Introduction
The human immune system is well organized comprising of many different immune cells like macrophages, neutrophils, T-lymphocytes, natural killer cells and various other specialized immune molecules like cytokines and antibodies that have evolved to mediate resistance against infections. Extensive use of antibiotics in infectious diseases, causes an emergence of multidrug-resistant strains of many pathogens that are posing serious challenges. There is a need to find suitable replacements for some of the currently used antibiotics.1 Medicines from ayurvedic plants are believed to promote good health and preserve organic resistance against infection by restoring body balance and conditioning the body tissues. Bioactive phytochemicals which include lignans, flavonoids, terpenoids, alkaloids, polyphenols, coumarins, saponins, tannins present in herbs can enhance immune system. Tinospora cordifolia (TC) is a valuable plant found to be a perfect immune-stimulatory herb.2 Apart from the normal anti-bacterial, anti-viral, anti-cancer, properties, and various health benefits, T. cordifolia exhibits immune-stimulatory efficiency by augmenting macrophage chemotaxis, phagocytosis and promotes interaction with other immune-regulatory lymphoid cells.
Table 0
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Taxonomical classification |
|
|---|---|
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Kingdom |
Plantae |
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Division |
Magnoliophyta |
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Class |
Magnoliopsida |
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Order |
Ranunculales |
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Family |
Menispermaceae |
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Genus |
Tinospora |
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Species |
Cordifolia2 |
Table 1
Vernacular names of TC2
Table 2
Morphological description2
Chemical composition of T. cordifolia
T. cordifolia contain many constituents which have been isolated and elucidated. They are diterpenoid lactones, phenolics, alkaloids, steroids, polysaccharides, glycosides, aliphatic compounds, and sesquiterpenoids. Diterpenoid lactones have anti-inflammatory, antioxidant and neuroprotective activity. Steroids used to treat rheumatoid arthritis, inflammatory bowel disease and asthma. Alkaloids used as anaesthetics and cardioprotective agent. Sesquiterpenoids and glycosides are used in cardiovascular disease and in antimalarials.2
Table 3
Chemical compositions of the Tinospora cordifolia herb2
Immunomodulatory Activity
Tinospora cordifolia due to its potential in improving the immune system and the body resistance against infections it has been extensively used in Ayurveda. Arabinogalactan polysaccharide (G1-4A) which is a compound found in T. cordifolia's stem. It has protective action against lipopolysaccharide-induced endotoxic shock by modulating cytokines and nitric oxide excretion by murine macrophages. Immunomodulatory active components present in T.cordifolia are N-methyl-2-pyrrolidone, N-formylannonain, 11-hydroxymustakone, cordifolioside A, tinocordiside, syringin, and magnoflorine have been reported for their ability to regulate the immune system.2
In mice, it has been studied and reported that the extract of T. cordifolia can upregulate the cytokine IL-6, with subsequent events that include activation of the inflammatory response and cytotoxic T cells as well as differentiation of B cells. Further it has been investigated on rats suggested that there is a cytotoxic effect of the active compounds, including compounds in aqueous extracts, such as alkaloids, glycosides di-terpenoid lactones, phenolics, steroids, aliphatic compounds, sesquiterpenoids, and polysaccharides. And studied that, the alpha-d-glucan derived from T. cordifolia was able to activate human lymphocytes and down regulate the production of inflammatory mediators.3
Pharmacological Activities of Tinospora Cordifolia
In-vitro studies
Extracts of TC has been found to enhance lysosomal secretion in several cell lines. TC powder (80 µg/ml) showed enhanced secretion of lysosome by macrophage cell line J774A according to different time intervals (24 & 48 h) this was due to activation of macrophage by immunomodulator. Production of nitric oxide and lysosome shows one of the main microcidal mechanisms of macrophage.
Apart from being immunomodulator, TC extracts (dry stem, 500 µg/ml) also enhanced antioxidant defences (increased SOD and Catalase) and decreased oxidative damage (reduced TBARS) in liver and spleen homogenates isolated from 8-12 week old CH3 mice,4
Table 4
Immunomodulatory activity of Tinospora cordifolia in vitro.
Animal studies
Upadhyaya and co-workers studied the effect of aqueous (Aq.) extract of T. cordifolia on B16F10 mice (at a dose of 1 mg/kg) helped in boosting of phagocytic activity of macrophages by increasing the production of NO from peritoneal murine macrophages. NO is the key molecule in the regulation of immune response and this further strengthens the role of macrophage in producing NO by direct lysis of B16F10 melanoma cells in vitro.6
Alsuhaibani and co-workers studied AECT and MECT of T. cordifolia on BALB/C mice (murine macrophage cell line J774) infected with Salmonella typhimurium (at a dose of 100 mg/kg orally for 7days). Result was measured by zone of inhibition, which showed anti-salmonella activity of methanol extract was higher as inhibition zone was 12 mm, where as in aqueous extract treated mice it was just 5 mm. However, macrophages treated with aqueous and methanol extract secreted greater levels of IFN-y, TNF-α, and IL-6 and thereby reduced the bacterial load.7
Bishayi and co-workers studied the effect of Aq. extraction T. cordifolia on adult male albino rats (at a dose of 100 mg/kg body weight for 15 days) had deleted the immunosuppressive effect (decreased phagocytic capacity, chemotactic migration and cell adhesiveness) of CCl4 intoxication because of significant increment in the functional capacities of rat peritoneal macrophages. SGOT, SGPT, SALP and bilirubin level will be decreased nearer to normal level as they were increased in CCl4 intoxication.8
Aranha and co-workers studied the effect of Aq. extract of T. cordifolia which was subjected to protein precipitation on BALB/c mice (at a dose of at 30 µg on days 1, 14, 21, 28, 35 and 42 through nostril) showed increase in body weight (p<0.005) on day 50 compared to day 1 in test group, thus showed humoral immune response (serum IgG and IgA increased) and indicated its intrinsic immunogenicity.9
Sachan and co-workers studied the Immunomodulatory potential of Aq. extract of T. cordifolia on (SPF) chicks infected with very virulent IBDV (vvIBDV) (at a dose of 50 µg/bird/day via intramuscular injection and 10 ml/bird/day orally for 4 weeks). It showed significant increase (p < 0.05) in immune response genes in PBMCs like IL-2 (5.657 _ 0.1663), IFN- (15.15 _ 0.2288), IL-4 (8.458 _ 0.277), and IL-1_ (13.09 _ 0.2681) expressions in chicken PBMCs compared to the control group as these were decreased in infection by virus.10
Ranjith and co-workers studied the effect of Aq. extract of T. cordifolia on Wistar rats (150-200g of body weight) (at a dose of 10 mg/kg body weight for 14 days) significantly increased the antibody production against SRBC. Even at a concentration of 5 microgram/ml showed.
Table 5
Immunomodulatory activity of Tinospora cordifolia in animals.
Human studies
Sharma and co-workers studied how Tinospora cordifolia enhances immunity in children. Shade dried T. cordifolia plant powder was administered orally to 200 children of age 1-15 years (at dose of 100 mg/kg bw twice daily after food with honey for 60 days). There was a significant increase in TLC, ALC and lymphocyte percentage on 30th day (p<0.05) as well as 60th day (p<0.001) as compared to 0th day and test group. They concluded that T. cordifolia can be used as adjuvant to vaccination in order to boost the immune system.12
Castillo and co-workers studied the effect of T. cordifolia lotion on Paediatric patients diagnosed with scabies caused by Sarcoptes scabiei, by applying on skin. Then the analysed peripheral blood samples collected from anticubital vein from 0th day, 14th day and 28th day showed the decrease level of interleukins at 14th and 28th day compared to control (IL-1, IL-6 & IL-8)y) and nearer to normal level. These interleukins serve as inflammatory agent inducing the production of acute phase and complement protein by hepatocytes.13
Table 6
Immunomodulatory activity of Tinospora cordifolia in humans.
Conclusion
A number of studies substantiate immunomodulatory activity of Tinospora cordifolia. Above discussed studies showed that how the aqueous and methanol extracts of T. cordifolia which contained active compounds in the form of alkaloids, glycosides, lactones and steroids have increased immune response and phagocytic activity. And also, these extracts fight against infections like in salmonellosis7 and IBDV10 by increasing interleukins level. Above studies also suggested to use T. cordifolia as vaccines in children12 Glycoproteins present in aqueous extract of T. cordifolia stem acts on macrophages and stimulates the production of effector molecules like nitric oxide and cytokine mediators and in augment the antigen specific recall response, thereby enhances immune response.6 T. cordifolia on (SPF) chicks infected with very virulent IBDV has decreased the infection10 T. cordifolia lotion on Pediatric patients diagnosed with scabies caused by Sarcoptes scabiei, has reduced the infection by its anti-inflammatory activity when applied on skin.13 T. cordifolia showed enhanced secretion of lysosome by macrophage cell line J774A according to different time intervals.5