|Year : 2020 | Volume
| Issue : 4 | Page : 73-84
Understanding COVID-19 in light of Ayurveda and exploring possible role of immune booster Kashaya in its management
Ram Kishor Joshi, Deepika Gupta, Shankar Gautam, Abhishek Upadhyay
Department of Kayachikitsa, National Institute of Ayurveda, Jaipur, Rajasthan, India
|Date of Submission||07-Aug-2020|
|Date of Decision||24-Sep-2020|
|Date of Acceptance||26-Sep-2020|
|Date of Web Publication||28-Dec-2020|
Ram Kishor Joshi
Department of Kayachikitsa, National Institute of Ayurveda, Amer Road, Jaipur - 302 002, Rajasthan
Source of Support: None, Conflict of Interest: None
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|| |
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, 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.,
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. The initial nonspecific immune response is known as innate immunity, while the acquired or specific response against invading pathogens is called as adaptive immunity. 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., 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. 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. 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.,, Active compounds of medicinal plants such as linalool, triterpene glycosides, and saikosaponins have anti-influenza, anticoronavirus activities by preventing viral attachment and penetration.,
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.
- 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|| |
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.
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. 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, 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.
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).
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).
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.
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.
In a study of 1099 patients with confirmed symptomatic COVID-19, the median incubation period was 4 days (interquartile range 2–7 days).
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. 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. 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:
- 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.
Pneumonia appears to be the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging. 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:
- 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.
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.
Other reported symptoms included headache, sore throat, and rhinorrhea. Conjunctivitis has also been reported.
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.,
In Ayurveda, Sannipataj Jwar as described by Acharya Charak has most approximate delineation:
- Kshadedahe-Kshadesheetam (frequent and alternate feeling of cold and hot)
- Asthi-Sandhi Ruja (pain in bone and joints)
- Shiro Ruja (headache)
- Sasrave-Kalushe-Rakt Lochan (watery, sticky, red eyes, i.e., conjunctivitis)
- Nirbhugne Lochan (drooping of eyelids)
- Swanou Karnou (tinnitus)
- Ruju Karnou (otalgia)
- Shukaireev-Avritah Kant (sore throat)
- Tandra (drowsiness)
- Moha (delusion)
- Pralapa (delirium)
- Kasa (cough)
- Swas (dyspnea)
- Aruchi (anorexia)
- Bhram (illusion)
- Paridagdha Jihva (ulcerated tongue)
- Kharasparsha Jihva (furred tongue)
- Sastra Mangata (flaccidity in body)
- Stheevanam Rakta Pittasya Kaphenunmishritasya (hemoptysis mixed with pus or sputum)
- Shiraso Lothanam (restless movement of head)
- Trisna (thrust)
- Nidranasha (insomnia)
- Hridivyatha (chest pain or cardiac distress)
- Swed-Mutra-Purishanam Chirat Darshanam Alpashah (delayed and less excretion of sweat, urine, and stool)
- Krishatvam Naatigatranam (not much emaciation of body)
- Pratham Kant Kujanam (continuous wheezing sound from throat)
- Kothanam Shyavaraktanam Mandalanam (bluish or reddish wheel or patches over skin)
- Mukatvam (aphasia)
- Srotasam Pako (necrotic changes in respiratory tract)
- Gurutvam Udarasya (heaviness in abdomen)
- 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 can include:
- Pneumonia in both lungs
- Organ failure in several organs
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%. 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.
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.
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.
- 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)
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.,, 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. 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., TC also demonstrated the immunostimulatory role by activation of macrophages and induction of IL-1 secretion. It improves the phagocytic function without affecting the cell-mediated or humoral immune system.
The active constituents such as phenols and flavonoids of Cyperus rotundus (CR) have antioxidant potential against free radical-induced oxidative damage. Due to the presence of triterpenoids, flavonoids, and proteins, CR showed significant anti-inflammatory and antipyretic effect similar to acetyl salicylic acid., Its component (+) nootkatone was found to have the most potent inhibitory effect on collagen, thrombin, and arachidonic acid-induced platelet aggregation. It has antidiarrheal activity due to the presence of tannins and flavonoids and has antimalarial activity due to components such as patchoulenone, caryophyllene alpha-oxide, 10,12-peroxycalamenene, and 4,7-dimethyl-l-tetralone.
Flacourtia indica (FI) showed significant and dose-dependent anti-inflammatory and antinociceptive activity., 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., 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.,
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.,,,,, 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. 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.
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.,, 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. 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.
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.,
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. E. officinalis-treated groups also produced high serum protein, especially serum globulin, and mice showed increased spleen weight suggesting increased immunocompetence. All these results indicated stimulant effect of E. officinalis on both CMI and HMI responses.
It has significant hepatoprotective, antioxidant, antimicrobial, anti-inflammatory, analgesic, antidiabetic, hypolipidemic, anticancer, gastroprotective, and wound-healing properties., The methanolic extract of the leaves exhibited radical scavenging activity for DPPH, nitric oxide (NO), and hydrogen peroxide., 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. 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.,
It has antioxidant, anti-inflammatory, and immunomodulatory properties., 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., 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.
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. On the other hand, aqueous extract has demonstrated viral propagation inhibition of HSV-1 and has activity against hepatitis B virus.,
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.,,,,,, It also showed immunostimulatory activity by the release of IL-12 from peritoneal macrophages, enhances the cell-mediated immune response, and protects from viral infection through IFN-γ-mediated pathways. 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.
It appeared to stimulate the phagocytic function while inhibit the humoral immune system. Antioxidant activity has been observed as it contains high free radical scavenging activity and phenolic material. 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.,,
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. 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.,, 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.,,
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. Other bioactive components such as α-turmerone, ar-turmerone, and β-sesquiphellandrene were demonstrated to induce PBMC proliferation and cytokine production. 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.
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.,,, 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. 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. 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.
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., One of the alkaloids vasicine has shown anti-inflammatory activity against lung damage in rats., The ash and decoction of leaves are used to treat bronchial ailments such as tuberculosis asthma and as antipyretic.,
| Discussion|| |
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. 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. An effective immune restoration process may be desirable in two different situations: (i) insufficient immune function and (ii) overly expressed immune function. 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. 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. 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|| |
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Belapurkar P, Goyal P, Tiwari-Barua P. Immunomodulatory effects of Triphala
and its individual constituents: A review. Indian J Pharm Sci 2014;76:467-75. [Full text]
Kumar UA, Manjunath C, Thaminzhmani T, Kiran YR, Brahmaiah Y. A review on immunomodulatory activity plants. Indian J Novel Drug Deliv 2012;4:93-103.
Chaplin DD. Overview of the immune response. J Allergy Clin Immunol 2010;125:S3-23.
Greenberg S, Grinstein S. Phagocytosis and innate immunity. Curr Opin Immunol 2002;14:136-45.
Patil U, Jaydeokar A, Bandawane D. Immunomodulators: A pharmacological review. Int J Pharm Pharm Sci 2012;4:30-6.
Agrawal SS, Khadase SC, Talele GS. Studies on immunomodulatory activity of Capparis zeylanica
leaf extracts. Int J Pharm Sci Nanotechnol 2010;3:887-92.
Ni L, Ye F, Cheng ML, Feng Y, Deng YQ, Zhao H, et al
. Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity 2020;52:971-7000.
Abdulamir AS, Hafidh RR. The possible immunological pathways for the variable immunopathogenesis of COVID-19 infections among healthy adults, elderly and children. Electron J Gen Med 2020;17:1-4. [doi: 10.29333/ejgm/7850].
Lin LT, Hsu WC, Lin CC. Antiviral natural products and herbal medicines. J Tradit Complement Med 2014;4:24-35.
] [Full text]
Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, et al
. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect 2020;9:221-36.
Hudson J, Vimalanathan S, Kang L, Amiguet VT, Livesey J, Arnason JT. Characterization of antiviral activities in Echinacea
root preparations. Pharm Biol 2005;43:790-6.
Choi HJ. Chemical constituents of essential oils possessing anti-influenza A/WS/33 virus activity. Osong Public Health Res Perspect 2018;9:348-53.
Cheng PW, Ng LT, Chiang LC, Lin CC. Antiviral effects of saikosaponins on human coronavirus 229E in vitro
. Clin Exp Pharmacol Physiol 2006;33:612-6.
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al
. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199-207.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al
. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al
. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: Estimation and application. Ann Intern Med 2020;172:577-82.
Bajema KL, Oster AM, McGovern OL, Lindstrom S, Stenger MR, Anderson TC, et al
. Persons evaluated for 2019 novel coronavirus-United States, January 2020. MMWR Morb Mortal Wkly Rep 2020;69:166-70.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239-42.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al
. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al
. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al
. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study. Eur Arch Otorhinolaryngol 2020;277:2251-61.
Cheung KS, Hung IF, Chan PP, Lung KC, Tso E, Liu R, et al
. Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong cohort: Systematic review and meta-analysis. Gastroenterology 2020;159:81-95.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al
. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20. [doi: 10.1056/NEJMoa2002032].
Colavita F, Lapa D, Carletti F, Lalle E, Bordi L, Marsella P, et al
. SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection. Ann Intern Med 2020;173:242-3.
Manalo IF, Smith MK, Cheeley J, Jacobs R. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermatol 2020;83:700.
Galván Casas C, Català A, Carretero Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez-Villa Lario A, et al
. Classification of the cutaneous manifestations of COVID-19: A rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol 2020;183:71-7.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al
. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180:934-43.
Sharma U, Bala M, Kumar N, Singh B, Munshi RK, Bhalerao S. Immunomodulatory active compounds from Tinospora cordifolia
. J Ethnopharmacol 2012;141:918-26.
Sharma U, Bala M, Saini R, Verma PK, Kumar N, Singh B, et al
. Polysaccharide enriched immunomodulatory fractions from Tinospora cordifolia
(Willd) Miers ax Hook. F. & Thoms. Indian J Exp Biol 2012;50:612-7.
Kapil A, Sharma S. Immunopotentiating compounds from Tinospora cordifolia
. J Ethnopharmacol 1997;58:89-95.
Mukherjee R, De UK, Ram GC. Evaluation of mammary gland immunity and therapeutic potential of Tinospora cordifolia
against bovine subclinical mastitis. Trop Anim Health Prod 2010;42:645-51.
Upadhyaya R, Pandey RP, Sharma V, Verma Anita K. Assessment of the multifaceted immunomodulatory potential of the aqueous extract of Tinospora cordifolia
. Res J Chem Sci 2011;1:71-9.
Sudhakaran DS, Srirekha P, Devasree LD, Premsingh S, Michael RD. Immunostimulatory effect of Tinospora cordifolia
Miers leaf extract in Oreochromis mossambicus
. Indian J Exp Biol 2006;44:726-32.
Raghu R, Sharma D, Ramakrishnan R, Khanam S, Chintalwar GJ, Sainis KB. Molecular events in the activation of B cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia
. Immunol Lett 2009;123:60-71.
Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. I: Preliminary screening. J Ethnopharmacol 1986;18:133-41.
Bashir A, Sultana B, Faheem H, Akhtar A, Munir M, Amjad Q, et al
. Investigation on the antioxidant activity of Dheela
grass (Cyperus rotundus
). Afr J Basic Appl Sci 2012;4:1-6. [doi: 10.5829/idosi.ajbas. 2012.4.1.032].
Birdar S, Kangralkar VA, Mandavkar Y, Thakur M, Chougule N. Anti-inflammatory, anti-arthritic, analgesic anticonvulsant activity of Cyperus
essential oils. Int J Pharm Parmaceut Sci 2010;2:112-5.
Gupta MB, Palit TK, Singh N, Bhargava KP. Pharmacological studies to isolate the active constituents from Cyperus rotundus
possessing anti-inflammatory, anti-pyretic and analgesic activities. Indian J Med Res 1971;59:76-82.
Seo EJ, Lee DU, Kwak JH, Lee SM, Kim YS, Jung YS. Antiplatelet effects of Cyperus rotundus
and its component (+)-nootkatone. J Ethnopharmacol 2011;135:48-54.
Uddin SJ, Mondal K, Shilpi JA, Rahman MT. Antidiarrhoeal activity of Cyperus rotundus
. Fitoterapia 2006;77:134-6.
Thebtaranonth C, Thebtaranonth Y, Wanauppathamkul S, Yuthavong Y. Antimalarial sesquiterpenes from tubers of Cyperus rotundus
: Structure of 10,12-peroxycalamenene, a sesquiterpene endoperoxide. Phytochemistry 1995;40:125-8.
Rao CV, Verma AR, Gupta PK, Vijayakumar M. Anti-inflammatory and anti-nociceptive activities of Fumaria indica
whole plant extract in experimental animals. Acta Pharm 2007;57:491-8.
Gupta PC, Sharma N, Rao ChV. A review on ethnobotany, phytochemistry and pharmacology of Fumaria indica
(Fumitory). Asian Pac J Trop Biomed 2012;2:665-9.
Habibi Tirtash F, Keshavarzi M, Fazeli F. Antioxidant components of Fumaria
species. World Acad Sci Eng Technol 2011;74:238-41.
Fazal H, Ahamad N, Khan MA. Physicochemical, phytochemical evaluation and DPPH-scavenging antioxidant potential in medicinal plants used for herbal formulation in Pakistan. Pak J Bot 2011;43:63-7.
Debnath M, Doyle KM, Langan C, McDonald C, Leonard B, Cannon DM. Recent advances in psychoneuroimmunology: Inflammation in psychiatric disorders. Transl Neurosci 2011;2:121-37.
Singh GK, Chauhan SK, Rai G, Chatterjee SS, Kumar V. Potential antianxiety activity of Fumaria indica
: A preclinical study. Pharmacogn Mag 2013;9:14-22.
Shivaprasad HN, Kharya MD, Rana AC, Mohan S. Preliminary immunomodulatory activities of the aqueous extract of Terminalia chebula
. Pharm Biol 2006;44:32-4.
Khan KH. Immunomodulatory activity of Terminalia chebula
against Salmonella typhimurium
in mice. Recent Res Sci Tech 2009;1:211-6.
Lee HS, Won NH, Kim KH, Lee H, Jun W, Lee KW. Antioxidant effects of aqueous extract of Terminalia chebula in vivo
and in vitro
. Biol Pharm Bull 2005;28:1639-44.
Lee HS, Jung SH, Yun BS, Lee KW. Isolation of chebulic acid from Terminalia chebula
Retz. and its antioxidant effect in isolated rat hepatocytes. Arch Toxicol 2007;81:211-8.
Tejesvi MV, Kini KR, Prakash HS, Subbiah V, Shetty HS. Antioxidant, antihypertensive, and antibacterial properties of endophytic Pestalotiopsis
species from medicinal plants. Can J Microbiol 2008;54:769-80.
Conforti F, Sosa S, Marrelli M, Menichini F, Statti GA, Uzunov D, et al
. The protective ability of Mediterranean dietary plants against the oxidative damage: The role of radical oxygen species in inflammation and the polyphenol, flavonoid and sterol contents. Food Chem 2009;112:587-94.
Aher V, Wahi AK. Immunomodulatory activity of alcohol extract of Terminalia chebula
Retz. combretaceae. Trop J Pharm Res 2011;10:567-75.
Tam PE, Hinsdill RD. Screening for immunomodulators: Effects of xenobiotics on macrophage chemiluminescence in vitro
. Fundam Appl Toxicol 1990;14:542-53.
Sabu MC, Kuttan R. Anti-diabetic activity of medicinal plants and its relationship with their antioxidant property. J Ethnopharmacol 2002;81:155-60.
Kovacević N, Colić M, Backović A, Doslov-Kokorus Z. Immunomodulatory effects of the methanolic extract of Epimedium alpinum in vitro
. Fitoterapia 2006;77:561-7.
Carreras MC, Riobó NA, Pargament GA, Boveris A, Poderoso JJ. Effects of respiratory burst inhibitors on nitric oxide production by human neutrophils. Free Radic Res 1997;26:325-34.
Hu ZQ, Toda M, Okubo S, Hara Y, Shimamura T. Mitogenic activity of (-) epigallocatechin gallate on B-cells and investigation of its structure-function relationship. Int J Immunopharmacol 1992;14:1399-407.
Sai Ram M, Neetu D, Deepti P, Vandana M, Ilavazhagan G, Kumar D, et al
. Cytoprotective activity of Amla
) against chromium (VI) induced oxidative injury in murine macrophages. Phytother Res 2003;17:430-3.
Ganju L, Karan D, Chanda S, Srivastava KK, Sawhney RC, Selvamurthy W. Immunomodulatory effects of agents of plant origin. Biomed Pharmacother 2003;57:296-300.
Suja RS, Nair AM, Sujith S, Preethy J, Deepa AK. Evaluation of immunomodulatory potential of Emblica officinalis
fruit pulp extract in mice. Indian J Anim Res 2009;113:103-6.
Kaneko JJ, Harvey JW, Bruss ML. Clinical biochemistry of domestic animals. 5th
ed. San Diego, California: Academic Press; 1997. p. 932.
Bulle S, Reddyvari H, Nallanchakravarthula V, Vaddi DR. Therapeutic Potential of Pterocarpus santalinus
L.: An Update. Pharmacogn Rev 2016;10:43-9.
Dhande PP, Gupta AO, Jain S, Dawane JS. Anti-inflammatory and analgesic activities of topical formulations of Pterocarpus santalinus
powder in rat model of chronic inflammation. J Clin Diagn Res 2017;11:FF01-4.
Arokiyaraj S, Martin S, Perinbam K, Marie AP, Beatrice V. Free radical scavenging activity and HPTLC finger print Pterocarpus santalinus
L.-An in vitro
study. Indian J Sci Technol 2008;1:1-3.
Krishnamoorthy P, Stella J, Mohamed AJ, Anand M. Radical scavenging and antibacterial evaluation of Pterocarpus santalinus
study. Int J Pharm Sci Res 2011;2:1204-8.
Acharya JD, Ghaskadbi SS. Protective effect of pterostilbene against free radical mediated oxidative damage. BMC Complement Altern Med 2013;13:238.
Kwon HJ, Hong YK, Kim KH, Han CH, Cho SH, Choi JS, et al
. Methanolic extract of Pterocarpus santalinus
induces apoptosis in HeLa cells. J Ethnopharmacol 2006;105:229-34.
Wu SF, Chang FR, Wang SY, Hwang TL, Lee CL, Chen SL, et al
. Anti-inflammatory and cytotoxic neoflavonoids and benzofurans from Pterocarpus santalinus
. J Nat Prod 2011;74:989-96.
Devi PU, Ganasoundari A. Modulation of glutathione and antioxidant enzymes by Ocimum sanctum and its role in protection against radiation injury. Indian J Exp Biol 1999;37:262-8.
Godhwani S, Godhwani JL, Vyas DS. Ocimum sanctum
--A preliminary study evaluating its immunoregulatory profile in albino rats. J Ethnopharmacol 1988;24:193-8.
Mondal S, Varma S, Bamola VD, Naik SN, Mirdha BR, Padhi MM, et al
. Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi
(Ocimum sanctum Linn.) leaf extract on healthy volunteers. J Ethnopharmacol 2011;136:452-6.
Mukherjee R, Dash PK, Ram GC. Immunotherapeutic potential of Ocimum sanctum
(L) in bovine subclinical mastitis. Res Vet Sci 2005;79:37-43.
Jamshidi N, Cohen MM. The clinical efficacy and safety of Tulsi in humans: A systematic review of the literature. Evid Based Complement Alternat Med 2017;2017:9217567.
Lad H, Bhatnagar D. Amelioration of oxidative and inflammatory changes by Swertia chirayita
leaves in experimental arthritis. Inflammopharmacology 2016;24:363-75.
Verma H, Patil PR, Kolhapure RM, Gopalkrishna V. Antiviral activity of the Indian medicinal plant extract Swertia chirata
against herpes simplex viruses: A study by in-vitro
and molecular approach. Indian J Med Microbiol 2008;26:322-6.
] [Full text]
Zhou NJ, Geng CA, Huang XY, Ma YB, Zhang XM, Wang JL, et al
. Anti-hepatitis B virus active constituents from Swertia chirayita
. Fitoterapia 2015;100:27-34.
Hoever G, Baltina L, Michaelis M, Kondratenko R, Baltina L, Tolstikov GA, et al
. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. J Med Chem 2005;48:1256-9.
Lin JC. Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus replication in vitro
. Antiviral Res 2003;59:41-7.
Lampi G, Deidda D, Pinza M, Pompei R. Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins. Antivir Chem Chemother 2001;12:125-31.
Crance JM, Scaramozzino N, Jouan A, Garin D. Interferon, ribavirin, 6-azauridine and glycyrrhizin: Antiviral compounds active against pathogenic flaviviruses. Antiviral Res 2003;58:73-9.
Sasaki H, Takei M, Kobayashi M, Pollard RB, Suzuki F. Effect of glycyrrhizin, an active component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients. Pathobiology 2002;70:229-36.
Miyake K, Tango T, Ota Y, Mitamura K, Yoshiba M, Kako M, et al
. Efficacy of stronger neo-minophagen C compared between two doses administered three times a week on patients with chronic viral hepatitis. J Gastroenterol Hepatol 2002;17:1198-204.
Yanagawa Y, Ogura M, Fujimoto E, Shono S, Okuda E. Effects and cost of glycyrrhizin in the treatment of upper respiratory tract infections in members of the Japanese maritime self-defense force: Preliminary report of a prospective, randomized, double-blind, controlled, parallel-group, alternate-day treatment assignment clinical trial. Curr Ther Res Clin Exp 2004;65:26-33.
Dai JH, Iwatani Y, Ishida T, Terunuma H, Kasai H, Iwakula Y, et al
. Glycyrrhizin enhances interleukin-12 production in peritoneal macrophages. Immunology 2001;103:235-43.
Utsunomiya T, Kobayashi M, Pollard RB, Suzuki F. Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus. Antimicrob Agents Chemother 1997;41:551-6.
Brush J, Mendenhall E, Guggenheim A, Chan T, Connelly E, Soumyanath A, et al
. The effect of Echinacea purpurea
, Astragalus membranaceus
and Glycyrrhiza glabra
on CD69 expression and immune cell activation in humans. Phytother Res 2006;20:687-95.
Ganapathy PS, Ramachandra YL, Rai SP. In vitro
antioxidant activity of Holarrhena antidysenterica
Wall. methanolic leaf extract. J Basic Clin Pharm 2011;2:175-8.
Bhusal A, Jamarkattel N, Shrestha A, Lamsal NK, Shakya S, Rajbhandari S. Evaluation of antioxidative and antidiabetic activity of bark of Holarrhena pubescens
wall. J Clin Diagn Res 2014;8:HC05-8.
Ganapathy PS, Ramachandra YL, Rai SP. Anti-inflammatory and analgesic activities of Holarrhena antidysenterica
Wall. Leaf extract in experimental animal models. Int J Biomed Pharmaceut Sci 2010;4:101-3.
Shwetha C, Latha KP, Asha K. A study on analgesic activity of Holarrhena antidysenterica
leaves. Int J Herb Med 2014;2:14-6.
Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, theanti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009;41:40-59.
Mazidi M, Karimi E, Meydani M, Ghayour-Mobarhan M, Ferns GA. Potential effects of curcumin on peroxisome proliferator-activated receptor-γ in vitro
and in vivo
. World J Methodol 2016;6:112-7.
Kim GY, Kim KH, Lee SH, Yoon MS, Lee HJ, Moon DO, et al
. Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets. J Immunol 2005;174:8116-24.
Alagawany M, Ashour EA, Reda FM. Effect of dietary supplementation of garlic (Allium sativum
) and turmeric (Curcuma longa
) on growth performance, carcass traits, blood profile and oxidative status in growing rabbits. Ann Anim Sci 2016;16:489-505. doi: 10.1515/aoas-2015-0079.
Ni H, Jin W, Zhu T, Wang J, Yuan B, Jiang J, et al
. Curcumin modulates TLR4/NF-κB inflammatory signaling pathway following traumatic spinal cord injury in rats. J Spinal Cord Med 2015;38:199-206.
Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 1999;39:41-7.
Lin MS, Sun YY, Chiu WT, Hung CC, Chang CY, Shie FS, et al
. Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo
and lipopolysaccharide-induced astrocyte reactivation in vitro
. J Neurotrauma 2011;28:1259-69.
Bansal S, Chhibber S. Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumoniae
B5055-induced lung infection in BALB/c mice. J Med Microbiol 2010;59:429-37.
Yue GG, Chan BC, Hon PM, Lee MY, Fung KP, Leung PC, et al
. Evaluation of in vitro
anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa. Food Chem Toxicol 2010;48:2011-20.
Aggarwal BB, Yuan W, Li S, Gupta SC. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res 2013;57:1529-42.
Zhao L, Zhang SL, Tao JY, Pang R, Jin F, Guo YJ, et al
. Preliminary exploration on anti-inflammatory mechanism of corilagin (beta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose) in vitro
. Int Immunopharmacol 2008;8:1059-64.
Gambari R, Borgatti M, Lampronti I, Fabbri E, Brognara E, Bianchi N, et al
. Corilagin is a potent inhibitor of NF-kappaB activity and downregulates TNF-alpha induced expression of IL-8 gene in cystic fibrosis IB3-1 cells. Int Immunopharmacol 2012;13:308-15.
Yuandani Y, Ilangkovan M, Jantan I, Mohamad HF, Husain K, Abdul Razak AF. Inhibitory effects of standardized extracts of Phyllanthus amarus
and Phyllanthus urinaria
and their marker compounds on phagocytic activity of human neutrophils. Evid Based Complement Alternat Med 2013;2013:603634.
Jantan I, Ilangkovan M, Yuandani, Mohamad HF. Correlation between the major components of Phyllanthus amarus
and Phyllanthus urinaria
and their inhibitory effects on phagocytic activity of human neutrophils. BMC Complement Altern Med 2014;14:429. [doi: 10.1186/1472-6882-14-429].
Xiao HT, Lin CY, Ho DH, Peng J, Chen Y, Tsang SW, et al
. Inhibitory effect of the gallotannin corilagin on dextran sulfate sodium-induced murine ulcerative colitis. J Nat Prod 2013;76:2120-5.
Jung J, Kim NK, Park S, Shin HJ, Hwang SG, Kim K. Inhibitory effect of Phyllanthus urinaria
L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro
. BMC Complement Altern Med 2015;15:255.
Yang CM, Cheng HY, Lin TC, Chiang LC, Lin CC. Acetone, ethanol and methanol extracts of Phyllanthus urinaria
inhibit HSV-2 infection in vitro
. Antiviral Res 2005;67:24-30.
Chavan R, Gohil D, Shah V, Kothari S, Chowdhary AS, Antiviral activity of Indian medicinal plant Justicia Adhatoda
against herpes simplex virus: An in-vitro
study. Int J Pharm Bio Sci 2013;4:769-78.
Kwon HJ, Kim HH, Yoon SY, Ryu YB, Chang JS, Cho KO, et al
. In vitro
inhibitory activity of Alpinia katsumadai
extracts against influenza virus infection and hemagglutination. Virol J 2010;7:307.
Rastogi S, Pandey DN, Singh RH. COVID-19 pandemic: A pragmatic plan for ayurveda intervention. J Ayurveda Integr Med 2020:S0975-9476(20)30019-X. doi: 10.1016/j.jaim.2020.04.002. Epub ahead of print.
Jain SP, Puri HS. Ethnomedicinal plants of Jaunsar-Bawar hills, Uttar Pradesh, India. J Ethnopharmacol 1984;12:213-22.
Schijns V, Lavelle EC. Prevention and treatment of COVID-19 disease by controlled modulation of innate immunity. Eur J Immunol 2020;50:932-8.
Andhavarapu S, Roy V. Immunomodulatory drugs in multiple myeloma. Expert Rev Hematol 2013;6:69-82.
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al
. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020;130:2620-9.
[Table 1], [Table 2]