key: cord-0812129-l1mi9gzq authors: Gautam, Shankar; Gautam, Arun; Chhetri, Sahanshila; Bhattarai, Urza title: Immunity Against COVID-19: Potential Role of Ayush Kwath date: 2020-08-17 journal: J Ayurveda Integr Med DOI: 10.1016/j.jaim.2020.08.003 sha: 103781d2bc53b7512afd7a25bb092317b59c99b1 doc_id: 812129 cord_uid: l1mi9gzq SARS-CoV-2 infection associated respiratory disease- COVID-19 has evolved into a pandemic but, being a new form of virus, pathogenesis of disease causation is not fully understood and drugs and vaccines against this virus are still being tested so that no effective drugs or vaccines have been advised by regulatory authority. In this context, the Ministry of AYUSH, Government of India has recommended ‘Ayush Kwath’ to improve the immunity and combat the infection. Our objective of this literature review is to review the role of immunity in pathogenesis of COVID-19 and role of Ayush Kwath against the virus and regulation of immunity. Current review was conducted using a search of available literature on COVID-19 and immunity, Vyadhikshamatwa, Ayurveda and COVID-19, Rasayana, Coronavirus, SARS-CoV-2, immunomodulatory effects of medicinal plants; Tulsi/Holy Basil/Ocimum sanctum, Dalchini/Cinnamon/Cinnamomum zeylanicum, Sunthi/Ginger/Zingiber officinale and Marich/Black Pepper/Piper nigrum. Ayurveda, being an ancient science have both medicinal and cultural values and had stimulated our kitchen and influenced what we ate in different seasons and the remedies we used for common ailments. Herbs such as Tulsi, Marich, Sunthi, Dalchini are the most commonly used and easily available drugs in home. Thus, Ayush Kwath due to its immune-modulatory, antiviral, anti-oxidant, anti-inflammatory, anti-platelet, anti-atherosclerotic, hepato-protective, reno-protective properties; seems to be effective in immuno-regulation for controlling viral infections like COVID-19. Further pre-clinical and clinical trials need to be done for the evaluation of safety and efficacy of this polyherbal formulation. major pathway of cell destruction is due to immune-mediated destruction [10, 11] . It has been mentioned that unlike adults, less vigorous cell-mediated immune response in alveoli of children results in being asymptomatic in the majority of cases [3] . The pathogenesis can be split into two stages: Non-severe and Severe [12] . 2.1. Non-severe stage: The virus fuses with the host cell membrane and enters inside the host cell through airway epithelium [13, 14] . The virus propagates and multiplies inside the host cell and can reach lower airway and alveoli. In adults with good innate cellular and humoral immunity propagation of virus can be limited and viral load reaching alveoli can be reduced thus recovery can take place within 2-3 weeks with mild symptoms [3] . Humoral immunity prevents the viruses to enter new cells while cell-mediated immunity targets on eradicating virus-infected cells [15, 1] . In this stage, a strong immune system can be helpful in preventing the propagation of the virus thus reducing the severity of the disease [12] . Once the immune system is breached, the virus propagates and reaches the lower respiratory tract and alveoli. Then the virus can penetrate alveoli and reaches systemic circulation causing viremia [3] . The virus binds to multiple organs having ACE2 receptor protein. During this stage, cell-mediated immunity becomes robust and starts releasing various proinflammatory cytokines (IFN-α, IFN-γ, IL-1B, IL-6, IL-12, IL-18, IL-33, TNF-α, etc.) and chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9, CXCL10, etc.) causing damage to multiple organs known as Cytokine storm [16, 17] . We may need to suppress the inflammation for improvement during this severe stage [12] . IL-6 receptor antagonist (Tocilizumab), and anti-inflammatory interleukin (IL-10) are proposed to have a therapeutic role in the reduction of severity and mortality of COVID-19 [18, 19] . As increased risk of thromboembolic phenomena is also found to be associated with COVID-19, prophylactic antithrombotic medications are advised during this stage [20] . J o u r n a l P r e -p r o o f 3. Ayurveda Purview: It seems that most early cases had a history of contact with the original market for seafood, but the disease has now advanced to be transmitted through human to human contact [1] . Thus this disease can be considered as Communicable-both contagious and infectious diseases. In Ayurveda, epidemics are discussed under the term of Janapadodhwamsa (C.S.Vi. 3/5-6) by Charaka and Maraka by Sushruta (S.S.Soo. 6/17) Strength, health, lifespan, and vital breath are dependent on the condition of Agni (C.S.Soo. Every society has its own medical system, which is deeply rooted in its culture and guided by African countries depend on TM for primary health care (PHC) needs [23] . Still, there is a high trend of using many herbs in religious and cultural works, therapeutically for common ailments and as spices for foods according to occasion specific and seasonal regimes. Ayurveda and TM have made a significant contribution to the prevention and alleviation of various communicable and non-communicable diseases for thousands of years. A long history of using many herbal remedies and experiences passed from generation to generation has resulted in people relying on herbal remedies and some simple home remedies for common diseases can be used even by illiterate citizens. The self-care, an integral part of PHC, with home remedies using various herbs is the most common treatment for India, Nepal, Bhutan, and China for different flu, common cold, fever, GI disorders, etc. Prevention of smallpox in China has been an epoch-making effort in the period of mankind's preventive care. One observational study found that the prevalence between the total number of COVID-19 cases per million population and the grams of spice supply per capita per day is clearly J o u r n a l P r e -p r o o f interrelated. Most nations with lower spice intake per capita reported more COVID-19 cases per million population and vice versa [24] . Nevertheless, with the invention of drugs, many herbal remedies used historically have become modern medicines. Few notable examples include morphine, digoxin, artemisinin and colchicine. As many herbs are found to have immunomodulatory role and possess antiviral activity, many people are being optimistic over the traditional system of Medicine. Ayurveda and TCM have descriptions of immunomodulation along with anti-viral treatments, even targeted to the coronavirus family [25, 2] . The key factor for COVID-19 to occur and evolve is the interaction between the virus and an individual's immune system [26] . As medicinal plants enhance NK cell activity, inhibit activated transcription factor 2 (ATF-2), down-regulate Th17-related cytokines including transcription factor RORc, IL-17A and Th2-related cytokines including IL-5, IL-13, and IL-6, inhibit GATA3, IL-4, IL-6, IL-1β, RORγt, IL-17A, TNF-α expression and increase the secretions of IL-10, INF-γ, etc., it shows that natural products have potent immunemodulatory and immune-boosting effects that may be helpful during the infection course by increasing innate immune response to infections [27, 28] . Considering the importance of immunity boosting measures in the wake of COVID-19 outbreak, the Ministry of AYUSH, Government of India with the interest of health promotion of the masses, recommends "Ayush Kwath' or 'Ayush Kudineer' or 'Ayush Joshanda' which comprises of four medicinal herbs (Table 1 ) [29, 30] . The herbs like holy basil, cinnamon, ginger, black pepper are highly available, accessible and widely used in the kitchen and are convenient to educate and train about its use to community health workers, community and even to all public that they can have cost-effective treatment with herbal home remedies. This will help to promote immunity and to lower the gatherings at hospitals and pharmacies in this pandemic. This type of public health measure would eventually promote 'health for all' with the theme 'our health in our own hands' making responsible to each and every people by active involvement in their own health instead of relying on mass distribution of some medicine. As people leave their homes to earn a living, this herbal decoction will ensure broad access to health care. The WHO SEARO adopted a resolution to revitalize PHC through health systems strengthening to achieve health for all with the emphasis on health promotion and disease prevention [31] . This Kwath is not just a mechanical mixture invented for the COVID-19 pandemic, but it is a revival of health tradition. tablet of aqueous extract, to be consumed like tea or hot drink by dissolving in 150 ml of boiled water, once or twice daily. Gud (Jaggery) / Draksha (Resins) and/or Lemon Juice can be added while consuming the formulation. Many in-vitro, animal and human experimental scientific studies showed that; due to presence of eugenol, phenolic compounds, linoleic acid, etc. compounds Tulsi has antimicrobial (including antibacterial, antiviral, antimalarial), anti-diarrheal, anti-oxidant, anti-inflammatory, hepato-protective, cardio-protective, reno-protective, analgesic, antipyretic, immune-modulatory properties and is thus recommended as a treatment for a range of diseases including features like cough, fever, asthma, anxiety, diarrhea, gastric, cardiac and genitourinary disorders [32, 33, 34, 35, 36] . Due to its anti-inflammatory and antioxidant properties, it protects against toxic chemical-induced injury, enhance the antioxidant enzymes and protect cellular organelles and membranes by clearing damaged free radicals [37] . The compounds such as ursolic acid, carnosol, rosmarinic acid, cirsilineol, apigenin, eugenol, and cirsimaritin present in O. sanctum increase haemoglobin concentration, enhance SRBC agglutinin titers, decrease cyclo-oxygenase (CoX)-2 and lipoxygenase (LOX)-5 enzymes activity, suppress NF-κB classical pathway, up regulation of IL-2, IFN-γ and TNFα, down regulation of IL-1β and produce of SRBC antigen-specific antibodies, which represent a major defense mechanism to assess T-cell-dependent antibody responses i.e. Tulsi by enhancing immune response boost the defense mechanism against the infection [38, 39, 40] . Several studies have shown that Tulsi (aqueous and methanol extract of leaf and seed oil) besides improving vital capacity also is an immune-modulator and regulator as it enhances immune response by increasing T-helper and NK cells; phagocytic activity and index with the rise in lymphocyte count, neutrophil count and antibody titer [41, 42] . In an acute toxicity study, it did not produce any hazardous symptoms or CNS and ANS toxicities or death and did not show any change in water and food consumption, body weight, and hematological and biochemical profiles [43] . It is a potent immune system booster and is used in various ailments like flu, indigestion, edema, cough, etc. [44, 45] . Cinnamon bark contains cinnamaldehyde, benzaldehyde, cuminaldehyde and terpenes [46] . In one study, cinnamon at high dose (100 mg/kg) showed immune-stimulant activity as it significantly increased the phagocytic index, serum immunoglobulin levels and antibody titer and decreased the percentage reductions in neutrophil count. Cinnamon low dose (10 mg/kg) increased serum immunoglobulin levels only. This showed that high dose increases both cell mediated and humoral immunity whereas low dose showed effect only on humoral immunity [47] . The studies also suggest that cinnamaldehyde can act as a strong regulator of monocyte/macrophage-mediated immune responses by inhibition of PI3K, PDK1 and NF-κB activation of signaling components. In addition to this, by the activation of CD29 and CD43, it blocked cell migration cell-cell adhesion induced but not cell-fibronectin adhesion and it was able to suppress both the production of nitric oxide (NO) and up regulation of surface levels of costimulatory molecules (CD69 and CD80) and pattern recognition receptors (TLR2 and CR3) [48] . Cinnamon bark decrease systemic levels of IFN-γ without altering the levels of IL-4 or IL-2, inhibit anti-CD3 Ab-stimulated IFN-γ and IL-4 at the mRNA and secreted protein levels, enhance IL-2 protein secretion at the cellular level which helps to decrease cell death, inhibit IL-2mRNA expression, inhibit anti-CD3-induced p38, JNK, ERK1/2, and STAT4 activation, but not IκBα degradation or STAT6 and ultimately alter the inflammatory responses in T cells. This shows the immune-modulatory effect of cinnamon on cytokine secretion and the involvement of intracellular signaling molecules in activated T cells. It also causes a reduction in the sub-G1 phase, accompanied by an increased ratio of apoptotic cells to necrotic cells [49] . The constituents like cinnamaldehyde, cinnamophilin etc are found to be a thromboxane A2 receptor antagonist, anticoagulative, anti-atherosclerotic and thus prevents unnecessary clumping of platelets and atherosclerotic CVD [50] . In a systematic review of its adverse events, relatively few self-limiting adverse effects were reported like allergic reactions and gastrointestinal disorders on clinical trials, case reports and case series. The evidence available show that cinnamon is safe for use as spice in daily diets or as a medication [51] . However, its use for therapeutic reasons, in high doses or for prolonged periods, can cause some adverse effects and should be observed clinically. An alcohol extract increases the immunological status of mice with increased phagocytosis by macrophages whereas crude extract was also shown to increase humoral and cell-mediated immune responses [52] . The bioactive compounds of ginger such as nevirapine, β-sitosterol, 6-gingediol, germacrene, methyl-6-shogaol, 6-gingerol, α-linalool, 6-shogaol, gingerdion, zingiberene, etc., are known to inhibit viral replication; among these the most potent inhibitors of reverse transcriptase (RT) enzyme is β-sitosterol, which is predicted to be used as non-nucleoside reverse transcriptase (NNRTIs) HIV-1 inhibitors [53, 54] . It is reported that Ginger contains TNF-α which is also known as an anti-influenza cytokine [55] . The rhizome of Ginger and its main components like gingerols, shogaols, etc inhibit prostaglandin and leukotriene biosynthesis, inhibit cyclooxygenase and lipoxygenase activities, inhibits the synthesis of pro-inflammatory cytokines such as IL-1, TNF-α, and IL-8 without any significant effect in IL-6 levels; inhibit the excessive production of NO, PGE (2), TNF-α, and IL-1beta, reduce the elevated expression of NFκB and TNF-α, down-regulate inflammatory iNOS and COX-2 gene expression, inhibit thromboxane synthetase, raise levels of prostacyclin without a concomitant rise in PGE 2 or PGE 2 alpha, inhibit platelet aggregation, decrease age-related oxidative stress markers and enhance fibrinolysis [56, 57, 58, 59, 60, 61] . The concentration of IgM and eosinophil count in non-smokers was significantly increased in a comparative study of the effect of ginger extract among male smokers and non-smokers, whereas the concentration of hemoglobin and lymphocyte count in smokers was strongly increased. This indicates that in non-smokers, ginger results in a stronger antibody response or humoral immunity than in smokers [62] . According to Ayurveda, it is contraindicated to be used in a few diseases: Kushtha, Pandu, Mutrakriccha, Raktapitta; and in Grishma (summer) and Sharada (autumn) Ritu. There are few minor adverse effects recorded that did not need care, such as mild gastrointestinal symptoms, sleepiness, mild diarrhea during prior few days of treatment. It is also explained that ginger has the ability to induce heartburn and as a gastric irritant with doses above 6 gram [63] . During pregnancy, ginger did not pose a major risk for side effects or adverse events [64] . It has been also found to increase bioavailability, thus enhance the therapeutic efficacy of In addition, piperine also inhibits the P-glycoprotein (P-gp) and CYP3A4 functions [70, 71, 72] . Piper nigrum is found to have dose dependent antifertility effects on mice [73] . According to Ayurveda, therapeutics is of two types: 1. Swasthasyorjaskara-which promotes There may be too high content of sugar and albumin in the urine [79] .These drugs seemed to increase Pitta, tend to have some adverse effects such as headache, sleepiness, mild diarrhea, etc. Also, there may be hypo or hyper immune sensitivity of this formulation or occurrence of chemical incompatibility due to many chemical constituents [80] . Though the maximum use of each herbs traditionally for a long time ensures that these herbs are safe but it is essential to determine dosage of PHF for adults and pediatrics in the form of bodyweight or dosage per kg and according to severity of disease, the person's Prakriti and his/her residing climate and region. Thus, this formulation must be evaluated using scientific methods to understand bioactive compounds responsible, their mechanism of action, and ways to regulate the activity of these compounds on COVID-19 related immunological factors. Toxicological studies and clinical trials must be done before its extensive usage. J o u r n a l P r e -p r o o f With various Ayurveda concepts and biomolecular studies, these Ayurveda herbs are seen to have rich sources to fight against the immuno-pathogenesis process of viral diseases, but to date, no study has been found about its effectiveness against COVID-19. Ayush Kwath due to its antiviral, immune-modulatory, antioxidant, anti-inflammatory, anti-platelet, antiatherosclerotic, hepato-protective, reno-protective properties; seems to be effective in regulating immunity for the prevention and reduction of viral disease complications. As there is lack of enough evidence to support its specific role against coronavirus, there is a requirement to validate the effectiveness of these formulations with extensive biotechnological, pharmacological, and clinical research. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that there is no conflict of interest regarding the publication of this article. J o u r n a l P r e -p r o o f Immunity Against COVID-19: Potential Role of Ayush Kwath A pneumonia outbreak associated with a new coronavirus of probable bat origin Antiviral natural products and herbal medicines The possible immunological pathways for the variable immunopathogenesis of COVID-19 infections among healthy adults, elderly and children High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9 COVID-19 in Children: Initial Characterization of the Pediatric Disease Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia The reproductive number of COVID-19 is higher compared to SARS coronavirus Destruction of Virus-Infected Cells by Immunological Mechanisms Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province COVID-19 infection: the perspectives on immune responses Roles of Host Gene and Non-coding RNA Expression in Virus Infection Identification of a receptorbinding domain of the spike glycoprotein of human coronavirus HCoV-229E Immune Defenses University of Texas Medical Branch at Galveston The mercurial nature of neutrophils: Still an enigma in ARDS? Human immunopathogenesis of severe acute respiratory syndrome (SARS) Epidemiology, Pathogenesis, and Control of COVID-19 The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality Caraka Samhita of Maharshi Agnivesa with Ayurvedadipika Susruta Samhita of Shree Susruta, elaboration of Nibandhasangraha of Shree Dalhan and Nyachandrika of shree Gayadasa Traditional herbal remedies for primary health care. WHO Regional Office for South-East Asia Immunity-Boosting Spices and the Novel Coronavirus Medicinal and therapeutic potential of herbs and plant metabolites/extracts countering viral pathogenscurrent knowledge and future prospects Pathological findings of COVID-19 associated with acute respiratory distress syndrome In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs A review of immunomodulators in the Indian traditional health care system Chaukhambha Bharati Academy, pg. 513 and 709 Self-care in the context of primary health care. WHO Regional Office for South-East Asia Tulsi -Ocimum sanctum: A herb for all reasons Lipidlowering and antioxidative activities of aqueous extracts of Ocimum sanctum L. leaves in rats fed with a high-cholesterol diet Ocimum sanctum linn. (TULSI)-an overview A reservoir plant for therapeutic applications: An overview Bioactive botanicals from basil (Ocimum sp Evaluation of cardioprotective activity of Ginkgo biloba and Ocimum sanctum in rodents an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages Antimicrobial and immunomodulatory effects of Tulsi (Oscimum Snctum Linn.) Immunomodulatory activity and Th1/Th2 cytokine response of Ocimum sanctum in in The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature A reservoir plant for therapeutic applications: An overview Toxicological Study of Ocimum sanctum Linn Leaves: Hematological, Biochemical, and Histopathological Studies Immunomodulatory activity of Cinnamomum zeylanicum bark Biological properties of Cinnamomum zeylanicum essential oil: phytochemical component, antioxidant and antimicrobial activities Immunomodulatory activity of Cinnamomum zeylanicum bark Regulatory effect of cinnamaldehyde on monocyte/macrophage-mediated inflammatory responses Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation Cinnamon: A systematic review of adverse events In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs The Amazing and Mighty Ginger Prediction of Novel Bioactive Compound from Z. officinale as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) of HIV-1 through Computational Study Ram Nath) & Chopra, Ishwar Chander, 1911-& Nayer, S. L. Glossary of Indian medicinal plants Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionineinduced hepatoma rats Protective effect of ginger, Zingiber officinale Rosc on experimental atherosclerosis in rabbits Molecular targets of dietary agents for prevention and therapy of cancer Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence Antiinflammatory effects of zingiber officinale in type 2 diabetic patients The effect of Zingiber officinale R. rhizomes (ginger) on plasma pro-inflammatory cytokine levels in well-trained male endurance runners Beneficial effects of an aqueous ginger extract on the immune system cells and antibodies, hematology, and thyroid hormones in male smokers and nonsmokers How Safe Is Ginger Rhizome for Decreasing Nausea and Vomiting in Women during Early Pregnancy? Foods A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting Prebiotic Potential of Culinary Spices Used to Support Digestion and Bioabsorption. Evidence-Based Complementary and Alternative Medicine A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices Phytochemical evaluation and antioxidant activity of Piper cubeba and Piper nigrum Biological action of Piper nigrum -the king of spices Calcio-herbal formulation, Divya-Swasari-Ras, alleviates chronic inflammation and suppresses airway remodelling in mouse model of allergic asthma by modulating pro-inflammatory cytokine response The protective role of Piper nigrum fruit extract in an ovalbumin-induced allergic rhinitis by targeting of NFκBp65 and STAT3 signalings Piperine Plays an Anti-Inflammatory Role in Staphylococcus aureus Endometritis by Inhibiting Activation of NF-κB and MAPK Pathways in Mice In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn Alkamides from Piper nigrum L. and Their Inhibitory Activity against Human Liver Microsomal Cytochrome P450 2D6 (CYP2D6) Ayurveda and COVID-19: Where psychoneuroimmunology and the meaning response meet COVID-19: consider cytokine storm syndromes and immunosuppression Herbal Medicine: Biomolecular and Clinical Aspects Polyherbal Formulation Concept for Synergic Action: A Review The Ayurvedic Pharmacopoeia of India Part-I and Volume-I, II and III. Ministry of Health and Family Welfare Ayurvedic Medicine: The Principles of Traditional Practice /books?id=hBT6yHZckS4C&printsec=frontcover#v=onepage&q &f=false Acessed on Formulation and Evaluation of a Polyherbal Ointment for Its Wound Healing Activity A pneumonia outbreak associated with a new coronavirus of probable bat origin Antiviral natural products and herbal medicines The possible immunological pathways for the variable immunopathogenesis of COVID-19 infections among healthy adults, elderly and children High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9 COVID-19 in Children: Initial Characterization of the Pediatric Disease Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia The reproductive number of COVID-19 is higher compared to SARS coronavirus Destruction of Virus-Infected Cells by Immunological Mechanisms Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province COVID-19 infection: the perspectives on immune responses Roles of Host Gene and Non-coding RNA Expression in Virus Infection Identification of a receptorbinding domain of the spike glycoprotein of human coronavirus HCoV-229E Immune Defenses University of Texas Medical Branch at Galveston The mercurial nature of neutrophils: Still an enigma in ARDS? Human immunopathogenesis of severe acute respiratory syndrome (SARS) Pathogenesis, and Control of COVID-19 The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality and on some places hindi commentary of Jalpakalpataru of Gangadhar. Varanasi, Chowkhamba Krishnadas Academy Susruta Samhita of Shree Susruta, elaboration of Nibandhasangraha of Shree Dalhan and Nyachandrika of shree Gayadasa Traditional herbal remedies for primary health care. WHO Regional Office for South-East Asia Immunity-Boosting Spices and the Novel Coronavirus Medicinal and therapeutic potential of herbs and plant metabolites/extracts countering viral pathogenscurrent knowledge and future prospects Pathological findings of COVID-19 associated with acute respiratory distress syndrome In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs A review of immunomodulators in the Indian traditional health care system Chaukhambha Bharati Academy, pg. 513 and 709 Self-care in the context of primary health care. WHO Regional Office for South-East Asia Tulsi -Ocimum sanctum: A herb for all reasons Lipidlowering and antioxidative activities of aqueous extracts of Ocimum sanctum L. leaves in rats fed with a high-cholesterol diet Ocimum sanctum linn. (TULSI)-an overview A reservoir plant for therapeutic applications: An overview Bioactive botanicals from basil (Ocimum sp Evaluation of cardioprotective activity of Ginkgo biloba and Ocimum sanctum in rodents an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages Antimicrobial and immunomodulatory effects of Tulsi (Oscimum Snctum Linn.) Immunomodulatory activity and Th1/Th2 cytokine response of Ocimum sanctum in myelosuppressed swiss albino mice The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature A reservoir plant for therapeutic applications: An overview Toxicological Study of Ocimum sanctum Linn Leaves: Hematological, Biochemical, and Histopathological Studies Immunomodulatory activity of Cinnamomum zeylanicum bark Biological properties of Cinnamomum zeylanicum essential oil: phytochemical component, antioxidant and antimicrobial activities Immunomodulatory activity of Cinnamomum zeylanicum bark Regulatory effect of cinnamaldehyde on monocyte/macrophage-mediated inflammatory responses Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation Cinnamon: A systematic review of adverse events In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs The Amazing and Mighty Ginger Prediction of Novel Bioactive Compound from Z. officinale as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) of HIV-1 through Computational Study Ram Nath) & Chopra, Ishwar Chander, 1911-& Nayer, S. L. Glossary of Indian medicinal plants Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats Protective effect of ginger, Zingiber officinale Rosc on experimental atherosclerosis in rabbits Molecular targets of dietary agents for prevention and therapy of cancer Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence Antiinflammatory effects of zingiber officinale in type 2 diabetic patients The effect of Zingiber officinale R. rhizomes (ginger) on plasma pro-inflammatory cytokine levels in well-trained male endurance runners Beneficial effects of an aqueous ginger extract on the immune system cells and antibodies, hematology, and thyroid hormones in male smokers and nonsmokers How Safe Is Ginger Rhizome for Decreasing Nausea and Vomiting in Women during Early Pregnancy? Foods A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting Prebiotic Potential of Culinary Spices Used to Support Digestion and Bioabsorption. Evidence-Based Complementary and Alternative Medicine A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices Phytochemical evaluation and antioxidant activity of Piper cubeba and Piper nigrum Biological action of Piper nigrum -the king of spices Calcio-herbal formulation, Divya-Swasari-Ras, alleviates chronic inflammation and suppresses airway remodelling in mouse model of allergic asthma by modulating pro-inflammatory cytokine response The protective role of Piper nigrum fruit extract in an ovalbumin-induced allergic rhinitis by targeting of NFκBp65 and STAT3 signalings Piperine Plays an Anti-Inflammatory Role in Staphylococcus aureus Endometritis by Inhibiting Activation of NF-κB and MAPK Pathways in Mice In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn Alkamides from Piper nigrum L. and Their Inhibitory Activity against Human Liver Microsomal Cytochrome P450 2D6 (CYP2D6) Ayurveda and COVID-19: Where psychoneuroimmunology and the meaning response meet COVID-19: consider cytokine storm syndromes and immunosuppression Herbal Medicine: Biomolecular and Clinical Aspects Polyherbal Formulation Concept for Synergic Action: A Review The Ayurvedic Pharmacopoeia of India Part-I and Volume-I, II and III. Ministry of Health and Family Welfare Ayurvedic Medicine: The Principles of Traditional Practice /books?id=hBT6yHZckS4C&printsec=frontcover#v=onepage&q &f=false Acessed on Formulation and Evaluation of a Polyherbal Ointment for Its Wound Healing Activity