TINOSPORA CORDIFOLIA CAN CURE SYSTEMIC LUPUS ERYTHEMATOSUS

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

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

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.

ACKNOWLEDGEMENT: Nil

CONFLICT OF INTEREST: Nil

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     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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