhatu (tissues and
and 2.08 Å for Gln 101. Docking of α‐terpineol ‐SARS‐CoV‐ components of reproductive system present in both males and
2 has DS (docking score energy) ‐10.9 kcal.mol−1 and RMSD females)44 which is circulated all over the body45 along with Rasa
(root mean square deviation) of 1.16 Å. Results show strongest dhatu (blood plasma). This may be the Ayurvedic explanation
inhibitory effects of α‐terpineol on ACE2 and PDB6LU7 proteins why plasma donation was once an off-label recommendation for
(main protease of the SARS‐CoV‐2)36. Another Mpro of novel patients to recover fast from COVID-19 as the Ojas/ antibodies
corona virus docking analysis with α -terpineol showed two (immune components) are in circulation with blood plasma, but
hydrogen bonds with GLU166; three hydrophobic alkyl and pi- was discontinued from COVID-19 treatment guidelines as the
alkyl bonds with MET49, MET165, and HIS41 residues; and five antibodies in donor’s plasma were not sufficient enough for
van der Waals forces with TYR54, LEU167, GLN189, ARG188, patient recovery and also researchers hypothesized the risk of
and ASP187 with a binding energy value of -5.43 kcal/mol and developing new variants of Virus. Sukra is the par excellence of
105.43 μM inhibitory constant37. well digested food said in Charaka samhita46 which is later
converted to Ojas (immune system components). Diminished
Linalool, a monoterpenoid is capable of binding to ACE2 and Sukra may lead to various diseases and even death so, one should
PDB6LU7 proteins and has quite good interactions with amino preserve the Sukra dhatu by indulging in wholesome food and
acid Asn 210 of ACE2 protein, and Gly 143 as well as Cys 145 lifestyle; hence potent Vajikarana (aphrodisiac) and Sukra
of PDB6LU7 protein. Docking of Linalool ‐ACE2 has DS Stambhana47 (drugs prolonging ejaculation time) herbs like
(docking score energy) of ‐10.9 kcal.mol−1, RMSD ((root mean Vijaya (Cannabis sativa Linn.) can improve Ojas (immune
square deviation) of 1.77 Å, and site‐site bonding interaction system). Vijaya (Cannabis sativa Linn.) is a Vata-Kapha
between -OH and amino acid Asn 210 is 1.96 Å. Docking alleviating herb which according to Acharya Charaka is an
of Linalool ‐SARS‐CoV‐2 has DS (docking score energy) of - essential Dosha karma for curing Shwasa (breathing
11.1 kcal.mol−1, and RMSD (root mean square deviation) of 1.18 difficulty/asthma)48. The cytokine storm is one of the major side
Å, and site‐site bonding interactions between –OH and amino effects of SARS-CoV-2 virus infection. Pro-inflammatory
acid Gly 143 and Cys 145 are 2.89 Å and 2.82 Å, respectively. cytokines like interleukins, TNF-α and TNF-γ are involved in the
Results exhibit the significant inhibition of linalool on ACE2 and inflammation of alveoli and damage the lungs. The
PDB6LU7 proteins (main protease of the SARS‐CoV‐2)38. endocannabinoid system inside the mammalian bodies controls
these IL-2, IL-4, IL-6, IL-12 interleukins along with Tumour
The docking study of Mpro with d-limonene, a monoterpenoid Necrosis Factor alpha and gamma (TNF-α, TNF-γ). Interleukin
has utilized an energy value of -5.18 kcal/mol and 159.51 μM IL-10 called human cytokine synthesis inhibitory factor (CSIF) is
inhibitory constant and 12 hydrophobic bonds were formed with a protein that inhibits the synthesis of a number of pro-
MET49, PRO52, TYR54, MET165, HIS41, CYS44 and ARG188 inflammatory cytokines is also increased by the activation of the
and three van der Waals interactions with HIS164, GLN189, and endocannabinoid receptors related to Phytocannabinoids of
ASP187 residues, the active sites of protein (Mpro of novel Vijaya (Cannabis sativa Linn.)16. In vitro experiment with CBD
corona virus). The molecular interaction analysis using Autodock (cannabidiol), a major Phytocannabinoid was effective in
4.2 software resulted in favourable interactions of limonene as a stopping the replication of SARS-CoV-2 in lung epithelial cells19.
possible inhibitor of main protease of SARS-CoV-239. CBD (cannabidiol) is a known anti-inflammatory and immune
modulator molecule. CBD (cannabidiol) being an agonist at
Anethole is an aromatic polyphenol related to lignols. It has been PPAR-γ receptor (peroxisome proliferator-activated receptor)
docked against the S1 receptor binding domain of the spike (S) reduced pulmonary inflammation and fibrosis in animal models
glycoprotein of SARS-CoV-2 in an in-silico studies. A receptor- of asthma. High CBD (cannabidiol) extracts have been reported
binding domain (RBD) is a short immunogenic fragment from a to downregulate Angiotensin-converting enzyme 2 (ACE2) and
virus that binds to a specific endogenous receptor sequence to Transmembrane Serine Protease 2 (TMPRSS2) receptors, viral
gain entry into host cells. Results prove Anethole exhibited good gateways in oral, lung and intestinal epithelia constituting
inhibition of RBD region of SARS-CoV-2 spike protein40. important routes of SARS-CoV2 invasion. In an animal study,
CBD (cannabidiol) caused marked amelioration of the pulmonary
Caryophyllene, a sesquiterpene is a component in the essential oil function by acting at adenosine A2 receptor site and reducing of
of Devadaru (Cedrus deodara (Roxb.) G. Don.) and is also leukocyte migration into the lung, accompanied to a marked
abundant in Vijaya (Cannabis sativa Linn.). Pi-alkyl interactions inhibition of both pro-inflammatory cytokines (TNF-α, IL-6) and
of Caryophyllene with PHE 294 were observed with an affinity chemokines (MCP-1 and MIP-2)22. THC (delta-9

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Tetrahydrocannabinol), the main Phytocannabinoid in an animal Devadaru (Cedrus deodara (Roxb.) G. Don) is a Sopha hara
study prevented mortality from ARDS (acute respiratory distress (anti-inflammatory), Jwaraghna (antipyretic), blood purifying
syndrome) by inducing apoptosis in immune cells responsible for and Kapha-Vata alleviating herb indicated in Kasa (cough),
increase in pro-inflammatory molecules, leading to the Shwasa (dyspnoea/asthma), Hikka (hiccups), Pinasa (rhinitis)
suppression of cytokine storm20. Ghrelin, a peptide hormone and various gastro-intestinal ailments like Vibandha
whose secretion is stimulated by THC (delta-9 (constipation), Ajirna (indigestion), Adhmana (abdominal
Tetrahydrocannabinol) can decrease the uncontrolled cytokine distension/ bloating), etc55. In silico studies on the flavonoid
production responsible for acute lung injury by upregulating taxifolin of Devadaru (Cedrus deodara (Roxb.) G. Don) inhibited
PPARγ and down-regulating NF-κB expression. Ghrelin also the Mpro of SARS-CoV-2 significatly34. Also;
enhance transcription factor Nrf2 expression in inflammatory Monoterpenoids of Cedrus deodara Viz. Alpha‐terpineol,
conditions which can suppress oxidative stress21. Linalool and D-limonene displayed strong inhibitory effect
against main protease of the SARS‐CoV‐2. While Alpha‐
Apart from Vijaya other herbs are, Punarnava (Boerhavia diffusa terpineol, Linalool also inhibited angiotensin converting enzyme
Linn.) a Sopha hara (anti-inflammatory), Hridya (Cardiotonic) (ACE2) cellular receptor36-39. Anethole, a polyphenol displayed
herb indicated in Kasa (cough), Shwasa (dyspnoea/asthma), good inhibition of RBD region of SARS-CoV-2 spike protein40.
Angamarda (tiredness)49 having Kapha-Pitta alleviating property This signifies the preliminary antiviral property of certain
included in Vayahsthapana daseimani (list of anti-ageing drugs) phytochemicals of Devadaru (Cedrus deodara (Roxb.) G. Don).
in Charaka Samhita50. In silico experiment on Main protease
(Mpro) of SARS-CoV-2 with the phytochemicals of Punarnava Ghee is promoter of Ojas (immune booster) conductive to Rasa
(Boerhavia diffusa Linn.) Viz. Biorobin, Bioquercetin and dhatu (blood plasma) and Sukra dhatu56 (tissues of reproductive
Boerhavisterol were found to be effective in inhibiting viral main system) commonly consumed for its Bala (strength), Swarya
protease which mediates viral replication and transcription23. This (Voice promoting), Medhya (intellect), Pushti (nourishment),
signifies the preliminary antiviral property of Punarnava Ayushya (longevity) and Vayahsthapana (anti-ageing)
(Boerhavia diffusa Linn.). properties57. Ghee improves digestive power, acts as Jwaraghna
(antipyretic), Visha hara (removes toxins from body) and
Bhunimba is controversial between two plants, Swertia chirata Rakshoghna (ward off various infectious micro-organisms)58.
which grows in north (Himalayan region) and Andrographis Due to its unique quality Samskarasya anuvartanat59 (assimilate
paniculata which grows in southern parts of India. Commonly the properties of other herbs infused in it), makes Ghee a good
Andrographis paniculata is used as a substitute for Swertia base material for powerful medications to fight against such
chirata as both plants have similar medicinal properties according viruses. Moreover; medicated Ghee (Sneha kalpana) has a unique
to Ayurvedic community51,52. Bhunimba is a famous Jwaraghna methodology of preparation to incorporate both non-polar (fat
(antipyretic) & blood purifying herb having Kapha-Pitta soluble) and polar (water soluble) compounds of the respective
alleviating property prescribed in Aruchi (loss of taste), Kasa herbs used for infusion which can be compared to liposomal drug
(cough), Shwasa (dyspnoea/asthma) and Sopha (inflammatory)53. delivery having quick absorption and greater bioavailability60.
As per the contemporary research Andrographis paniculata Also; the phytochemicals in infused Ghee preparations (Sneha
(Burm. f.) Nees. was taken as Bhunimba in the present kalpana) move across the BBB (blood brain barrier) easily by
formulation Punarnavadya Ghrita which was also approved by simple diffusion61.
directorate of AYUSH. In silico experiments on main protease
(Mpro) of SARS-CoV-2 with the phytochemical Excess mucus/phlegm secretions in throat, nostrils, sinus cavities,
Andrographolide of Andrographis paniculata, a well-known trachea, etc, may increase the severity of bacterial, viral or fungal
antiviral showed strong binding affinity towards SARS-CoV-2 infections developing in the body especially in the lungs. All the
proteins associated with host attachment and viral replication five herbs of Punarnavadya Ghrita have Kapha Dosha
namely, spike protein, main protease enzyme (Mpro), papain-like alleviating property and are Shotha hara (anti-inflammatory) in
protease (PLpro) and RNA-dependent RNA polymerase common which can decrease the excess mucus and helps to
(RdRp)26,28. An in vitro study with the model of infected human recover from respiratory ailments like Shwasa (breathing
lung epithelial cell and Calu-3 with Andrographis paniculata difficulties), Kasa (cough). The formulation is placed in Shotha
extract and phytochemical Andrographolide was able to inhibit roga chikitsa Prakarana (chapter related to the treatment of
the infectious SARS-CoV-2 virion production displaying IC50 of inflammations) which conveys its potent anti-inflammatory
0.036 μg/mL and 0.034 μM, respectively with a high safety potential to control the cytokine storm.
margin for major human organs viz. lung, brain, liver, kidney and
intestine in cell culture models27. Evidence based research is the prerequisite for establishing the
efficacy of any drug which also applies to age old time tested
Shunthi (Zingiber officinale Rosc.) is a Sopha hara (anti- Ayurvedic medicines and are being revalidated accordingly. As
inflammatory), Hridya (Cardiotonic), Swarya (voice promoting), per the available contemporary research placed above, the five
Vrishya (aphrodisiac) and Kapha-Vata alleviating herb which is herbal ingredients showed favourable preliminarily results
indicated in Kasa (cough), Shwasa (dyspnoea/asthma), Hikka towards symptoms of COVID-19. More intense research is
(hiccups), Pinasa (rhinitis) and various gastro-intestinal ailments needed to establish these herbs as an alternate remedy for
like Vibandha (constipation), Ajirna (indigestion), Mandagni symptomatic treatment of COVID-19. In Ayurveda polyherbal
(low appetite), Sula (pain in abdomen), Hrillasa (nausea), Anaha combinations are much more effective than single herbs. Also;
(abdominal distension/ bloating), etc54. In silico experiments with whole herb (full spectrum) if used as medicines will have an
the phytochemicals of Shunthi (Zingiber officinale Rosc.) entourage effect with negligible side effects when compared to
displayed effective binding energies towards angiotensin extracts and isolated phytochemicals. So, we postulate the
converting enzyme (ACE2) cellular receptor and the spike combination of these herbs in the form of Punarnavadya Ghrita
protein, Mpro of SARS-CoV-2 whose interactions are may act in synergy to amplify the benefits which needs to be
responsible to the entry of virus into the host. This shows the further scientifically evaluated with proper clinical trials.
preliminary antiviral property of the API’s (Active
Pharmaceutical Ingredient) of Shunthi (Zingiber officinale
Rosc.).

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