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Role ofHerbal Medicine inBoosting Immune System

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3 Immunity

The body’s inherent defense mechanism against a wide range of illnesses and conditions is referred to as immunity [16]. The human immune system is very complex but controls many infections by generating a limitless variety of cells. There are certain medicines, natural or synthetic, that make the immune system optimum so it works effectively, are known as immunomodulators. The diseases like cancer and autoimmune, apart from other diseases have been treated by the immunomodulators. Immunosuppressants and immunostimulants are two distinct types of immunomodulators in use [17]. One of the biological research areas that is expanding quickly is immunology, which holds enormous potential for treating a wide range of illnesses and disorders. In general, human immunity is grouped into two types: innate and adaptive. A rst-line defense from pathogens is known as innate immunity. The pathogens try to go inside the human body but they are prevented by protective barriers. The other system known as adaptive immunity (also called acquired immunity) recognizes the pathogens and then further regulation done by cells and organs. An adaptive immune response includes the two immune response which is called humoral immune response that involves lymphocytes and cellmediated cytotoxic response mediated by T cells. All the immune system’s cells, including their stem cells, are made in the bone marrow in a process called hematopoiesis. Either they develop into mature cells or they move to other distant areas to move [18]. Along with a wide variety of immune cells with specialized functions, certain molecules called cytokines, one of the key immune system mediators, mediate communication between the immune system’s specialized cells. This fully integrates the behavior and action responses of the cells [19].

4 Herbal Medicine inBoosting

theImmune System

Plants can improve immune function because they are high in avonoids, vitamin C, or carotenoids. Herbs high in avonoids may potentially have a slight anti-inammatory effect. They are known to have anti-inammatory and immunestimulating effects. It can enhance phagocytosis, stimulate the synthesis of interferon, and stimulate lymphocyte activity. Approximately 500 medicinal plants are mentioned in ancient literature, and approximately 800 plants have been used in indigenous medical systems. India is home to a vast array of medicinal plants used in traditional medical treatments [20]. Several plant species are used to treat various ailments in indigenous systems such as Siddha, Ayurveda, Unani, and Allopathy [21]. Many scientic studies have highlighted the importance and contribution of many plant

families used as medicinal plants, including Asteraceae, Liliaceae, Apocynaceae, Solanaceae, Caesalpiniaceae, Rutaceae, Piperaceae, and Sapotaceae. Medicinal plants are important in the development of new drugs. In India, natural products account for 70% of modern medicines. India has a very small (1.6%) share of this rapidly expanding global market. To compete in a growing market, it is critical to use and scientically validate more medicinally useful plants [22].

Indian Materia Medica, which made great use of leaves, bark, owers, roots, fruits, tubers, and uids, was predominately composed of vegetable materials. Ayurvedic pharmacology was founded on the theories of rasa, vipaka, virya, and prabhava, which did not clearly distinguish between diet and medication because both were essential elements of treatment [23, 24]. More than 700 herbal medications were documented by Charak, Sushruta, and Vagbhata along with their characteristics and medical use. Based on clinical results, 50 different drug categories have been identied, including digestive stimulants, laxatives, anti-diarrhea, antihemorrhoids, anti-emetic, antipyretic, anti-inammatory, anti-pruritic, antiasthmatic, antiepileptic, antihelminthic, hemopoietic, hemostatic, analgesics, sedative, promoter of life (Rasayana), promoter of strength [23].

The practice of Ayurveda, which experienced signicant neglect at the hands of the colonial authorities, was hampered by the introduction of Western medicine in the eighteenth century. Numerous laboratories and university departments carried out a tremendous amount of characterization of medicinal plants after the discovery of reserpine, but the results were depressing due to the poorly coordinated, diffused, and unfocused work [23]. Ayurveda and contemporary medicine now have a new interface, thanks to molecular pharmacology. Numerous Ayurvedic medicine categories could produce inventive molecular probes when used using contemporary methods. It is now possible to investigate how Ayurvedic medicines work using the most recent understanding of molecular pharmacology.

Indian science has been aware of the use of herbal therapy for jaundice, most likely caused by viral hepatitis, since the Vedic era. There have been reports of about 170 phytoconstituents with liver protecting properties, identied from 110 plants from 55 families. The number of commercial herbal preparations used as hepatoprotective medications is thought to be around 6000. In the Indian market, there are roughly 40 patent polyherbal compositions made from combinations of 93 Indian herbs from 44 families [25]. However, the most effective herbal remedies for the treatment of viral hepatitis have been identied as the following four:

(a) Silymarin derived from Silibum marianum seeds. (b) Picrorrhiza kurroa, often known as ‘Kutaki’ extracts.

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niruri and Phyllanthus amarus, have extracts that have been employed as hepatoprotective agents.

(d) With varying degrees of success, glycyrrhizin prepara-

tion has been used in the past to treat liver disorders and peptic ulcers [26].

4.1 The Eects ofMedicinal Plants ontheImmune System

In addition to other qualities that are known to either balance or strengthen the organism’s defense and response, a wide variety of plants that can be found all over the world include immunomodulatory capabilities [27]. These features regulate our system to support every part of our body. The information in this study focuses on herbal plants that have immunomodulatory qualities as well as antiviral, antioxidant, antibacterial, or anti-inammatory capabilities. Some of the representative plants have been discussed to understand the utility of herbal medicines in protecting the immune system. A list of plants and their formulations have been listed in Tables 1 [16–18, 28–51] and 2 [52–60].

4.1.1 Turmeric

Originally from Asia, the Zingiberaceae family includes turmeric (Curcuma longa). The plant material obtained from its roots and rhizomes has shown potential for various medicinal applications. Due to its pharmacological characteristics, turmeric has been utilized for millennia. Curcuminoids give turmeric its yellow color, and curcumin and curcuminoids together make up most of this well-known culinary spice [61]. Historically used topically to heal wounds or treat skin ulcers [62], as well as to treat rheumatism, sinusitis, the common cold, and liver disorders [63]. According to recent investigations, curcumin is regarded as a potent immunomodulatory drug capable of altering immune cell activity and reducing proinammatory cytokines [64], as well as exhibiting antioxidant [65] and anti-inammatory actions [66]. Both invitro evidence and invivo have demonstrated its valuable therapeutic properties in a variety of illnesses, including anxiety and depression [67] as well as cancer [68], cardiometabolic disorders, and lung and liver diseases [69].

Turmeric acts as a scavenger of oxygen free radicals and it can also prevent hemoglobin from oxidation. The main curcuminoid present in turmeric is curcumin which exhibits strong antioxidant properties [70], whereas other curcumanoids present

Table 1 Herbs with their botanical name and applications in immune system

S.No. Name of herb (botanical name) [Ref] Type of immune system

1. Aloe vera (Aloe barbadensis miller) [28–30]

2. Garlic (Allium sativum) [14, 15, 31, 32] Anti-inammatory, antioxidant, antibacterial, antiviral,

3. Tea (Camellia sinensis) [33–35] Antimicrobial, antioxidant, anti-inammatory, antifungal,

4. Senna [36] Antioxidant

5. Ashwagandha (Withania somnifera) [37,

38]

6. Tulsi (Ocimum sanctum) [39, 40] Antiviral, anti-inammatory, anti-diabetic, antimicrobial

7. Amla (Phyllanthus emblica) [16] Antioxidant, anti-diabetic

8. Neem (Azadirachta indica) [17] Antiviral, antifungal, and antibacterial

9. Ginger (Zingiber ofcinale) [18, 41, 42] Antioxidant, anti-inammatory, anticancer, antibacterial,

10. Cinnamon (Cinnamomum verum) [43, 44] Anti-diabetic, hypolipidemic, antifungal, antibacterial,

11. Black pepper (Piper nigrum) [45] Antihypertensive, anti-Alzheimer’s, antidepressant,

12. Shalaparni (Desmodium gangeticum) [46] Antiviral, antiasthamatic

13. Lasuna (Allium sativum) [46] Antibacterial, antiviral

14. Bahera (Terminalia bellirica) [47] Immunostimulant

16. Guduchi (Tinospora cordifolia) [48] Immunostimulant, anti-rheumatic, antiallergic

17. Gunja (Abrus precatorius) [49] Immunostimulant

18. Sada Bahar (Catharanthus roseus) [50] Immunostimulant, induces antibody production

20. Turmeric (Curcuma longa) [51] Immunostimulatory, anti-inammatory

Anti-inammatory, immune-boosting, antiviral, anti-diabetic, immune-modulatory, anti-inammatory, antioxidant, immunestimulant, antiviral, anti-inammatory

anticancer, immune-stimulant, antibacterial, antiviral, anticancer, anti-diabetic

antiviral, anti-infective, antioxidant

Antioxidant, ant-inammatory, anti-inammatory

antiviral, antifungal, antioxidant, anti-inammatory, and immune-booster

anti-inammatory

antiplatelets, anti-inammatory, antioxidant, antipyretic, antitumor, antiasthamatic, analgesic, antimicrobial

Role ofHerbal Medicine inBoosting Immune System

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Table 2 Combination of herbs with their botanical name and applications in immune system

S.No. Formulations of herbs [Ref] Type of immune system

1. Ashwagandha (Withania somnifera) and Maitake (Grifola frondosa) [52]

2. Ashwagandha (Withania somnifera) and Brahmi (Bacopa monnieri) [53]

3. Nyctanthes arbor-tristis L. and Withania somnifera [54]

4. Sweet basil, holy basil, Tulsi [55] Antitumor, antioxidant, anti-inammatory, antifungal,

5. Spearmint, peppermint [56] Antimicrobial, antispasmodic, carminative, and antiviral

6. Cinnamon, Ceylon, Cassia, Saigon [57] Antibacterial, antimicrobial, antioxidant, anti-inammatory,

7. Cumin, black cumin, black seed [58] Antimicrobial, antioxidant, anticancer, antitumor, antifungal,

8. Chili pepper, paprika [59] Antimicrobial, chemo-preventative, analgesic, antioxidant,

9. Echinacea purpurea, Astragalus membranaceus, and Glycyrrhiza glabra [60]

Cellular immunity

Enhances immunoglobulin production

Immunomodulatory, anti-inammatory, antitumor, inhibition of oxidants

antiviral, antibacterial

agents, antioxidant, antiulcer, cytoprotective, hepatoprotective, cholagogue, chemo-preventive, antiinammatory, antidiabetogenic

anti-diabetic, antifungal, antiviral

antibacterial, anti-inammatory

anticancer, antifungal, antiviral Immunomodulator

393

are demethoxycurcumin and bisdemethoxycurcumin (Fig. 2) [71], they possess radical molecules that prevent free radical formation. Curcumin has been shown to have antiallergic properties by inhibiting histamine release from mast cells [72]. It also acts as an immunomodulator by inhibiting the entry and replication of SARSCoV-2 virus into host cells [73].

4.1.2 Common g

The Mediterranean region’s tropical and temperate g (Ficus carica) tree, a member of the Moraceae family, is a source of

avonoids, phenolics, and polysaccharides [74]. The primary bioactive substance derived from F. carica is polysac- charide, which has been shown to have high antioxidant activity [75], antitumor capabilities [76], and, most importantly, immunoregulation function [77]. However, it has previously been demonstrated in induced colitis invivo testing [78]. This has positive effects on remodeling gut microbiome and treating colitis symptoms. More research is still required to conrm its anti-inammatory characteristics.

4.1.3 Astragalus

Astragalus (Astragalus membranaceus), a member of the Fabaceae family of plants that is mostly grown in China, Mongolia, and Korea, has been the subject of numerous studies and has been shown to have several advantages [79]. Immunomodulation [80], antioxidant activity [81], antiinammatory effects [82], anticancer activity [83], and antiviral activity [84] are the principal uses for this herb. The amount of active chemicals in its dried roots varies depending on where they were grown and when they were initially

picked [85], and it can be mixed with other herbs for enhanced performance. Enhancing the immune system, or using it as a tonic to strengthen the body’s defenses [86], can help with immunodeciency disorder therapies by decreasing the side effects brought on by conventional pharmacological treatments [87].

4.1.4 Garlic

Another amazing plant that has a signicant impact on the immune system is garlic (Allium sativum). It comprises a bulb from the Liliaceae family. It grows from 1.5 to 2.5cm and has traits and an Aromatic Odor. Bulb colors range from pink to white. It has been found that using garlic to improve immunity causes natural killer cells to become more active. For instance, certain studies strongly imply that garlic is a viable candidate for an immunological modulator that protects the immune system’s homeostasis [34]. This is because it contains more sulfur compounds, which are what give it its medicinal properties. Other medical conditions that can be treated with garlic’s chemical components include cancer, diabetes, atherosclerosis, and hyperlipidemia. Alliin, volatile oil, and allicin are present in garlic. Garlic is used to treat lung infections and is a carminative, expectorant, antimicrobial, and disinfectant [88]. The immunomodulatory effect

(i) inhibits the growth of cancer cells, (ii) modulates activity of chemical carcinogens, (iii) enhances capillary skin perfusion, and, (iv) enhances macrophage (oxidative burst) and

T- lymphocytes [88].

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Fig. 2 Chemical structures of curcumin and its derivatives

Fig. 3 Pictures of curry leaves and guava from DTU campus

A. Dabas et al.

4.1.5 Curry Leaves

Curry leaves (Fig.3), also known as Murraya koenigii, are a type of tree that grows in tropical and subtropical climates and belongs to the Rutaceae family. Originally from India, it is presently grown in another region of the world. The tree is tiny, at 6m tall. Bipinnate in structure, the leaves have 9–25 or more leaets on a short stalk [89]. Due to its distinctive aromatic quality, it is regarded as an herb and frequently employed as a avoring agent and enhancer. Conversely, curry leaves are shown to have positive health impacts when added to food or ingested in other ways due of their nutritious qualities [90]. Curry leaves include the following bioactive substances: Murrayanine, Scopoletin, Murrayanine glycosides, Koenine, Mahanine, Girinimbine, Koenidine, Koenigine, and Isomahanine [91]. Additionally, it is abundant in minerals like calcium, iron, and phosphorus as well as vita-

mins like vitamins A, B (niacin, thiamine, and riboavin), and C.Researchers have discovered that curry leaves have hepatoprotective, anti-inammatory, anti-diabetic, antimicrobial, and anti-hypercholesterolemia characteristics. Additionally, it aids in the treatment of vomiting, diarrhea, and a calcium shortage [88]. The leaves also contain the triterpenoid alkaloids cyclomahanimbine and tetrahydromahanimbine. There are tonic, stomachic, and carminative properties in the leaves, roots, and bark. Additionally, the leaves exhibit anti-emetic qualities. The stem distillate of the leaves has proven to have purgative qualities [92]. In addition to having anti-diabetic properties, its leaf extracts also have some actions that control immunology in relation to oxidative stress metabolism. Expression of the cytokines interleukin (IL)-2, 4, 10, and tumor necrosis factor-alpha (TNF-alpha) demonstrated this immunomodulatory and anti-inammatory action [93].

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4.1.6 Ghritkumari (Aloe Vera)

This succulent perennial plant, a member of the genus Aloe, is native to the desert regions of the Arabian Peninsula. It has a distinctive appearance because of the gel-like substance found in its thick, eshy leaves, which has led to its popularity as a decorative plant. Due to its extraordinary healing powers, aloe vera has been utilized for millennia in both traditional and alternative medicine. Its gel was used to treat burns, wounds, and other skin conditions. According to ancient Chinese, Indian, and Greek literature, aloe vera was highly prized for its therapeutic benets [87]. It has the following immunomodulatory effects:

(i) Its polysaccharides exhibit adjuvant activity for the for-

mation of antibodies and DTH, and it prevents UV-

induced suppression of DTH. (ii) Reduces inammation. (iii) Promotes faster healing of wounds and serves as an

oxygen radical scavenger. (iv) Cooperates with NO. (v) Promotes tumor regression [94].

4.1.7 Guava

Guava (Fig.3) is a tropical fruit, high in nutrients such as potassium, vitamin A, and vitamin C [95]. It also has a variety of phytochemicals and antioxidants. Because of its nutritional content and bioactive compounds, many studies suggest that guava may help boost the immune system in humans [96]. Guava is one of the richest sources of vitamin C, vitamin C acts as antioxidant and protects our immune system by neutralizing harmful free radicals which can damage cells and weaken the body’s defenses [97]. It also helps to produce white blood cells, which are necessary for ghting infections. Guava contains minerals such as Mg and Cu, all of which are important for immune system health. Guava components have anti-inammatory properties, which may help in the reduction of inammation. Guava contains antioxidants such as carotenoids, polyphenols, and avonoids that help in the reduction of oxidative stress in the body [98]. Oxidative stress can have a negative impact on the immune system but can be mitigated by eating antioxidant-rich foods like guava. Guava is also high in dietary ber, which is good for gut health. A healthy gut is associated with a stronger immune system because it houses a large portion of the body’s immune cells [99]. The active compounds present in guava extract such as polyphenol compounds act as an immunostimulant though these are not only compounds responsible for immunostimulatory activity but they play the major role. Phenolic compounds are mainly responsible for the high antioxidant activity in Guava [44].

4.1.8 Ginger

Ginger contains bioactive compounds such as phenolic groups, alkaloids, and steroids, all of which have medicinal properties [100]. Gingerol is the active compound that has powerful anti-inammatory effects [100]. It also contains antioxidants, which help protect our cells from free radical oxidative stress, when our cells are protected from these damages, our immune system works more efciently [101]. Ginger is benecial for increasing immunity due to its high antioxidant content, lowering stress due to its inuential anti-inammatory properties, and improving blood circulation [102].

Ginger is used to boost immune system because of its antibacterial nature. Health benets of ginger are as follows: relieves nausea, aids digestion, reduces oxidative stress, reduces the risk of heart disease, mitigates obesity [102]. The mechanisms for its anti-inammatory properties include:

(a) inhibition of arachidonic acid-induced platelet aggrega-

tion and formation of thromboxane B,

(b) upregulation of histone H3 acetylation, and suppressed

histone deacetylase (HDAC)1 expression,

of inammatory inducible NO synthase (iNOS).

4.1.9 Neem

Neem plant parts have antimicrobial properties due to their inhibitory effect on microbial growth. Neem has blood purifying properties as well. Neem leaves strengthen our immune system while also cooling our body internally. Neem has antibacterial and antifungal properties, which help to keep your skin clean, radiant, and healthy. Neem extracts contained immunomodulators that stimulated cells and macrophages [103]. The active ingredient in neem is nimbin, which has antioxidant and anti-inammatory properties [103]. Numerous biologically active substances, such as nimbin, nimbidin, nimbolide, and limonoids, are present in neem. Quercetin and β-sitosterol were the rst polyphenolic avonoids isolated from fresh neem leaves [104]. Neem has antiinammatory properties that can aid in the reduction of proinammatory cytokines and mediators [104]. This action aids in the regulation of excessive immune responses, which can result in chronic inammation and tissue damage. Macrophages are immune cells which help in engulfment of foreign substances and pathogens. Neem can increase macrophage activity, boosting the immune response to infections [105]. Neem has antimicrobial properties that can aid in the ght against pathogens such as bacteria, viruses, and fungi. Neem helps the immune system ght infections by inhibiting the growth and replication of these microbes [104].

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Fig. 4 Flavonoids/ polyphenols as immunomodulator against COVID-19

A. Dabas et al.

4.1.10 Arjuna

Terminalia arjuna (Roxb.) Wight & Arn., commonly referred to as Arjuna is one of the most prevalent and useful medicinal plants in traditional medicine. It is prevalent across India’s tropical and semitropical regions. Each component of Terminalia arjuna, including leaves, stem bark, roots, and fruit ha medicinal properties [106]. It contains analgesic, anti-inammatory, and immunostimulatory effects and has been utilized to treat a variety of human diseases as well as to maintain good health. The bark extract has a long history of use as a cardiac stimulant for its favorable effects in angina, i.e., “hritshool,” and is used in the treatment of heart failure, atherosclerosis, and hypercholesterolemia [107]. The herbal immunomodulator that contains T. arjuna is quite benecial for strengthening immunity and battling against Caecal coccidiosis [108]. The saponin glycosides are thought to be responsible for its inotropic effects, while avonoids/ phenolics may provide antioxidant activity as well as vascular strengthening activity, conrming the medicinal plant’s multifaceted role in cardio-protection [108].

Compared to their synthetic counterparts, many herbs and spices naturally have higher concentrations of bioactive chemicals. Ginger, a common spice, is used in both food and medicine since it has long been known to help with digestion. Basil, rosemary, cilantro, mint, and turmeric are just a few of the various herbs and spices that have historically been researched for their therapeutic benets [109]. Due to their high concentration of phytonutrients and other bioactive substances, herbs and spices can offer signicant benets to overall nutrition and hence toward immunity. Individuals with current eating patterns may nevertheless be decient in the critical nutrients needed for optimal health. The enormous array of health advantages of herbs and spices has been found to be unknown to many people [109]. Now, there is a growing interest and desire among both the general public and healthcare experts to understand more about the use of herbs and spices in health promotion. Regular use of these nutrients may help to strengthen immune defenses, which may reduce health risks and may speed up recovery. Recent studies have even concentrated on the use of herbs and spices to treat obese, metabolic syndromeaficted, and overweight people in order to lessen the effects of cytokine cascades of inammation in the body, which are comparable to those seen in COVID-19 instances (Fig.4) [110].

5 Some Specic Eect ofHerbal

Medicines

5.1 Modulation ofCytokines by Herbal Plant Products

Numerous invitro and invivo investigations to determine the impact of herbal medicine on cytokines have demonstrated that they have a signicant impact on a variety of cytokines. Interleukins (ILs), interferons, chemokines, and other soluble extracellular proteins or glycoproteins known as cytokines are essential for both innate and acquired kinds of immunity. These cytokines, which are secreted by all nucleated cells in an induced response to damage, maintain physiological stability through intermolecular interactions [19]. In reality, understanding the medical literature on numerous diseases makes it clear that these disease situations are connected to cytokine releases. These cytokines play a signicant part in most psychiatric disorders as well as diseases of the central nervous system, and aberrant discharges of these molecules have been shown. Under the control of cytokines, numerous neurochemicals, neuroendocrine, and neuroimmune substances have manifested [111]. Numerous behavioral changes, good and negative emotions, stress, infections, and other factors have all been shown to trigger cytokine release, and their signicance in cases of depression [112], Alzheimer’s disease [113], and schizophrenia [114] has been well documented.

5.2 Prebiotic Eects onHumoral Immunity inMedicinal Herbs

The gut microbiome, which is made up of more than 1000 different microbial species and is the rst barrier to overcome when taking herbal medications orally, is crucial for both localized immune system training and food absorption that affects lipid metabolism, which indirectly affects immunological prole [115]. It is well known that the active components of herbs have the potential to change the dynamic of microbial composition when considering individual gut enterotypes [116]. A higher concentration in the intestinal lumen and epithelium can signicantly affect the gut micro-

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biota given the low dose of active herbal components and difculties in being absorbed by the human body [117]. In addition to the direct impact of herbal ingredients on immune cells, lactobacilli and bidobacteria, which control the microbiota, play a critical role in immunological maturation and, ultimately, pathogen defense [118]. Prebiotics have a signicant impact on probiotic-mediated immunological improvement that is connected with modication of effector and regulatory T cell responses, according to randomized clinical trials on humans and multiple animal studies. In fact, oligosaccharides, such as inulin, fructooligosaccharides, and galactooligosaccharides, which are active components of herbs, promote the selective proliferation of these benecial bacteria in the gut, polarizing the immune response toward Th1 or Th2, and determining the outcome of antibody production by activated B cells [119]. Glabra Glycyrrhiza com- paring recognized plants with such efcient production, such as Lens culinaris and Camellia sinensis, Radix typically had the biggest magnitude increase in prebiotic benets [120].

5.3 Herbal Medicine that Directly Stimulates B Cells

in immunodecient patients with HIV infections, clinical trial studies on the ingestion of Phyllanthus emblica, Echinacea purpurea, and Plantago asiatica showed their herbal components serve as a potential immunostimulatory formulation with a signicant increase in effector and cytotoxic T cells and indirectly B lymphocytes response [126].

5.5 Bioavailability

A factor of great signicance is the herb’s active ingredients’ bioavailability. A substance must enter the bloodstream from the gastrointestinal tract before it can act systemically. Surprisingly little is known about herbal ingredients in this area. Goldenseal (Hydrastis canadensis L.), a well-known plant, contains substances like berberine and hydrastine that are virtually not absorbed after oral ingestion. Parenteral dosing of these alkaloids has been used in all animal studies demonstrating systemic effects. However, Goldenseal (Hydrastis canadensis) continues to be one of the most popular herbs, is heavily advertised, and is recognized as a general immunostimulant by an uninformed audience [127].

Only a limited portion of the medicinal component can be absorbed and get to the Peyer’s patches and rst-cluster gutassociated lymphoid tissue. By taking immunomodulatory herbs, it is possible to control the immunological response in Peyer’s patches [121]. Thuja summitates, Echinacea purpurea radix, Echinacea pallida radix, Baptisia tinctoria radix, and Echinacea pallida radix may all be able to activate B cells within Peyer’s patches cells [122]. Additionally, these herbs can enhance the activation of antibodies against other infections, such as lipopolysaccharide (a gram-negative bacterium’s endotoxin from its cell wall). It is widely known that 1,3-D-glucan, which is present in Sclerotinia sclerotiorum, is one of the active macromolecules incorporated by M cells (transporting particles with diameter range of 100 nm to 10 m) via endocytosis to reach the Peyer’s plaques [123]. However, this glucan also activates peritoneal macrophages and causes the production of cytokines that helps to modulate immunity. Additionally, Glycyrrhiza glabra Radix, Withania

somnifera Radix, Astragalus propinquus Radix, Oldenlandia diffusa, and Carthamus tinctorius have experimental data

supporting their ability to modulate B-cell activity [124].

5.4 Herbal Remedies that Indirectly Stimulate Cellular Immunity

Follicular helper T cells and dendritic cells, in particular, have the ability to drastically alter both the number and quality of the humoral response of B cells to antigens [125]. Even

6 Representative Examples ofNatural

Products withImmunomodulating Properties

The active ingredients from herbal medicines are mainly responsible for their biological activities [128–130]. The natural products belonging to the groups which are also known as secondary metabolites like phenolics, saponins, terpenoids, alkaloids, fatty acids, etc. play crucial role in enhancing the human immune system. The compounds like curcumin, quercetin, luteolin, propolis, and other secondary metabolites had shown potential immunostimulatory actions [4]. Some examples of natural products have been discussed here.

A avonoid quercetin is present in many plant species and not synthesized in human body. The studies show that this compound possesses antioxidant, antibacterial, antiinammatory, and antiviral properties [131]. In one of the clinical trials patients with rheumatoid arthritis were put on quercetin medication with 50mg/day for 8weeks. This was observed that the disease symptoms improved with reduction in pain plasma and levels of hs-TNF compared with the placebo group [132].

A dietary ber glucan which is a polymer of D-glucose is a natural product and linked in various combination through glycosidic bond. These are present in cell walls of many fungi, algae, and bacteria. Also, these are present in wheat, rye, barley, and oats. The studies have shown that the β-glucan enhances the cytotoxic activity of macrophages and NK cells, this helps in improvement in host immunity [133].

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These bers also interact with several cell surface receptors such as lactosylceramide selected scavenger, dectin-1, and complement receptor 3 and enhances immune system [4,

133]. The mushroom reishi (Ganoderma lucidum) produces

a glycan which enhances immunity through IgG or Iga expression in small intestinal and serum uid [4].

Another immunoregulator natural product molecule is melatonin, an indole derivative hormone. This molecule has been obtained from grapes, polives, maize, cherries, black pepper, seeds of Coffea arabica, Curcuma longa, Hypericum perforatum, etc. This molecule lowers the proinammatory cytokines and inhibits the immunity response [134].

7 Conclusions

The immune system plays a pivotal role to maintain human health by protecting the body from pathogens. The adaptive and innate types of the immune system encounter viruses, bacteria, or fungi to eliminate them and guard the body. However, the over expressive immune system is a problem to human beings as this leads to autoimmune diseases and allergies. The dietary balance, adequate food, minerals, and vitamins help in developing strong immunity systems. The traditional knowledge along with modern scientic tools has established the role of herbal medicines along with different natural ingredients in enhancing the immunity. The presence of bioactive phytochemicals like avonoids, terpenoids, polyphenols, vitamins, etc. in herbal materials showed immunomodulatory properties. The bioactive phytochemicals control the optimum functioning of immune cells, including basophils, NK cells, neutrophils, lymphocytes, macrophages, and mast cells, thereby enhancing the human immunity.

The role of herbal medicines in health-promoting effects including immunity still has to go a long way because there is lack of scientic evidences and clinical trials of various herbal materials and formulations. Another challenge is the quantication of active ingredients which keep changing due to change in altitude, ecology, and environments. Future research in this eld requires proper quantication of phytochemicals, efcacy of the extracts, proper dose range, etc.

Acknowledgments The authors Anchal Dabas, Parul Yadav, and Ram Singh are thankful to DTU, and Geetanjali to Kirori Mal College for infrastructural support.

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