INTRODUCTION:

SARS-CoV-2 is a single-stranded RNA virus belonging to the family Coronaviridae. It is contagious, spread rapidly from one person to another. The virus has spread in almost all the countries of the world and has created a global threat to mankind. World Health Organization (WHO) on February 11, 2020, named the infection as COVID-19 as an acronym for ‘coronavirus disease-2019’ and on March 11, 2020, declared the outbreak a pandemic¹. COVID-19 can affect all the people without discrimination, however, older, immune-compromised and people with health problems like diabetes, obesity, chronic respiratory illness and cardiovascular ailments are more susceptible.

The virus chiefly spread through droplet infection from an infected person to healthy one by coughing, sneezing or with infected hands when touched to eyes, nose or mouth. Coronaviruses are said to have glycoproteins composed of two subunits, S1 and S2 which form the viral surface and in fact guide the host receptors². Strong immune response in the host against the virus, labelled as a cytokine storm, results in serious tissue damage. Interleukin-6 produced by leukocytes is considered to be the protagonist of this whole storm. The infection may begin with a dry cough, tiredness, headache, mild fever, and rarely diarrhea, sore throat, nasal congestion or running nose^3,4. In severe cases, the patient may experience high-grade fever, pneumonia, breathlessness, and severe acute respiratory syndrome. A good percentage of people remain asymptomatic⁵. Diagnostic tests currently in use involve polymerase chain reaction, serological assay, and rapid antigen test. A chest X-ray or CT scan can be helpful for detecting pathological changes in the lungs. So far no specific treatment is available for novel coronavirus-2019 and the patients have to be managed only with symptomatic treatment. In the case of breathlessness oxygen therapy is recommended and in case of respiratory failure mechanical ventilation is needed while as septic shock requires hemodynamic support⁶. Various antivirals and antimicrobials used in different countries to curtail the disease include Lopinavir/Ritonavir (400/100mg 12 hourly), Chloroquine (500mg 12 hourly) and Hydoxychloroquine (200mg 12 hourly)⁷. Some suggest human IgG1 monoclonal antibody, commonly used in rheumatoid arthritis treatment. Moreover, social distancing, quarantine and isolation of suspected cases are the best tools for containing the disease. Maintenance of proper hygiene, washing hands frequently with soap or alcohol (> 70 %) based sanitizers, and use of masks at public places have the utmost importance. As of April 30, 2020, more than 33 lakh cases and about 234000 deaths have been reported throughout the globe. USA is the worst- hit country till date where more than 60,000 mortalities have been recorded, followed by Italy, Spain, France and the UK. The average mortality rate is about 3-4 per cent. In the current pandemic viral infection (COVID-19) it is clear that those with a weak immune system are highly susceptible to this infection and its worst outcomes⁸. Thus, immune-enhancing herbs may be helpful for the body to combat COVID-19 infection⁹. The traditional medicines include the use of herbs, nutrition and spices that are widely available and used in day to day life by the Asian population¹⁰.

The immune system helps to prevent death by producing antibodies by binding to the antigens of infectious agents. The immune system defends against bacterial infection through frequently interacting innate and adaptive mechanisms. The immune system estimates the amino acid sequence space of potential antibodies for identifying attacking pathogens. The adaptive immune system and two components of the innate immune system form the pervasive immune system. The innate system includes extrinsic defenses like serum proteins, nonspecific phagocytic leukocytes, mucous membranes and the skin¹¹. This system is a primary to build into cells that are located on the front line of defense against bacterial invasions, including epithelial cells in the gut, lung, skin, periodontium, neutrophils and macrophages. The adaptive immune system takes a longer time to develop the response specifically. In fact, it provides a specific response against attacking organisms after evolvement. As reported in the literature, different immune function parameters are affected by viruses including immunoglobulin levels, antibody generation, and induction of immunological tolerance, graft-versus-host reaction, delayed-type skin reaction, graft rejection, lymphocyte transformation, and phagocytosis¹².

Spices and Herbs have many Phytoconstituents that helps to boost immunity. Additionally, they have many medicinal properties. In India, traditional medicines are available widely and according to WHO, about 80% of the population all over the world use spices and condiments to prevent and manage different diseases and disorders¹³.

An ancient Indian text states that “aushadham ucchyathe sarvam”, which implicit that food is the absolute cure and healer. Ayurveda is a traditional Indian medicine system that stimulates several herbs, roots and spices to boost the immune system naturally¹². In Ayurveda, spices and herbs are used to cure long-standing health conditions by eliminating metabolic conditions and commonly termed as ‘cleansers’. Traditionally, in Indian cuisine, herbs and spices are used in a dish according to their nutritional benefits and their ability to strengthen our immune system, which in turn, can protect us from ailments and infections. A strong immune system helps the body fight against flu, disease-causing viruses, as well as bacteria. People with weak immunity are more susceptible to fall sick and their symptoms for any disease are more severe as compared to others. That’s why they need for a strong immune system is extremely important because that will enable us to live a healthy life. According to the World Health Organization, around 80% of the world population uses herbal medicines for primary health care, particularly across South Asia and Europe. Research studies stated the herbs build the body’s immunity and have anti-inflammatory properties and have fewer side effects. This review discussed some important immunomodulatory herbs that can be used as immunity boosters¹⁴.

Currently, there is no specific treatment for COVID-19. Herbal medicines can be used as immunomodulators to fight against COVID-19 infection. The herbs contain various active constituents which have antiviral, antimicrobial, anti-inflammatory and immunostimulant properties. Thus it can be suspect that herbs can be used for preventing or treating COVID-19 infection¹⁵.

IMMUNOMODULATING HERBS:

Allium Sativum- Lehsun (Garlic):

Allium sativum is belonging to the species in the onion genus, Allium. It includes the onion, shallot, leek, Chinese and chive onion¹⁶. Garlic is indigenous to Central Asia and Northern Iran over 6000 years ago and employed as a medicinal agent¹⁷. Garlic is one of the most important and common of all plants which are marked in the mankind history¹². Garlic contains many active chemical constituents including alliin, allicin, ajoene, vinyldithin, S-allylcycsteine and diallyl sulphides which are having antioxidant, anti-inflammatory, immune-modulating, antibiotic, bacteriostatic, antifungal, antiviral, antihelminthic, antithrombic, hypotensive, hypoglycemic, and hypocholesterolemic properties^18,19.

One of the most important constituent of garlic is allicin which attacks more than 23 kinds of bacteria, including salmonella, as well as 60 types of yeast and fungi, and also effective against all of 17 most dangerous fungi (Candela albicans), expels tapeworms and restores sensation in areas affected by leprosy.

When garlic is crushed or chewed, the compound turns into allicin which is the main active ingredient responsible for its taste and smell. Allicin is unstable and quickly converts to other sulphur-containing compounds which exhibit medicinal properties. These compounds boost the disease-fighting response of leukocytes in the body when they kill viruses, such as the viruses that cause the common cold or flu²⁰. Aged garlic extract contains fructans (fructooligosaccharides) which selectively stimulate some beneficial bacteria in colon, modulating immune responses²¹. Various garlic preparations such as aqueous extract, aged garlic extract and garlic oil are sold in the market with distinct health benefits. The raw garlic as well as garlic preparations is effective.

The role of garlic in immuonutrition is immunostimulant and immunosuppressant. The consumption of garlic results in an improvement in haematological attributes, e.g., total leukocytes counts as well as homeostasis characteristics. Consumption of garlic increase the production and release of nitric oxide (NO) that is responsible for enhanced release of IFN-α in humans, beneficial against viral, or proliferative diseases. The overall improvement in the immune system could be attributed to the activation of specific responses and detoxification mechanisms. There are some possible routes of garlic for its immunomodulatory properties are a proliferation of lymphocytes; infiltration of macrophages and lymphocytes, macrophage phagocytosis and stimulating release of IL-2, TNF-α, and IFN-γ. Additionally, it enhances NK cell and lymphokine-activated killer cell activities and represents effective stimulation of the immune responses²².

Garlic inhibits the growth of cancerous cells. It has also been reported from the last decade that garlic and its preparations may possess anticancer activities against the skin, prostate, mammary carcinoma colon, lungs, gastric cancer, etc.^23,24

Due to the unavailability of accurate drugs and vaccines, the global health authorities are working on the use of traditional medicine system against the contagious agents and thus, for curing the disease. Garlic is known for centuries related to its protecting capacity against diseases along with immune-boosting activities. It is effective against various viruses, bacteria and fungi hence it is well known for its antibacterial, antiviral and antifungal properties. The garlic possesses antioxidants properties with free radicals²⁵. The garlic also possesses an antiviral property which may be useful in reducing the severity of colds, flu or COVID-19 infection. Hence, Garlic helps to boosts the immune response and in fighting against viruses and other diseases²⁶.

An old folk tale states that: “Eat onions in March and garlic in May, then rest of the year, your doctor can play. Garlic in its natural form incorporated with a healthy diet is beneficial to health, prevents disease and will help prolong life.

Zingiber officinalis- Adrak (Ginger):

Zingiber officinalis is a famous spice for its dietary and medicinal properties in India and in other countries. Ginger has been used for the treatment of rheumatism, catarrh, nervous diseases, gingivitis, toothache, stroke, asthma, constipation and diabetes in Ayurvedic, Chinese and Tibb-Unani herbal medicines²⁷. The medicinal, pharmacological and chemical properties of ginger have been considerably reviewed the evidence for its effectiveness as an -inflammatory agent antioxidant, anti-nausea compound, and anticancer agent. The protective effects of ginger against other disease conditions are also reviewed²⁸. Many researchers have proved that whenever someone suffers from common cold or flu, Ginger Tea or Ginger extract is recommended to get relief from the symptoms. Ginger possesses many effective plant compounds and has excellent anti-viral properties and treating respiratory issues²⁹. The pungent chief active constituent present in Ginger is Gingerol along with other sulphur-containing compounds (allicin, alliin, and ajoene²⁵), zingiberine, sesquiterpenes, shogaol, gingerdione, hexahydrocurcumin, paradol and gingerenone A³⁰ and enzymes (allinase, peroxidase, and myrosinase). The constituents present in Ginger increases the antioxidant activity i.e. superoxide dismutase and glutathione peroxidase in the body in combating the Viral Infections. Ginger prevents severe damage to the lungs ameliorates allergic asthma and inflammation^31,32.

The aqueous extract of Ginger and Clove is very effective in the prevention of the contamination. To prevent the fresh vegetables from decontamination, the aqueous extracts of six raw food materials (fenugreek seeds, garlic and onion bulbs, flower buds of clove, ginger rhizomes, and jalapeno peppers) were tested against the foodborne infection³³.

In comparison to the dried ginger, the fresh ginger is reported to inhibit human respiratory syncytial virus (HRSV)-induced plaque formation when taken in proper doses in both A549 (adeno carcinomic human alveolar) and HEp-2 (human laryngeal carcinoma) cell lines. Also, 300 μg/mL of fresh ginger is found to reduce the plaque counts to 19.7% (A549) and 27.0% (HEp-2) compared to the control group, respectively³⁴.

Ginger is consumed in many cultures as immune boosters, and its anti-inflammatory potential has been highlighted in a number of scientific investigations. The mechanisms for its anti-inflammatory properties.

include inhibition of arachidonic acid-induced platelet aggregation and formation of thromboxane B, upregulation of histone H3 acetylation, and suppressed histone deacetylase (HDAC), inhibition of IL-1, TNF-α and IL-8, downregulation of inflammatory inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) gene expression through inactivation of Nuclear Factor Kappa B (NF-KB)³⁵.

Cinnamomum zeylanicum- Dalchini (Cinnamon):

Cinnamon is reddish-brown bark with a good smell belongs to the family Lauraceae. It is said to be hot and most commonly used as a spice. It is used in the treatment of respiratory ailments like cough and asthma. It is also having phlegmagogue, cardiotonic and aphrodisiac, anti-inflammatory, antimicrobial and antioxidant actions. In addition to these, researchers have found that this herb is effective in diabetes, ischemic heart disease, hypertension, gastric cancer, Alzheimer’s disease, dyslipidemia. It can be used in the form of decoction or powder form with a dosage of 1-2 gm. The active chemical constituents present in cinnamon are cinnamaldehyde, cinnamic acid, cinnamate and essential oils like trans-cinnamaldehyde, eugenol, caryophyllene oxide, cinnamyl acetate, L-borneol, E-nerilidol, b-caryophyllene, α-cubebene, α-thugene, α-terpinol, and terpinolene. The extensive study revealed the antimicrobial activity of cinnamon. The cinnamon is proven to have antiviral activity against H7N3 influenza A virus³⁶. Cinnamon along with other medicines is highly effective in acute and chronic human infections fungal, bacterial or viral³⁷. Cinnamon derived compound, Procyanidin type A inhibits the entry of hepatitis C virus³⁸. It was found that inhibits the TNF-α-induced inflammation through suppression of NF-κB activation. Cinnamaldehyde decreases the production of prostaglandins (PGEs) by decreasing IL-1β-induced COX-2 activity and lowering the hyper inflammation in a dose-dependent manner. Researchers showed the evidence that cinnamaldehyde is a potential anti-inflammatory bioactive compound and could be useful in mitigation of SARS-CoV-2 induced hyper inflammation in the lung³⁹.

Curcuma longa-Turmeric (Haldi):

Curcuma longa is also called “Indian saffron”. Turmeric belongs to the ginger (Zingiberaceae) family and the Curcuma genus^40,41. It is a rhizome which is yellow orange in color and well-known spice and has numerous medicinal benefits. Curcuma longa rhizome (turmeric), commonly used as spice and is well known for its medicinal value in the Indian traditional system of medicine. In the Unani medicinal system it is used as anti-inflammatory, phlegmagogue, analgesic, antipyretic, blood purifier, and has healing properties. The herb can be utilized in the form of decoction or powder with a dose of 1-3 gm⁴⁰. Scientists have reported that it is having immunomodulating, antioxidant, anti-inflammatory, antimicrobial and anticancer activities. The main constituent of Curcuma longa is Curcumin (diferuloylmethane) which is responsible for the biological activity and gives yellow colour to turmeric. Curcumin is strongly effective in acute respiratory distress syndrome, COPD’s, pulmonary fibrosis and acute lung injury⁴². Turmeric suppresses TNF-α and inhibits NF-κB and acts as a potent anti-inflammatory agent⁴³. Curcuma extract is effective against various pathogenic bacteria including Staphylococcus, Streptococcus Klebsella pneumoniae, Helicobacter pylori, Vibrio chlolera, Bacillus subtilis, etc. Turmeric also contains dihydrocurcumin, and hexahydrocurcumin. Some volatile constituents like α-phellandrene, cinol, borneol, zingiberine and different sesquiterpenes⁴⁴. The herb of the turmeric acts against the viruses like H1N1, H6N1, respiratory syncytial virus, herpes simplex virus, parainfluenza virus type-3, coxsakievirus B3, Japanese encephalitis, hepatitis B virus, hepatitis C virus, human papillomavirus-16 and -18^45,46. It has also been found to inhibit HIV-1 long terminal repeat-directed gene expression.

A new study suggested that an interplay between COVID-19 and the renin-angiotensin-aldosterone system (RAAS). A preclinical study demonstrated that an ACE inhibitor or angiotensin-receptor blocker (ARB) might increase ACE2 expression. In addition, another study indicated that the administration of RAAS inhibitor did not influence the ACE2 receptor⁴⁷. It can be concluded that the results are inconsistent regarding the administration of the RAAS inhibitor since they may or may not increase the ACE2 receptor. Based on the data, there is a possibility that the administration of curcumin prevent COVID-19 may cause a highly susceptible individual to get infected with SARS CoV- 2 and eventually become worse⁴⁸.

Ocimum sanctum Linn- Holy basil (Tulsi):

Tulsi is noted as “mother medicine of nature” and it shortens the course of all illness. Tulsi is also called holy basil. It is an indigenous plant to India and is highly renowned for its medicinal properties in Ayurvedic and Siddha medicinal system. Tulsi has immunomodulatory activity, antibacterial, antioxidant, anti‑inflammatory, anti-carcinogenic activity, anti-diabetic, antipyretic, and also analgesic property, anti-viral and anti-fungal activity. A decoction of the Tulsi leaves is beneficial for the treatment of respiratory disorders like asthma, bronchitis, influenza, and cough and cold^49,50.

Tulsi leaves contain bright, yellow coloured and pleasant volatile oil (0.1% - 0.9%). The percentage of oil content of the drug varies depending upon the type, the place of cultivation and season of its collection. It contains approximately 70% eugenol, carvacrol (3%), and eugenol-methyl-ether (20%). It also contains caryophyllin. Tulsi seeds contain fixed oil with good drying properties.

The plant also contains glycosides, alkaloids, tannins, saponin, a considerable amount of vitamin C and traces of maleic, tartaric and citric acid.

In Ayurveda, Tulsi is denoted as “Elixir of life” for its healing activity and promising potential in curing different health diseases including bronchitis, rheumatism pyrexia, asthma, skin diseases, parasitic and microbial infections, gastric and hepatic disorders, etc.

Tulsi is used for curing pain, diarrhoea, cough and fever, which are common symptoms related to COVID-19, thus it can be used in controlling COVID-19. Tulsi is a well known herb to treat pneumonia⁵¹. The essential oils like Eugenol of Tulsi leaves produce anti-viral activity against different viruses namely, poliovirus type 3, herpes virus (HSV), hepatitis B virus etc⁵². Ethanolic extract of leaves of Tulsi plant in the concentration of 22.5mg/ml, inhibit polio type 3 virus replication. The extracted components of Tulsi like linalool and ursolic acid have shown broad- spectrum antiviral activity against DNA viruses like RNA virus and adenoviruses⁵³.

Tulsi helps in the prevention and controlling of COVID-19. Social Science Research Network (SSRN, Elsevier) studied the binding affinity of seven photophilic compounds from Tulsi i.e., tulsinol A, B, C, D, E, F, G, and dihydrodieuginol B, with SARS CoV receptors. This study confirmed that the use of Tulsi extract against COVID-19 due to its recognized role in inhibiting replication of SARS-CoV with ACE II blocking properties⁵⁴.

Glycyrrhiza glabra- (Liquorice) Mulethi, Yashtimadhu:

From the ancient time, Glycyrrhiza glabra is indicated for the symptoms of respiratory disease, namely, cough sore throat. Potential uses of Glycyrrhiza glabra for anti-tumour, anti-microbial, antiviral, anti-inflammatory, immune regulatory and several other activities that contribute to the recovery and protection of the nervous, alimentary, respiratory, endocrine, and cardiovascular systems⁵⁵. Liquorice for medicinal purposes is used mostly in the form of decoction with a dosage of 3-7gm.

A number of active constituents have been isolated such as glycyrrhizin, glabridin, 18-beta-glycyrrhetinic acid, liquiritigenin, licochalcone A and licochalcone E, responsible for its broader activities⁵⁶. The chief constituent of liquorice root is glycyrrhizin (glycyrrhizic acid or glycyrrhizinic acid) which is sweetened in taste. Glycyrrhizin is well known to have various immunomodulating and biological response-modifier activities. The phytoestrogens namely isoflaveneglabrene, isoflavaneglabridin and chalcones are also present in the liquorice root⁵⁷.

The extract of Glycyrrhiza is found to be effective against hepatitis C virus, coxackievirus B3, H5N1 influenza A virus, H3N2 influenza virus, human respiratory syncytial virus, coxsackievirus A and enterovirus^58,59.

The researchers investigated the antiviral properties of glycyrrhizic acid derivatives against SARS-CoV virus. They tested 15 Glycyrrhizin derivatives for their antiviral activity against SARS-CoV and reported that amides and conjugates of Glycyrrhizin with two amino acid residues and 30 free -COOH functional groups represent up to 70-fold increased activity against SARS-CoV⁶⁰.

Ginseng:

Ginseng is also known as “man-root”. It is a slow-growing root herb that has been used medicinally by practitioners of traditional Chinese medicine for more than 3000 years. Ginseng is indigenous to Asia and America and is very popular for its many beneficial medicinal products from years⁶¹. It has antimicrobial antioxidative, antidiabetic, anti-inflammatory, anti cardiovascular disease and anticancer properties. It helps to enhance the immunity, combating various cardiovascular diseases, neurological disorders and diabetes⁶².

Ginseng is treated as an adaptogen, a substance thought to enhance the body’s ability to resist physical and mental stress⁶³. Traditional herbalists also consider it to be a “general tonic,” a substance that helps protect the body against disease, much as one would expect from an immunostimulant. Several species are commonly referred to as ginseng. The three species of ginseng are most commonly used are Asian or Korean ginseng (Panax ginseng), American ginseng (Panax quinquefolius), and Siberian ginseng, more properly called “eleuthero” (Eleutherococcus senticosus). The Panax species is considered as “true” ginseng⁶⁴.

The main chemical constituents of ginseng are triterpenoid, protopanaxadiols, protopanaxatriols, steroidal saponins (ginsenoid, polysaccharides) and proteins which show strong activities against antibacterial or like other activity especially for microorganisms that cause respiratory infections in the human body. Furthermore, the antimicrobial activity of ginseng and their bioactive constituents was found to be effective against various bacteria (Escherichia coli, Helicobacter pylori, Staphyllococcus aureus, Pseudomonas aeruginosa, Propionibacterium acnes), fungi (Fusarium oxysporum) and yeast (Candida albicans) species⁶¹. It is also effective against different human viral infections such as rhinovirus, influenza virus, human immunodeficiency virus hepatitis virus, enterovirus, norovirus, human herpes virus, rotavirus and coxsackievirus respiratory syncytial virus⁶⁵.

The research study stated that the ginseng was effective against viral infections such as H1N1 and decreased the formation of free radicals such as reactive oxygen species (ROS)⁶⁶. The marketed formulations as Ginseng supplementation are widely available in the market, which helps to improve immunity and also used as anti-viral properties. The extract of the Ginseng can help to manage COVID -19 pandemic⁶⁷.

Black pepper:

Black pepper is used in many cuisines that hold a very useful among medicinal plants⁶⁸. It is well known as ‘king of spices’ and widely used as a flavoring agent and taste enhancer of various dishes. It is rounded, small and black fruit of a plant somewhat bitter in taste and zesty in nature. It is said to be effective in fevers, asthma, breathlessness and other respiratory diseases. It is used for its anti-inflammatory, analgesic, phlegmagogue, anti-flatulent, anti-thyroid, anti-tumour, anti-bacterial, appetizer, anti-venom, aphrodisiac, neuroprotective, cardioprotective and health-boosting actions^36,69. More than 600 phytochemicals including lignans, terpenes, alkaloids/amides, neolignans etc. are present in this plant. Various chemical constituents obtained from black pepper include piperine, piperamide, piperic acid, piperolein-B, piperlonguminine, pellitorine, piperitine, eugenol and kusonokinin in addition to some volatile oils⁷⁰. Piperine shows a strong anti-inflammatory activity and thus can be repurposed for suppression of hyper inflammation induced during COVID-19³⁹. Also, piperine is a potent antioxidant and protect against oxidative damage by neutralizing free radicals, ROS, and hydroxyl radicals⁷¹. Due to these properties, piperine can be used as a therapeutic compound to protect from the oxidative stress and hyper inflammation due to COVID-19³⁹.

Emblica officinalis- Amla:

Emblica officinalis is also known as Phyllanthus emblica. It is one of the major constituents of many Ayurvedic tonics prescribed for recuperation, rejuvenation and vitality⁷². Amla is the richest source of vitamin C and sour in taste. It is widely used in common cold, fever, dyspepsia, hair growth, liver disorders etc. Amla fruits are rich in various minerals like phosphorus, iron and calcium. It also contains various chemical constituents like ellagic acid, gallic acid, norsesquiterpenoids, gearaniin, and prodelphinidins. It has different biological activities like immunomodulatory, antioxidant, anticancer, cytoprotective, analgesic, antimicrobial, antipyretic, antitussive and hepatoprotective effect⁷³. Amla is well known for its anti-oxidant property as it balances pro-oxidant and anti-oxidant homeostatic phenomenon in the body. It also reduces the side effects induced by radiotherapy and chemotherapy⁷². Amla improves both cell-mediated and humoral immune response. It intensifies gamma –IFN, IL-2, and natural killer (NK) cell activity⁷⁴. Amla shows extreme immune empowering property and thus it is believed to be effective against viral infections⁷⁵.

Withania somnifera- Ashwagandha:

Ashwagandha is known as Indian winter cherry and Indian ginseng and belongs to the family Solanaceae. It is one of the most important herb in Ayurveda and used for improving good physical and mental health, immunomodulation, management of stress and combating infectious agents⁷⁶. It is widely used as a nerve tonic, body tonic, aphrodisiac, anti-inflammatory, antiarthritic antivenom, antihypertensive and anti-tumour medicine. It is used as an immunomodulator and used as a dietary supplement in the form of churna^77,78.

Ashwagandha consists of sterols, alkaloids, saponins, amino acids and polysaccharides. Alkaloids such as ashwagandhine, cuseohygrine, trpine, isopelletierine, anaferine etc. have been isolated from Ashwagandha. The multiple numbers of sterols are isolated from this herb which includes withaferins, withasomidienone, withasomniferin A, withanolides, and withanone. Sitoindisides (VII, VIII, IX and X) and withaferin A, have shown antidepressant properties⁷⁹. Withaferin A, a constituent of ashwagandha have a high binding affinity towards neuraminidase and inhibit neuraminidase of H1N1 influenza virus potently⁸⁰.

Researchers found that Ashwagandha increases the production of antibodies in the body. These antibodies engulf the toxins and excrete them in the form of mucus, sweat, faeces and urine⁸¹. It also increases the production of Nitric Oxide, which is responsible for the activation of macrophage actions of the immune system with the improved ability of ingestion of invader cells⁸². The extract of Ashwagandha when added with DPT (Diptheria, Pertussis and Tetanus) vaccine gives protective immune response against fatal outcomes of Diptheria and Pertussis toxins⁸³. It is also reported that the SARS-Cov-2 directly attack on ACE 2 in the human body with the help of spike proteins. To respond it, the phytoconstituents present in the Ashwagandha have effects on binding of the virus in the human body. That is why; Ashwagandha could be the best choice among various medicinal plants to fight against COVID-19 as the roots have high antiviral activity⁶⁷.

Tinospora cordifolia- Giloy:

Giloy or Guduchi or Amruta is a large climbing shrub belonging to the family Menispermaceae. It is found throughout India. Tinospora cordifolia has importance in traditional Ayurvedic medicine and used for the treatment of chronic diarrhoea, dysentery, cancer, jaundice, bone fracture, pain, asthma, skin disease, poisonous insect, snake bite and eye disorders⁸⁴. It gives relief from chronic cough, breathlessness, tuberculosis, syphilis, gonorrhoea and leprosy in Unani medicine⁸⁵. It also improves learning and memory power⁸⁶. Giloy has many medicinal properties like anti-inflammatory, anti-osteoporotic, anti-arthritic, antioxidant, anti-allergic, antihyperglycemic, immunomodulatory, antipyretic, anti-infective, hepatoprotective, antileprotic, antifertility, antimutagenic, antiobesity, antineoplastic and radioprotective activity⁸⁷. Different classes of chemical constituents are present in Giloy are lactones, alkaloids, glycosides, sesquiterpenoids, diterpenoids, steroids, phenolics, essential oils, polysaccharides, aliphatic compounds and flavonoids. The chief constituents are tinosporone, tinosporine, tinosporic acid, cordifolisides A to E, syringe, berberine and giloin⁸⁸.

Giloy also contains high fibre content (15.8%), protein (4.5%-11.2%), carbohydrate (61.66%), and low fat (3.1%), high chromium (0.006%), potassium (0.845%), sufficient iron (0.28%) and sufficient calcium (0.131%). Nutritive value of T. cordifolia nutritive is 292.54 calories per 100 grams⁸⁹. Researchers have found that methanolic extract of Giloy is found to have broad-spectrum antimicrobial effectiveness against various strains which are Staphylococcusaureus, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Shigella flexneri, Salmonella paratyphi, Salmonella typhimurium, Salmonella typhi, Enterobacter aerogene, Serratia marcesenses and Proteus vulgaris⁹⁰.

1, 4-alpha-D-glucan which is one of the constituent of Tinospora cordifolia found to activate macrophages, NFκB translocation and cytokine production, and hence activates the immune system⁹¹. Favorable effects of Tinospora cordifolia was seen in HIV positive patients when it was used with conventional antiviral treatment⁹². Tinosporin is effective against HIV and other viral diseases as immunomodulatory and selective inhibition of the virus to target T helper cell.

Sanshamani Vati (also called Guduchi ghana vati) which is made from the aqueous extract of T. cordifolia can be administered as 500mg twice a day, 15 days with warm water as a preventive and prophylactic drug for COVID-19⁹³ .

The combined herbal formulation of Giloy, six leaves of tulsi, one or two tablespoon of ginger juice and four to six seeds of black pepper receiving enormous popularity and found to be helpful for preventing COVID-19 disorder. This mixture is crushed or grind into a fine powder and use it as herbal tea or consume with honey. It can control fever, cough and support immunity⁹⁴.

Echinacea purpurea- Coneflower:

The genus Echinacea (coneflower, family Asteraceae) is indigenous to North America. Echinacea preparations are commonly used as immunostimulants and prevent cold and other respiratory infections and conditions associated with respiratory discomfort. These preparations widely used as dietary supplements in Europe and the United States. In Germany, Echinacea containing products have the greatest popularity and approved for supportive treatment of respiratory and urinary infections⁹⁵.

Preparations of Echinacea purpurea can be made in the form of tinctures, extracts and sprays. Echinacea purpurea preparations stimulate phagocytosis of neutrophils both in vitro and in vivo and activate cellular immunity. It contains chemical constituents like caffeic acids, polysaccharides, chicoric acid, alkylamides, essential oils, hydroxycinnamic acids, tannins, saponins, flavonoids, echinacin, echinacoside, echinolone, organic acids, resins and phenolcarboxylic acids⁹⁶.

The extract of E. purpurea has antiviral activity against virus-induced diseases. It is effective against herpes simplex virus, influenza and rhinovirus. Depending on different studies, it can be concluded that E. purpurea can be used for the prevention and treatment of COVID-19⁴⁸.

Azadirachta indica- Margosa (Neem):

Scientific name of neem is Azadirachta indica found everywhere in India. Every part of the neem tree such as leaves, root, fruit, bark, oil seeds and gum are useful and it is used to cure or control diseases arises from parasitic, bacterial, viral or any other causes⁹⁷. Neem tree is used in the treatment of certain medical conditions such as hypertension, cancer, heart diseases and diabetes⁹⁸.

It is known that compounds in neem extracts have antifungal, antibacterial, antimalarial, anti-hyperglycemic, immune-modulator, anti-carcinogenic, anti-inflammatory, anti-mutagenic, anti-oxidant anti-ulcer, antinephrotoxicity, wound healing effect, neuroprotective activity and anti-viral effects^99,100. The neem tree effectively helps to purify the air. The main phytoconstituents present in neem are limonoids and terpenes.

The chief chemical constituents present in the neem tree are sodium nimbidate, catechin, gallic acid, nimbidin, nimbolide, gedunin, mahmoodin, margolone, isomargolone and polysaccharides which are responsible for their anti-inflammatory, antifungal, anti-bacterial and anti-inflammatory activities⁹⁴.

Neem oil possesses antifungal, antimalarial and antipyretic activities. Neem oil contains Azadirachtin which have strong anti-feedant, insecticidal and antimalarial property¹⁰¹.

The neem extract have anti-viral effects against herpes virus, chickenpox, smallpox, polio virus, dengue virus, coxsackie B group virus and HIV virus¹⁰².

In urban areas, many people use the neem extract from leaves for bath to prevent infection against chicken pox which is caused due to varicella-zoster virus. Neem leaves in small amount taken orally to kill the harmful worms inside the body. It also helps for maintaining blood sugar level in body⁹⁴. Research showed that the several molecules extracted from the neem extract showed inhibitory effect on protein of the SARS-CoV-2¹⁰³.

Piper betel – Paan:

The scientific name of betel leaves is Piper betel L. belongs to the family Piperaceae. In ancient books of Ayurveda, the importance of Betel leaves has been described. In Chinese folk medicine, betel leaves are used for the treatment of various disorders and have detoxification, anti mutation and antioxidant properties. It has many vernacular names as in Sanskrit; it is known as Nagvelleri, Tamboolavalli or Tamboola, in Malayalam, it is called, Vetta or Vettila. It is a perennial climbing vine with semi-woody stem and short adventitious climbing roots. The leaves are glabrous with aromatic odour and pungent taste and extensively found in damp forests. In Hindu culture, betel leaves play an important role in various cultural, social, and religious occasions. The leaves are edible and have medicinal, religious and ceremonial value and consumed as a mouth freshener having a strong pungent and sweet taste with a strong aromatic flavor. The leaves vary from pungent taste too sweet in taste depending varieties of leaves, nutritional composition and chemical compounds¹⁰⁴.

Traditionally betel leaves are used for healing the illnesses like headache, scanty or obstructed urination, and weakness of nerves, sore throat, respiratory disorders, constipation, and problem of breast milk secretion, wounds, inflammation and boils¹⁰⁵.

The main constituents of Piper betel are Chavibetol acetate (15.5%) Chavibetol (53.1%). Other constituents are chavibetol methyl ester, allypyrocatechol, α-pinene, β-pinene, eugenol, safrole, α-limonene, 1,8-cineole. The chief chemical constituents of Piper betel are chevibitol, catechol, chavicol, charvacrol, allyl pyrocatechol, Vitamin A, B, C and essential oils having strong antioxidant and immunomodulatory activity against some bacterial and viral infections^94,106.

Piper betel possesses many pharmacological activities like antimutagenic, anticancer, anti-inflammatory, anti-amoebic, antigiardial, anti-microbial, mosquito larvicidal, antiulcerogenic, immunomodulatory, antifungal, radioprotective and antileishmanial activity¹⁰⁷.

Leaves contain essential oil, is used in respiratory catarrhs. Thus, it is used in the treatment of cough and easiness from the difficulty of breathing. Piper betel fruits with honey are an effective remedy for cough treatment¹⁰⁸. Betel leaf extracts also have the antioxidant and anti-inflammatory characteristics, are capable of scrimmaging against influenza-like disease¹⁰⁹.

Researchers also showed that betel leaf ingredients with commercially available influenza-specific antiviral showed a synergistic activity. Thus, it reduces the effective dose of antiviral drug and helps to reduce the cost of drug, pressure and development of resistant viral strains in the patient¹¹⁰.

Eugenia caryophyllata- Clove (Lavang):

The scientific name of clove is Eugenia caryophyllata L. Merr. & Perry (synonym: Syzygium aromaticum) belongs to the family Myrtaceae. It is used in the treatment of respiratory disorders, dental disorders, sore throats and headaches in traditional medicines in Australia and several Asian countries. Clove possesses anti-fungal, anti-microbial, anti-viral, anti-inflammatory, cytotoxic and anaesthetic properties. Clove also possesses anti-oxidant property and lipid peroxidation¹¹¹. The clove plant is rich in protein, carbohydrates, vitamins (A, C, E and K), thiamin, riboflavin, folate, niacin, dietary fibres and minerals¹¹².

The main chemical constituents of clove are eugenol (50-87%), eugenyl acetate, tanene, thymol and cariophyllene¹¹³. One study demonstrated that the ethanolic and aqueous extract of clove which is rich in eugenol have anti-oxidant activity¹¹¹.

The clove oil contains many phenolic compounds like eugenol, eugenol acetate, α- humulene and β- caryophyllene. It was also reported that clove oil has strong anti-inflammatory activity. It is revealed that eugeniin, one of the phytoconstituent of clove have good antiviral activity against the herpes virus. It inhibits the virus DNA polymerase enzyme and prohibiting the DNA synthesis¹¹⁴.

Cinchona:

The scientific name of Cinchona is Cinchona calisaya wedd belonging to family Rubiaceae. There are around 40 Genus of Cinchona tree. Cinchona ledgeriana and Cinchona officinalis are other species of Cinchona. Traditionally, Cinchona is used in the treatment of inflammation, fevers and other ailments. Cinchona is also used for influenza, leg cramps, common cold, etc.¹¹⁵ Many chemical compounds are derived from the Cinchona bark are chinoline derivatives such as quinine, cinchonine, cinchonidine, and quinidine. Quinine has strong antimalarial activity¹¹⁶. It shows other pharmacological activities like anti-arrhythmic, anti-parasitic, anti-protozoal, anti-spasmodic, cardiotonic and as a bitter digestive aid to stimulate digestive juices¹¹⁷.

Quinine is designated as an immunomodulatory agent, but it has been known for its immunostimulant and immunosuppressant activities against viral infections⁴⁸.

Chloroquine is a synthetic derivative of quinine, known since 1934 for the treatment of malaria. Due to its properties and mechanism of action encouraged, it is used in the treatment of different diseases. Currently, chloroquine (CQ) and its hydroxyl-analogue hydroxychloroquine (HCQ) cannot be used as antimalarial drugs. They are effective in the treatment of rheumatoid arthritis. Because they are low in cost and toxicity, high tolerability and immunomodulatory properties, CQ and HCQ have been proposed for use against viral infections¹⁰⁹.

When quinine increases the production of the IFN- α, it acts as an immunostimulator to inhibit viruses.

Otherwise, quinine inhibits the release of TNF-α secretion and shows immunosuppressant effect. These two different activities may have a beneficial effect on people who are infected with COVID-19 but routine consumption of this herbal medicine by healthy people for the prevention of COVID-19 is not recommended because it may cause various harmful events⁴⁸.

Nigella sativa- Black cumin (Kalonji):

Nigella sativa or black cumin is also known as Kalonji, are seeds of a flowering plant belonging to family Ranunculaceae. It is bitter in taste¹¹⁸.

Black cumin is reported to cure a variety of ailments including rheumatism, jaundice, diabetes, conjunctivitis, anorexia, intrinsic haemorrhage, cough, asthma, bronchitis, fever, influenza, anorexia, hypertension, dysmenorrhoea, scorpion poisoning and snakebite¹¹⁹. Black cumin possesses many pharmacological activities such as antiviral, anti-tussive, anti-inflammatory, immunomodulatory, anti-coagulant, bronchodilatory, anti-histaminic, spasmolytic, diaphoretic, antineoplastic, carminative and potent analgesic activity^119,120.

The important phytoconstituents present in black cumin are thymoquinone, dithymoquinone, α-pinene, p-cymene, thymohydroquinone, carvacol, pentacyclic triterpene, sesquiterpene, terpineol and saponins. Thymoquinone is the chief phytoconstituent present in black cumin which is responsible for most of its therapeutic properties¹²¹.

There are trace elements such as vitamins (Vitamin E, Thiamine, Niacin, Riboflavin, Folic acid, Pyridoxine,), and minerals (Phosphorus, Magnesium, Sodium, Potassium, Copper, Calcium, and Iron)¹²².

Black cumin shows antibacterial activity against staphylococcus aureus, Salmonella typhimurium, pseudoaeruginosa and H-pylori¹²³.

Black cumin seed oil possesses antioxidant property and inhibits certain types of short-lived local tissue hormone which are responsible for inflammation. The antioxidants which are present in the oil help to slow the cartilage degeneration.

Nigella sativa seeds and oil possess antiviral properties against viruses like hepatitis C virus (HCV) and HIV¹²⁴.

Researchers reported that the administration of Nigella sativa seed oil capsules in the dose of 450 mg, three times daily for 3 months to patients with Hepatitis C Virus (HCV) resulted in a significant decrease in viral load with increased Total Antioxidant Capacity (TCA) and improved laboratory biomarkers such as total protein, red blood cell, and platelet count, fasting blood glucose decreased and postprandial glucose in both diabetic and non-diabetic HCV patients¹²⁵. It was also reported that patients with COVID-19 received Nigella sativa seeds (80 mg/Kg/day) with honey (1 gm/Kg/day), significantly improved the symptoms, viral clearance and mortality in COVID-19 patients. Thus, Nigella sativa seeds and honey can be used alone or with other treatment for the prevention of COVID-19¹²⁶.

For the prevention of cold and cough, one can make a warm healthy tea mixture of crushed Black cumin seeds with pure honey and warm water.

Cuminum cyminum – Cumin (Jira):

The scientific name of cumin is Cuminum cyminum, belonging to the family Apaiaceae. It is referred to as Jira, Afedziiraa, Safedjiiraa, zeera in various parts of India. The name ‘Cumin’ derived from the Latin word ‘Cuminum’¹²⁷.

Cumin seeds are oblong and yellow–grey. Since ancient times cumin seeds in whole as well as in ground forms are used in several cuisines of many different food cultures. In India, cumin seeds have been used since ancient times as a traditional ingredient of numerous dishes including kormas and soups and also form an ingredient of several other spice blends¹²⁸.

The flavor of the seeds is due to the presence of the flavor component cumin aldehyde. Traditionally, cumin seeds are used as carminative, eupeptic, antispasmodic, astringent and used in the treatment of diarrhea, dyspepsia, mild digestive disorders, flatulence, morning sickness, colic, dyspeptic headache and bloating, and promote the combination of other herbs and to improve liver function¹²⁹.

Nutritionally cumin seeds contain proteins, fats, carbohydrates, soluble dietary fibres, vitamins (thiamine, riboflavin and niacin) and moisture¹²⁷.

The seeds contain major phytoconstituents are cuminaldehyde, limonene, α- and β-pinene, 1, 8-cineole, o- and p-cymene, α- and γ-terpinene, safranal and linalool, alkaloids, anthraquinone glycosides, flavonoids, resin, saponins, coumarin, tannin and steroids¹²⁹.

The seeds have also been used in bronchopulmonary disorders and as a cough remedy and as an analgesic. The mixture of seeds, alcohol and castor oil has been used for the treatment of scabies¹²⁰.

The cumin seeds possess multiple medicinal properties namely, antidiabetic, neuroprotective, cardioprotective, chemoprotective, anti-inflammatory, immunomodulatory, anti-oxidant, digestive stimulant, dyspepsia, anti-microbial and osteoprotective¹³⁰. Cumin seeds’ oil shows anti-inflammatory activity in lipopolysaccharides-stimulated RAW cells by inhibiting NF-κB and mitogen-activated protein kinase¹³¹.

In a recent study, it was found that oral treatment with cumin showed immunomodulatory activity in normal and immune-suppressed species by the stimulation of T cells (CD4 and CD8) with TH1 cytokines¹³².

FUTURE PERSPECTIVE AND CONCLUSION:

Due to the COVID-19, there is a need to discover new medicines for the prevention and cure of the deadly disease. There are a number of medicines of synthetic origin which are used to boost the immune system but there are a number of side effects and their cost is high. Thus, one can use Ayurvedic formulations and medicinal plants to boost immune system without any side effects. There are several medicinal plants that have been used for centuries for the treatment of various diseases in Ayurveda. They are considered as potential clinical agents against viral diseases due to their immunomodulatory and anti-viral properties. Many clinical trials are ongoing on these herbal medicinal plants for the prevention and treatment of COVID-19. The formulations derived from these herbal plants composed of a number of phytoconstituents such as terpenoids, sesquiterpenoids, alkaloids, flavonoids, tannins, resins, phenols, polyphenols, polysaccharides, saponins, proteins, lipids and peptides that possess various functions against viral invasion, penetration, replication, expression, assembly and release.

Many scientists all over the world are continuously working to develop a suitable antidote for this virus. In recent years, the use of medicinal plants is gaining more acceptances due to their versatility, safety, and cost-effectiveness. Many herbal medicinal plants show immunomodulatory, antiviral, anti-inflammatory and antioxidant properties, it may be considered for the treatment of COVID-19. There is a need to carry out standard clinical trials for scientifically prove its efficacy. The Council of Scientific and Industrial Research (CSIR) along with the AYUSH ministry work collaboratively on four Ayurvedic formulations for validation against COVID-19. The herbs which are mentioned in this review are used as immunomodulators and help to fight against the virus. Additionally, these herbs possess anti-inflammatory, antiviral, antioxidant, antimicrobial, anticarcinogenic, antiulcer and antinephrotoxicity activities in different studies. This herbal medicinal therapy can be used as primary and adjuvant therapy for the prevention and cure from the deadly coronavirus.

ACKNOWLEDGEMENT:

The author is thankful to P R Patil Institute of Pharmacy for continuous guidance and support.

CONFLICT OF INTEREST:

The author has no conflict of interest.

REEFERENCES:

1. Gadge SS, Game MD, Salode VL. Review on COVID-19 and its impact on Indian Economy. International Journal of Pharmacy and Biomedical Research. 2020; 7(3): 25-32.

2. Pilau MR, Alves SH, Weiblen R, Arenhart S, Cueto AP, Lovato LT. Antiviral Activity of the Lippia graveolens (Mexican Oregano) Essential Oil and its Main Compound Carvacrol Against Human and Animal Viruses. Brazilian Journal of Microbiology. 2011; 42(4): 1616-1624.

3. Kumar A, Chawla A, Gaganpreet, Diksha. A Valuable Insight to the Novel Deadly COVID-19: A Review. Research Journal of Pharmacology and pharmacodyanamics. 2020; 12(3): 111-116.

4. Dewagan V, Sahu R, Satapathy T, Roy A. The Exploring of Current Development Status and the Unusual Symptoms of Coronavirus Pandemic (COVID-19). Research Journal of Pharmacology and Pharmacodyanamics. 2020; 12(4): 172-176.

5. Chidgey SM, Broadley KJ. Respiratory Syncytial Virus Infections: Characteristics and Treatment. Journal of Pharmacy and Pharmacology. 2005; 57(11): 1371-1381.

6. Ball LA, Knipe DM and Howley PM. Virus replication strategies in field of virology. Lippincott Williams and Wilkims. USA. 2007.

7. Patil PA, Jain RS. Theoretical Study and Treatment of Novel COVID-19. Research Journal of Pharmacology and Pharmacodyanamics. 2020; 12(2): 71-72.

8. Rokade M, Khandagale P. Coronavirus Disease: A Review of a New Threat to Public Health. Asian Journal of Pharmaceutical Research. 2020; 10(3): 241-244.

9. Naresh BV. A Review of the 2019 Novel Coronavirus (COVID-19) Pandemic. Asian Journal of Pharmaceutical Research. 2020; 10(3): 233-238.

10. Debnath S, Chakravorty R, Devi D. A Review on Role of Medicinal Plants in Immune System. Asian Journal of Pharmacy and Technology. 2020; 10(4): 273-277.

11. Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yelen KY. Genomic Characterization of the 2019 Novel Human-Pathogenic Coronavirus Isolated from A Patient with Atypical Pneumonia After Visiting Wuhan. Emerging Microbes and Infections. 2020; 9(1): 221-236.

12. Durouiche S. Current Review on Herbal Pharmaceutical Improve Immune Responses Against COVID-19 Infection. Research Journal opf Pharmaceutical Dosage Forms and Technology. 2020; 12(3): 181-184.

13. Sharma L. Indian Spices: Hidden Treasure to Manage Ailments. EPRA Journals. International Journal of Multidisciplinary Research. 2017; 3(3): 226-230.

14. Khokra SL, Parashar B, Dhamijia HK, Bala M. Immunomodulators: Immune System Modifiers. Research Journal of Pharmacy and Technology. 2012; 5(2): 169-174.

15. Patil SB, Awale VB. Some Medicinal Plants Used by People of Sangli District, Maharashtra. Asian Journal of Pharmaceutical Research. 2011; 1(2): 42-43.

16. Block, Eric. Garlic and other Alliums: The Lore and the Science. Royal Society of Chemistry.

17. Butt MS, Sultan MT, Buitt MS, Iqbal J. Garlic: Nature’s Protection Against Physiological Treats. Critical Reviews in Food Science and Nutrition. 2009; 49(6): 538-555.

18. Shang A, Cao SY, Xu XY, Gan RY, Tang GY, et al. Bioactive Compounds and Biological Functions of Garlic (Allium sativum L). Foods. 2019; 8(7): 246.

19. Tsai Y, Cole LL, Davis LE, Lockwood SJ, Simmons V, Wild GC. Antiviral Properties of Garlic: In Vitro Effects on Influenza B, Herpes Simplex and Coxsackie Viruses. Planta Medica. 1985; 51(5): 460-461.

20. Nantz MP, Rowe CA, Muller CE, Creasy RA, Stanilka JM, Percival SS. Supplementation with Aged Garlic Extract Improves Both NK and δ-T Cell Function and Reduces the Severity of Cold and Flu Symptoms: A Randomized, Double-blind, Placebo-Controlled Nutrition Intervention. Clinical Nutrition. 2012; 31(3): 337-344.

21. Chandrashekhar PM, Prashanth KV, Venkatesh YP. Isolation, Structural Elucidation and Immunomodulatory Activity of Fructons from Aged Garlic Extract. Phytochemistry. 2011; 72(2-3): 255-264.

22. Sultan MT, Buttxs MS, Qayyum MN, Suleria AR. Immunity: Plants as Effective Mediators. Critical Reviews in Food Science and Nutrition. 2014; 54(10): 1298-1308.

23. Wu XJ, Hu Y, Lamy E, Sundermann VM. Apoptosis Induction in Human Lung Adenomacarcinoma Cells by Oil-Soluble Allyl Sulfides: Triggers, Pathways and Modulators, Environmental and Molecular Mutagenesis. 2009; 50(3): 266-275.

24. Altonsy MO, Andrews SC. Diallyl Disulphide, A Beneficial Component of Garlic Oil, Causes A Redistribution of Cell-Cycle Growth Phases, Induces Apoptosis, and Enhances Butyrate-Induced Apoptosis in Colorectal Adenomacarcinoma Cells (HT-29). Nutrition and Cancer. 2011; 63(7): 1104-1113.

25. Chen CY, Huang CF, Tseng YT, Kuo SY. Diallyl Disulphide Induces (Ca²⁺) Mobilization in Human Colon Cancer Cell Line SW480. Archives of Taxicology. 2012; 86: 231-238.

26. Schoeman, Fielding BC. Coronavirus Envelope Protein: Current Knowledge. Virology Journal. 2019; 16: 69.

27. Mashhadi NS, Ghiasvand R, Askari G, Hariri M, et al. Anti-oxidative and Anti-inflammatory Effects of Ginger in Health and Physical Activity, Review of Current Evidence. International Journal of Preventive Medicine. 2013; 4 (Suppl 1): S36-42.

28. Da Silveira e Sa Rde C, Andrade LN, deSousa DP. Sesquiterpenes from Essential Oils and Inflammatory Activity. Natural Product Communications. 2015; 10(10): 1767-1774.

29. Chang JS, Wang KC, Yeh CF, Shieh DE, Chiang LC. Fresh Ginger (Zingiber officinale) has Antiviral Activity against Human Respiratory Tract Cell Lines. Journal of Ethanopharmacology. 2013; 145(1): 146-151.

30. Bode AM and Dong Z. The amazing and mighty ginger. Boca Raton (FL) : CRC Press-Taylor and Francis. 2011.

31. Townsend EA, Siviski ME, Zhang Y, Xu C, Hoonjan B, Emala CW. Effects of Ginger and Its Constituents on Airway Smooth Muscle Relaxation and Calcium Regulation. American Journal of Respiratory Cell and Molecular Biology. 2013; 48(2): 157-163.

32. Cifci A, Tayman C, Yakut I, Halil H. Ginger (Zingiber officinale) Prevents Severe Damage to the Lungs Due to Hyperoxia and Inflammation. Turkish Journal of Medical Sciences. 2018; 48(4): 892-900.

33. Srivastava AK, Chaurasia JP, Khan R, Dhand C, Verma S. Role of Medicinal Plants of Traditional Use in Recuperating Devastating COVID-19 Situation. Medicinal and Aromatic plants. 2020; 9 (359): 1-16.

34. Kannappan R, Gupta SC, Kim JH, Reuter S and Aggrawal BB. Neuroprotection by Spice-Derived Neutraceuticals: You Are What You Eat! Molecular Neurobiology. 2011; 44(2): 142-159.

35. Rani MP, Padmakumari KP, Sankarikutty B, Cherion OL, Nisha VM, Raghu KG. Inhibitory Potential of Ginger Extracts against Enzymes Linked to Type II Diabetes, Inflammation and Induced Oxidative Stress. International Journal of Food Science and Nutrition. 2011; 62(2): 106-110.

36. Bhat SA, Rather SA, Iqbal A, Qureshi HA, Islam N. Immunomodulators for curtailing COVID-19: A Positive Approach. Journal of Drug Delivery and Therapeutics. 2020; 10(3-S): 286-294.

37. Brochot A, Guilbot A, Haddioui L, Roques C. Antibacterial, Antifungal and Antiviral effects of Three Essential Oil Blends. Microbiology Open. 2017; 6(4): e00459.

38. Fauvelle C, Lmbotin M, Heydmann L, et al. A cinnamon Derived Procyanidin Type A Compound Inhibits Hepatitis C Virus Cell Entry. Hepatology International. 2017; 11(5): 440-445.

39. Mritynjaya M, Pavitra V, Janhavi P, Neelam R, Halami PM, Ravindra PV. Immune-boosting, Antioxidant and Anti-inflammatyory Food Supplements Targeting Pathogenesis of COVID-19. Frontiers in Immunology. 2020; 11: 2337.

40. Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017; 6(92): 1-11.

41. Nadkarni KM and Nadkarni AK. Indian Materia Medica. Popular Prakashan Pvt Ltd. Bombay. 1976

42. Lelli D, Sahebkar A, JohnstonTP, Pedone C. Curcumin Use in Pulmonary Diseases: State of the Art and Future Perspectives. Pharmacological Research. 2017; 115: 133-148.

43. Shakibai M, Jhon T, Tanzil GS, Lehmann I, Mobasheri A. Suppression of NF-KB Activation by Curcumin Leads to Inhibition of Cyclo-oxygenax-2 and Matrix Metalloproteinase-9 in Human Articular Chondrocytes: Implicvations for the Treatment of Osteoarthritis. Biochemical Pharmacology. 2007; 73(9): 1434-1445.

44. shankhdhar PK, Mishra P, Kannojia P, Joshi H. Turmeric: Plant Immunobooster Against COVID-19. Research Journal of Pharmacognosy and Phytochemistry. 2020; 12(3): 174-177.

45. De R, Kundu P, Swarnakar S, Ramamurthy T, et al. Antimicrobial Activity of Curcumin Against Helicobacter pylori Isolates from India and During Infections in Mice. Antimicrobial Agents and Chemotherapy. 2009; 53(4): 1592-1597.

46. Singh RK, Rai D, Yadav D, Bhargava A, Balzarini J, De Cleroq E. Synthesis, Antibacterial and Antiviral Properties of Curcumin Bioconjugates Bearing Dipeptide, Fatty Acids and Folic acid. European Journal of Medicinal Chemistry. 2010; 45(3): 1078-1086.

47. Voduganthan M, Vardeny O, Michel T, McMurray, et al. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with COVID-19. The New England Journal of medicine. 2020; 382(17): 1653-1659.

48. Nugraha RV, Ridwansyah H, Ghozali M, Khairani AF, Atik N. Traditional Herbal Medicine Candidates as Complementary Treatments for COVID-19: A Review of Their Mechanisms, Pros and Cons. Evidence-based Complementary and Alternative Medicine. 2020: 1-12.

49. Cohen MM. Tulsi-Ocimum sanctum: A herb for All Reasons. Journal of Ayurveda and Integrative Medicine. 2014; 5(4): 251-259.

50. Godhwani S, Godhwani JL, Vyas DS. Ocimum sanctum: An Experimental Study Evaluating its Anti-Inflammatory, Analgesic and Antipyretic Activity in Animals. Journal of Ethanopharmacology. 1987; 21(2): 153-63.

51. Goothy SSK, Goothy S, Chaoudhary A, Potety CG, Chakraborty H, Kumar AHS, et al. Ayurveda’s Holistic Lifestyle Approach for the Management of Coronavirus disease (COVID-19): Possible Role of Tulsi. International Journal of Research in Pharmaceutical Sciences. 2020; 11(Suppl 1): 16-18.

52. Ravi V, Parida S, Desai A, Chandramuki A, Gourie-Devi M, Grau GE. Correltaion of Tumour Necrosis Factor Levels in the Serum and Cerebrospinal Fluid with Clinical Outcome in Japanese Encephalitis Patients. Journal of Medical Virology. 1997; 51 (2): 132-136.

53. Sangeetha P, Poornamathy JJ. In Vitro Assessment of Anti-inflammatory Activity of Ocimum sanctum (Karunthulasi leaves). International Journal of Pharma and Bio Sciences. 2015; 6(2): 1387-1391.

54. Khaerunnisa S, Kurniawan H, Awaluddin R, Suhartati S, Soetjipto S. Potential Inhibitor COVID-19 Main Protease (Mpro) from Several Medicinal Plant Compounds by Molecular Docking Study. 2020.

55. Yang R, Wang LQ, Yuan BC, Liu Y. The Pharmacological Activities of Licorice. Planta Medica. 2015; 81(18): 1654-1669.

56. Wang L, Yang R, Yuan B, Liu Y, Liu C. The Antiviral and Antimicrobial Activities of Licorice, a Widely Used Chinese Herb. Acta Pharmaceutica Sinica B. 2015; 5(4): 310-315.

57. Damle M. Glycyrrhiza glabra (Liquorice)- A Potent Medicinal Herb. International Journal of Herbal Medicine. 2014; 2(2): 132-136.

58. Matsumoto Y, Matsuura T, Aoyagi H, Matsuda M, Hmwe SS, Date T. Antiviral activity of glycyrrhizin against hepatitis C virus in vitro. PLoS One. 2013; 8(7): e68992.

59. Ashfaq UA, Masoud MS, Nawaz Z, Riazuddin S. Glycyrrhizin as Antiviral Agent Against Hepatitis C Virus. Journal of Translational Medicine. 2011; 9:112.

60. Srivastava AK, Chaurasia JP, Khan R, Dhand C, Verma S. Role of Taditional Plants of Medicinal Use in Recuperating Devastating COVID-19 Situation. Medicinal and Aromatic Plants. 2020; 9(5): 359.

61. Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee J, et al. Pharmacological Potential of Ginseng and its Major Component Ginsenosides. Journal of Ginseng Research. 2020.

62. Im K, Kim J, Min H. Ginseng, the Natural Effectual Antiviral: Protective Effect of Korean Red Ginseng against Viral Infection. Journal of Ginseng Research. 2016; 40(4): 309-314.

63. Kumar R, Grover SK, Divekar HM, Gupta AK, Shyam R, Srivastava KK. Enhanced Thermogenesis in Rats by Panax ginseng, Multivitamins and Minerals. International Journal of Biometeorology. 1996; 39(4): 187-191.

64. Block KI, Mead MN. Immune System Effects of Echinacea, Ginseng and Astragalus: A Review. Integrative Cancer Therapies. 2003; 2(3): 247-267.

65. Iqbal H, Rhee DK. Ginseng Alleviates Microbial Infections of the Respiratory Tract: A Review. Journal of Ginseng Research. 2020; 44(2): 194-204.

66. Lee JS, Hwang HS, Ju-Ko, Lee YN, et al. Immunomodulatory Activity of Red Ginseng Against Influenza A virus Infection. Nutrients. 2014; 6(2): 517-529.

67. Luxita Sharma. Immunomodulatory Effect and Supportive Role of Traditional Herbs, Spices and Nutrients in Management of COVID-19. Journal of PeerScientist. 2020; 3(2): 1-8.

68. Bang JS, Oh DH, Choi HM, Sur B-J, Lim S-J, Kim JY, et al. Anti-inflammatory and Antiarthritic Effects of Piperine in Human Interleukin Beta-Stimulated Fibroblast-like Synoviocytes and in Rat Arthritis Models. Arthritis Research and Therapy. 2009; 11(2): R49.

69. Ahmad N, Fazal H, Abbasi BH, Farooq S, Ali M, Khan MA. Biological Role of Piper nigrum L (Black pepper): A review. Asian Pacific Journal of Tropical Biomedicine. 2012; 2:1945-1953.

70. Takoori H, Aumeeruddy MZ, Rengasamy KR, et al. A Systemic Review on Black Pepper (piper nigrum L): from Folk Uses to Pharmacological Applications. Critical Reviews in Food Science and Nutrition. 2019; 59(1): 210-243.

71. Mittal R, Gupta RL. In Vitro Antioxidant Activity of Piperine. Methods and Findings in Experimental and Clinical Pharmacology. 2000; 22 (5): 271-274.

72. Mittal B, Chand T. Global Care through Ayurveda in Pandemic of COVID-19. International Journal of Health Sciences and Research. 2020; 10(6): 165-172.

73. Baliga MS, Dsouza JJ. Amla (Emblica officinalis Gaertn), A Wonder Berry in the Treatment and Prevention of Cancer. European Journal of Cancer Prevention. 2011; 20(3): 225-239.

74. Saini A, Sharma S, Chibber S. Protective Efficacy of Emblica officinalis against Klebsiella Pneumonia Induced Pneumonia in Mice. Indian Journal of Medical Research. 2008; 128(2): 188-193.

75. Khare CP. Indian medicinal plants - An illustrated Dictionary. Springer Science+ business media, New York. 2007.

76. Tiwari R, Chakraborty S, Saminathan M, Dhama K, Singh SV. Ashwagandha (Withania somnifera): Role in Safeguarding Health, Immunomodulatory Effects, Combating Infections and Therapeutic Applications: A review. Journal of Biological Sciences. 2014; 14(2): 77-94.

77. Singh N, Bhalla M, Jager P, Gilca M. An overview on ashwagandha: A Rasayana (Rejuvenator) of Ayurveda. African Journal of Traditional, Complementary and Alternative Medicines. 2011; 8(5 Suppl): 208-213.

78. Shah VV, Shah ND, Patrekar PV. Medicinal Plants from Solanaceae family. Research Journal of Pharmacy and Technology. 2013; 6(2): 143-151.

79. Bhattacharya SK, Goel RK, Kaur R, Ghosal S. Anti-stress Activity of Sitoindosides VII and VIII. New Acylsterylglucosides from Withania somnifera. Phytotherapy Research. 1987; 1(1): 32-37.

80. Cai Z, Zang G, Tang B, Liu Y, Fu X, Zhang X. Promising Anti-influenza Properties of Active Constituent of Withania somnifera Ayurvedic Herb Targeting Neuroaminidase of H1N1 Influenza: Computational study. Cell Biochemistry and Biophysics. 2015; 72(3): 727-739.

81. Mikolai J, Erlandson A, Murison A, Gregory WL, et al., In Vivo Effects of Ashwagandha (Withania somnifera) Extract on the Activation of Lymphocytes. The journal of Alternative and Complementary Medicine. 2009; 15(4): 423-430.

82. Vuksan, Sievenpipper, Vladimir, et al. Current Clinical Evidence for Korean Red Ginseng in management of Diabetes and Vascular Disease: a Toronto’s Ginseng Clinical Testing Program. Journal of Ginseng Research. 2010; 34(4): 264-273.

83. Gautam M, Diwanay SS, Gairola S, Shinde YS, Jadhav SS, Patwardhan BK. Immune Response Modulation to DPT Vaccine by Aqueous Extract of Withania somnifera in Experimental System. International Immunopharmacology. 2004; 4(6): 841-849.

84. Ashish Kumar, Jnanesha AC and Saudamalla Nagaraju. Cultivation and medicinal properties of Giloy [Tinospora cordifolia (Thunb) Miers]. Medicinal and Aromatic Plants. 2019; 18(1): 57-58.

85. Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolila (Wild.) Hook.f. and Thoms. (Guduchi)- Validation of the Ayurvedic Pharmacology through Experimental and Clinical Studies. International Journal of Ayurveda Research. 2010; 1(2): 112-121.

86. Nadig PD, Revankar RR, Dethe SM, Narayanswamy SB, Aliyar MA. Effect of Tinospora cordifolia on Experimental Diabetic Neuropathy. Indian Journal of Pharmacology. 2012; 44(5): 580-583.

87. Singh D, Chaudhari PK. Chemistry and Pharmacology of Tinospora cordifolia. Natural Product Communications. 2017; 12(2): 299-308.

88. Antul K, Amandeep P, Gurwinder S Chaudhary. Review on Pharmacological profile of Medicinal vine: Tinospora cordifolia. 2019; 35(5): 1-11.

89. Hartmann HT, Kester DE, Davies FT and Geneve RL. Plant Propogation Principles and Practices. Prentice-Hall of India Pvt. Ltd., New Delhi. 1997.

90. Saha S, Ghgosh S. Tinospora cordifolia: One plant, Many Roles. Ancient Science of Life. 2012; 31(4): 151-159.

91. Nair PK, Rodriguezs, Ramachandran R, Alamo A, Melnick SJ, Escalon E, et al. Immune stimulating Properties of a Novel Polysaccharides from the Medicinal Plant Tinospora cordifolia. International Immunopharmacol. 2004; 4(13): 1645-1659.

92. Sachan S, Dhama K, Latheef SK, Samad HA, Mariappan AK, Manuswamy P, et al. Immunomodulatory Potential of Tinospora cordifolia and CpG ODN (TLR 21 Agonist) against the Very Virulent Infectious Bursal disease virus in SPF chicks. Vaccines (Basel). 2019; 7(3): 106.

93. Srivastava N, Saxena V. A Review on Scope of Immunomodulatory Drugs in Ayurveda for Prevention and Treatment of COVID-19. Plant Science Today. 2020; 7(3): 417-423.

94. Srivastava AK, Chaurasia JP, Khan R, Dhand C, Verma S. Role of Medicinal Plants of Traditional Use in Recuperating Devastating COVID-19 Situation. Medicinal and Aromatic plants. 2020; 9(5): 1-16.

95. Hudson J, Vimalnathan S. Echinacea- A Source of Potent Antivirals for Respiratory Virus Infections. Pharmaceuticals. 2011; 4(7): 1019-1031.

96. Srivastava N, Saxena V. A Review on Scope of Immunomodulatory Drugs in Ayurveda for Prevention and Treatment of COVID-19. Plant Science Today. 2020; 7(3): 417-423.

97. Bhowmik D, Chiranjib, Yadav J, Tripathi KK and Kumar KP. Herbal Remedies of Azadirachta indica and its Medicinal Applications. Journal of Chemical and Pharmaceutical Research. 2010; 2: 62-72.

98. Islas JF, Acosta E, Buentello ZG, Delgado JL, et al. An Overview of Neem (Azadirachta indica) and its Potential Impact on Health. Journal of Functional Foods. 2020; 74: 1-13.

99. Alzohairy MA. Therapeutics Role of Azadirachta indica (Neem) and their Active Constituents in Diseases Prevention and Treatment. Evidence-based Complementary and Alternative Medicine. 2016.

100.Subapriya R, Nagini S. Medicinal Properties of Neem Leaves: A Review. Current Medicinal Chemistry- Anti-cancer Agents. 2005; 5(2): 149-156.

101.Biswas K, Chattopadhyay I, Banerjee RK, Bandopadhyay U. Biological Activities and Medicinal Properties of Neem (Azadirachta indica). Current Science. 2002; 82(11): 1336-1345.

102.Udeinya I, Mbah A, Chijioke C, Shu E. An Antimalarial Extract from Neem Leaves. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2004; 98(7): 435-437.

103.Baildya N, Khan AA, Ghosh NN, Tanmoy Dutta T, Chattopadhyay AP. Screening of Potential Drug from Azadirachta indica (Neem) Extracts for SARS-CoV-2: An Insight from Molecular Docking and MD-Simulation Studies. Journal of Molecular Structure. 2020.

104.Madhumita M, Guha P, Nag A. Bio-actives of Betel Leaf (Piper betel L.): A Comprehensive Review on Extraction, Isolation, Characterization and Biological Activity. Phytotherapy Research. 2020; 34(10): 1-19.

105.Sengupta R, Banik JK. A Review on Betel Leaf (PAN). International Journal of Pharmaceutical Sciences and Research. 2013; 4(12): 4519-4524.

106.Chauhan ES, Aishwarya J, Akriti Singh A, Tiwari A. A Review: Neutraceuticals Properties of Piper Betel (Paan). American Journal of Phytomedicine and Clinical Therapeutics. 2016; 4(02): 28-41.

107.Ramji N, Iyer R, Chandrasekaran S. Phenolic Antibacterials from Piper Betel in the Prevention of Halitosis. Journal of Etanopharmacology. 2002; 83(1-2): 149-152.

108.Arujothi S, Uma C, Sivagurunathan P. Comparative Evaluation on the Antibacterial Activity of Kapoori Variety Piper Betel Leaves against Certain Bacterial Pathogens. International Journal of Science and Research Methodology. 2016; 3(3): 35-45.

109.Akaike T, Noguchi Y, Ijiri S, Setoguchi K, Suga M, Zheng YM, Dietzschold B, Maedah H. Pathogenesis of Influenza Virus-induced Pneumonia: Involvement of both Nitric Oxide and Oxygen Radicals. Proceedings of the National Academy of Sciences of the United States of America. 1996; 93(6): 2448-2453.

110.Lakshmi BS, Naidu KC. Comparative morphoanatomy of Piper Betel L. Cultivars in India. Annals of Biological Research. 2010; 1(2): 128-134.

111.Dibazar SP, Fateh S, Daneshmandi S. Immunomodulatory Effects of Clove (Syzygium aromaticum) Constituents on Macrophages: In Vitro Evaluations of Aqueous and Ethanolic Components. Journal of Immunotoxicology. 2015; 12(2): 124-131.

112.Gulcin I, Elmastas M, Aboul-Enein HY. Antioxidant Activity of Clove Oil-A Powerful Antioxidant Source. Arabian Journal of Chemistry. 2012; 5(4): 489-499.

113.Ghorab AE, Massry KF. Free Radical Scavenging and Anti-oxidant Activity of Volatile Oils of Local Clove [Syzygium aromaticum] and Cinnamon [Cinnamomum zeylanicum] Isolated by Supercritical Fluid Extraction. Journal of Essential Oil Bearing Plants. 2003; 6(1): 9-20.

114.Lee KG, Shibamato T. Antioxidant Property of Aroma Extract Isolated from Clove Buds [Syzygium aromaticum (L.) Merr. et Perry]. Food Chemistry. 2001; 74(4): 443-448.

115.Jie An, Minie M, Sazaki T, Woodward JJ, Elkon KB. Antimalarial Drugs as Immune Modulators: New Mechanism for Older Drugs. Annual Review of Medicine. 2017; 68: 317-330.

116.Maraunder A, Ganzera M. Quantitative Determination of Major Alkaloids in Cinchona Bark by Supercritical Fluid Chromatography. Journal of Chromatography A. 2018; 1554: 177-122.

117.Rizk JG, Zadeh KK, Mandeep R Mehra MR, Lavie CJ, Rizk Y, Forthal DN. Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs. 2020; 80: 1267-1292.

118.Majdalawiech AF, Hmaidan R, Carr RI. Nigella Sativa Modulates Splenocyte Proliferation, Th1/Th2 Cytokine Profile, Macrophage Function and NK Anti-tumour Activity. Journal of Ethanopharmacology. 2010; 131(2): 268-275.

119.El-Hack MA, Alagawany M, Farag MR, Tiwari R, Kumaragurubaran K, Dhama K. Nutritional, Healthical and Therapeutic Efficacy of Black cumin (Nigella sativa) in Animals, Poultry and Humans. International Journal of Pharmacology. 2016; 12(3): 232-248.

120.Ahmad A, Husain A, Mujeeb M, Khan SA, et al. A Review on Therapeutic Potential of Nigella sativa: A Miracle Herb. Asian Pacific Journal of Tropical Biomedicine. 2013; 3(5): 337-352.

121.Al- Jassir MS. Chemical Composition and Microflora of Black Cumin (Nigella sativa L.) Seeds Growing in Saudi Arabia. Food Chemistry. 1992; 45: 239-242.

122.Kulyar MF, Rongrong Li, Mehmood K, Waqas M, Kun Li, Jiakui Li. Potential influence of Nigella Sativa (Black cumin) in Reinforcing Immune System: A hope to decelerate the COVID-19 Pandemic. Phytomedicine. 2020.

123.Salem EM, Yar T, Bamosa AO, Al-Quorain A, Yasawy MI, Alsulamain RM, et al. Comparative Study of Nigella sativa and Triple Therapy in Eradication of Helicobacter Pylori in Patients with Non-ulcer Dyspepsia. The Saudi Journal of Gastroenterology. 2010; 16(3): 207-214.

124.Molla S, Azad MAK, Hasib MAAA, Hossain MM, Ahammed MS, Rana S, Islam MT. A review on Antiviral Effects of Nigella sativa. Pharmacologyonline. 2019; 2: 47-53.

125.Maideen NM. Prophetic Medicine-Nigella sativa (Black cumin seeds)-Potential Herb for COVID-19? Journal of Pharmacopuncture. 2020, 23(2): 62-70.

126.Ashraf S, Ashraf S, Ashraf M, Imran MA, Kalsoom L, Siddiqui UN, et al. Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A Multi-center Placebo-controlled Randomized Clinical Trial. 2020.

127.Snafi AE. The Pharmacological Activities of Curcumin cyminum-A review. IOSR Journal of Pharmacy. 2016; 6(6): 46-65.

128.Srinivasana K. Cumin (Cuminum cyminum) and Black cumin (Nigella sativa) seeds: Traditional Uses, Chemical Constituents and Nutraceutical Effects. Food Quality and Safety. 2018; 2(1): 1-16.

129.Johri RK. Cuminum cyminum and Carum carvi: An update. Pharmacognosy Reviews. 2011; 5(9): 63-72.

130.Wei J, Zhang X, Bi Y, Miao R, Zhang Z, Su H (2015). Anti-inflammatory Effects of Cumin Essential Oil by Blocking JNK, ERK, and NF-kb Signaling Pathways in LPS-stimulated RAW 264.7 cells. Evidence-Based Complementary and Alternative Medicine. 2015: 474509.

131.Chauhan PS, Satti NK, Suri KA, Amina M, Bani S. Stimulatory Effects of Cuminum cyminum and Flavonoid Glycoside on Cyclosporine-A and Restraint Stress Induced Immune-suppression in Swiss Albinomice. Chemico- Biological Interactions. 2010; 185(1): 66-72.

132.Zandi K, Teoh BT, Sam SS, Fong WP, Mustafa MR, Sazaly A. Novel Antiviral Activity of Baicalein against Dengue Virus. BMC Complementary and Alternative Medicine. 2012; 12: 214.

Received on 21.02.2021 Modified on 08.03.2021

Res. J. Pharmacognosy and Phytochem. 2021; 13(2):81-94.

DOI: 10.52711/0975-4385.2021.00014