Guduchee (Tinospora cordifolia)

Guduchee (Tinospora cordifolia)

Introduction

From Indian mythology to Ayurveda and modern medicine Guduchee (Tinospora cordifolia) is extolled as a remedy par excellence for the treatment of many diseases especially those of the liver.

It has a noble place in the epic Raamaayana: During the war between Raama and Raawana, to resurrect the army of Raama, Lord Indra gave “amrita” i. e. “divine nectar” to Raama’s army. The Guduchee plant grew from the few drops of ‘nectar’ that fell on the ground. [1]

From fever to cancer the herb protects the body from diseases; hence the epithet Guduchee (the one that protects, the one that acts as a savior from diseases). Another synonym of the plant is Madhuparnee (the one whose leaves are full of nectar). When we cut a fresh spring from Guduchee tree and hang it from a cord in the air; it will continue to grow without any visible or perceptible nutritional support. It gains its ‘life energy’ from environment. Hence in Sanskrit it is called ‘Amritaa’ meaning immortal or imperishable! As the plant confers vitality, vigor and youthful longevity or imparts immortality on any one who consumes it, the plant is called ‘Amritaa’ (divine nectar of longevity). The other Sanskrit epithets used for Guduchee are: Chhinnaruhaa/Chhinnodbhawaa (the plant that grows from the cut side), Watsadini (eaten by grazing animals), Rasaayanaa (the plant possessing capacity to improve Rasa Dhaatu), Chakraangi/Chakralakshnaa (having wheel-like appearance), Jwaranaashee/Jwaraari (potent antipyretic), Wayastha (age-stabilizer, prevents ageing), Amritasambhawaa (ambrosia) and Bhishakpriyaa (favorite of physicians). [2]

Guduchee has been described as “one which protects the body”. The word Amritaa is derived from ancient Hindu scriptures where Amritaa was used to bring the dead back to life and keep gods from growing ill and old. It for these reasons Guduchee is also referred to as “nectar of immortality” and “heavenly elixir”   [3] 

The name of its genus Tinospora is derived from the Greek teino which means “to stretch like a bow” and spora which means “seed”. Its leaves are heart shaped; hence the name of the species is cordifolia. [4]

In Ayurveda Guduchee has long been used as a tonic, vitalizer and as a drug to treat many ailments. Along with many beneficial properties of Guduchee, the noted Ayurvedic surgeon Sushruta described it as ‘shukra-shodhana’ meaning sperm purifier. Its property of imparting vigor and vitality and its ‘shukra-shodhana’ ability are probably misconstrued in the ‘Kaama-Sootra’ as ‘aphrodisiac’. In his translation of the classic text ‘Kaama-Sootra’ in 1883, Sir Richard Burton writes (free rendition by me): If the juice of fennel (English: Anise, Marathi: Badeeshepa) and milk are mixed with equal quantities of ghee, honey, sugar and liquorice (Glycyrrhiza glabra), the mixture acts like nectar and is said to be sacred, provocative of sexual vigor and stabilizer of age and life. SS Richard Montgomery Matter refers to Sir Richard Burton’s aphrodisiac formula: guduchi (Tinospora cordifolia), pippali-long pepper (Piper longum) and licorice (Glycyrrhiza glabra) boiled in milk, honey and sugar has aphrodisiac effect.
Kamasutra-SS Richard Montgomery Matter
(www.ssrichardmontgomery.com/download/nlink/karmasutra.pdf)

However Ayurvedic sources express mixed opinion. Some mention it, some don’t.  
George Playfair’s translation of the Indian Materia Medica, Taleef Shereef, 1833 does mention Guduchee but certainly not as being aphrodisiac! 

The first botanical reference to Guduchee in the English can be found in Transactions of the Linnean Society of London Volume 13, 1822. [5], [6]

Other Names

Botanical: Tinospora cordifolia (Wild), Miers ex Hook, f. and Thoms
Sanskrit: Guduchee, Madhuparnee, Amritaa, Chhinnaruhaa, Watsadaanee, Taantrikaa, Kundalanee, Chakralakshanika and many more
English: Tinospora
Bengalee: Gulancha/Palo
Gujarati: Galo
Hindi: Giloy, Guduchee, Gurach
Kannada:  Amritaa bali
Malayaalam: Ambrithu, Chittamritu
Marathi: Gulawela
Punjabee: Gilo
Tamil: Shindilakodi, Amudom, Chindil
Telugu: Tippaa tiga

AKA: Ambervel, Heart-leaved Moonseed, Heavenly Elixir, Jetwatika. [7], [8] 

Taxonomic Classification

Kingdom: Plantae-Plants.
Unranked: Angiosperm.
Division: Magnoliophyta- Flowering Plants
Class: Magnoliopsida, Liliopsida-Monocotyledons. 
Order: Ranunculales,  Zingiberales.
Family: Menispemaceae, Zingiberaceae- Ginger family. [9]

Geographical distribution
This plant is found throughout tropical part of India; typically growing in deciduous and dry forests. It is also indigenous to Myanmar and Sri Lanka.
    
The plants are long-lived and often locally abundant. It does not require any particular type of soil. It has adapted to grow in any soil and climate that offers good moisture and sunlight. It can grow in any temperature and in India can thrive 1200 meters above sea level. [10]

Plant Morphology


            
  Guduchi plant                                      Guduchi root


             
    Guduchi stem                                                 Guduchi leaves

                          

      Guduchi flowers                                        Guduchi fruits

Macroscopic Characteristics

Guduchee (T. cordifolia) is a large, deciduous, extensively spreading, perennial herbaceous vine of weak and fleshy stem found throughout India. T. cordifolia is a big twining glabrous climber which generally climbs with several elongated twining branches on large trees preferring the support of mango and neem trees. 

Roots are tuberous, long thread like, aerial; arise from branches, often growing on neem or mango trees.

Bark is thin, succulent, creamy white to grey in color, with deep clefts spotted with lenticels. (A lenticel is an opening that allows gaseous exchange between air and the inner tissues of a plant)

Stem succulent, fleshy, twining, 0.5 to 5 cm in diameter, green when young, with smooth surface and swelling at nodes; older ones are brown in color with warty protuberances.

Branches are grey-green, up to 40 mm in diameter, becoming brown with age 

Leaves are heart-shaped, smooth, simple, alternate, exstipulate; petiole up to 15 long, roundish, pulvinate (having a swelling), both at the base and apex with the basal one longer and twisted partially and half way around. Lamina broadly ovate or ovate-cordate, 10-20 cm long, 8-15 cm broad, 7 nerved and deeply cordate at base, membranous, pubescent above, whitish tomentose with a prominent reticulum beneath.

Flowers are small, leafless, yellowish-greenish in color, growing in lax axillary, terminal racemes (Marathee: Pushpamanjiree) emerge from nodes on old wood in spring. They are unisexual (male and female flowers are formed on different plants). Male flowers clustered, female usually solitary. Sepals six, free in two series of three each, the outer ones are smaller than the inner. Petals six, free, smaller than sepals obovate and membranous.

Fruits are drupes, pea like, aggregate of 1-3, up to 10 mm in diameter, smooth, oval, glossy, succulent, fleshy, on thick stalk, single seeded, turning scarlet or orange-red when ripe, up to 10 mm in diameter.

Seeds are curved, pea-sized.

Microscopic Characteristics

Root: The aerial root is characterized by tetra- arch to penta- arch structure. The cortex has outer thick walled zone representing the velamen (a spongy epidermis that covers the roots of some plants) and inner parenchymatous zone containing secretory canals. Starch is present throughout the parenchyma of the aerial root. The starch grains are elliptical in shape, mostly simple but sometimes as compound grains of 2 to 5 components, with faintly marked concentric striations and central hilum appearing like a point.

Stem: Stem is characterized by the presence of bicollateral vascular bundles surrounded by pericycle fibers. The cork arises in the sub-epidermal layers giving rise to 2-3 layers of cork. Starch is present throughout the parenchyma of the stem. 

(Note: The bicollateral vascular bundle consists of two patches of phloem, two strips of cambium and one patch of xylem at the center. It is confined to certain dicot stems only) [12]

Leaf: In transverse section the petiole is more or less circular in outline. No trichomes (fine outgrowths or appendages) found. The cross section shows a single layered epidermis and a wide zone of cortex composed of 3-4 layers of endodermis. The vascular bundles consist of radial rows of xylem on the inner side and a few rows of cambium cells on the outer side followed by phloem. The mid-rib is more or less circular in outline and palisade does not extend over the stellar tissue. The cross section of lamina shows a dorsiventral structure with its mesophyll differentiated into palisade and spongy tissue. The mesophyll is clearly differentiated into a palisade layer made up of one row of thin-walled columnar cells which occupy a little more than half of the width of mesophyll. Glandular hair are present in lower surface only. They are unicellular and somewhat club shaped. The base is surrounded by 4 to 5 epidermal cells. Starch is present throughout the tissue.  [13]

Parts used

Every part of the plant has medicinal use. In Auyrveda the whole plant is valued.

In Ayurvedic pharmacopoeia the stem is approved because of higher content of alkaloid in it. The traditional preparation ‘Guduchee Sattwa’is obtained from the herb growing with the support of neem (Azadirachta indica). The preparation is said to incorporate the medicinal values of neem. Hence the preparation is bitterer and more efficacious.

Phytochemistry

According to the class of chemical to which they belong, a large number of chemical compounds isolated from T. cordifolia can be described as: 

Alkaloids

Berberin, Tembetarine, Magnoflorine, Choline, Tinosporin, Isocolumbine, Palmatine, Tetrahydropalmatine, bitter gilonin, non-glycoside gilonin gilosterol [14]
Glycosides
18-neoclerodane glucoside, Furanoid-diterpene glucoside, Tinocordiside, Tinocordifolioside, Cordioside, Cordifolioside A to E, Syringin, Syringin-apiosyl glucoside, Palmatosides C and F, Amritoside

Diterpinoid lactones

Furanolactone, Clerodane derivatives, Tinosporin, Tinosporides and Jateorine

Recently four new clerodane furano diterpene glucosides (amritosides A, B, C and D) have been isolated as their acetates from stems. [15]

Cordifolide A, a sulfur-containing Clerodane Diterpene Glycoside has been isolated from Tinospora cordifolia. Probably this is responsible for anti-microbial activity of the plant. Cordifolide B and C have also been isolated as a white powder in the form of a mixture that could not be further separated by any chromatographic methods.[16]

Sterols

Beta Sitosterol, Delta Sitosterol, 20- Beta Hydroxy ecdysterone, Makisterone A, Giloinsterol (Gilosterol)

Sesquiterpenoid

Tinocordifolin

Aliphatic Compound

Octacosanol, Heptacosanol

Phenolic compounds

Miscellaneous
Nonacosan, Jatrorrhizine, Tinosporidine, Cordifol, Cordifelone, N-Trans-feruloyl Tyramine diacetate, Giloin, Gilonin, Tinosporic acid,

The adaptogenic compounds for which the plant is valued most need a special mention. They are:

Diterpine compounds, Tinosporin, Tinosporides, Berberine, Giloin, Giloinin, Arabinogalactan, Picrotene and bergenin.

A new hypoglycaemic agent was isolated from the plant. It was found to be 1, 2-substituted pyrrolidine. [17]

The phytochemical analysis of T. cordifolia revealed that alkaloids, flavonoids, tannins, phenols, saponins, glycosides, aminoacids and steroids contained in the plant might be accountable for its antimicrobial potential. [18]

Identity, Purity and Strength
(1)
For dried drug-
Foreign matter:  Not more than 2 percent
Total ash:  Not more than 16 percent
Acid-insoluble ash:  Not more than 3 percent
Alcohol-soluble extractive: Not less than 3 percent
Water-soluble extractive:  Not less than 11 percent

For fresh drug----
Foreign matter: Nil   
Moisture content: 75 percent.  [19]

(2) Standards for Identity and Purity accepted by other experts:

Foreign matter: Not more than 2 percent
Total ash: Not more than 7 percent
Acid-soluble ash: Not less than 0.8 percent
Ethanol- extractive: Not less than 6 percent
Loss on drying: Not more than 7.5 percent
Lead: Not more than 10 ppm
Arsenic: Not more than 2 ppm
Heavy metals: Not more than 20 ppm
Total bacterial count: Not more than 3000 CFU/gm
Yeasts and moulds: Not more than 100 CFU/gm
Bitters content on dry basis by Gravimetry/HPTLC Not less than 3 percent w/w


(3) Standards accepted by Indian Pharmacopoeia (IP) in 2010

Foreign organic matter: Not more than 2.0 per cent
Ethanol-soluble extractive: Not less than 1.5 per cent
Water-soluble extractive: Not less than 9.0 per cent
Total ash: Not more than 10.0 per cent
Acid-insoluble ash: Not more than 3.0 percent

Heavy metals: 1.0 g complies with the limit test for heavy metals
Loss on drying: Not more than 10.0 per cent, determined on 5.0 g by drying in an oven at 1050 (0 C or 0 F is not mentioned)
Microbial contamination: Complies with the microbial contamination tests.
Assay: Determined by liquid chromatography [20]

TLC pattern
On TLC identity test the drug showed six major molecules having Rf value and color 0.24 (Yellow); 0.35 (dark green) (tinosporoside); 0.42 (green); 0.44 (light yellow); 0.76 (dark green) and 0.79 (dark green) using chloroform and methanol (9:1) as a solvent system and anisaldehyde - sulphuric acid as spraying reagent  [21]

HPCL chromatogram
By HPCL chromatogram of methanol extract of T. cordifolia the standard quantity of berberine in the plant has been determined [22]

Cytological Identity

9  Chromosome counts in Tinospora cordifolia (Willd.) Miers [23]

Genetic study
With the help of molecular techniques like Random Amplified Polymorphic DNA (RAPD), Amplified Fragment Length Polymorphic DNA (AFLP), Restricted Length Polymorphic DNA (RFLP) and Inter Simple Sequence Repeat (ISSR) etc. The identification of plant species has now become very accurate. [24]

Safety Tests
No safety data for each specific species of herb is available. Here are general guidelines: 
Heavy Metals:
Arsenic:          Not more than 5.0 mg/kg
Mercury:        Not more than 0.5mg/kg
Lead:              Not more than 10.0 mg/kg
Chromium:    Not more than 0.3 mg/kg

Microbial Limits:
Total bacterial count:                                  Not more than 105cfu/g
Total yeast and mould count:                     Not more than 104cfu/g
Bile tolerant gram negative bacteria:          Not more than 104cfu/g

Specific Pathogens:

Salmonella spp:                          Absent in 25 g
Escherichia coli:                         Absent in 1g   
Staphylococcus aureus:             Absent in 1g          
Pseudomonas aeruginosa:        Absent in 1g  [25]


Properties and Pharmacology   

Ayurvedic Properties

Ganas (Classical Categories)

Charaka Ganas: Vayahsthaapana (Anti aging, Age stabilizer), Daaha prashamana (Respites burning sensation, Anti-inflammatory, Anti-histaminic), Trishnaa nigrahana (Quenches thirst), Stanya shodhana (Milk purifier).
Sushruta+Ganas: Guduchyaadi, Patolaadi, Aaragwadhaadi, Kaakolyaadi, Wallipanchaka

 

Energetics


Rasa (Taste): Kashaaya (Astringent), Tikta (Bitter)
Weerya (Energy State): Ushna (Hot)
Wipaaka (End result, Post digestive effect): Madhura (sweet)
Prabhaawa (Special Effect, Prominent Effect): Wishaghna (Alexipharmic, acting as antidote to poisons)
Gunas (Qualities): Guru (heavy), Snigdha (Anointing)

Effects on Doshas: Waata, Pitta, Kapha, (Tridoshaghna i. e. passifies the three ‘doshas’)
Actions on Dhaatus (Tissues): Rasa (Lymph), Rakta (Blood), Maansa (Muscles), Meda (Adipose tissue, Fat), Majjaa (bone marrow), Aartava (Menstrual blood?) and Shukra (Semen)
Srotas (Systems): Rasawaha (Lymphatic), Annawaha (GI system), Raktawaha (Hemopoetic system), Medowaha (Adipose system)

Medowaha Srotas: Adipose system
Eons ago Ayurveda recognized Meda (Fat) as one of the components of Adipose system. Ayurveda also described some functions of Meda. However, for centuries Modern medical science did not recognize adipose tissue as a component of any system. It is only recently we say ‘Fat is not a lump of lard!’  

Now according to modern view, Adipose tissue is a complex, metabolic and endocrine organ. It is highly active. The adipose tissue contains adipocytes, connective tissue matrix, nerve tissue, stromal cells, and immune cells. These components function as an integrated unit. Adipose tissue responds to afferent signals from endocrine system and the CNS. It secretes leptin, cytokines, adiponectin, complement components, plasminogen activator inhibitor-1, proteins of the renin-angiotensin system, and resistin. Adipose tissue (system?) is a major site for metabolism of sex steroids and glucocorticoids. Collectively they perform important endocrine functions.

Well! This is not the place to discuss in detail about the ‘Adipose System’. However the author decided to give only an overview necessary for the current context. [26]
 AyurvedicActions

Deepana - Appetizer
Aamapaachana- Free radical scavenger
Anulomana - Prokinetic
Balya - Strengthening tonic
Daaha hara – Respites burning sensation, anti-inflammatory, antihistaminic.
Graahee - Constipating
Jwaraghna -Anti-pyretic
Kaasahara – Anti tussive
Kushthaghna - Antileprotic
Pramehaghna - Anti-diabetic
Rasaayana – Rejuvenator, Adaptogen
Stanya shodhana- Purifier of the breast milk
Shwaasahara –Allays breathlessness
Waatahara -Pacifies Waata
Wishagna – Alexipharmic, acting as antidote to poison

When taken internally routinely (daily) Guduchee choorna (powder) can delay aging. Thus Guduchee acts as wayahsthaapak rasaayana (anti aging, age-stabilizer-rejuvenator).

Guduchee improves microcirculation, hence it is recommended for correcting ischemic vascular diseases like PVDs.

Guduchee possesses antiseptic and analgesic properties.

Because of its Snigdha Guna and Madhur Wipaaka, Guduchee is a very good aphrodisiac. [27]

Guduchee (T.cordifolia) is antipyretic, antiperiodic (a remedy possessing the property of preventing the periodic exacerbations), blood purifier, paandunaashaka (anti-anemic), waataraktahaaraka (anti-gout), daaha prashamana (the one which respites or allays or relieves burning sensation), kushthanaashaka, (anti-leprotic), walee-palita naashaka (arrests and prevents balding), trishaa shaamaka (alleviates and quenches excessive thirst), bitter, appetizer, digestive (digestant), antiemetic, anthelmintic, kaamalaahara (allays  jaundice), hepatoprotectant, antitussive, antiasthmatic, hridroganaashaka (relives cardiac disorders), mehanaashaka (antidiabetic), diuretic, balya (tonic, increases strength), wayah-sthaapaka (stabilizes age and prevents aging), adaptogen, rasaayana (rejuvenator), chakshushya (beneficial to eye and useful in ophthalmic disorders), nervine tonic and memory booster ( does it mean prevention of  Alzheimer’s disease?), tonic and vitalizer, wrishya (aphrodisiac). The well-ground whole plant paste is applied on fractures.

Maharshi Charaka makes a special mention about it as ‘stanya shodhana’ (the one which purifies breast milk)

Sushruta the noted surgeon mentioned it as ‘shukra shodhana’ (the one which purifies the semen and sperms) 

Modern View

T. cordifolia has anti-inflammatory, antioxidant, immunomodulatory, antipyretic, anti-allergic, anti-leprotic, antispasmodic, antiemetic, cholagogue, hepatoprotective, detoxicating, antiarthritic, adaptogenic, antidiabetic, antimalarial and anti-neoplastic activities. The main target organs for Guduchee are liver, spleen and kidney.

Alpha-D-Glucan

Molecular formula: C6H12O6, HO (C6H10O5)n
Structural formula:
  [28]


It activates the immune system through the activation of macrophages. [29]

The signaling mechanism of (1, 4)-alpha-D-glucan (RR1) was investigated in macrophages to evaluate its immune-stimulating properties. [30]

Further study revealed that this activity is mediated via TLR6 signaling, NF kappa B translocation and cytokine production.

Arabinogalactan (AG)

Pharmacological actions of AG have been discussed in detail in the chapter on Bhoomyaamalakee (P. amarus)  

Beta-ecdysone

Molecular formula: C27H44O6

Structural formula:

  [31]


Ecdysteroids are steroids found in invertebrates and plants. In mammals they have protein anabolic effects. Beta Ecdysone has anti-osteoporosis activity. In oophorectomized rats Guduchee (Tinospora cordifolia) was found to increase the thickness of atricular cartilage of the lower end of femur and upper end of tibia and epiphyseal growth plates and trabacular bone in the region of metaphyseal region of tibia. The whole epiphyseal growth plate and its proliferative and hypertrophic zones were also increased. Therefore Guduchee (Tinospora cordifolia) can be used to prevent osteoporosis and osteo-arthritis which explains Guduchee being used as ‘Rasaayana’ in Ayurveda. [32]

Ecdysteroids have cytotoxic properties. [33]

The ethanolic extract of stem of Tinospora cordifolia has anti-osteoporotic effect. This effect is attributed to ecdysteroids contained in it. [34]

Berberine

Molecular formula: C20H18NO4+

Structural formula: 



Berberine is strongly yellow in color. Under ultraviolet light it shows a strong yellow fluorescence. 
Berberine is considered antibiotic. In combination with 5- methoxyhydnocarpin berberine breaks multidrug resistance of many microorganisms. Berberine inhibits the growth of Staphylococcus aureus. Berberine increases adiponectin expression.

Berberine prevents glucocorticoid induced osteoporosis. [36]

Berberine is a quaternary ammonium salt. It belongs to protoberberine group of isoquinoline alkaloids. It has pleiotropic properties and actions.

Berberine shows antifungal activity. It is synergistic to fluconazole but is active even against fluconazole resistant Candida albicans.

Berberine is active against Staphylococcus aureus and methycillin resistant Staphylococcus aureus (MRSA).

Berberine is active against trachoma virus. Hence it is used in some eye-drop formulations.

In some centers berberine is an established treatment for leishmaniasis.

Berberine is a very potent anti-inflammatory agent. It inhibits pro-inflammatory cytokines, such as E-selectin.

Berberine is a very potent antioxidant. It restores cellular REDOX balance. Its anti-inflammatory and anti-oxidant properties are beneficial to cardiovascular system (CVS). Berberine reduces elevated levels of total cholesterol, LDL, TG and apolipoprotein B by a mechanism different from that of statins. Berberin acts directly on PCSK9 (Proprotein Convertase Subtilisin Kexin 9) receptor, a natural inhibitor of LDL receptor and not through HMG-Co-A. Therefore berberine does not cause side effects typical to statins. Berberine and plant stanols acting synergistically inhibit cholesterol absorption. Thus berberine aggressively controls dyslipidemia and prevents atherosclerosis. Berberine is also useful in advanced congestive cardiac failure (CCF).

Berberine acts on insulin receptors and stimulates them, inhibits aldose reductase, and like metformin overcomes insulin resistance. Thus berberine is very useful for the treatment of metabolic syndrome.

Berberine reduces hepatic fat content in the liver. It is therefore useful for the treatment of non alcoholic steatohepatitis (NASH). Berberine also prevents proliferation of HSCs (Hepatic Stellate Cells) which are responsible for the development of liver fibrosis.     

Berberine ameliorates pro-inflammatory cytokines-induced intestinal epithelial damage. Berberine can be useful in diarrhea, dysentery, chronic colitis and inflammatory bowel disease (IBD).

According to a Chinese report, berberine combined with cyclosporine A (Cs A) could markedly increase the concentration of (Cs A) in the blood. Berberine thus can reduce the dosage of (Cs A), saving the cost of therapy and avoiding the untoward side effects. 

Berberine has anti-neoplastic activity. It can suppress leukemia, epidermoid carcinoma, melanoma, oral cancers, cancers of the tongue, GI cancers, hepatoma, pancreatic cancers, genito-urinary cancers, glioblastoma, breast cancer etc.

The mechanism of anti-cancer activity of berberine is nebulous. Various explanations offered are:

1. It inhibits angiogenesis
2. It modulates cyclooxygenase (COX-2), MDR, TNF, IL-6, iNOS, IL-12 etc.
3. It binds and inhibits stress induced mitogen-activated protein kinase activation
4. It induces apoptosis of cancer cells
5. Its anti-inflammatory and anti-oxidant properties prevent carcinogenesis
6. It suppresses NF-kappa B activation induced by various inflammatory agents and carcinogens.

Berberine 300 mg thrice a day taken orally inhibits complications of abdominal radiation (Radiation Induced Acute Intestinal Symptoms). Berberine is a cytostatic agent.

Berberine is antidepressant, neuroprotective in neurodegenerative conditions. Berberine is said to be useful in schizophrenia and Alzheimer’s disease (AD) by antioxidant property and through cholinesterase inhibitory and beta-amyloid pathway.

Recent studies show that, anti-inflammatory and macrophage activation properties of berberine may be useful for the treatment of HIV infection.

It seems that all the pharmacological actions of T. cordifolia are in fact the actions of berberine! [37]


For more details of pharmacology of berberine refer to my monograph on Daaru-haridraa (Berberis aristata) 

Alkaloids

The protection offered by T. cordifolia against afflatoxin-induced nephrotoxicity is attributed to the presence of alkaloids such as choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine and magnoflorine.  [38]

Magnoflorine

Molecular formula:  C20H24NO4     
Structural formula:   

  [39]


Magnoflorine (Mf) is a quaternary ammonium salt. It is ganglion blocking agent. Some curare-like action has also been noticed. It has practically no effect on the adrenergic system. The hypotensive action of magnoflorine is therefore, mainly associated with ganglionic blockade. [40]

Tinosporin, Tinosporic acid, Tinosporol, Cordifolioside A and Syringin are immunomodulatory agents.

 N-Methyl-2-pyrollidone, N-formylannonain, magnoflorine and tinocordiside enhance phagocytic activity. [41]


Some testimonials from modern research:

Anti-Inflammatory Activity
 
The polysaccharides contained in T. cordifolia show anti-inflammatory activity and enhance phagocytosis in vivo. [42]

The alcoholic extract of T. cordifolia is effective against acute and subacute inflammations. [43]

T. cordifolia growing with the support of Neem (Azadirachta indica) is known as Neem Giloe. The water extract of Neem Giloe exhibits much superior anti-inflammatory activity. When given orally and intraperitoneally (50 mg/100gram of bodyweight) it significantly inhibited in mice the acute inflammation induced by carrageenan. It also significantly inhibits antibody formation by ‘typhoid H’ antigen. [44]

This effect is probably because of synergism with chemicals derived from Neem. [45]

In an animal model, aqueous extract of T. cordifolia was used to treat cotton pellet granuloma and formalin induced arthritis. The extract produced a significant anti-inflammatory activity which was comparable with indomethacin. The extract was effective in both acute and sub acute inflammations. T. cordifolia was more effective than acetylsalicylic acid in acute inflammation. But in subacute inflammation T. cordifolia was found to be inferior to phenylbutazone. [46]

A compound preparation ‘Rumalaya’by Himalaya Pharmaceuticals (Disclaimer: I have no financial interest)  containing T. cordifolia was reported to significantly reduce pain in patients suffering from rheumatoid arthritis. [47]

Antioxidant Activity

In vitro, extract of T. cordifolia inhibits the lipid peroxidation and super oxide and hydroxyl radicals. To achieve 50 % inhibition the concentration needed was 6mg and 12.5 mg/ ml respectively. At 25mg/kg body weight for 10 days the extract also ameliorated the toxicity of cyclophosphamide. These effects are attributed to antioxidant property of T. cordifolia. [48]

AG isolated from T. cordifolia showed good protection against gamma-ray induced damage. This is attributed to antioxidant and free radical scavenging activity of AG. [49]

Oral administration of alcoholic extract of the root of T. cordifolia at 100mg/kg for six weeks to diabetic rats reinstates the depleted levels of glutathione in the liver and kidney; thus protecting these organs from oxidative stress injury. [50]

During and after ischemia and hypoxia of the brain, free radical insult leads to necrosis and brain cell death. Antioxidant activity of T. cordifolia counters these insults and exhibits neuroprotective activity. [51]

Metal chelating and free radical scavenging properties of T. cordifolia show radioprotective effect. [52]

Immunomodulatory activity

In some experimental studies on mice, by modulating the proinflammatory cytokines; G1-4A, a polysaccharide from T. cordifolia protected them against septic shock. [53]

In some experimental studies on Swiss Albino mice of either sex weighing between 18 and 20 grams; pretreated with T. cordifolia, Thatte UM, Kulkarni MR, Dahanukar SA, injected intraperitoteally, 108 E. coli to induce peritonitis. These animals showed marked bacterial clearance and phagocytic activity against the bacteria as well. T. cordifolia also prevented the development of sepsis. [54]

Syringin and Cordiol contained in T. cordifolia inhibited immunohemolysis of antibody coated sheep RBCs by guinea pig serum. These compounds also increased Ig G in the serum.  However the humoral and cell mediated immunity was dose dependent. Cordoside, Cordiofolioside A and Cordiol contained in the plant also activated macrophages. [55]

In some studies the water and ethanolic extract of the stem of T. cordifolia was found to inhibit the cyclophosphamide induced immunosuppression [56]

In summary one can say T. cordifolia can build up specific and nonspecific immunity against many diseases. 
Antimicrobial Activity

The alcoholic extract of the stem shows activity against E. coli. Active principles identified from the plant extract were found to inhibit in vitro the growth of Mycobacterium tuberculosis. [57]

The plant extract showed in vitro to inactivate Hepatitis B surface antigen. [58]
Dr. Nirmala Rege HOD, Dept. Pharma and Therapeutics and Ayurveda, G. S. Medical College, Mumbai, India is of the opinion that T. cordifolia is superior to P. niruri in this regard.

In a clinical trial at Regional Research Institute (Ayurveda) Jaipur, India; 20 patients of infective hepatitis (viral hepatitis, type of viruses not mentioned) were treated with tablets (500mg per tablet) prepared from stem of T. cordifolia. Each patient received 500mg tablet with water three times a day for four weeks. Fifteen patients were cured and five patients improved. [59]

Hepatoprotective Activity

T. cordifolia stimulates the regeneration of hepatic tissue, normalizes the hepatic enzymes and prevents the liver fibrosis.

In experimental studies on mature albino rats, extract of T. cordifolia protected the animals from CCl4 insult. This effect was attributed to hepatoprotective and immunomodulatory properties of T. cordifolia. [60]

In chronic liver disease Kupffer cells are damaged as indicated by suppressed Kupffer cell function. T. cordifolia improves the cell function and may even normalize it. [61]

The antituberculosis treatment after 3 months can induce liver damage as is evident by altered liver enzymes and histological changes of liver necrosis. However administration of 100mg/kg of T. cordifolia showed reduction of liver damage, while administration of 300mg/kg of Phyllanthus emblica prevented the liver damage.  

Some researchers also tried curcumin from Curcuma longa to protect the liver from the hepatotoxicity caused by anti-tubercular drugs. [62], [63]

In Jammu, Thailand and Philippines T. cordifolia, T. crispa and T. rumphii Boerl are used as hepatoprotectants against many toxins. Recent research has shown that a combination of Turmeric extract (Curcuma longa) and Guduchee extract (T. cordifolia) offers better hepatoprotection than T. cordifolia alone to counter the side effects of anti-tubercular drugs. [64]

Extrahepatic obstructive jaundice is associated with immunosupression, deranged hepatic function and sepsis. This may mar the surgical outcome. Addition of T. cordifolia 16 mg/kg/day orally to conventional management (i. e. biliary drainage, antibiotics, vitamin K etc.) improved surgical outcome by boosting host defenses. [65]

 
Extracts of T. cordifolia were useful for the treatment of Hepatitis B and E. The extracts also showed in vitro activity against these viruses inactivating them in 48 to 72 hours. [66]
  
Berberine contained in T. Cordifolia reduces hepatic fat content in rats of NASH or NAFLD. Berberine also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. [67]

Guduchee shows anti HBV, anti HCV activity, activity against obesity and NASH. These activities are due to berberine. The pharmacology of berberine has been discussed in detail in the chapter on Daaru-haridraa (Berberis aristata

Culinary uses

The fruit of the plant has a great capacity to absorb oxygen free radicals. Hence it should be included in daily dishes.

Medicinal Actions and Uses

Traditional Uses

From proverbial grandmothers’ medicinal chest, from folk medicine to classic text books of Ayurveda, Guduchee (T.cordifolia) is a popular medicine.

It is used to treat PUO, malaria and periodic fever, allergic rhinitis, sinusitis, upper respiratory tract infections (URTI), bronchial asthma, in ophthalmic disorders, as tonic to boost immunity and body resistance, GI disorders, diarrhea, jaundice, as hepatoprotectant, in ascites, anemia, Rheumatoid arthritis (RA), Osteoarthritis (OA), gout, diabetes, skin allergies, leprosy, as adaptogen and rejuvenator, in gynecological problems, as aphrodisiac, as nervine tonic and in psychosomatic disorders. 

Usages in folk and tribal medicine in India
     
The tribals of Naugarh and Chakia Block of Varanasi prepare pills of the stem of Guduchee (T. cordifolia) and the roots of Bhatkatiaya (Solanum surattense) and use in the treatment of fever.

The fishermen along the sea coast of Mumbai use T. cordifolia in the treatment of fever, jaundice, dysentery and chronic diarrhea. 

The tribals of Khedbrahma, North Gujarat use powdered stem and root of T. cordifolia with milk for the treatment of (?liver) cancer; decoction of root to cure diarrhea and dysentery and decoction of old stem for the treatment of fever.
     
The people of Jammu and Kashmir, Bigwada (Rajasthan), Bhuvaneshwar (Orissa), Patiyala (Punjab) use T. cordifolia for the treatment of fever.

The tribals of Maharashtra use cold water infusion (faanta or sheeta) or hot water decoction (kwaatha) of the stem (3-4 gm) in the morning on empty stomach as tonic for general debility. 

Paste or juice of Amritaaa (T. Cordifolia) leaves and Sarshapa beeja choorna (seed powder of Brassica campestris) is applied locally for daaha (burning sensation).
     
A mixture of equal parts of Amritaa (Tinospora cordifolia), Hareetakee (Terminalia chebula), and Ajwain (Trachyspermum ammi) powders with salt is administered orally once daily early morning by the people of Dhurala (Haryana) for the treatment of cough.   

Lambative of Guduchee (T. Cordifolia) and 5 seeds of Krishna Marich (Piper nigrum) is administered orally by women of Arjunpura (Rajasthan) to women suffering from menorrhagia (excessive vaginal bleeding)
    
The inhabitants of Badala (U.P.) take the juice of the stem of T. cordifolia with honey for the treatment of shwaasa (Bronchial asthma)

Decoction of stem is administered orally by the people of Dehrabara Kolaras, Shivpuri District of M. P. for the treatment of skin- diseases.

The Muslim tribals of Rajouri, Jammu comprising Gujjar and Backwals use the plant for the treatment of fractured bones. [68]

Usages in Ayurveda

As adaptogen it is recommended for routine, continuous use for the wellbeing of physical and mental health.
      It is used to treat Pyrexia of Unknown Origin (PUO)
      It is used to treat many skin disorders
      It is used to treat Osteoarthritis (OA), Rheumatoid arthritis (RA), and gout
      It is used to quench thirst.
      It is recommended for all GI disorders (loss of appetite, acid-peptic disease, intestinal colic, diarrhea, dysentery, worm infestation)
     It is specially recommended for biliary colic, jaundice, alcoholic liver disease, portal hypertension and hepatosplenomegaly
     It is used to treat anemia.
     It is used for diabetes
      It is useful to treat disorders of central and peripheral nervous system 
      It is used to treat ED (erectile dysfunction) [69]

Usages in Modern Medicine

Inspite of favourable results of modern research on T. cordifolia the herb is not utilized properly in modern practice. It is used as an adjuvant to treat:

Chronic diarrhea and dysentery
Viral hepatitis
Obstructive jaundice
Portal sepsis
NASH
Septic shock
To boost non specific immunity
Some disorders of bone marrow
Anemia
Diabetes and allied conditions

Toxicity

That Ayurvedic medicines especially herbal preparations have no untoward side effects is a common misconception. T. codifolia can show interactions with other drugs. It can be dangerous in patients with Ca prostate. 

Possible Interactions:

It can potentiate the action of Oral Hypoglycemic Agents (OHAs).
One should stop using it 2-3 weeks before surgery.

Contraindications

It is advisable not to use it during pregnancy and lactation

Preparations and dosages

Powder of the Stem: 3-6 gm
Decoction: 50-100 ml
Guduchyaadi kwaatha: 10 - 20 ml
Amritaarishta: 10 -20 ml
Amritaa Ghrita: ¼ - ½ tea spoon with water usually before food once or twice a day.
Samshamanee Watee: 1 gm twice a day
Sudarshana Choorna: 3-6gm
Guduchee Kashaya: 10-20 ml.
Guduchee Ghana: 250 mg three times a day
Guduchee Loha (Iron): Dose not mentioned
Tablets: 250 mg three times a day
Capsules: 250 mg three times a day
Giloy sattwa, Gulawel sattwa: Dose not mentioned
Guduchyaadi tailam: For external use only
For PUO: Fresh decoction: 15 ml or Guduchee Ghana: 250 mg three times a day for 7 days
For URTI: It has been used for prophylactic and therapeutic purposes. Guduchee Ghanawatee 250 mg three times a day
For Gout: It is used in combination with guggul. This combination is known as Kaishor guggul. Dose: 500 mg B.D. for one month. [70]

To boost immunity or strengthen immune system 1-2 capsules twice a day after meal or as directed by Ayurvedic physician [71]

 Additional Information

Formulations, preparations and Dosages reported by Dr. N. N. Rege et al:

Swaras (Juice from the fresh Strm): 10-20 ml/day
Kalka (Paste of the fresh Stem): 10g/day
Choorna (Powdered dry stem): 1-3 g/day
Kwaatha (Decoction or hot water extract from the ground dried Stem): 20-30 mL two or three times a day
Fant (Hot water infusion): 10-20 mL/day
Arishta (Stable processed formulation from decoction containing self generated alcohol): 10-20mL/day
Sattwa (Sedimented starch extract of the Stem): 750mg to 2g/day
Ghana (Solidified aqueous extract): 500mg to 1g three to four times a day
Guduchee Ghrita (Guduchee processed in ghee): 10 to 20 g/day
Guduchee Tailam:  Guduchee processed in oil for external use.

Reference:

1. http://herbtime.wordpress.com/guduchi-giloy-tinospora-cordifolia

2. Raja Vallabham, Guduchi, an aphrodisiac, http://books.google.co.in

3. Carla Kennedy, Guduchi: The one who protects the body, California college of Ayurveda, 2009; http:// www.ayurvedacollege.com/articles/students/Guduchi

4. See Atlantic Journal 1(6): 177 1883; South African Journal of Botany 74(1): 2-9 2008, CRC World Dictionary; https://books.google.co.in  

5. http://tribes.tribes.net, Jun 10, 2010



8. http://www.iamj.in

9. http://en.wikipedia.org/wiki/Tinospora_cordifolia

10. http://en.wikipedia.org/wiki/Tinospora_cordifolia

11. https://www.google.co.in / images     

12. http://www.preservearticles.com          

13. http://www.niscair.res.in/sciencecommunication/ResearchJournals

14. Devprakash, K. K. Shrinivasan et al; Tinospora Cordifolia:- A Review On Its Ethnobotany, Phytochemical & Pharmacological Profile: Asian Journal of Biochemical and Pharmaceutical Research: Issue 4 (Volume 1) 2011.

15. Maurya R et al; Amritosides A, B, C and D : Clerodane furano diterpene glucosides from Tinospora cordifolia , Phytochemistry 2004; 65: 205 1-5

16. Li Pan et al; Kinghorn.4@osu.edu

17. C. P. Khare, Indian Medicinal plants: An Illustrated Medical Dictionary,2008

18. Archa Vermani, Navneet, Shiv Shanker, Gautam; Screening of Antibacterial Activity of Tinospora cordifolia Miers. Extracts Against Dental Pathogens, Journal of Pharmacology and Toxicology 05/2013; 8(1): 28-34


20. http://www.ipc.gov.in/writereaddata/linkimages/admin9640017989.pdf
21. Kirti Sinha, N. P. Mishra, J Singh, P. S. Khanuja; Tinospora cordifolia (Guduchi), a reservoir plant for therapeutic applications: A review; Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow 226015, U.P. Received 15 October 2003; Revised 18 May 2004; www.niscair.res.in/.../Tinospora

22. G. V. Sriniwasan , K. P. Unnikrishnan, A. B. Rema Shree, Indira Balachandran; HPCL Estimation of berberine in Tinospora cordifolia and Tinospora sinensis, Indian J Pharm Sci. 2008, Jan-Feb; 70(1): 96-98

23. Chromosome Count Data Base, http://ccdb.tau.ac.il/Angiosperms
24. http://shodhagana.inflibnet.ac.in/bitstream/10603/4494/8/08_chapter%202.pdf

26. Kershaw EE, Flier JS; Adipose tissue as an endocrine organ, J Clin Endocrinol Metab. 2004 Jun; 89(6):2548-56;

27. www.evaidyaji.com, http://www.ayurwiki.info/wiki/guduchi


29. Nair PK et al, Int Immunopharmacology, 2006 December 5; 6 (12); Epub
2006 August 28

30. Nair PK, Melnick SJ, Ramachandran R, Escalon E, Ramachandran C
Mechanism of macrophage activation by (1, 4)-alpha-D-glucan isolated from Innospora cordifolia. Int Immunopharmacol 2006; 6: 1815-24   

 31. http://en.wikipedia.org/wiki/Ecdysone

32. Kapur P, Wuttke W, Jarry H, Seidlova-Wuttke D, Beneficial effects of beta-Ecdysone on the joint, epiphyseal cartilage tissue and trabecular bone in ovariectomized rats, Phytomedicine 2010 Apr; 17(5): 350-5


34. Kapur P, Jarry H, Wuttke W, Perira BM, Seidlova-Wuttke D;  Evaluation of the antiosteoporotic potential of Tinospora cordifolia in female rats, Maturitas 2008 Apr 20; 59(4): 329-38




38. Rekha Gupta, Veena Sharma, Toxicology International, Original Article, Volume 18, Issue 2, 2011


40. http://en.cnki.com.cn  

41. Sharma U, Bala M, Kumar N, Singh B, Munshi RK, Bhalerao S;  Immunomodulatory active compounds from Tinospora cordifolia, J Ethnopharmacol. 2012 Jun 14; 141(3): 918-26

42. Pereira BM et al, Rio de Janeiro, Brazil, Phytochemistry, June 2000

43. Wesley JJ, Christina AJ, Chidambaranathan N, Effect of alcoholic extract of Tinospora cordifolia on acute and subacute Inflammation, Pharmacologyonline 2008; 3: 683-7

44. VK Pendse, AP Dadhich, PN Mathur, BR Madan, Antiinflammatory, immunosuppressive and some related pharmacological actions of Neem Giloe (Tinospora cordifolia): A preliminary report, Indian J Pharmacology, 1977; Volume: 9, Issue: 3, page: 221-224

45. Vedavathy S, Rao KN, Antipyratic activity of six indigenous medicinal plants of Tirumala Hills, Andhra Pradesh, India, Journal of Ethnopharmacology 1991; 33: 193-196

46. Jana U, Chattopadhyay RN, Preliminary studies on anti-inflammatory activity of Zingiber officinale Rosc, Vitex negundo Linn, and Tinospora cordifolia (Willid) Miers in albino rats. Indian J Pharm 1999; 31: 232-233   

47. Anonymous. Wealth of India: Raw materials; Vol X. New Delhi: CSIR, 1976

48. Mathew S, Kuttan G; Antioxidant activity of Tinospora cordifolia and its usefulness in the amelioration of cyclophosphamide induced toxicity; J Exp Clin Cancer Research, Dec. 1997, 16: 4

49. Subramaian M, Chintalwar GJ, Chattopadhyay S, Antioxidant properties of a Tinospora cordifolia polysaccharide against iron-mediated lipid damage and gamma-ray induced protein damage; Redox Rep 2002;7(3): 137-43

50. Prince PS, Padmanabhan M, Menon VP; Restoration of antioxidant defense by ethanolic Tinospora cordifolia root extract in alloxan-induced diabetic liver and kidney; Phytother Res 2004 Sep; 18(9): 785-7

51. Avinash K  Rawal, Manohar G Muddeshwar, Saibal K Biswas, Research article: Rubia cordifolia, Fagonia cretica linn, Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation; BMC Complement Altern Med. 2004 August 13; 4:11

52. Goel HC, Prem Kumar I, Rana SV, Free radical scavenging and metal chelation by Tinospora cordifolia, a possible role in radioprotection; Indian J Exp Biol 202, Jun; 40(6): 727-34 

53. Rashmi Raghu et al; Molecular events in the activation of B cells and macrophages by a non-microbial TLR4 agonist, G1-4A from Tinospora cordifolia; 
Immunological letters, 24 March 2009; Epub, 20 February 2009 

54. Thatte UM, Kulkarni MR, Dahanukar SA, Immunotherapeutic modification of Escherichia coli peritonitis and bacteremia by Tinospora cordifolia, J Postgrad Med. 1992 Jan-Mar; 38(1): 13-5

55. A. Kapil and S. Sharma; Immunopotentiating compounds from Tinospora cordifolia By Pharmacological Division, Regional Research Laborarory, Jamu Tawi 180 001 India, 21 July 1997

56. Manjrekar PN, Jolly CI, Narayanan S. Comparative studies of the immunomodulatory activity of Tinospora cordifolia and Tinospora  sinensis
Fitoterapia 2000; 71: 254-257

57. C. P. Khare, Indian Medicinal Plants, 2008

58. Indian Drugs, 1993, 30, 549

59. Database on Medicinal Plants Used in Ayurveda by P. C. Sharma and others, Vol. 3, 2001

60. Bishayi B et al, Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats J Toxicol Sci 2002; Aug; 27 (3): 139-46

61. Nagarkatti DS, Rege NN, Desai NK, Dahanukar SA, Modulation of Kupffer cell activity by Tinospora cordifolia in liver damage, J Postgrad Med 1994 Apr-Jun; 40(2): 65-7

62. Adhvaryu MR, Reddy N, Vakharia BC, Prevention of hepatotoxicity due to anti tuberculosis treatment: a novel integrative approach; World J Gastroenterol 2008 Aug 14; 14(30): 4753-62.

63. Panchabhai TS, Ambarkhane SV, Joshi AS, Samant BD, Rege NN, Protective effect of Tinospora cordifolia, Phyllanthus emblica and their combination against antitubercular drugs induced hepatic damage, phytother Res 2008 May; 22(5): 646-50
64. The Ayurvedic Pharmacopoeia of India, Part I, 1st edition, Volume 1, New Delhi: Department of AYUSH, Ministry of Health and FW; 2001, 53-55 

65. Rege N, Bapat RD, Koti R, Desai NK, Dahanukar SA, Immunotherapy with Tinospora cordifolia: A new lead in the management of obstructive jaundice. Indian J Gastroenterol. 1993; 12: 5-8
    
66. Mehrotra R, Katiyar CK, Gupta AP, Hepatoprotective compositions and compositions for treatment of conditions related to Hepatitis B and E, US Patent 749296, 2000

    

69. www.evaidyaji.com, http://www.ayurwiki.info/wiki/guduchi


  

















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