Guduchi

Tinospora cordifolia (of the family Menispermaceae) is a genetically diverse shrub grown at high altitudes;^[1][2] it is most well known as Guduchi (Sanskrit) or Amrita with other names for this herb being makabuhay (Philipines^[3]), Giloe,^[4] and Giloya^[5] whereas if referring to the carbohydrate portion of the stem itself it is called Guduchi-satva, and when it is used alongside a carrier of ghee (Ghrita) or oil (Taila) it is referred to as Guduchi ghrita and Guduchi taila respectively.^[6]

Most names for tinospora cordifolia are translated along the lines of 'heavenly elixir' or 'divine nectar' in reference to its renown in traditional medicine.

It is known as a rasayana due to the claims of it enhancing longevity and vitality and is used in Ayurveda for a variety of purposes (a 'general tonic') associated with inflammation and allergies, neurology, and glucose metabolism^[7][8] although it has also been recommended at times for intestinal disorders and diarrhea, fevers, and liver disorders (jaundice and hepatotoxicity)^[9] and at times even aphrodisia.^[10] While the leaves and roots are considered somewhat medicinal, the main medicinal component of this plant is the mature stem (aerial parts).^[9]

Tinospora cordifolia is a medicinal plant stem which is used mostly to treat or prevent disorders of the brain and of glucose metabolism. It is also reported to be a potent immunostimulant and vitality/longevity enhancing medicine, and appears to be fairly well renowned

Tinospora cordifolia contains (stem unless otherwise specified):

• Berberine^[11] at 0.3192% of the stem (dry weight)^[12] as well as structurally related alkaloids Jatrorrhizine,^[13][14] Palmatine, and Tetrahydropalmatine^[15]
• Other alkaloids such as Magnoflorine (0.075%),^[8][16] N-formylannonain,^[8] and the two Tinoscorsides A (N-formylasimilobine glycoside) and B (N-acetylformylasimilobine glycoside)^[17]
• Tinoside,^[13] Tinocordiside,^[8] and tinocordifolioside; glycosides of 11-hydroxymustakone^[8]
• Tinocordifolin (sequesterpene)^[18]
• The diterpenes columbin, (0.01-0.05% of the stem^[19]) 8-hydroxycolumbin,^[20] 10-hydroxycolumbin,^[20] and isocolumbin^[13] as well as the columbin glycoside 'cordioside'^[21][22] at 0.01-0.05%^[19]
• Related diterpene structures tinosporin, 8-hydroxytinosporide,^[20] tinosporaside^[23][24] with the latter at 0.01-0.05% of the stem^[19]
• The norditerpene furan glycosides Cordiofolioside A (0.1-0.7%^[25])^[8][21] through C,^[26] which are based off of the shorter glycoside Syringin (also present^[21][8]) which is a glycoside of sinapyl alcohol (converts to sinapic acid)
• Tinosporafuranol (4-seco-cleroda-19-ol-13-furanoid), Tinosporafurandiol (4-seco-cleroda-6-en-18,19-diol-13-furanoid), Tinosporaclerodanol (cleroda-1(10)-en-6β-ol) and Tinosporaclerodanoid (cleroda-1-one-2-en-11β,15,16,18-tetraol-12,19-olide)^[27] and Tinosponone.^[28] A series of Clerodane-type Furanoditerpenes are known as Amritosides A-D^[29]
• The sulfur containing clerodane diterpene known as Cordifolide A^[23] and Cordifolides B-C (no sulfur)^[23]
• The norditerpene series of Cardifolisides A-C^[9]
• Borapetosides B and F (norditerpenes)^[17]
• Polypodine B (steroidal saponin)^[17]
• Palmatoside C-D^[23]
• Tincordin (diterpene)^[20]
• The lignans angelicoidenol (as 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside), pinoresinol (as di-O-glucoside), and secoisolariciresinol (as 9′-O-β-d-glucopyranoside)^[17]
• N-methyl-2-pyrrolidone^[8]
• Saponarin (apigenin-6-C-glucosyl-7-O-glucoside^[30]) at 32.1-45.5mg/g (3.2-4.5%) of a basic leaf water extract, declining with age^[30] and also present in the flowers of aloe vera^[31]
• Tembetarine (alkaloid glycoside at 0.012%^[16])
• Giloinsterol and Giloin^[7]
• Ecdysterone, makisterone, and Hydroxyecdysone (Ecdysteroids)^[12][32] with 20β-hydroxyecdysone at around 0.05-0.15% of the plant^[19]
• Choline^[16]
• Vitamin C at 41.36mg/g (4.1%) water extract^[15]
• Glutathione at 6.86mg/g (0.7%) water extract^[15]
• Octosanol and a few other molecules referred to as policosanol^[33]
• β-sitosterol, δ-sirosterol, and 2β,3β,14α,20β,22α-25 hexahydroxyl-5β-cholest-7-en-6-one^[27]
• (1,4)-α-D-glucan^[34]

The main bioactives in this plant can be broken down into a few classes; the alkaloids (berberine, dihydropalmatine, etc.), the diterpenes and their glycosides (Columbin, Amritosides, and Tinosporaside as examples), and the glycosides that are based on small phenolic molecules (Tinocordifolioside and Tinocordiside based off of 11-hydroxymustakone and the Cordiofoliosides based off of sinapic acid). In addition to these few classes, saponarin appears to be relevant

There are polysaccharides present in tinospora cordifolia known as arabinogalactans such as HTCP3 (13% glucose, 18% arabinose, and 36% fructose by weight), HTCP13 (12% glucose and 25% arabinose by weight, only 45% sugars overall), and BPTD02 (98% glucose and the rest xylose) which show immunostimulant properties in vitro.^[13] Previous studies note a glucose-rich arabinoglycan,^[35][36] which may simply be BPTD02. The reason HTCP13 may be so low in sugars by weight is that it was found to be complexed to some alkaloids (columbin, tinoside, jatrorrhizine, and an unknown furanoditerpene).

Another polysaccharide is known as G1-4A which seems to target macrophages and dendritic cells.^[37] It is 31% galactose, 32% arabinose, and 35% galacturonic acid.^[13]

An immunomodulatory 25kDa protein also exists at 150mg per 100g dry stem powder (absent in leaves), which does not possess lectin properties and stimulates splenic cell proliferation and macrophage activity.^[38]

There are some bioactive polysaccharides in this plant that appear to interact with the immune system. Interestingly enought, the polysaccharides may complex with the alkaloids and phenolic glycosides (theoretically acting as a transport vessel of sorts; implications of this not known)

Tinospora cordifolia is said to synonymous with both tinospora rumphii and spica due to them being able to be used interchangeably at times^[3] and two other species (tinospora sinensis^[12] and tinospora malaberica^[9]) appears to also be somewhat acceptable substitutions.

The plants are not 100% similar, as sinensis has some unique components (malabarolide, tinosinen I, and menispermacide) and a third of the berberine content relative to cordifolia.^[12] Cordifolia also has a greater starch content (source of bioactive polysaccharides)^[9] which may mean different immunomodulatory properties.

Some practitioners refer to cordifolia as the 'true' Guduchi rather than the other species.^[3]

Similar to other ayurvedic herbs, there are a few which are seen as practically interchangeable. This extends to other species in the tinospora genera but in an ideal situation cordifolia is used

Tinospora cordifolia is a component of the Ayurvedic formulations Amritarishtam (alongside Dashamoola (10 herbs), Trikatu (3 peppers), and nigella sativa), Dhanvantaram tailam (Highly confounded), Cheriya rasnadi kashayam, and Valiya marmagulika.^[12]

Solanum surattense (Bhatkatiaya) is sometimes paired with tinospora cordifolia as a paste for the treatment of fever.^[9] Elsewhere, cough is treated with a combination of equal parts tinospora cordifolia, brassica campestris seeds (Sarsapa Beeja Churna), and terminalia chebula (Haritaki).^[9]

The combination of this herb with 5 seeds of black pepper (Krishna Marich) has been traditionally used for Leukorrhea.^[9]

Traditional usage of tinospora cordifolia is quite vast and multiple combinations exist; usually these are catered towards well being and breathing (asthma) but have not been investigated at all

A product known as 'Pepticare' exists for the treatment of stomach ulceration, and this is a combination of tinospora cordifolia with licorice (specifically, glycyrrhiza glabra) and emblica officinalis^[39] Larger formulations include 'Hyponidd' for the treatment of diabetes (momordica charantia, melia azadirachta, pterocarpus marsupium, gymnema sylvestre, enicostemma littorale, emblica officinalis, eugenia jambolana, cassia auriculata and turmeric)^[40] and 'Dihar' (similar to the aforementioned but with syzygium cumini and azadirachta indica added and cassia, pterocarpus, and melia removed).^[41] A third formulation known as 'Livwin' involves this herb alongside picrorhiza kurroa, Boerhaavia diffusa, Phyllanthus niruri, Terminalia Arjuna, Berberis aristata and Ashwagandha.^[42]

'Pepticare', 'Hyponidd', and 'Livwin' are three formulations of which include tinospora cordifolia but are highly confounded with other herbs

Perhaps the most popular compound formulation are Ghana tablets, consisting of equal parts tinospora cordifolia with tribulus terrestris and emblica officinalis; used for depression and stress.^[43]

Ghana tablets seem much less confounded and are fairly straight forward (equal parts of three common herbs)

Tinospora cordifolia at an oral intake of 250-500mg/kg to mice appears to increase the binding affinity of dopaminergic D2 receptors in a dose-dependent manner^[44] and elsewhere the antidepressant effects of tinospora cordifolia are blocked by sulpiride (D2 antagonist) amongst other things.^[45] The antidepressant effects are thought to be related to inhibition of MAO-A and MAO-B which was seen with the petroleum ether extract to a potency similar to imipramine.^[45]

Tinospora cordifolia appears to influence dopaminergic signalling, with the antidepressant effects likely mediated indirectly via MAO inhibition. Overall though, it isn't a well researched interaction

50-200mg/kg of a petroleum ether extract for two weeks exerts antidepressant effects in a manner which is hindered with prazosin (α1 adrenergic antagonist), suggesting that the increase in signalling via MAO inhibition plays a role in depression.^[45]

Limited research into the adrenergic activity of tinospora cordifolia

50-200mg/kg of a petroleum ether extract for two weeks appears to exert antidepressant effects which are attenuated slightly with blocking of the GABA_B receptor (baclofen).^[45]

Limited ressearch into the GABAergic activity of tinospora cordifolia

A 50% ethanolic:water extract of tinospora cordifolia at 250-500mg/kg failed to modify locomotor activity in mice either in isolation or when paired with amphetamine (5.5mg/kg)^[44] and two weeks ingestion of 50-200mg/kg of the petroleum ether extract (sufficient to exert antidepressant effects) failed to modify locomotion.^[45]

No significant alterations in locomotion, suggesting no stimulatory effect of the herb

When given at 0.96g/kg guduchi ghrita (Guduchi in a base of Ghee) or guduchi taila (sesame seed oil) to rats over 10 days, which is equivalent to a human dose of 10g, it appeared that both forms are capable of reducing stress in a forced swim test as assessed by ulcer formation and hypothermia;^[6] this has been replicated elsewhere.^[46]

In the form of Ghana tablets (with equal parts tribulus terrestris and emblica officinalis) at 260mg/kg in rats (human equivalent of 2,000mg), antidepressive and antistress effects occur although with a potency lesser than the reference drugs diazepam (2mg/kg) and imipramine (5mg/kg).^[43]

There appears to be anti-stress effects of combination therapy (Ghana tablets or Ghee), but an inhernet anti-stress or adaptogenic effect of isolated tinospora cordioflia extract has not been determined

50-200mg/kg of a petroleum ether extract for two weeks in rats subject to a tail suspension and forced swim test noted antidepressant effects (no dose dependence but the lowest trending to be most potent) comparable to 15mg/kg imipramine and 20mg/kg sertraline.^[45] This antidepressant effect was blocked by sulpiride, baclofen, prazosin, and p-CPA and credited to the inhibitiong of monoamine (MAO-A and MAO-B) which had a potency comparable to imipramine.^[45]

The petroleum ether extract (not the commonly supplemented water extract) appears to have antidepressant effects via MAO inhibition; it is not sure how this relates to the water extract

In a comparative study between tinospora cordifolia (200mg/kg) and equal doses of Bacopa monnieri or evolvulus Alsinoides in a rat model of scopolamine-induced amnesia, it appears that bacopa monnieri was the most potent anti-amnesiac herb yet it was outperformed by a combination of all three (equal parts totalling 200mg/kg).^[47] There appears to be a role for tinospora cordifolia as the combination of all three herbs outperformed the combination of the other two herbs without tinospora cordifolia.^[47]

Appears to have anti-amnesiac properties, and while it does not exceed that of other herbs it may have a role in combination therapy. Potential synergisms not yet elucidated

The stem extract of tinospora cordifolia appears to inhibit α-glucoside (IC₅₀ 3mg/mL^[4]) which may be related to the saponarin (apigenin-6-C-glucosyl-7-O-glucoside) content which appears to be a mixed competitive inhibitor of intestinal maltase (IC₅₀ of 48μM) and sucrase (IC₅₀ of 35μM) albeit weaker than that of salacinol and kotanalol from salacia reticulata.^[30] There are likely other bioactives as saponarin is highly present in the leaves^[30] while the water extract of the stem is still effective,^[4] possibly due to the protoberberine alkaloids jatrorrhizine (IC₅₀ values of 36.25μg/mL and 22.05μg/mL on sucrase and maltase, respectively), palmatine (23.46μg/mL and 38.42μg/mL), and magnoflorine (9.8μg/mL and 7.6μg/mL).^[48]

20-80mg/kg of isolated saponarin appears to be able to reduce blood glucose following a maltose test meal in rats with a potency comparable to 100-200mg/kg arcabose and appears to prevent all maltose absorption (no increase in serum glucose).^[30] Despite being weaker in vitro, the authors noted higher overall activity with the plant extract and suggested synergism or other bioactives^[30] and elsewhere a water extract of the plant's stem at 300mg/kg is able to prevent spikes in serum maltase in both diabetic and normal rats with a potency exceeding 60mg/kg arcabose^[4] and 20mg/kg of any isolated protoberberine alkaloid was effective.^[48]

High levels of the stem extract as well as isolated saponarin appear to potently inhibit sugar enzymes in the enzyme, with particularly strong efficacy against maltase (high levels causing near complete inhibition)

A hydroalcoholic extract of tinospora cordifolia at 10μg/mL and palmatine at 625nM (concentrations of peak efficacy) in myotubes appears to enhance glucose uptake via stimulating the insulin receptor and signalling thought PI3K, which mobilizes GLUT4 vesicles.^[49] This stimulation of glucose uptake is also seen in adipocytes (200μg/mL aqueous extract) with a potency comparable to emblica officinalis and similar in the sense that both of them worked when insulin was not present and hindered the action of insulin itself.^[50]

Appears to act on the insulin receptor, and due to working well in the absence of insulin but hindering the actions of insulin there may be a modulatory effect at the level of the receptor

In skeletal muscle cells, PPARγ is downregulated by both tinospora cordifolia (10μg/mL) and palmatine (625nM) to 0.67 and 0.38 fold baseline values.^[49]

May downregulate PPARγ, which is not necessarily a beneficial insulin sensitizing effect (as PPARγ positively mediates glucose uptake)

Tinospora cordifolia appears to inhibit the rat aldose redutase enzyme with an IC₅₀ value of 176µg/mL, which was less than the reference of Quercetin (82µg/mL).^[51] Elsewhere, the IC₅₀ value has been determined to be 103µg/mL with a concentration of 5-25µg/mL causing 6-20% inhibition.^[52]

This is thought to be traced back to the isoquinoline alkaloids, as relatively potent inhibitory potential on rat aldose reductase is seen with jatrorrhizine (3.23µg/mL), palmatine (3.45µg/mL) and magnoflorine (1.25µg/mL).^[53]

Appears to inhibit aldose reductase, which can be traced back to the protoberberine alkaloids; the inhibition is quite potent at this is thought to be biologically relevant

The hypoglycemic effect of tinospora cordifolia appears to be related to the isoquinoline alkaloids, as berberine is known to have hypoglycemic effects via AMPK activation and the other alkaloids (palmatine, jatrorrhizine and magnoflorine) appear to stimulate insulin release from the pancreas.^[54] 50-200mg/kg of this fraction is able to acutely reduce blood glucose when fed to rats.^[54]

The isoquinoline alkaloids (berberine and related structures) are thought to be biologically relevant molecules for the anti-diabetic effects. This is possible related to interactions at the insulin receptor (stimulation) and aldose reductase (inhibition)

400mg/kg tinospora cordifolia extract in streptozotocin induced diabetic mice was able to reduce blood glucose by 9.07%, which underperformed relative to 200mg/kg momordica charantia and eugenia jambolana (around 20% each).^[55] Elsewhere, supplementation of 100-400mg/kg tinospora cordifolia over 15 days in this same model of rats has failed to reduce blood glucose^[52] yet 24 weeks of 250mg/kg is able to restore blood glucose one fifth of the way to control (21% of the difference restored).^[56]

Six weeks supplementation of 100-400mg/kg tinospora cordifolia (water and ethanolic extracts) in severe hyperglycemia or 120 days of moderate hyperglycemia noted that the herb exerted dose and time dependent benefits to reduce blood sugar although with a potency lesser than 50-200mg/kg eugenia jambolana (200mg/kg able to normalize blood glucose).^[57]

Some studies use the alloxan toxin to induce diabetes and an increase in blood glucose, and 2.5-5g/kg of the root extract to rats for six weeks appears to be more potent than the reference drug glibenclamide although 7.5g/kg was wholly ineffective; these changes seem to be associated with improvements in antioxidant enzymes.^[58][59][60] The lower dosage range of 400mg/kg has also been tested in alloxan-induced diabetic rats, and it appears to significantly reduce blood glucose (38.01-40.41% over four months) albeit still less potent than eugenia jambolana and momordica charantia at 200mg/kg each.^[61]

While there do appear to be glucose lowering effects in diabetic animals, they are not overly potent (outperformed by other herbs traditionally used for diabetes) and may take up to one month to work. The Berberine content of this plant appears to be too low to exert similarly potent glucose reducing properties

HbA1c has been noted to be reduced in diabetic mice given 250mg/kg of the water extract for 24 weeks.^[56]

400mg/kg tinospora cordifolia extract in streptozotocin induced diabetic mice for 50 days has once failed to modify tail-flick latency (suggesting no effect in diabetic neuropathy)^[55] yet a followup study with 100-400mg/kg in rats (4.8% bitters) noted that its efficacy in improving tail-flick latency was dose-dependent and statitistically comparable to the reference therapy of glibenclamide (5mg/kg) with metformin (25mg/kg).^[52] The reason for this discrepancy is not known.

In regards to neuropathy (nerve damage from diabetes), tinospora cordifolia has mixed evidence but remains promising

In rat models of diabetic retinopathy, 400mg/kg for four months is able to reduce the occurrence of cataract formation^[61] and 250mg/kg of the water extract for 24 weeks is able to reduce the formation of cataracts associated with less expression of VEGF and PKC in the retina and less systemic IL-1β expression;^[56] both IL-1β (and TNF-α)^[62] and the two proteins VEGF and PKC^[63][64] play roles in the pathology of retinopathy.

Possible related to antiinflammatory effects, tinospora cordifolia appears to reduce the progression rate of diabetic retinopathy

In 50 persons with diabetes given tinospora cordifolia (dosage not specified) over 18 months appeared to be beneficial in reducing the amount of required debridements yet failed to reduce wound parameters (severity, depth, healing rate) or global rating of improvement.^[65]

The one study on diabetic ulceration failed to specify the dosage of tinospora cordifolia and failed to show significant promise

Various norditerpene structures such as cordifolioside A, phenolics such as N-methyl-2-pyrrolidine and 11-hydroxymustakone (maximal potency at 1µg/mL), alkaloids such as magnoflorine and tinocordioside (maximal potency at 500ng/mL)^[21][8] appear to stimulate macrophages and 0.1-5µg/mL of various lipophilic fractions (to concentrate diterpenes) appear to be similar in potency to PMA stimulation.^[8]

The polysaccharide known as G1-4A^[66] also appears to be stimulatory and has been confirmed to be an agonist of the TLR4 receptor on macrophages;^[66] it is possible that G1-4A is a selective TLR4 receptor modulatory similar to Ganoderma lucidum as it can protect mice from LPS-induced endotoxicity.^[67] Another molecule in this herb, (1,4)-α-D-glucan, is a TLR6 receptor agonist^[68] and the 25kDa protein is known to stimulate macrophage activity at 1-10μg/mL (mechanisms unknown).^[38]

There are a wide variety of molecules in this plant which appear to have immunostimulant properties, extending to the alkaloids and diterpenes (usually contained in ethanolic extracts) as well as the carbohydrates and protein components (usually contained in the water extract)

In accordance with the increased activity, increases in the secretion of O_2-, H₂O₂, and TNF-α^[69] as well as MPO^[70] are noted, which are thought to be due to increasing the activity of NADH and NADPH oxidase;^[70] activation of TLRs are known to activate NADH and NADPH oxidase^[71] and 80µg/mL of the water extract has a potency comparable to 10µg/mL LPS.^[70][72]

When activated, macrophages seem to have reliably increased phagocytosis and the phagocytotic index (40mg/kg of a water extract to mice for 15 days being reported to increase it 47%^[73] and noted in humans^[65]) yet there may not be an increase in intracellular killing capacity in otherwise normal macrophages.^[8] In instances where killing potential would be hindered such as CCl₄ toxicity^[73] and surgery (16mg/kg in humans),^[74] tinospora cordifolia does increased intracellular killing capacity. In the case of CCl₄ toxicity, it was confirmed that alterations in macrophage morphology and DNA fragmentation were abolished^[73] suggesting protective effects.

The increase in phagocytosis (consumption of target molecules) by macrophages appears to occur per se after ingestion of this plant, whereas there is a conditional increase in the ability of macrophages to kill their targets. It seems that due to protective properties on macrophages, tinospora cordifolia prevents reductions in killing capacity rather than causing unidirectional increases

Increased activation of macrophages is thought to underlie tinospora cordifolia's known microbicidal and tumoricidal properties^[69][72] similar to Ganoderma lucidum.

In regards to bacteria, tinospora cordifolia appears to both directly and indirectly (via macrophages) inhibit bacterial growth.^[72]

In regards to tumors, tumor associated macrophages (TAMs) have been demonstrated to have their activity increased with oral supplementation of this herb to rodents (increase in TAM activity associated with reductions in tumor size) at 200mg/kg of the ethanolic extract^[75][76] and the activation of dendritic cells from activated macrophages (dendritic cells possessing tumoricidal properties^[77]) appears to be biologically active even when transplanted from a tinospora cordifolia fed rat to a tumor-bearing one.^[78]

Activation of macrophages from oral ingestion of tinospora cordifolia appears to underlie anti-tumor and anti-bacterial properties of this herb, possibly secondary to activated macrophages (via secreting more IL-1) activating dendritic cells

In a model of carbon tetrachloride (CCl₄) toxicity, which is known to be immunosuppressant due to damaging macrophages,^[79] 40-100mg/kg of a water extract to mice is able to abolish the increase in DNA fragmentation and abnormal changes in macrophage morphology.^[73][80]

Acute administration of 200mg/kg one hour prior to radiation is able to half the radiation-induced DNA fragmentation in macrophages and effectively normalize adverse changes in spleen weight and splenocyte apoptosis;^[81] the immunosuppressive effects of radiation (as assessed by macrophage adhesion and cell size) were not only fully prevented but exceeded that of non-irradiated control.^[81]

Relatively low doses of the water extract (orally ingested) appear to be remarkably protective against toxin damage to macrophages, and this preservative effect is thought to partly underlie how Guduchi can increase macrophage activity (via preventing declines in activity, causing a relative increase)

In neutrophils, polysaccharides from tinospora cordifolia 0.1-5µg/mL appears to promote phagocytosis with peak values at 0.1µg/mL (HTCP3) 0.25µg/mL (HTCP13) and 0.5µg/mL (BPTD02) although the latter two peaked on the phagocytotic index at 1-5µg/mL. The peak efficacy of the first two polysaccharides being comparable to PMA.^[13] Increased neutrophil content (leucocytosis) has been noted in mice given 100mg/kg of the water extract for 15 days (reaching 82% higher than control).^[82]

Components of the water soluble extract of tinospora cordifolia appear to promote activity and content of neutrophils

In humans, subjects with allergic rhinitus experience a reduction in neutrophils in their nasal mucosa following prolonged supplementation of 300mg of a water extract^[5] while serum neutrophils in persons with HIV^[83] and diabetics^[65] seem unaffected.

While a reduction in neutrophils has been noted in allergic rhinitus, blood concentrations in humans without allergic diseases have failed to find an influence with the standard doses of tinospora cordifolia

Eosinophils in nasal mucosa of persons with allergic rhinitus appears to be significantly reduced with oral supplementation of 300mg tinospora cordifolia thrice daily^[5] and is reduced in persons with HIV given the same dose by approximately 30%.^[83]

A significant reduction in eosinophils has been noted in serum and nasal mucosa, and this is thought to be related to the anti-allergic properties of tinospora cordifolia

Activated macrophages are known to secrete more IL-1^[84] which has been seen with oral ingestion of tinospora cordifolia in rodents;^[76] IL-1 is known to have a proliferative effect on dendritic cells^[85][86] and dendritic cells that associated with macrophages from tinospora cordifolia fed rats appears to be biologically altered.^[78]

G1-4A (polysaccharide) appears to directly stimulate dendritic cells as assessed by increased CD40, CD80, CD86, and MHC-II expression (confirmed with injections of the polysaccharide at 12.5mg/kg in mice^[37]) and this increased dendritic cell maturation is additive with LPS.^[37]

Components of tinospora cordifolia appear to directly and indirectly (via macrophages) stimulate the activity of dendritic cells; this may ultimately underlie some immunostimulatory and anti-tumor properties of the herb

An arabinogalactan from tinospora cordifolia (G1-4A) appears to have B-cell mitogenic properties, with a stimulation index of 11 before hydrolysis and of 66.8 after isolation from the protein fragment and purification.^[87] On B-cells, it acts as a direct agonist of the TLR4 receptor^[66] and its mitogenic effects are inhibited with mTOR inhibition (similar to lipopolysaccharide activation of B-cells).^[66]

The polysaccharide G1-4A appears to be a ligand at the TLR4 receptor and thus is mitogenic (proliferative and supportive) of B-cells

G1-4A appears to activate CD8+ T-cells secondary to enhancing dendritic cell maturation and appears to be active as killing potential increased in vitro and injections of 12.5mg/kg of G1-4A to tumor bearing mice is able to hinder tumor growth.^[37]

When looking at human studies, an increase in lymphocytes has been detected in persons with allergic rhinitus (magnitude of increase not disclosed)^[5] but such an increase has failed to occur in persons with HIV at the same oral dose.^[83]

Tinospora cordifolia appears to be able to reduce bronchospasms induced by histamine, and reduces the amount of perturbed mast cells.^[88]

Appears to have some anti-allergic properties against histamine via stabilizing mast cells

In persons suffering from allergic rhinitus supplementing with tinospora cordifolia (300mg of a water extract containing at least 5% bitter principles, thrice daily) for eight weeks was associated with complete resolution of sneezing (88% of subjects), nasal discharge (69%), nasal pruritis (71%), and nasal obstruction (61%) despite the majority of the placebo group experiencing no resolution.^[5]

In a nasal smear test, eosinophil and neutrophil count were markedly reduced and goblet cells absent. In serum, leucocytes were increased in 69% of subjects given the herb although the magnitude was not stated.^[5]

The lone study conducted in persons with allergies had a remarkable effect size, with near complete resolution of allergic symptoms

Tinospora cordifolia has been paired with Ginger and given to persons with rheumatoid arthritis over 24 weeks to reduce symptoms in 44% of subjects (assessed by amount of persons to meet the requirements of ACR 20), which was comparable in potency to the reference drug (hydroxychloroquine sulfate) and the herb Sernecarpus anacardium.^[89] This has been noted elsewhere where tinospora cordifolia in Ghee with a bit of ginger (15g Amrita Ghrita) for 45 days noted significant improvements in the treatment of rheumatism with 43% of persons reporting improvement of symptoms exceeding 75% resolution (80% above 50% improvement and all subjects reporting more than 25% improvement).^[90]

The pairing of Tinospora cordifolia with ginger appears to be useful for the treatment of rheumatism, and while evidence for the combination is preliminary it seems effective

In persons with HIV/AIDS, the main immunodeficiency appears to be related to a reduction in thymus derived lymphocytes (T₄) expressing CD4 receptors;^[91] while antiviral therapy to target the virus itself is used as the main intervention, usage of immunostimulant compounds are sometimes used as an adjuvant.

300mg of a tinospora cordifolia water extract thrice daily for six months in HIV positive subjects is able to reduce hemoglobin (7.6%) and eosinophils (30%) with no apparent influencing on lymphocytes (nor CD4 count), monocytes, or platelets.^[83] Reported symptoms were reduced in 60% of persons and increased in 10% of the experimental group whereas they were improved in 40% of placebo (exacerbated in 20%);^[83] this study has been critiqued elsewhere due to some methodological issues.^[92]

While the herb is still bioactive, it appears that the reduction in CD4 expression on T-cells is not beneficially influenced by supplementation of tinospora cordifolia in persons with HIV

In rams given 1g/kg tinospora cordifolia in their feed, there were no observed fluctuations in testosterone concentrations over the observation period (lasting four months).^[93]

Limited evidence does not support alterations in serum testosterone concentrations

Incubation of prostate cells (LCNaP) with 1-100μg/mL (but not 100nM) of an ethanolic extract of tinospora cordifolia appears to proliferate cells with a potency comparable to 1nM DHT and is fully blocked by the androgen receptor antagonist flutamide.^[94]

The ethanolic extract of tinospora cordifolia appears to be a phytoandrogen, with a fairly respectable potency in vitro but currently no animal studies

A 80% hydroalcoholic extract at 50-100mg/kg for two weeks in mice is able to increase microsomal and cytosolic liver protein synthesis and increase overall P450 enzymes 1.5 and 1.81-fold (dose dependence).^[95] Increases were seen in glutathione-S-transferase (57-72% increase), DT-diaphorase (31-46%), glutathione peroxidase (18% at 50mg/kg), glutathione reductase (57% at 50mg/kg), superoxide dismutase (25% at 50mg/kg), and catalase (21-32%)^[95] and these changes were greater than the reference drug of 0.75% Butylated hydroxyanisole (with exception to glutathione-S-transferase) and associated with 31-40% reductions in lipid peroxidation.^[95]

Appears to induce antioxidant enzymes in the liver at relatively low oral doses, and seems to increase levels of all tested antioxidant enzymes in this tissue

When assessing Kupffer cells, their activity appears to be somewhat preserved in the face of toxins when rats are fed 100mg/kg of the stem's water extract.^[96]

It is thought that there are some hepatoprotective properties of tinospora cordifolia

In persons with suspected malignant extrahepatic biliary tract obstruction given Tinospora cordifolia at 16mg/kg of a water extract of the stem alongside biliary drainage (compared to a drainage group as well as a tinospora cordifolia in isolation group) noted that supplementation alone for three weeks before surgery failed to significantly influence bilirubin levels yet was associated with the least mortality following surgery and a normalized macrophage function.^[74]

Some possible protective effects related to the liver, but this may be secondary to the immune system with no direct beneficial effects on hepatic tissue.

A 80% hydroalcoholic extract at 50-100mg/kg for two weeks in mice is able to increase activity of the antioxidant enzymes superoxide dismutase (17% at 50mg/kg) and catalase (27-33%).^[95]

50-200mg/kg tinospora cordioflia ethanolic extract to mice for 25 days alongside aflatoxin was able to attenuate the oxidative changes in the kidney induced by the toxin (TBARS, ROS, and antioxidant enzymes) without per se affecting these biomarkers not in the presence of the toxin.^[15] Histological examination shows similar trends, with no changes occurring in tinospora cordifolia control yet attenuations of the damage induced by aflatoxin.^[15]

A 80% hydroalcoholic extract at 50-100mg/kg for two weeks in mice is able to increase levels of antioxidant enzymes in the forestomach including glutathione-S-transferase (55% at 50mg/kg), DT-diaphorase (8-17%), and superoxide dismutase (33% at 50mg/kg).^[95]

A 80% hydroalcoholic extract at 50-100mg/kg for two weeks in mice is able to increase levels of the antioxidant enzymes known as superoxide dismutase (22-41%), catalase (21-42%), and glutathione-S-transferase (32% at 50mg/kg).^[95]

An increase in antioxidant enzymes are seen in lung tissue following oral consumption of the plant extract

In otherwise healthy rams given 1g/kg tinospora cordifolia failed to modify any sperm parameter associated with fertility, although a trend to reduce DNA damage was noted associated with an increase in antioxidative enzymes (SOD and glutathione).^[93]

70% methanolic extract of the stems at 100mg/kg in male rats appears to be somewhat toxic to the testicles, causing a significant impairment of spermatogenesis and reductions in testicular and prostate size causing impaired fertility.^[97]

While the water extract doesn't seem to have much associated with it aside from some possible protective effects on DNA damage, the methanolic extract appears to be toxic at relatively low concentrations

Scabies is an infection caused by the Sarcoptes scabiei mite which causes skin problems (intractable pruritus with mild cutaneous lesions).^[98][99] Topical application of tinospora cordifolia appears to be effective in treating scabies^[100] and over five weeks appears to be equally effective as 5% permethrin lotion in reducing infestation (trending to be more effective) and skin symptoms^[3] and comparable to topical Crotamiton.^[101]

Appears to be effective in reducing scabies infections, with efficacy comparable to the reference drugs for topical application

Bacopa Monnieri (Brahmi) and Evolvulus alsinoides (Shankhapushpi) are two ayurvedic herbs used for the purpose of cognitive enhancement. While both of them individually (at 200mg/kg oral ingestion to rats with amnesia) are more effective than tinospora cordifolia and any pair merely suggests that bacopa monnieri is the most potent single herb, the combination of all three herbs at a combined 200mg/kg appears to be most effective which suggests synergism.^[47]

May be a synergism among the three herbs that is not seen with any pairing of two of them

Ginger is a spice that is also traditionally used as an ayurvedic medicine, and it appears to commonly be used alongside tinospora cordifolia for the treatment of rheumatism;^[89][90] synergism or additive benefits have not yet been demonstrated.

Traditional medicine suggests some synergism, but this has not yet been investigated

Tinospora cordifolia water extract has failed to show mutagenic or carcinogenic properties in vitro.^[10]

In mice, oral ingestion of 150-250mg/kg of the water extract for one week has failed to exert any toxicological signs.^[10]