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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 14  |  Issue : 4  |  Page : 73-84

Understanding COVID-19 in light of Ayurveda and exploring possible role of immune booster Kashaya in its management


Department of Kayachikitsa, National Institute of Ayurveda, Jaipur, Rajasthan, India

Date of Submission07-Aug-2020
Date of Decision24-Sep-2020
Date of Acceptance26-Sep-2020
Date of Web Publication28-Dec-2020

Correspondence Address:
Ram Kishor Joshi
Department of Kayachikitsa, National Institute of Ayurveda, Amer Road, Jaipur - 302 002, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joa.joa_130_20

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  Abstract 


Background: A new virus of corona family known as novel coronavirus causes coronavirus disease 2019 (COVID-19) also known severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A good number of principles are found in the classical texts of Ayurveda, which can be compared with the concepts of SARS-CoV-2, and many herbal drugs written in the Ayurvedic text, through its immunomodulatory effect, may enhance host–defense mechanism against such diseases to decrease the mortality. Aim: Our objectives of this review are (i) to understand the concepts of SARS-CoV-2 in light of Ayurveda with their approximate delineation through theoretical analysis; (ii) to review the role of Immune Booster Kashaya Special (IBKS) in boosting and regulating immunity and in preventing complications; and (iii) to explore the effectiveness of each drug among scientific community to facilitate for their extensive research. Methodology: We also searched for relevant keywords in various texts of Ayurveda as well as on online databases such as PubMed, Science Direct, Scopus, CrossRef, and Google Scholar to understand the concepts of SARS-CoV-2 in light of Ayurveda and to explore the possible role of 14 medicinal plants of “immune booster Kashaya” formulation. Result: We found that SARS-CoV-2 is symptomatically very much similar to Sannipataj Jwar as described in Ayurveda and the content of IBKS possesses antiviral, immunomodulatory, antioxidant, antipyretic, anti-inflammatory, cardioprotective, antianxiety, and phagocytic properties. It seems to promote the body's immune mechanism against viral activity and to prevent complications such as inflammation-induced damage and cytokine storming in COVID-19. Conclusion: As there is a lack of an effective SARS-CoV-2 virus-specific medicine or vaccine, these immunomodulatory strategies may be implemented before or shortly after viral exposure and may be paired with antiviral therapies to improve antiviral immune responses by providing interferon-inducing agents or by nonspecific boosting of immunity with innate factors. Immune booster Kashaya should be gone through extensive in vivo and in vitro studies and clinical trials for further validation.

Keywords: Agantuja Roga, Ayurveda, complementary and alternative medicine, coronavirus, coronavirus disease 2019, immunomodulation in coronavirus disease, Sannipataj Jwar, Vyadhikshamatva


How to cite this article:
Joshi RK, Gupta D, Gautam S, Upadhyay A. Understanding COVID-19 in light of Ayurveda and exploring possible role of immune booster Kashaya in its management. J Ayurveda 2020;14:73-84

How to cite this URL:
Joshi RK, Gupta D, Gautam S, Upadhyay A. Understanding COVID-19 in light of Ayurveda and exploring possible role of immune booster Kashaya in its management. J Ayurveda [serial online] 2020 [cited 2021 Jan 22];14:73-84. Available from: http://www.journayu.in/text.asp?2020/14/4/73/304888




  Introduction Top


To treat any disease through Ayurvedic drug, it is important to understand the concept of causation of disease/etiology of disease, pathogenesis, classification of disease, modes of communicable disease transmission, prognosis, and natural history of the disease in light of Ayurvedic concepts. Ayurvedic science is based on three main regulatory functional factors of the body, principle/pathophysiological factors Dosha (Vata, Pitta, and Kapha), Dhatu, and Mala,[1] and it focuses on the treatment different ailments by balancing these three pillars of life. Since time immemorial, various herbominerals have been used in balancing the physiological factors of the body and treating various diseases. Nowadays, various in vivo and in vitro phytochemical analyses of these herbominerals and their effects on various disease conditions are being undergone extensive research, which showed that these have an immunomodulatory role against the infectious factor and restore, rejuvenate, and re-establish body's physiological factors to maintain equilibrium.[2],[3]

The involvement of immune cells with white blood cells (WBCs), lymphocytes, neutrophils, monocytes, and macrophages and with specialized immune molecules such as antibodies, cytokines, and complement proteins produces an effective immune response.[4] The initial nonspecific immune response is known as innate immunity, while the acquired or specific response against invading pathogens is called as adaptive immunity.[5] Immunomodulation is the process that restores the immune imbalance by altering the immune system either as immunostimulant or immunoadjuvant or immunosuppressant; thus, it enhances disease tolerance and controls the host's immune disorders by optimizing the balance between regulatory and effector cells.[6],[7] Various medicinal plants have an immunomodulatory effect which regulates the immune system and enhances host defense mechanism against diseases. Clinically, several papers showed that the host immune system is involved in the pathogenesis, and there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T-cells as most COVID-19 patients developed lymphopenia as well as pneumonia with higher plasma levels of pro-inflammatory cytokines in severe cases.[8] There is high mortality among immunocompromised patients and those with some underlying pathology, which implies that the factors that can improve immunity and can prevent serious manifestations due to COVID-19 infection.[9] Besides this, several herbs are also effective as an antiviral against herpes simplex virus (HSV), influenza virus, and coronaviruses; thus, there may be a possibility for immunomodulatory and antiviral drug development against COVID-19 too.[10],[11],[12] Active compounds of medicinal plants such as linalool, triterpene glycosides, and saikosaponins have anti-influenza, anticoronavirus activities by preventing viral attachment and penetration.[13],[14]

With these immunomodulation qualities of herbs, an alternative Ayurvedic formulation named as Immune Booster Kashaya Special (IBKS) has been developed by the National Institute of Ayurveda as a prophylaxis management for novel COVID-19 disease to either activate the host defense mechanism in early stage, i.e., in case of an impaired immune response, or selectively suppress it in conditions such as autoimmune and hypersensitivity condition at a later stage.

Objectives

  • To understand the concepts of SARS-CoV-2 in light of Ayurveda with their approximate delineation through theoretical analysis
  • To review the role of IBKS in boosting and regulating immunity and in preventing complications
  • To explore the effectiveness of each drug among scientific community to facilitate for their extensive research.



  Methodology Top


The literature review was conducted by searching relevant keywords in various Ayurveda texts to understand the concepts of SARS-CoV-2 in light of Ayurveda. Relevant keywords such as COVID-19, coronavirus, SARS-CoV-2, immunity; antiviral/immunomodulatory effect of medicinal plants/Ayurvedic herbs; English, Sanskrit, and botanical name of the plants were also searched online using various databases, including PubMed (http://www.ncbi.nlm.nih.gov/pubmed), ScienceDirect (http://www.sciencedirect.com/), Scopus (http://www.scopus.com/), CrossRef (https://www.crossref.org/), and Google Scholar (http://www.scholar.google.com/), and other texts of Ayurveda published in recent decades. The methodological activities involved during a literature review were (1) designing the review concept, (2) conducting review of Ayurvedic literature, (3) conducting the review on publications such as review papers, research papers, official website of related authorities, and books, (4) conducting critical analysis of gathered literature, data, and publications, and (5) writing up the review based on the potential source.

Causes

According to the WHO, people can catch COVID-19 from others who have the virus. The disease spreads primarily from person to person through small droplets from the nose or mouth, which are expelled when a person with COVID-19 coughs, sneezes, or speaks. People can catch COVID-19 if they breathe in these droplets from a person infected with the virus. These droplets can land on objects and surfaces around the person such as tables, doorknobs, and handrails. People can become infected by touching these objects or surfaces and then touching their eyes, nose, or mouth.

According to Acharya Charak based on Prakriti, diseases are of two types Nija and Agantuja.[15] Nija Roga occurs due to vitiation of Sharirik Dosha influenced by inner factor while Agantuja Roga occurs due to some external factor on the body, one of which is Bhuta,[16] which are considered as minute pathogens that are not seen through naked eyes such as virus and bacteria. In Agantuja Roga, initially, ailment develops proceeded by the vitiation of Doshas; the vitiated Doshas then produce further symptoms.[17]

Agantuja Roga occurring due to Bhutābhisanga (infection) may be contagious and can spread through different ways as stated by Acharya Sushruta in his classical treatise Sushruta Samhita. He says that by physical contact (Gātrasansparśāt), expired air (Niḥśvāāt), eating with others in the same plate (Saha bhōjanāta), sharing a bed (Sahaśayyāsanācāpi), using clothes, garlands, and paste (Vastamālyānulēpanāt), infectious diseases spread from person to person. These concepts are very much relevant today. Moreover, the modern texts of communicable disease epidemiology describe similar modes of disease transmission. In addition, he has also given examples of some diseases that spread through all these modes, such as different types of skin diseases (Kusṭha), pyrexia (Jwar), pulmonary tuberculosis (Sōṣa), and conjunctivitis (Nētrābhisyanda).[18]

Pathogenesis

Due to the lack of extensive research, till date, it is difficult to determine the structural characteristics of SARS-COV-2 that underlies the pathogenic mechanism and to draw definitive pathophysiological information.

Ayurveda states health as a state of equilibrium of three Doshas Vata, Pitta, and Kapha and any imbalance in any of the three or more may lead to the development of a pathogenic cascade, leading to the development of a disease in due course. This imbalance may occur due to innumerable factors, one of which is inoculation with a disease causing pathogen as in the case of SARS-CoV-2 in Pranavaha srotas (respiratory tract), further leading to vitiation of Sharirik Doshas, which not only produces pathological changes in the respiratory system but also spread in the whole body to produce Sarvadhik lakshan (systemic manifestations).[17]

Pathological components

Looking at the symptoms of the disease, following pathological components seem to play a role in the development of the disease:

  • Dosha - Kapha-Vata pradhan tridosha
  • Dushya - Rasa, Rakta
  • Srotas - Pranavaha, Raktavaha
  • Sroto Dushti - Sanga followed by Vimarga Gamana
  • Udbhava Sthana - Amashaya
  • Adhisthana - Phuphus (lungs) and Sarva Shareera (whole body)
  • Roga Marga - Madhyama
  • Jatharagni - Mandya.


Incubation period

The incubation period for COVID-19 is thought to be within 14 days following exposure, with most cases occurring approximately 4–5 days after exposure.[19]

In a study of 1099 patients with confirmed symptomatic COVID-19, the median incubation period was 4 days (interquartile range 2–7 days).[20]

Using data from 181 publicly reported, confirmed cases in China with identifiable exposure, one modeling study estimated that symptoms would develop in 2.5% of infected individuals within 2.2 days and in 97.5% of infected individuals within 11.5 days.[21] The median incubation period in this study was 5.1 days.

Spectrum of illness severity

The spectrum of symptomatic infection ranges from mild to critical; most infections are not severe.[22] Specifically, in a report from the Chinese Center for Disease Control and Prevention that included approximately 44,500 confirmed infections with an estimation of disease severity:[23]

  • Mild (no or mild pneumonia) was reported in 81%
  • Severe disease (e.g., with dyspnea, hypoxia, or >50% lung involvement on imaging within 24–48 h) was reported in 14%
  • Critical disease (e.g., with respiratory failure, shock, or multiorgan dysfunction) was reported in 5%
  • The overall case-fatality rate was 2.3%; no deaths were reported among noncritical cases.


Clinical manifestations

Pneumonia appears to be the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging.[24] There are no specific clinical features that can yet reliably distinguish COVID-19 from other viral respiratory infections. In a study describing 138 patients with COVID-19 pneumonia in Wuhan, the most common clinical features at the onset of illness are:[25]

  • Fever in 99%
  • Fatigue in 70%
  • Dry cough in 59%
  • Anorexia in 40%
  • Myalgias in 35%
  • Dyspnea in 31%
  • Sputum production in 27%.


Although not highlighted in initial cohort study from China, smell and taste disorder (e.g., anosmia and dysgeusia) have also been reported as the common symptoms in patients with COVID-19.[26]

In addition to respiratory symptoms, gastrointestinal symptoms were reported in patients with confirmed COVID-19, the pooled prevalence was 18% overall, with diarrhea, nausea/vomiting, or abdominal pain in 13%, 10%, and 9%, respectively.[27]

Other reported symptoms included headache, sore throat, and rhinorrhea.[28] Conjunctivitis has also been reported.[29]

Dermatologic findings in patients with COVID-19 are not well characterized. There have been reports of maculopapular, urticarial, and vesicular eruptions and transient livedo reticularis. Reddish-purple nodules on the distal digits similar in appearance to pernio (chilblains) have also been described, mainly in children and young adults with documented or suspected COVID-19, although an association has not been clearly established.[30],[31]

In Ayurveda, Sannipataj Jwar as described by Acharya Charak has most approximate delineation:[32]

  1. Kshadedahe-Kshadesheetam (frequent and alternate feeling of cold and hot)
  2. Asthi-Sandhi Ruja (pain in bone and joints)
  3. Shiro Ruja (headache)
  4. Sasrave-Kalushe-Rakt Lochan (watery, sticky, red eyes, i.e., conjunctivitis)
  5. Nirbhugne Lochan (drooping of eyelids)
  6. Swanou Karnou (tinnitus)
  7. Ruju Karnou (otalgia)
  8. Shukaireev-Avritah Kant (sore throat)
  9. Tandra (drowsiness)
  10. Moha (delusion)
  11. Pralapa (delirium)
  12. Kasa (cough)
  13. Swas (dyspnea)
  14. Aruchi (anorexia)
  15. Bhram (illusion)
  16. Paridagdha Jihva (ulcerated tongue)
  17. Kharasparsha Jihva (furred tongue)
  18. Sastra Mangata (flaccidity in body)
  19. Stheevanam Rakta Pittasya Kaphenunmishritasya (hemoptysis mixed with pus or sputum)
  20. Shiraso Lothanam (restless movement of head)
  21. Trisna (thrust)
  22. Nidranasha (insomnia)
  23. Hridivyatha (chest pain or cardiac distress)
  24. Swed-Mutra-Purishanam Chirat Darshanam Alpashah (delayed and less excretion of sweat, urine, and stool)
  25. Krishatvam Naatigatranam (not much emaciation of body)
  26. Pratham Kant Kujanam (continuous wheezing sound from throat)
  27. Kothanam Shyavaraktanam Mandalanam (bluish or reddish wheel or patches over skin)
  28. Mukatvam (aphasia)
  29. Srotasam Pako (necrotic changes in respiratory tract)
  30. Gurutvam Udarasya (heaviness in abdomen)
  31. Chirat Pakascha Doshanam (delayed restoration of body function) [Table 1].
Table 1: Comparison between clinical features of COVID-19 and Sannipataj Jwar

Click here to view


Complications

Complications can include:[33]

  • Pneumonia in both lungs
  • Organ failure in several organs
  • Death.


Acute respiratory distress syndrome (ARDS) is a major complication in patients with severe disease. In the study of 138 patients described above, ARDS developed in 20% after a median of 8 days, and mechanical ventilation was implemented in 12.3%.[34] In another study of 201 hospitalized patients with COVID-19 in Wuhan, 41% developed ARDS; age greater than 65 years, diabetes mellitus, and hypertension were each associated with ARDS.[35]

Prognosis

According to a Joint World Health Organization (WHO)-China Fact-Finding Mission, the case-fatality rate ranged from 5.8% in Wuhan to 0.7% in the rest of China.[36]

Most of the fatal cases have occurred in patients with advanced age or underlying medical comorbidities (including cardiovascular disease, diabetes mellitus, chronic lung disease, hypertension, cancer, chronic kidney disease, obesity, smoking, liver disease, and immunocompromising conditions).

According to Acharya Charak, Sadhyasadhyata (prognosis) of any disease depends on multiple factors that remain same for almost all diseases including COVID-19.[37]

  • The disease is easy to cure when prodromal symptoms and symptoms are absent or are less in number and that too mild in intensity
  • The disease becomes difficult to cure when many prodromal symptoms and symptoms are present and that too with moderate severity, when patient is elderly, children, or pregnant lady
  • The disease may reoccur when other systems of the body get involved or there is frequent remission and aggravation of symptoms or when symptoms persist for long time
  • The disease becomes incurable when no treatment modality works on patient, when multiple system of the body gets involved, when there is severe restlessness or patient become unconscious, or when sensory organs loss there function, or when severe symptoms are present in an emaciated and weak patient.


Immune booster Kashaya (special)

The IBKS has been formulated by the National Institute of Ayurveda, an apex Institute under the Ministry of AYUSH to promote growth and development of Ayurveda as a model Institute for evolving high standards of teaching, training, research, and patient care and to invoke scientific outlook to the knowledge of Ayurvedic System of Medicine. This formulation constitutes equal amount of some medicinal plants (as listed in [Table 2]).
Table 2: Name and action (Karma) of constituent of Immune Booster Kashaya Special (IBKS)

Click here to view


Method of preparation and use

Method of use

Boil 10 g crude drug of IBKS in two glasses of water with low heat until it remains half glass of water and take it once or twice daily 1 h before meal.

Explore the effectiveness of each drug of immune booster Kashaya (special)

Tinospora cordifolia

The active compounds, such as N-methyl-2-pyrrolidone, N-formylannonain, 11-hydroxy mustakone, cordifolioside A, tinocordiside, syringin, and magnoflorine, as well as polysaccharides, such as arabinose, glucose, and fructose, show immunomodulatory and cytotoxic effects.[38],[39],[40] Direct infusion of its hydromethanolic extract in the mammary gland enhances local immunity by increasing IL-8, phagocytic activity, and lysosomal enzyme content in the milk polymorphonuclear cells.[41] The extract of Tinospora cordifolia (TC) exerts a favorable impact for upregulation of the cytokine IL-6 and immunity-enhancer cells, activation of the inflammatory response and cytotoxic T-cells, as well as differentiation of B-cells.[42],[43] TC also demonstrated the immunostimulatory role by activation of macrophages and induction of IL-1 secretion.[44] It improves the phagocytic function without affecting the cell-mediated or humoral immune system.[45]

Cyperus rotundus

The active constituents such as phenols and flavonoids of Cyperus rotundus (CR) have antioxidant potential against free radical-induced oxidative damage.[46] Due to the presence of triterpenoids, flavonoids, and proteins, CR showed significant anti-inflammatory and antipyretic effect similar to acetyl salicylic acid.[47],[48] Its component (+) nootkatone was found to have the most potent inhibitory effect on collagen, thrombin, and arachidonic acid-induced platelet aggregation.[49] It has antidiarrheal activity due to the presence of tannins and flavonoids[50] and has antimalarial activity due to components such as patchoulenone, caryophyllene alpha-oxide, 10,12-peroxycalamenene, and 4,7-dimethyl-l-tetralone.[51]

Flacourtia indica

Flacourtia indica (FI) showed significant and dose-dependent anti-inflammatory and antinociceptive activity.[52],[53] The free radical scavenging activity or antioxidant effects due to the fatty acids were recorded from ethanolic extracts of FI, using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method.[54],[55] In a study, it is demonstrated that neurotransmitters such as serotonin and noradrenaline concentrations in prefrontal cortex FI-treated rats. It modulates the monoaminergic functions of the central nervous system by decreasing the cytokines such as TNF-α, IL-1β, and IL-10; thus, FI has antianxiety properties.[56],[57]

Terminalia chebula

The gallic acid, chebulagic acid, and ellagic acid of Terminalia chebula neutralize reactive oxygen species (ROS), increase humoral antibody titer, and scavenge free radicals. Thus, it inhibits the release of cytokines such as IL-1, TNF-α, and interferon (IFN)-β, responsible for causing inflammation. This shows that it has immunomodulatory and anti-inflammatory activity and is highly potent antioxidant.[58],[59],[60],[61],[62],[63] In another study, the alcoholic extract of T. chebula increases the levels of different antioxidant enzymes, glutathione and T- and B-cells, suggesting its role in immunostimulation.[64] Further, the study reported increase in concentration of melatonin in the pineal glands, as well as the cytokines such as IL-2, IL-10, and TNF-α, which play a crucial role in immunity, thereby focusing on its immunostimulant property.[2]

Terminalia bellirica

Gallic acid has been reportedly responsible for stimulation of the immune system as it increases the production of ROS in macrophages, resulting in increased phagocytic activity.[65],[66],[67] Terminalia bellirica fruit is also rich in gallic acid and thus has been reported to be responsible for increasing macrophage phagocytic activity. The other mechanism for increased phagocytic activity of the extract is due to some alteration in the mechanism of action of related enzymes such as phosphotyrosine phosphatase, which results in the production of superoxide anion.[68] Due to the enhancement of T-cell-independent B-cell proliferation, it is reported to be a potent stimulus for enhanced T-lymphocyte, suggesting better cell-mediated immunity (CMI) than humoral-mediated immunity (HMI). It is also documented as inducing mouse splenic B-cell via T-cell-independent mechanism.[69]

Emblica officinalis

Various studies have proved the fruit extract to be strongly immunomodulatory as it possesses antiapoptotic property, restores IL-2 and IFN-γ production, ceases DNA fragmentation, and restores antioxidant status against free radical production back to control level, thus countering the immunosuppressive effect on lymphocyte proliferation.[70],[71]

In another study, it is suggested to have the ability to stimulate hemo-lymphopoietic system as it increased in the WBC count and % lymphocyte distribution, had significantly higher antisheep RBC titer and delayed-type hypersensitivity reaction, significantly increase migration area as well as nitro blue tetrazolium (NBT) reduction of peritoneal macrophages, indicating the role of extract in macrophage activation. This was accompanied by a burst of oxidative metabolism-generating ROS detected through NBT assay, confirmed the intracellular killing property of phagocytosing macrophages.[72] E. officinalis-treated groups also produced high serum protein, especially serum globulin, and mice showed increased spleen weight suggesting increased immunocompetence.[73] All these results indicated stimulant effect of E. officinalis on both CMI and HMI responses.

Pterocarpus santalinus

It has significant hepatoprotective, antioxidant, antimicrobial, anti-inflammatory, analgesic, antidiabetic, hypolipidemic, anticancer, gastroprotective, and wound-healing properties.[74],[75] The methanolic extract of the leaves exhibited radical scavenging activity for DPPH, nitric oxide (NO), and hydrogen peroxide.[76],[77] The in vitro studies also revealed strong antioxidant activity of pterostilbene against free radicals such as DPPH, 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonate), hydroxyl, superoxide, and hydrogen peroxide.[78] The constituents such as specific lignans, namely, savinin, calocedrin, and eudesmin, benzofurans, neoflavonoids, and pterolinus isolated from heartwood, including pterolinus B, showed potenti to inhibitory effect against TNF-α, anti-inflammatory activity, and antiproliferative effect.[79],[80]

Ocimum sanctum

It has antioxidant, anti-inflammatory, and immunomodulatory properties.[81],[82] Due to the presence of flavonoids in the leaves, it was found to increase immune response by proliferating the cells and increasing the activity of T-helper cells (CD3+CD4+) and NK cells (CD16+CD56+); increase IFN-γ and IL-4 levels, improve VO2 max, reduce creatine kinase, and improve immune response to herpes virus infection.[83],[84] However, there were no significant changes in B-cells (CD19+) and T-cytotoxic cells (CD3+CD4+). It was also reported to improve viral encephalitis and viral hepatitis and the dried Tulsi leaves improved vital capacity and provided relief of asthmatic symptoms.[85]

Swertia chirayita

The alkaloids, flavonoids, saponins, ascorbic acid, glycosides, steroids, and triterpenoids of Swertia chirayita show antioxidant and immunomodulatory effects by scavenging of free radicals, reducing/inhibiting serum pro-inflammatory cytokines such as TNF-α and IL-1a and the pro-inflammatory mediators such as TNF-α, IL-6, PGE2, COX-2, iNOS, MMPs, and NF-jB/I-jB and JAK2/STAT3 signaling.[86] On the other hand, aqueous extract has demonstrated viral propagation inhibition of HSV-1 and has activity against hepatitis B virus.[87],[88]

Glycyrrhiza glabra

Glycyrrhizin and 18 β-glycyrrhetinic acid-like components of Glycyrrhiza glabra possessed antiviral activity against SARS-CoV, herpes viruses, flaviviruses, human immunodeficiency virus, hepatitis C, and upper respiratory tract infections.[89],[90],[91],[92],[93],[94],[95] It also showed immunostimulatory activity by the release of IL-12 from peritoneal macrophages, enhances the cell-mediated immune response,[96] and protects from viral infection through IFN-γ-mediated pathways.[97] It was reported that consumption of Glycyrrhiza along with Echinacea purpurea and Astragalus membranaceus formulation increased CD69 expression in human volunteers, but their effect on NK cell activation was not mentioned.[98]

Holarrhena antidysenterica

It appeared to stimulate the phagocytic function while inhibit the humoral immune system.[45] Antioxidant activity has been observed as it contains high free radical scavenging activity and phenolic material.[99] The alcoholic extract of stem bark suppressed acetic acid-induced writhing response, showed increased levels of superoxide dismutase and glutathione, and exhibited decreased levels of NO and malondialdehyde levels; this suggests Holarrhena antidysenterica (HA) exhibits significant analgesic, antidiarrheal, and anti-inflammatory activities.[100],[101],[102]

Curcuma longa

Curcumin is the major constituent of Curcuma longa. Curcumin has been found to regulate the expression of numerous transcription factors, cytokines, adhesion molecules, and enzymes related to inflammation.[103] It increases serum levels of IgG and IgM, upregulation of peroxisome proliferator activated receptor (PPAR)-γ, inhibits the interfere in the myeloid dendritic cell maturation, suppresses CD80 and CD86 expression, activates T-cell, impairs pro-inflammatory cytokine production (IL-12) by the inhibition of mitogen-activated protein kinase (MAPK) activation and nuclear factor kappa B (NF-κB) translocation, thus suggesting that curcumin can induce an anti-inflammatory effect and improve immune functions.[104],[105],[106] Curcumin has the potential to modulate the chemotaxis process in the immune response as it decreases the release of pro-inflammatory cytokines TNF-α, IL-1 β, and IL-6, reduces the levels of IL-2 and macrophage inflammatory protein, lowers the NF-κB activity and regulated on activation, normal T-cell expressed and secreted (RANTES) production.[107],[108],[109]

Curcumin showed a significant reduction in the influx of neutrophils into the lungs and a significant decrease in the synthesis of NO activity, MPO activity, and TNF-α levels, thus preventing BALB/c mice from lung inflammation caused by Klebsiella pneumoniae.[110] Other bioactive components such as α-turmerone, ar-turmerone, and β-sesquiphellandrene were demonstrated to induce PBMC proliferation and cytokine production.[111] Further, other curcumin-free turmeric components, such as elemene, turmerin, curdione, cyclocurcumin, furanodiene, bisacurone, calebin A, and germacrone, have been found to exhibit different biological activities including anti-inflammatory activity.[112]

Phyllanthus urinaria

It has bioactive compounds corilagin, geraniin, gallic acid, phyllanthin, hypophyllanthin, and ellagic acid. The role of gallic acid has been discussed earlier. The compounds such as corilagin, gallic acid, and phyllanthin promote release of anti-inflammatory factor HO-1, affect IL-8 gene expression in TNF-alpha-treated IB3-1 cells, suppress the IL-10 release, and inhibit pro-inflammatory cytokines and mediators production including TNF-α, IL-1β, IL-6, NO (iNOS), and COX-2 at both gene and protein levels by inhibiting NF-κB/DNA interactions, scavenged DPPH and hydroxyl and superoxide radicals, treated RAW 264.7 cells, and significantly repressed NO production.[113],[114],[115],[116] The colon tissues of mice treated with corilagin showed the reduced secretion of TNF-α, IL-6, and IL-1β and downregulated expression of cleaved caspase-3 and cleaved caspase-9.[117] Phyllanthus extract effectively inhibits replication of the hepatitis B virus by inducing the expression of IFN-β, COX-2, and IL-6, which in turn activates the innate immune response.[118] It was observed that methanol, ethanol, and acetone extracts inhibit HSV-2 infection by disturbing the early stage of virus infection and by diminishing the virus.[119]

Justicia adhatoda

The studies showed that principle compound like vasicine has potent antiviral activity against viruses such as HSV and influenza viruses possibly by blocking viral attachment through inhibition of viral HA protein, by blocking the viral adsorption to cells, by synergistically binding to the free virus particles or by blocking the sialic acid receptors to prevent virus entry into the cells, and by inhibiting the replication of influenza virus or virus budding from the infected MDCK cells.[120],[121] One of the alkaloids vasicine has shown anti-inflammatory activity against lung damage in rats.[122],[123] The ash and decoction of leaves are used to treat bronchial ailments such as tuberculosis asthma and as antipyretic.[122],[124]


  Discussion Top


Ayurveda has its own appeal that cannot be exactly compared with the concepts of every newly emerging disease as described in modern science. In the process of theoretical analysis, the concept of causation of disease/etiology of disease, pathogenesis, classification of disease, modes of communicable disease transmission, prognosis, and natural history of the disease as described in Ayurveda helps understand the novel coronavirus in terms of Ayurvedic scenario with their approximate delineation. Exploration of keywords in Ayurvedic text revealed that SARS-CoV-2 is symptomatically very much similar to Sannipataj Jwar and its use of immunomodulatory drugs can help decrease morbidity as well as mortality.

Ingredients mentioned in IBKS, being consumed from long period by people in different cultures and civilizations in various ways like food supplements, as medicines either in a single form or in compound form in Ayurveda, Traditional Chinese Medicine (TCM), and many other traditional and complementary medicine system. Many Ayurveda drugs have a rich resource with enough potential and possibilities for antiviral drug development and prevention and treatment of COVID-19.[123] As there is a lack of an effective SARS-CoV-2 virus-specific medicine or vaccine, these immunomodulatory strategies may be implemented before or shortly after viral exposure and may be paired with antiviral therapies to improve antiviral immune responses by providing interferon-inducing agents or by nonspecific boosting of immunity with innate factors.[125] An effective immune restoration process may be desirable in two different situations: (i) insufficient immune function and (ii) overly expressed immune function.[126] In few patients of SARS-CoV infection, due to overexpressed immune function, there is deadly uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines (IFN-a, IFN-g, IL-1b, IL-6, IL-12, IL-18, IL-33, TNF-α, TGFb, etc.) and chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9, CXCL10, etc.) by immune effector cells.[24] Thus, we must be aware of using immunomodulatory drugs rather than using immunostimulant drugs so that, in early stage, there will be an increase in the immune system, whereas, in later stage, cytokine storming and hypersensitivity can be controlled. A recent report on patients with severe COVID-19 disease reported reduced numbers of CD4+ and CD8+

T-cells, higher levels of IL-2R, IL-6, IL-10, and TNF-α, and a trend toward lower INF-γ expression in CD4+ T cells.[127] As the role of immunomodulatory drugs is to keep balanced immunity by the regulation of the immune system either as immunosuppressant or immunostimulant or immunoadjuvant. The above-mentioned many drugs seem to have the ability to play a role according to the immune and severity condition and have antiviral, antioxidant, anti-inflammatory, immunomodulatory, antipyretic, antianxiety, and phagocytic activities. Among these 14 herbs, many herbs play a role in the inhibition of serum pro-inflammatory cytokines such as TNF-α and IL-1a and the pro-inflammatory mediators such as TNF-α, IFN-β, IL-6, IL-1 β, IL-10 PGE2, COX-2, iNOS, MMPs, and NF-jB/I-jB and JAK2/STAT3 signaling. Some drugs play a role in the regulation of IL-6, IL-8, IL-2, IL-12, IFN-γ, and immunity-enhancer cells, increase ROS production, enhance T-lymphocyte, stimulate hemo-lymphopoietic system, enhance the CMI response, and protect from viral infection through IFN-γ-mediated pathways. Beside these activities, Ocimum increases the activity of T-helper cells (CD3+CD4+) and NK cells (CD16+CD56+); increases IFN-γ and IL-4 levels; improves VO2 max; and reduce creatine kinase. CL increases serum levels of IgG and IgM; upregulation of PPAR-γ suppresses CD80 and CD86 expression, activates T-cell, and impairs pro-inflammatory cytokine production (IL-12) by the inhibition of MAPK activation and NF-κB translocation.


  Conclusion Top


Through literature review, we can conclude that the COVID-19 is symptomatically similar to Sannipataj Jwar described in Ayurveda. Herbs used in IBKS possess antiviral, immunomodulatory, antioxidant, antipyretic, anti-inflammatory, cardioprotective, antianxiety, and phagocytic properties and can be useful in preventing COVID-19, as it tends to promote the body's immune system against viral activity and to prevent complications such as inflammation-induced damage to the respiratory tract and cytokine storming. Due to lack of effective medicine and vaccine, till date, the harness of innate immunity to accelerate early antiviral immune responses must be the immediate priority to combat this pandemic. For further validation, this formulation should be passed through extensive in vivo and in vitro studies and clinical trials.

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Conflicts of interest

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