TINOSPORA CORDIFOLIA CAN CURE SYSTEMIC LUPUS ERYTHEMATOSUSHTML Full Text
TINOSPORA CORDIFOLIA CAN CURE SYSTEMIC LUPUS ERYTHEMATOSUS
Arya Tanmay Gupta
Ramanujan College (University of Delhi), New Delhi - 110019, Delhi, India.
ABSTRACT: Tinospora cordifolia (T. col.), a plant which has great significance in the Ayurvedic system of medicine, has been tested according to modern medical techniques for numerous therapeutic effects like immunomodulation, reducing tumor cells, purification of blood, reducing fatty lipids from body, reduction of glucose and increasing glucose tolerance in case of diabetes and increasing body weight. T. col has been used even during various rheumatic diseases like rheumatoid arthritis and has shown positive therapeutic effects. T. col. reduces the unwanted lipids. It enhances the humoral immune response. It also cleans out the immune complexes from the body. T. col. acts as an adaptogen. It has been reported to both increase and decrease activities of substances in the body, so as to normalize its functionality. It enhances immunity, but on the other hand, it inhibits autoimmunity. This paper is a review of the findings of the medical benefits of T. col., and combining all the information to propose that this plant may be used in the treatment of another rheumatic disease, systemic lupus erythematosus (SLE).
Tinospora cordifolia, Ayurved, immune complex, immunomodulation, Systemic lupus erythematosus
INTRODUCTION: Tinospora cordifolia (T. col.) is a large, glabrous, perennial, deciduous, climbing shrub. It has a weak stem and is found throughout India. It is widely used in folk and Ayurvedic systems of medicine 1, 2. The shrub of T. Col. has been reported to contain alkaloid, diterpenoid lactone, glycoside, steroid, sesquiterpenoid and phenolic molecules. It also contains aliphatic compounds and polysaccharides 3. According to Upadhyay et al., 2010; Kulkarni, Kellaway, and Kotwal, 2005, 1, 2 major properties and uses of Tinospora cordifolia which are acquiring scientific validity are as follows T. col.:
(1) acts as alleviator, (2) alleviates from severe fevers, (3) acts as moderator of vata, pitta, and kapha; medical situations related to air-related organs like the organs involved in respiratory systems, fluid organs like pancreas and gall bladder and organs related to cough, (4) acts as inhibitor of inflammation, (5) alleviates blockage in breathing, (6) alleviates jaundice, (7) alleviates skin diseases, jaundice and gout diseases, (8) acts as antipyretic, (9) treats parasites, (10) treats gonorrhea, (11) treats hemorrhoids, (12) alleviates heart situations.
Scientific research has reported that T. col. inhibits diabetic, pyretic, spasmodic, inflammatory, arthritic, oxidant, allergic, stress, leprotic, malarial, and neoplastic activities in the human body. It also shows hepato-protective, immuno-modulatory activities. T. col. also exhibits chemopreventive ability against immunological disorders and cancer and has a history of use against spasms, inflammation, arthritis, allergy, diabetes, cardio-toxicity, and immunosuppression 4. This paper is a review of the scientific findings of the therapeutic benefits of T. col. In section 3, its immunomodulatory effects are described, specifically the effects of T. col. on the immune system; section 2 describes the therapeutic effects of T. col. in all other organ systems and related diseases. In section 4, all the therapeutic benefits of T. Col. are summarized. In section 5, the findings of the characteristics of systemic lupus erythematosus (SLE) are described; the behavior of the body of the patients of SLE, along with the existing medication procedures and their side effects are discussed. Then in section 6, this paper advocates the use of T. col. to cure SLE. Finally, we conclude our findings discussing the future perspective of the use of T. col. in medical procedures.
Effect of administration of T. cordifolia:
A) Tumour Growth: Administration of T. col. has shown a reduction in tumor growth in various works. Mathew and Kuttan, 1999 showed that methanolic extract of stem of T. col. could reduce tumor cells in BALB/c mice (200 mg/kg, i.p., daily for 5 days). Mathew and Kuttan, 1999 have also reported that this extract synergistically acted with cyclophosphamide and reduced the animal tumors to 83% 5. Jagetia and Rao, 2006 has reported a dose-dependent reduction in tumor cells in the mice transplanted with ehrlich ascites carcinoma 6. Thatte et al., 1992 7 showed that T. Col. reduces polymorph phagocytosis. Mittal and Singh, 2009 4 reported that Tinospora exhibits anti-cancer properties. col. has shown to upregulate the antitumor activity of tumor-associated macrophages (TAM). It enhances differentiation of TAM to dendritic cells (DC) in response to granulocyte/macrophage-colony-stimulating factor, IL-4, and tumor necrosis factor. T. col. shows tumor cytotoxicity. It leads the production of tumouricidal soluble molecules like TNF, IL-1, and NO 8.
B) Bone Marrow: Mathew and Kuttan, 1999 5 showed an increase in bone marrow cellularity 18.16 × 106 / femur along with ⍺-esterase in bone marrow (1423/4000 cells). This indicated increased maturation of stem cells. Aher and Wahi, 2010 9 has also reported an increase in bone marrow cells in treatment with T. col.
C) Cardiovascular System, Blood: Babu et al., 2017 10 has shown that T. col., used in combination with Carica papaya, leaf extract can increase the platelet count in case of dengue or other microbial infections, in cancer patients and thrombo-cytopenia. Nayampalli et al., 1986 reported decreased capillary permeability (in rats) because of T. col 11.
D) Diabetes: Rajalakshmi et al., 2009; Stanely et al., 2000; Stanely et al., 2003 reported that T. col. shows potent anti-diabetic activity and reduces blood sugar. It reversed the reduction of glucokinase and increased glucose-6-phosphatase activity, which was stimulated when rats were induced with streptozotocin diabetes. T. col. also improves Insulin and C-peptide levels. They also reported that β-cells, which secrete insulin, were regenerated substantially 12, 13, 14. T. col. has been used to treat diabetes mellitus 15, 16, 17. T. col. reduces serum and tissue cholesterol, phospholipids and free fatty acids in alloxan diabetic rats. Stanely et al., 1999, Stanely et al., 2000 have shown T. col. to lower hepatic glucose-6-phosphatase and serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase in diabetic rats 18, 19. T. col. reduces blood glucose level and increases glucose tolerance 19, 20. Stanely et al., 2000 reported that T. col. reduced brain lipids in diabetic rats; its aqueous root extract caused an increase in their body weight 13.
E) White Blood Cells: Mathew and Kuttan, 1999 has shown that the total count of WBCs was increased in BALB/c mice 5. Bishayi et al., 2002 has reported that water extract of T. col. increases the WBC count in mice; Tinospora sinensis is even more effective 21. Goel et al., 2004 opined that T. col. treatment restored total lymphocyte counts (TLC) 22. Aher and Wahi, 2010 has reported an increase in WBC count on treatment with T. col. alcohol extract 9. T. col. enhances phagocytosis 23, 24, 25. Ahmad et al., 2015 reported that Tinospora crispa enhances the chemotactic activity of neutrophils. Ahmad et al., 2015; Thatte et al., 1992 reported that T. col. enhances the phagocytosis activity of neutrophils 26, 7. T. col. activates / proliferates nuclear killer cells 27-32. Gupta et al., reported a significant increase in the mean phagocytic index 33. ⍺-D-glucan, a polysaccharide derived from T. col., shows the activation of nuclear killer (NK) cells 34. Raghua et al., 2009 has reported that treatment by G1-4A, a polysaccharide from Tinospora cordifolia, increased in the CD69 expression in lymphocytes 35.
F) Body Humor and Lipids: Mathew and Kuttan, 1999 has observed that T. col. has increased the plaque-forming cells in the spleen (1575 PFC/106 spleen cells) and circulating antibody titer (256) in BALB/c mice 5. Raghua et al., 2009 reported that G1-4A increased spleen cellularity and upregulated anti-apoptotic genes T. col. improves improve humoral immune response 35. Kapil and Sharma, 1997 has reported an increase in humoral immunity dose-dependently 36. Jagetia and Rao, 2006 has reported a drastic increase in lipid peroxidation to reduce tumor cells in mice 6. Desai et al., 2002 has reported that partially purified T. col. prevented lipid peroxidation to reduce thiobarbituric acid reactive substances in the liver when they were increased and increase the activities of superoxide dismutase and catalase when it was reduced in mice exposed to radiation 37. Subramanian et al., 2002 reported that T. col. showed good protection against iron-mediated lipid peroxidation of rat brain homogenate and provided protection to proteins against ɣ-ray induced damage 38.
G) Central Nervous System: Tinospora cordifolia Menispermaceae has been mentioned as an adaptogen 39, 40, 41. Adaptogens have been associated with stimulating and stress-protective effects in the central nervous system (CNS) and vegetative nervous systems, the endocrine system, and the immune system comprising by definition the parts of a neuroendocrine immune complex stress system.
H) Other Organ Systems: CCl4 is harmful to liver. Bishayi et al., 2002 has reported that the liver of albino rats was protected by cordifolia, which were first administered with CCl4 earlier 21. Bairy et al., 2004 has shown that T. col. has enhanced verbal learning and memory, and logical memory 42. Agarwal et al., 2002 reported that T. col. administration enhances cognition (learning and memory) in rats 43. The stem of T. col. is useful in treating skin diseases. The root and stem of T. cordifolia are prescribed in combination with other drugs as an antidote to snakebite and scorpion sting 44, 45, 46, 47, 48. Sannegowda et al., 2015 showed that T. col. extract treatment limits bone damage. It shifts the balance of mediators of bone remodeling in favor of anti-osteoclastic activity to accomplish this. An example of such a mediator of bone remodeling is receptor activator of nuclear factor-kB ligand [RANKL] and MMP-9 49. T. col. inhibits the growth of Mycobacterium tuberculosis 50. Nayampalli et al., 1986 have reported that T. col. decreased the bronchospasm induced by 5% histamine aerosol 11.
Sushrut Samhita has suggested almost 50 drugs in different groups for the prevention of pregnancy loss. 11 ingredient herbs out of them were selected to make the combination of Torchnil. One of them is Tinospora cordifolia. This formulation combats the infections, immune complexes and stress of lipid peroxidation in placenta. It proved to be effective against HIV also 51. T. col. causes protease inhibition 52, 53.
I) Irradiation: Tinospora exhibits radioprotective properties 4. Mice were administered with T. Col. before full-body gamma irradiation; Goel et al., 2004 reported 76.3% survival. Goel et al., 2004 has also opined that because of its radioprotective manifestation, T. col. can be exploited for human applications 22. Radiation produced reactive oxygen and nitrogen species (ROS/RNS) were generated by photosensitization/peroxynitrite in mice. Photosensitization caused a significant increase in thiobarbituric acid reactive substances in liver. The activities of superoxide dismutase and catalase were reduced. T. col. restored activities of both these enzymes. Oxidative damage caused by peroxynitrite was inhibited by T. col. The degradation of proteins due to photosensitization was significantly reduced 37.
Immunomodulatory Effects of Tinospora cordifolia:
A) Immune System and Antibodies: Bishayi et al., 2002 has reported that the immunosuppressive effect of CCl4 in albino rats was inhibited by cordifolia 21. Manjrekar et al., 2000 has reported that T. col., because of its immunomodulatory properties, inhibited cyclophosphamide induced anemia 54. Aher and Wahi, 2010 has opined that T. col. shows potent immunomodulatory activity 9. Kapil and Sharma, 1997 reported a dose-dependently increase in cell-mediated immunity 36. T. col promotes the production of antibodies 55 and also enhances lysozyme activity and antibody responses 29, 30, 31. Sudhakaran et al., 2006 reported that ether and petroleum extracts of T. col. enhanced the secondary antibody response. T. col. also enhances neutrophil activity, provides protection against A. hydrophila 56. Ranjith et al., 2008 reported that T. Cordifolia aqueous and ethanolic extracts enhanced antibody production when sheep red blood cells were used as antigens 23. T. Col. provides protection against sepsis and cecal ligation. It also provides protection against E. coli induced peritonitis in mice and E. coli induced cholera in humans 57-63.
More and Pai 2011; Panossian and Wikman 2005 also reported the protection provided by T. col. from E. coli. Administration of T. col. resulted in a significant increase (P<0.05) of total serum immunoglobulin 64, 7, 33. Dry barks of T. cordifolia has anti-spasmodic, anti-pyretic 65, 66, 67, anti-allergic 68, anti-inflammatory 69, 70, 52, 53 and anti-leprotic properties 71. T Col. has been observed effective against acute inflammation and has been functional as non-steroidal anti-inflammatory agent 72. Nayampalli et al., 1986 reported that T. col. reduced the number of disrupted mast cells (in rats) 11. Nair et al., 2006 reported that (1,4)-α-d-glucan inhibited the binding and internalization of opsonized zymosan A bioparticles. The anti-CD11b mAb inhibits the zymosan A-induced tumor necrosis factor (TNF)-α synthesis 73.
B) Complement System: Kapil and Sharma, 1997 reported that when antibody-coated sheep erythrocytes by guinea pig serum are treated with T. col., Syringin (T. col.-4) and cordiol (T. col.-7) inhibit the in vitro immunohaemolysis. This inhibition was found to be due to inhibition of the C3-convertase of the classical complement pathway 36. Col. has also shown to activate the complement system 27-32, 24, 25, 55, 74, 75, 34, when required by the body in cases like chronic tonsillitis, gamma irradiation.
C) Macrophage: col stimulates the secretion/ proliferation of macrophages 55. Raghua et al., 2009 reported that G1-4A has resulted in an increase in macrophage count 35. Mathew and Kuttan 1999 has reported a significant enhancement in macrophage activation 5.
Kapil and Sharma, 1997 has reported that macrophage activation was reported for various polysaccharides of Tinospora cordifolia, such as cordioside (T. col.-2), cordiofolioside A (T. col.-5) and cordiol (T. col.-7); with increasing incubation times, this activation was more pronounced 36. Abood et al., 2014 showed that T. crispa crude extract significantly stimulates RAW 264.7 cells 76. More and Pai, 2011 reported that T. col. enhanced secretion of lysozyme by macrophage cell line J774A 64.
D) T and B Cells: col. activates / proliferates T and B cells 32, 55, 74, 35. Desai et al., 2002 reported that dry stem crude extract (DSCE) of Tinospora cordifolia contained a polyclonal, G1-4A, which is a B cell mitogen 37. Nair et al., 2006 reported that (1, 4)-α-d-glucan activated NF-κB, an enhancer of activated B cells, time and dose-dependently 73. This modulation of nuclear NF-κB activity is associated with the degradation of I-κBα thus facilitating the translocation of NF-κB into the nucleus; I-κBα inhibits the NF-κB transcription factor. G1-4A activated Akt, ERK and JNK, which finally activated IKK, degraded IκB-α and translocated NF-κB to the nucleus. Also, an increase in macrophage count 35.
E) Cytokines: col activates Th1 pathway cytokines 34. Abood et al., 2014 showed that T. Crispa crude extracts significantly stimulate intracellular expression of cytokines INF-γ, IL-6, and IL-8 76. Raj et al., 2016; Debnath et al., 2014 have reported that T. col. activates Th1 pathway cytokines, coupled with low nitric oxide synthesis 27, 28. Sannegowda et al., 2015 showed that T. cordifolia reduces pro-inflammatory cytokines such as: IL-1β, TNF-α, IL-6, and IL-17; the frequency of IL-17-producing T cells; and the production of chemokines such as RANTES. Ahmad et al., 2015 reported that T. col. enhanced the proliferation of splenocytes and a significant increase in Th1 (TNF-α, IL-2, and IFN-γ) and Th2 (IL-4) cytokines 49. Castillo et al., 2014 reported that Tinospora lotion significantly reduces IL-1 and IL-6 in scabies patients and thus inhibits hyperkeratosis and infiltration of inflammatory cells into scabietic lesion 77. Raghua et al., 2009 reported that G1-4A has protected mice against septic shock by modulating the pro-inflammatory cytokines 35.
F) Autoimmune Diseases: Aiyer and Kolammal 1963 has opined that crispa possesses the immunostimulatory activity and has therapeutic potential for the prevention of immune diseases 44. Sannegowda et al., 2015 reported that T. cordifolia has shown anti-arthritic activity using the rat adjuvant-induced arthritis model of human rheumatoid arthritis 49. Choubey et al., 2013 reported that T. col. significantly reduces pain in rheumatoid arthritis patients 78. Sudhakaran et al., 2006 reported that T. col. acts as an immunoprophylactic 56. Tinospora cordifolia is one of the ingredients of the Rasna saptak kashaya. Piper longum Linn. is one of the ingredients of the Pippali Vardhamana Rasayana. Both these rasayanas are suggested in amavata, whose symptoms are similar to rheumatoid arthritis. Pippali Vardhamana Rasayana acts against autoantibody, decreases the immune complex, and provides symptomatic relief with decrease the erythrocyte sedimentation rate 79.
G) Immune Complex: col. is a disease-modifying drug and inhibits the immune complex formation. T. col. is used in the treatment of rheumatic diseases 80. Palep 2015 presented a formulation called Torchnil which contained T. col.; this has been effective in combat with immune complex, also HIV 51.
Discussion on Therapeutic Properties of Tinospora cordifolia: Tinospora cordifolia has shown modulatory activities in various organ systems and modulates the body contents to normalize them for normal functioning. T. col. has shown anticancer and antitumour properties. It has shown maturation of stem cells and an increase in bone marrow cellularity.
In combination with Carica papaya, it has shown an increase in blood platelet count in patients with cancer, dengue and thrombocytopenia. T. col decreases blood capillary permeability. It has shown to reduce serum, tissue cholesterol, phospholipids and free fatty acids in case of diabetes. It reduces blood sugar and increases body weight. It also increases blood insulin levels and glucose tolerance. T. col. has been reported to increase WBC count; also, it restores total lymphocyte count (TLC). It proliferates/ activates/ increases the activity of neutrophils, nuclear killer cells, other lymphocytes. T. col. improves the humoral immune response. It increases the plaque-forming cells in the spleen. It has shown to increase lipid peroxidation to reduce tumor cells. On the other hand, it has shown to prevent lipid peroxidation to provide protection in various cases when the subject was exposed to gamma radiation.
It has also been opined that T. col. provides protection to CNS. It has also been reported to enhance memory. T. col. been reported to show positive effects in the treatment of various skin diseases like scabies. It has been used as an antidote to snakebite and scorpion sting. It has also shown anti-osteoclastic activity and protection against bone damage. It has also been used against tuberculosis and even HIV and shown positive therapeutic effects. It has shown an increase in spleen cellularity and upregulation of anti-apoptotic genes.
T. col. exhibits radioprotective properties and has especially shown protection against gamma irradiation; it has reduced protein degeneration. T. col. has provided protection against immuno-suppression caused by CCl4, cyclophosphamide induced anemia. It has shown to enhance the production and response of immunoglobulin and other antibodies. It has shown antipyretic, anti-allergic, and anti-leprotic. It has also shown protection against E. coli and reduced the number of disrupted mast cells. T. col. has been reported to inhibit the complement system in order to provide protection against immunohaemolysis. In other various cases, it has shown to enhance the complement system where required by the subject’s body. T. col. has shown to stimulate the secretion/ proliferation of macrophages. T. col. activates and proliferates T and B cells. On the other hand, T. col. has also shown anti-inflammatory properties.
In various cases, T. Col. has been reported to significantly increase the Th1 and Th2 cytokines. On the other hand, it has shown to reduce IL-1 and IL-6 to provide protection against hyperkeratosis and scabies. It has also shown protection against pro-inflammatory cytokines. It has also provided protection against various autoimmune diseases such as rheumatoid arthritis; it has reduced pain in RA patients significantly.
Piper longum Linn. (PLL), an ingredient of the Pippali Vardhamana Rasayana, has shown protection against autoantibody and Erythrocyte Sedimentation Rate. PLL and T. col. have shown protection against immune complexes and have been used against a number of rheumatic diseases. The experimental results and reviews of papers on the medicinal benefits of Tinospora cordifolia are summarized in Table 1. The table cells where target is not given are from the references where it is not discussed explicitly. The target here is considered to be human. The table cells where administration is not discussed are from the references where the particular administration is not discussed. Here, the administration is considered to be the combination of all three excerpts of the T. col. plant, i.e., root, stem, and leaves in powder, or aqueous extract from.
TABLE 1: EXPERIMENTAL RESULTS AND REVIEWS OF PAPERS ON MEDICINAL BENEFITS OF TINOSPORA CORDIFOLIA
|S. no.||Subject in body / Abnormality||Target||Administration||Effect|
|1||Tumour Growth||BALB/c mice||Stem methanolic extract, 200 mg/kg, i.p, daily for 5 days||Acted with cyclophosphamide and reduced the animal tumors to 83%5|
|2||Mice Transplanted with Ehrlich Ascites Carcinoma||Stem dichloromethane extract, doses of various strengths||Dose-dependent reduction in tumor cells 6|
|3||Adults Swiss Albino Mice injected with 1 x 108 E. coli||Stem aqueous extract 100mg/kg/d||Polymorph phagocytosis reduced7|
|5||Upregulate antitumor activity of tumor-associated macrophages8|
|6||Bone Marrow||BALB/c mice||Stem methanolic extract, 200 mg/kg, i.p, daily for 5 days||Increase in bone marrow cellularity 18.16 ×106 / femur along with ⍺-esterase in bone marrow (1423/4000 cells) 5|
|7||Rats||Stem alcohol extract, 100 mg/kg/d, oral||Increase in bone marrow cellularity along with ⍺-esterase 9|
|8||Cardiovascular system, blood||Humans with dengue thrombocytopenia and cancer||Leaf extract [with Carica papaya], 5ml, twice daily||Platelet count was increased 10|
|9||Rats||Stem aqueous extract||Decreased the capillary permeability 11|
|10||Diabetes||Rats induced with hyperglycemia||Stem hexane, ethyl acetate, methanol extracts 250mg/kg/d||Anti-diabetic activity 12|
|11||Diabetic rats||Root extract||Anti-diabetic activity 14-17|
|12||Tinospora cordifolia||reduces blood glucose level and increases glucose tolerance 19, 20|
|13||Alloxan diabetic rats||Root extract||reduces serum and tissue cholesterol, phospholipids and free fatty acids 18|
|14||Diabetic Rats||Root aqueous extract, doses of various strengths||Anti-diabetic activity, reduction in brain lipids, increase in body weight 13|
|15||White Blood Corpuscles||BALB/c mice||Stem methanolic extract, 200 mg/kg, i.p, daily for 5 days||WBC count increases 5|
|16||CCl4 intoxicated albino rats||Water extract, 100mg/kg/d||WBC count increases 21|
|17||Male mice, Various doses of gamma irradiation||Stem extract, 200 mg/kg before irradiation||Restored total lymphocyte counts 22|
|18||Rats||Stem alcohol extract, 100 mg/kg/d, oral||WBC count increases 9|
|19||Wistar rats||Stem aqueous, ethanol, ethyl acetate, chloroform extract, different doses||WBC count increases 23|
|20||Wistar Kyoto rats||Stem ethanol extract, doses of various strengths||Chemotactic activity and phagocytosis activity of neutrophils enhanced; nuclear killer cells proliferated 26|
|21||Humans with chronic tonsillitis||Kumarabharana rasa (tablet), 500 mg once daily||Nuclear killer cells activated/proliferated 27|
|22||Fish||Water-soluble fraction, doses of various strengths||Nuclear killer cells activated/proliferated 31|
|23||Gamma irradiated swiss albino mice||Alcohol-water extract, 5mg/kg/d||Nuclear killer cells activated / proliferated 32|
|24||Shrimp hemocyanin||Antiviral activity against phagocytosis, WBC count increase 24|
|25||Fish||Antiviral activity against phagocytosis, WBC count increase25|
|26||Cows||Dry stem powder, 100 mg/kg/d||Mean phagocytic index significantly increased 33|
|27||Mice||G1-4A||CD69 expression in lymphocytes increased 35|
|28||Body Humour and Lipids||BALB/c mice||Stem methanolic extract, 200 mg/kg, i.p, daily for 5 days||Increase in plaque-forming cells in the spleen (1575 PFC/106 spleen cells)and circulating antibody titre (256) 5|
|29||Sheep infected with guinea pig serum||Cordioside (TC-2), Syringin (TC-4), cordiofolioside A (TC-5) and cordiol (TC-7)||A dose-dependent increase in humoral immunity 36|
|30||Mice Transplanted with Ehrlich Ascites Carcinoma||Stem dichloromethane extract, doses of various strengths||Drastic increase in lipid per-oxidation to reduce tumour cells 6|
|31||Photosensitized C3H mice Liver Homogenate treated with peroxynitrite||G1-4A||Prevented lipid peroxidation to reduce thiobarbituric acid reactive substances in liver 37|
|32||Lipid peroxidation of rat brain homogenate||An arabinogalactan polysaccharide TSP from stem methanol extract||Protection against iron-mediated lipid peroxidation of rat brain homogenate 38|
|33||Mice||G1-4A||Spleen cellularity increased, anti-apoptotic genes upregulated 35|
|34||Central Nervous System||As an adaptogen||Stimulation and stress-protective effects in the central nervous system 39-41|
|35||Other Organ Systems||CCl4 intoxicated albino rats||Water extract, 100mg/kg/d||Liver was protected 21|
|36||Humans, age 18-30 years||500mg tablets daily||Enhanced verbal learning and memory, and logical memory 42|
|37||Adjuvant Arthritis induced male Lewis rats||Aerial part methanol extract, 1g/kg/d||Limiting of bone damage, shifting the balance of mediators of bone remodeling in favour of anti-osteoclastic activity 49|
|38||Humans||Stem||Therapeutic effect in skin diseases 44, 45|
|39||Humans||Root and stem||Therapeutic effect in snake bite and scorpion stings 46, 47, 48|
|40||Humans with Mycobacterium tuberculosis||Alcohol extract||Inhibition of the growth of Mycobacterium tuberculosis 50|
|41||Wistar Albino rats||Alcohol extract (100 and 200 mg/kg/d) and aqueous extract (100mg/kg/d)||Enhanced cognition 43|
|42||Bronchospasm induced guinea pigs by 5% histamine aerosol||Stem aqueous extract||Decreased bronchospasm 11|
|43||Humans with HIV||Anti-HIV activity 51|
|44||Humans||Alcohol extract||Protease inhibition 52|
|45||Irradiation||Male mice, Various doses of gamma irradiation||Stem extract, 200 mg/kg before irradiation||76.3% survival (30 days) 22|
|46||Photosensitized C3H mice Liver Homogenate treated with peroxynitrite||G1-4A||Degradation of proteins due to photosensitization was significantly reduced 37|
|47||Radioprotective properties 4|
|48||Immune System and Antibodies||CCl4 intoxicated albino rats||Water extract, 100mg/kg/d||Immunosuppressive effect of CCl4 was inhibited 21|
|49||Humans||Stem water and ethanol extract (and T. sinesis)||Inhibition of cyclophosphamide-induced anemia 54|
|50||Sheep infected with guinea pig serum||Cordioside (TC-2), Syringin (TC-4), cordiofolioside A (TC-5) and cordiol (TC-7)||A dose-dependent increase in cell-mediated immunity 36|
|51||Rats||Stem alcohol extract, 100 mg/kg/d, oral||Potent immunomodulatory activity showed 9|
|52||Wistar rats||Stem aqueous, ethanol, ethyl acetate, chloroform extract, different doses||Aqueous and ethanolic extracts enhanced antibody production against injected sheep red blood cells 23|
|53||Mice, Humans||Protection against peritonitis, cholera. Immunomodulation 57, 58, 60, 61, 62, 63|
|54||Mice infected with E Coli||Water extract 100gm/kg/d||Cellular immune function improved, mortality reduced 59|
|55||Infected albino rats||Stem powder, 50mg/kg/d||Effective against acute inflammation; functional as non-steroidal anti-inflammatory agent 72|
|56||Oreochromis mossambicus||Leaf petroleum ether extracts, doses of various strengths||Enhanced the secondary antibody response 56|
|57||Rats||Reduced the number of disrupted mast cells 11|
|58||Bronchospasm induced guinea pigs by 5% histamine aerosol||Stem aqueous extract||Decreased bronchospasm 11|
|59||Humans||Promotion of antibodies 55|
|60||Fish||Water-soluble fraction, doses of various strengths||Enhanced lysozyme activity and antibody responses 31|
|61||Adults Swiss Albino Mice injected with 1 x 10(8) E. coli||Stem aqueous extract 100mg/kg/d||Protection from E. coli 7|
|62||(1,4)-alpha-D-glucan||inhibition of binding and internalization of opsonized zymosan A bioparticles 73|
|63||Cows||Dry stem powder, 100 mg/kg/d||Total serum immunoglobulin significantly increased 33|
|64||Complement System||Sheep infected with guinea pig serum||Cordioside (TC-2), Syringin (TC-4), cordiofolioside A (TC-5) and cordiol (TC-7)||Inhibition of the C3-convertase resulting in inhibition of in-vitro immune haemolysis 36|
|65||Humans with chronic tonsillitis||Kumarabharana rasa (tablet), 500 mg once daily||Activation of complement system 27|
|66||Activation of complement system 28-30, 34, 75|
|67||Fish||Water-soluble fraction, doses of various strengths||Activation of complement system 31|
|68||Gamma irradiated Swiss albino mice||Alcohol-water extract, 5mg/kg/d||Activation of complement system 32|
|69||Shrimp hemocyanin||Activation of complement system 24|
|70||Fish||Activation of complement system 25|
|71||Humans||Activation of complement system 55|
|72||Macrophage||BALB/c mice||Stem methanolic extract, 200 mg/kg, i.p, daily for 5 days||Signiphicant enhancement in macrophage activation 5|
|73||Sheep infected with guinea pig serum||cordioside (TC-2), Syringin (TC-4), cordiofolioside A (TC-5) and cordiol (TC-7)||Macrophage activation 36|
|74||T Crispa ethanol extracts, doses of various strengths||Stimulation of RAW 264.7 cells 76|
|75||Macrophage J774A.1 cell line||5ul of 80ug/ml daily||Macrophage activation enhancement; protection from E. coli 64|
|76||Humans||Stimulates of secretion / proliferation of macrophages 55|
|77||Mice||G1-4A||Macrophage count increased 35|
|78||T and B Cells||Photosensitized C3H mice Liver Homogenate treated with peroxynitrite||G1-4A||B Cell mitosis 37|
|79||Gamma irradiated swiss albino mice||Alcohol-water extract, 5mg/kg/d||Activation / proliferation T and B Cells 32|
|80||Humans||Activation / proliferation T and B Cells 55|
|81||(1,4)-alpha-D-glucan||Activation of NF-κB time and dose-dependently 73|
|82||Mice||G1-4A||Akt, ERK and JNK activated, which finally activated IKK; IκB-α degradated and NF-κB translocated to the nucleus 35|
|83||Cytokines||T. crispa ethanol extracts, doses of various strengths||Stimulation of intracellular expression of cytokines 76|
|84||Adjuvant Arthritis induced male Lewis rats||Aerial part methanol extract, 1g/kg/d||Reduced pro-inflammatory cytokines, the frequency of IL-17-producing T cells, production of chemokines such as RANTES 49|
|85||Wistar Kyoto rats||Stem ethanol extract, doses of various strengths||Splenocytes proliferated; Th1 (TNF-α, IL-2, and IFN-γ) and Th2 (IL-4) cytokines significantly increased 26|
|86||Humans with scabies||Tinospora lotion on the skin||IL-1 and IL-6 significantly reduced, thus hyperkeratosis and infiltration of inflammatory cells into scabietic lesion inhibited 77|
|87||Humans with chronic tonsillitis||Kumarabharana rasa (tablet), 500 mg once daily||Activation of Th1 pathway cytokines, coupled with low nitric oxide synthesis 27|
|88||Mice||G1-4A||protected mice against septic shock by modulating the proinflammatory cytokines 35|
|89||Autoimmune diseases||Adjuvant Arthritis induced male Lewis rats||Aerial part methanol extract, 1g/kg/d||an anti-arthritic activity using the rat adjuvant-induced arthritis model of human Rheumatoid Arthritis 49|
|90||Humans||Stem||Immunostimulatory activity. Therapeutic for the prevention of immune diseases 44|
|91||Humans with arthritis||Significant reduction of pain in rheumatoid arthritis patients 78|
|92||Oreochromis mossambicus||Leaf petroleum ether extracts, doses of various strengths||Immunoprophylactic 55|
|93||Humans with Juvenile Rheumatoid Arthritis||Rasna saptak kashaya||Symptomatic relief with decrease the erythrocyte sedimentation rate 79|
|94||Immune Complexes||Humans with rheumatic diseases||Modifies disease. Inhibits immune complex formation 80|
Systemic Lupus Erythematosus (SLE):
A) SLE: The Disease: In SLE, different cytokines and other mediators of inflammation are released and hence contribute to its progression. This systemic disease results in hyperactivated leukocytes as well as the pathogenic autoantibodies and immune complexes, which cause local autoimmunity and end-organ disease 81. In SLE, all pathways lead to the production of interferon α (IFNα) mediated by endogenous nucleic acids. SLE autoimmune response is initiated by increased production of autoantigens during apoptosis, decreased disposal, deregulated handling 82.
Activation of DCs and B cells is promoted by nucleosomes that contain endogenous danger ligands, that can bind to pathogen-associated molecular pattern receptors, are incorporated in apoptotic blebs. Activation of DCs causes the production of interferons (IFN) and the activation of B cells causes the production of autoantibodies 82. In SLE Maintenance mechanisms of T- and B-cell tolerance is broken down; removal autoreactive B cells are depleted, leading to cell death induced by FcgRIIb, inhibition of migration and control plasma cell survival, which contribute to autoimmunity and infection; phagocytosis is depleted, along with depletion of clearance of apoptotic blebs, impaired nitroblue tetrazolium reduction, and reduced production of IL–8 and IL-12 by polymorph nuclear cells; toll-like receptor (TLR) for self-antigens are inappropriately activated, along with TLR3 ds-RNA, TLR7 ss-RNA, and TLR9; complement- and Fc-mediated uptake is reduced, leading to delay in clearance of IgG-coated erythrocytes and soluble IC 83.
According to 151, Cuchacovich et al, 2009, the following microorganisms are found in patients with SLE most frequently. The patient might contain bacteria, Staphylococcus aureus, non-typhoidal Salmonella, Escherichia coli, Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella spp, Acinetobacter spp, Pseudomonas spp, Mycoplasma spp. The patient might also contain Virus, Parvovirus B19, Cytomegalovirus, Epstein-Barr virus, Herpes simplex/varicella zoster, Human papillomavirus, Hepatitis A. A patient might also be affected with Fungus, Candida spp, Aspergillus spp, Nocardia spp, Cryptococcus neoformans, Mycobacterium, non-tuberculous mycobacterium, or otherwise Mycobacterium chelonae, M. tuberculosis, M. avium complex, M. haemophilum, M. fortuitum, M. marinum. A patient may contain many or any of the discussed cells which might degrade the medical condition 83.
B) Fatalness of SLE: The major cause of death in patients with SLE is renal failure. The renal autoimmunity is initiated when immunoglobulin and complement start to deposit on the glomerular basement membrane. This follows engagement of activating Fc receptors by circulating monocytes, endothelial activation, chemokine secretion, recruitment of activated lymphocytes and finally release of proapoptotic factors that result in renal cell death, which is irreversible 84. Similarly, all other organ systems are affected, majorly by the deposition of these immune complexes on the tissues of organs followed by the destructive action of immune system, like the renal system 84, 85, integumentary system (especially the skin), skeletal system (especially bone joints), central nervous system, lymphatic system and spleen 86, cardiovascular system, gastrointestinal system 87, 88, reproductive system (especially in females during pregnancy) 82.
C) Medications: The drugs that are used in the treatment process of SLE patients in present medical procedures are shown in Table 2.
TABLE 2: DRUGS BEING USED TO TREAT SLE
|S. no.||Treatment procedures / Drugs||Effects against|
|1||Antimalarials||Articular and mucocutaneous manifestations of SLE;
Fatigue and serositis; Improvement of lipid profile;
Flares 89, 90, 91, 92, 93, 94, 95
|2||Azathioprine||Diffuse proliferative glomerulonephritis; lupus nephritis 85, 96, 97, 98, 99, 100|
|3||Cyclophosphamide||Lupus nephritis 93, 99, 101, 102, 103, 104, 105|
|4||Cyclosporin A||T-cell mediated responses; thrombocytopenia; proteinuria; histological lesions; reduces steroid requirements 106-114|
|6||Mycophenolate mofetil||LN and proteinuria; Suppresses autoimmunity 115-120|
|7||Autologous bone marrow transplantation||Good disease control and survival 121-127|
|8||Dapsone||Vasculitic lesions, bullous LE, sub-acute cutaneous lupus, oral ulcers, severe leukopenia, thrombocytopenia 128-131|
|9||Thalidomide||Cutaneous lupus; discoid lupus 132-133|
|10||Dehydroepiandrosterone||Disease activity, flares 134, 135|
|11||Bromocriptine||Disease activity 105|
|12||Nucleoside analog (fludarabine and cladribine - 2-chloro-2’-deoxy-adenosine)||LN (fludarabine and cladribine);
SLE (fludarabine) 136-140
|13||Tacrolimus||Similar to Cyclosporin A 141|
|14||Anti-CD40 ligand antibodies||CD40:CD40L interaction, CD40:B cell interaction, renal disease 142|
|15||DNase||Antigenic load, immune complexes 84|
|16||LJP 394||anti-dsDNA antibody 143|
|17||Bindarit||Disease development, proteinuria, renal disease, anti-dsDNA and antinuclear antibodies;
urinary albumin, urinary IL-6 144, 145
|18||Belimumab||Functioning of B-Cell, B-lymphocyte stimulator 145|
|19||Micro-antibodies||B-Cell (ultimate target) 146|
|20||Anti-cytokines||Inflammation response (by inhibiting one or more of the cytokines) 146|
D) Side Effects of Medications: The major issue in the medication of systemic lupus erythematosus is the management of side effects that arise from the drugs administered to the patients.
Anti-malarials have shown side effects when the drug is discontinued 147. Long-term use of Cyclophosphamide has shown major infections, premature ovarian failure, amenorrhea, malignancy, cervical dysplasia 106, 99, 104, 105, 148.
Cyclosporin A has caused hypertension, hypertrichosis, gingival hypertrophy in patients 81, 84. Methotrexate causes dyspepsia and increase in hepatic-enzyme serum levels 149. Mycophenolate mofetil has caused pancreatitis and severe febrile pancytopenia in a few patients. Dapsone may cause hematological hemolysis and neurological polyneuritis 106. Thalidomide may cause neuropathy, which may be irreversible; and may also induce nerve damage, which is dose-dependent 150. In case of treatment with autologous bone marrow transplantation, it is required to identify the patients who are suitable for this treatment. The risks involved are relatively high which include fatality in suitable cases 151.
Dehydroepiandrosterone may result in acne, hirsutism and irregular menses. The main side effects of bromocriptine are headaches and nausea 106. Treatment with anti-CD40 ligand antibodies may cause asthenia, dizziness, nausea and headache 152. LJP 394 has adverse effects including headache and insomnia 106. No medical procedure being used has shown complete cure for SLE.
Tinospora over the Existing Drugs to Cure SLE:
A) Current research scenario on modern medicine, SLE and T. Col.: In spite of the strict side effects of the drugs being currently used in the therapy of SLE, they are being used in the treatment process. Tinospora cordifolia has numerous benefits and can be used in the SLE treatment process. The only side effect of Tinospora recorded so far is that it results in constipation. SLE is a dysfunction of the immune system, majorly the B-cells. T. col. has been recorded to show immunomodulatory properties and properties of modulation of T and B-cells, along with cytokines and antibodies. It purifies blood and cleans out the unwanted lipids and enhances the humoral immune response. It has also been reported to clean out the immune complexes from the body.
B) T. Col. as a Strong Hope towards Successful Treatment of SLE: The strange, but best activity was shown by T. col. is that it acts as a moderator. It has shown to both increase and decrease activities of substances in the body, as required according to the medical state and requirements to normalize the functionality of numerous systems by the body. These substances include T and B cells, antibodies (and autoantibodies) and cytokines. These therapeutic properties of T. col. are potent, which advocate its exploitation in the treatment of systemic lupus erythematosus.
CONCLUSION: There are numerous benefits of Tinospora cordifolia stated in the Indian Ayurvedic texts. Many of them have been tested according to modern testing techniques for medicine and it has started to be used to treat a large variety of abnormalities in the human body. Because of the immunomodulatory and antitumor properties, and numerous others, along with no major side effect, T. col. can be used in the treatment of systemic lupus erythematosus, a rheumatoid autoimmune disease. Tinospora cordifolia may be administered along with Piper longum Linn., Carica papaya, Tinospora sinensis as well as Tinospora crispa.
CONFLICT OF INTEREST: Nil
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How to cite this article:
Gupta AT: Tinospora cordifolia can cure SLE. Int J Pharmacognosy 2019; 6(7): 237-52. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.6(7).237-52.
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