Haridraa-Turmeric (Curcuma longa)

Haridraa (Turmeric) (Curcuma longa)

Introduction 
For more than 6000 years Haridraa AKA Turmeric (Curcuma longa) has been used as ‘medicine’ in Ayurveda and Ancient Egypt. The distinct reference of Haridraa being used as ‘medicine’ is documented in Ayurveda. It was then prescribed to charm away (ward off, cast away) jaundice. Reference to its medicinal use can also be found in the text       of Yaajnavalkyasamhitaa (4000 BC) written at the time of Raamaayana.  

Since time ancient, though it was used as a medicinal plant in India, in Assyrian civilization (about 2600 BC) it was    used not as a medicinal plant but as a coloring agent. To the ancients it was not a spice but a remedy for many     ailments and a coloring agent. Haridraa (Turmeric) attained the special importance with the discovery that the powder  of its rhizome when added to food preparations, preserved their freshness and nutritive value. It might have been then introduced in cooking for preservation of food and food products. Possibly, subsequently it was used to impart color to dishes. Now in India, it is a traditional “Indian food spice”. In medieval Europe it became known as “Indian saffron”. Thanks to the brilliant yellow color it imparts to the dishes. There it was used as an alternative to far more expensive saffron spice. Needless to say Turmeric is no way match to the flavor of saffron. 

Turmeric should not be confused with “Turmeric root”. This is a colloquial name for the plant Goldenseal (Hydrastis canadensis) which is included in buttercup or Ranunculaceae family. Though both boast of a bright yellow root they     are not related. Goldenseal can be toxic if overused and used too frequently whereas Turmeric is not; though few     adverse effects of Turmeric have been recorded. 

The travelers might have been carrying the rhizome of the plant as a remedy for common ailments such as diarrhea, stomach upset and cuts and wounds; the travelers were usually subjected to suffer.  

Evidence clearly indicates that Haridraa (Turmeric) was cultivated in India from ancient times; though Marco Polo in 1280 AD mentioned Turmeric as growing in Fukien region (Now called Fujian region) of China. 

There are about 30 varieties of Haridraa (Turmeric). They are named after the region where they grow. Alleppey Finger, Erode Turmeric, Salem Turmeric, Rajapuri Turmeric, Sangli Turmeric, Nizamabad Finger are some popular varieties. 

In the world market there are two dominant types of Turmeric: ‘Madras’ and ‘Alleppey’ (named after the regions of production in India). The latter is imported by the US as spice and a food colorant. The former is preferred by the British and Middle Eastern markets. (1)         
  
Postage stamp:  In admiration of this valued herb the Government of India released a postage stamp. (2)

 Because the rhizome of the plant is yellow in color, the plant is known as Haridraa. The scholars have identified forty six epithets of the herb such as Peetaa meaning “yellow”, Gauree “Lit. She whose complexion is fair” (probably because the herb imparts a yellowish fair complexion to the subject who consumes it or uses it for cosmetic skin application); and many more. Interestingly some epithets signify “night”. The reference to “night” might have been derived from the tradition that married women apply Haridraa on their cheeks in the evening, in anticipation of the visit by Goddess of wealth Lakshmee, at that time. The custom still practiced in India, is probably the remnant of ancient tradition of sun-worship. In many languages the names of Turmeric just mean “yellow root”. (Dutch: Geelwortel, German: Gelbwurz, French: Terre merite, Arabic: Uqdah safra etc) It is said, the name Turmeric is derived from Latin Terra merita, meritorious earth or deserved earth, probably because ground Turmeric resembles ochre. Curcuma the name of its genus is derived from Persian Karkam for saffron. Most dictionaries claim that Arabic Kurkum was corrupted into Latin Terra merita, from which French Terra merite was derived and finally English Turmeric was formed.  (3), (4), (5), (6), (7)

Scientific studies carried out for about a century or so, validated many ancient claims about Haridraa (Turmeric). 

Way back in 1933, N. C. Kelkar and B. S. Rao of Indian Institute of Science, Bangalore, India, isolated essential oils from the rhizome of Curcuma longa. For every proud Indian their pioneering work is indelible.

Today we know that the peculiar flavor of Haridraa is due to ketone and sequiterpene alcohols it contains. This was however revealed to the scientific fraternity by N. C. Kelkar and B. S. Rao in 1934. (8), (9)

Indian researchers found evidence for anti-inflammatory properties of Turmeric in 1971. Later curcumin a pleiotropic compound was isolated from Turmeric. The surge of research on C. longa compelled modern medical science to recognize it as “medicinal plant”. 

The US patent office granted patent to the US for the use of Turmeric for wound healing. In 1995, based on Indian traditional knowledge, Dr. R. A. Mashelkar, then Director of CSIR (Council of Scientific and Industrial Research) promptly challenged to the US patent. Dr. Mashelkar valiantly fought and revoked the US patent in India’s favor. (10)

The metamorphosis of C. longa from the exotic spice to a topnotch drug is amazing!

Other Names 
Taxonomic: Curcuma longa Linn.
Sanskrit: Haridraa, Peetaa, Hemaraaginee, Mehaghnee, Gauree etc.
English: Turmeric
Assamese: Haldhi,  Haladhi
Benaalee: Halud, Haldi
Gujarati: Haldar.
Hindi: Haldi, Hardi 
Kannada: Arishina, Arisina
Kashmiri: Ledar, Ledhir
Malayalam: Manjal
Marathi: Halad.
Oriya: Haladi
Punjabi: Halad
Tamil: Manjal
Telugu: Haridra, Pasupu
Urdu: Haldi, Zard chub (11), (12), (13)

Scientific Classification 
Kingdom: Plantae- plants.
Unranked: Angiosperm.
Unranked: Monocots
Unranked: Commelinids
Division: Magnoliophyta- Flowering plants.
Class: Liliopsida- Monocotyledons.
Order: Zingiberales.
Family: Zingiberaceae- Ginger family. (14) 

In 1753, Linnaeus described the genus Curcuma. Since then about 130 species have been assembled in the genus so far. Some of the species are without scientific botanical identification. Therefore legitimate status of many species remains nebulous. However 80 species in the family Zingiberaceae have been accepted in the genus Curcuma

Haploid plants have one set of chromosomes (n=1) which is the same as gamete (pollen or egg cell). An organism or a cell having double the basic haploid number is known as diploid organism or diploid cell. An organism or a cell having three times the haploid number of chromosomes is known as triploid organism or triploid cell. Turmeric is a sterile triploid plant. It does not produce seeds. It is said to have arisen by continued selection and vegetative propagation of a hybrid between the diploid Turmeric and the wild Turmeric. (15)  

Geographical distribution

This flowering perennial is native to tropical South Asia. It is indigenous to India. It is likely that from India it spread to Southeast Asia and gradually to East Asia particularly to china. It was introduced to China in 700 A.D., Africa in 800 A.D. and western Africa in 1200 A.D. It gradually became harvested throughout the tropics. It needs 20 degrees to 30 degrees C of temperature and a considerable amount of annual rainfall to thrive. Although it appears in some wild places, it is not truly a wild plant. The plant prefers the soil pH between 5 and 7.5. It can be grown in well-drained, loose, friable, fertile loam or clay loam with good organic matter manure. It cannot stand water-logging and does not grow in stony, heavy and gravelly soils. It does well in partial shade.   

Plant Morphology
 


Plant:
Haridtaa (Turmeric) Curcuma longa is a robust perennial, erect, tillering plant (the plant whose stem does not produce woody, persistent tissue and dies at the end of each growing season). It reaches up to 1.5 meter in height.











Roots are filiform (threadlike or filamentous), tough, pulpy, often swollen into an ellipsoidal tuber, oblong or palmate, bright yellow to orange in color inside, about 50 to 60 cm in length.






Rhizome is a fleshy complex with an ellipsoidal primary tuber, bright yellow to orange inside and outside, about 5cm long and 2.5 cm broad, at the base of each aerial stem, surrounded with old scales of leaves, when mature bearing numerous lateral rhizomes called fingers which are again repeatedly branched.  









Leaves are lily-like, about 60 cm long, lanceolate, alternate, smooth, tapering at each end, of uniform green color.
    












Flowers are spike, cylindrical, dull yellow in color, three to five appearing together, surrounded by dense, hairy bracteolae (pleural of bracteole. Bracteolae are leaf like structures having protection and attraction function). The flowers never produce fruits.(16), (17) 




Microscopic structure
Root- The transverse section of the adventitious root is circular in outline.
The TS of central part shows:
Epiblema- Single layered. Consists of thick walled cutinized cells. In old specimen the epiblema is withered and is replaced by ten-layered rectangular cork cells
Cortex-Heterogenous, differentiated into--
Outer cortex- Composed of parenchymatous tissue of secondary and primary cortex
Middle cortex- Made up of radially arranged air chambers separated by one cell-thick partition wall-the trabaculae
Endodermis- In the innermost layer of the cortex, the cells are rectangular and barrel shaped.
Pericycle- Three to four layered, consists of rectangular cells
Vascular tissue- Radially arranged. Phloem patches and xylem are arranged alternately
Pith- Well developed and thick walled parenchymatous

Rhizome- TS of rhizome is triangular to circular. It consists of:
Epidermis- single layered, composed of very thick-walled cells, covered with thick cuticle
Cortex- three to five layered, thick walled cholenchymatous cells
Endodermis- ill developed
Pericycle- well-defined cells radially arranged and placed compactly
Pith- large, parenchymatous, a large number of cells are filled with starch grains or sphaeraphides, a number of vascular traces traversing in the pith may be leaf traces.
Vascular tissue- vascular bundles are conjoint and scattered, xylem consists of vessels and xylem parenchyma. Phloem composed of sieve tubes and phloem parenchyma
Leaf- TS of leaf lamina shows:
Epidermis- both upper and lower epidermis are identical, it is single layered covered with cuticle and perforated by stomata
Mesophyll- palisade and spongy parenchyma not demarcated, they are intermixed in mesophyll, and entire mesophyll is chlorophyllens with scattered oil cavities. The wall of oil cavities is well defined and made up of epithelial cells.
Vascular bundles- they are mixed with oil cavities, each bundle is conjoint and collateral with an arch of sclerenchyma over xylem (18) 

Parts Used 
Rhizomes and tubers 

Phytochemistry

After the initial landmark and probably pioneering work by N. C. Kelkar and B. S. Rao on essential oils from C. longa, there was a surge and a spate of research on C. longa; especially after 1971 when its anti-inflammatory property was detected. Since then about a hundred chemicals have been isolated. It is not necessary to enumerate all. Hence I mention medicinally active ones. It must be emphasized that the actions exhibited by the plant are not actions of any single chemical but they are of synergism of chemicals. Here is the list of useful chemicals hitherto identified and isolated from C. longa.

Resin: a glucoside, Turpethin.
Oils: Volatile oil, Alpha pinene, Beta pinene, Caryophyllene, Cinnamic acid, O and P Coumaric acid.
Curcumenol, Curdeone, Guiacol, Limonene, Alpha Terpineol (ACE inhibitor 100 microgram/ml).
Lignin, Vanillin, Vanillic acid, Caffeic acid, Caprilic acid, Protocatecheuic acid and Syringic acid
Minerals: Copper, Iron (ferric oxide), Manganese, Nickel, Phosphorus, Zinc.
Phenolic compound: Curcumin and related compounds called Curcuminoids.
Azulene, Tumerone, Zingiberene, Phellandrene, Beta Sequiphellandrene, Cineole, Carbinol, sabinene, Borneol (2-Bornanal), Isoborneol, Monoterpenes.
Vitamins: Beta carotene, Vitamin C, E, Niacin, Riboflavin, Thiamin and other vitamins in small quantity.
2- Hydroxy-methyl-anthraquinone (Anti leukemic agent?)
Feruloyl-P-Coumaroyl-Methane, P-Cymene.

Identification-

(1) On addition of Concentrated Sulphuric acid or a mixture of Concentrated Sulphuric acid and alcohol to the powder of Turmeric a deep crimson color is produced

(2) A piece of filter paper is impregnated with an alcoholic extract of Turmeric powder, dried and then moistened with a solution of Boric acid slightly acidified with Hydrochloric acid, dried again, the filter paper assumes a pink or brownish red color which becomes deep blue or greenish-black on addition of alkali

IDENTITY, PURITY AND STRENGTH

Foreign matter Not more than 2 percent
Total Ash Not more than 9 percent
Acid-insoluble ash Not more than 1 percent
Alcohol-soluble extractive Not less than 8 percent
Water-soluble extractive Not less than 12 percent
Volatile oil Not less than 4 percent (19)

Water Not more than 12 percent
Microbial contamination complies with the microbial contamination test
(19 a)

Chromosome number of Haridraa (Turmeric) (Curcuma longa)
2n=64 (Suguguira 1931, 1936)

Genetic identification

By using DNA (DAMD) and Inter Simple Sequence Repeats (ISSR) methods Sushma Verma et al established accurate    identity of Haridraa (Turmeric) (Curcuma longa

Safety Tests

There are no specific guidelines regarding safety tests, permissible microbial limits in a given pharmaceutical preparation of...... 
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

Properties and Pharmacology

Ayurvedic Properties

Ganas (Classical Catagories)
Charak Ganas: None
Sushrut Ganas: None

Energetics

Rasa (Taste): Tikta (Bitter), Katu (Acrid, Spicy, Pungent)
Weerya/Virya: (Energy State): Ushna (Hot)
Wipaaka (End result, Post Digestive Effect): Katu (Acrid, Spicy, Pungent, Piquant)
Prabhaawa (Special Effect, Prominent Effect): Antibacterial, Regulates blood sugar

Gunas (Qualities): Rooksha (Dry)
Effects on Doshas: Waata, Pitta, Kapha
Actions on Dhatus (Tissues): All Tissues
Actions on Srotas (Systems): Raktawaha (Hemopoetic system), Praanawaha (Respiratory System), Annawaha (GI System), Rasawaha (Lymphatic System)

Ayurvedic Actions 

Aartavajanana - Emmenagouge
Deepana - Appetizer
Jwaraghna - Anti-pyretic
Krimighna - Anthelmintic
Kushthaghna –Anti-leprotic
Lekhana – Reduces weight, reduces fat
Paandughna – Anti-anemic
Pramehaghna - Anti-diabetic
Raktashodhana - Blood purifier
Saandhaneeya -Hheals fractures
Stanyashodhaka –Purifies the breast milk
Wedanaasthaapana –Anti-nociceptive, Aanalgesic
Wishaghna- Alexipharmic (acting as antidote to poison)
It is described as warnya drawya (beneficial for complexion, complexion enhancer)

It corrects metabolisms, corrects anemia
Because of ushna weerya it is analgesic (20)

In the indigenous system C. longa enjoys the reputation as astringent, pungent and bitter. It is blood purifier, aromatic, antiseptic, anti-pruritic, vulnerary, stomachic and cholagogue. It reduces phlegm and edema. It improves complexion of the skin.

Modern View
Turmeric has anti-inflammatory, anti-oxidant, immunomodulator, antibacterial, antiviral, antifungal, antiseptic, anti-pruritic, anti-tussive, expectorant, gastroprotective, hepatoprotective, cholagogue, vulnerary and anti-tumor properties.

Alpha Pinene, Beta Pinene
Molecular formula: Alpha Pinene-C10H15, Beta Pinene C10H15 
Structural formula:
                                      

  Fig. showing synthesis of alpha and beta pinene (Wikipedia)                                            
These essential oils are allelochemicals (toxic chemicals produced by plants to defend themselves and allergic to those who are hypersensitive to them). In human subjects they exhibit anti-inflammatory, antibacterial, antiviral, antifungal, sedative and tranquilizer actions. (21), (22)

Alpha Terpineol
Molecular formula: C10H18O
Structural formula:




The extract of C. longa containing Alpha terpineol (100 microgram/ml) is weak ACE inhibitor and Aldose reductase inhibitor. It is antibacterial, antiviral, anthelmintic, antiseptic and sedative. It exhibits anti-tumor activity. (23)










Azulene
Molecular formula: C10H8
Structural formula: (24)

Azulene is anti-histaminic, anti-inflammatory, antipyretic, antispasmodic, gastroprotective and hepatoprotective. It has TXA2 receptor antagonistic activity.  (25)
Azulene allays the chemical induced pharyngitis (26)
When administered orally (30mg/kg) to rats, Azulene was found to be potent antagonist of dopamine and 5-HT receptors and a weak antagonist of H-1 receptors in the thalamus. Its anti-histaminic action is weaker than that of Olanzepine. It seems that Azulene can be effective for the treatment of schizophrenia and bipolar mania without such dreads as extrapyramidal symptoms, prolactin elevation and weight gain. (27) 

Azulene and Azulene related compounds protect the cells from UV induced cell injury. (28)  

Egualen sodium (ES) is a new derivative of Azulene. It is more stable and potent than Azulene. Both prevent histamine release from the mucosal histaminocytes. This effect is attributed to their stabilizing action on the cell membrane.  (29) 

HNS-32 is a newly synthesized compound having chemical structure similar to Azulene. Its action on isolated pig coronary artery was investigated by Yoshio Tanka Makoto Kamibayashi and others. They found that the compound is a potent coronary dilator. They think although inhibition of Calcium channel and protein kinase C may be responsible for this effect, some direct action may be involved in coronary relaxation. (30)

Well! Things are not what they seem!! All is not well with Azulene, especially with the purified molecule. It has many side effects. At cellular level it inhibits respiration and growth of the cells. It may delay nerve conduction and exhibit local anesthetic effect. Some hypersensitive persons can develop skin irritation and skin allergy. 

Beta Sesquiphellandrene
Molecular formula: C15H24
Structural formula:
 



It is an enzyme. It exhibits antiviral and expectorant activity. (31)










Borneol
Molecular formula: C10H18O
Structural formula:

            
    Borneol    


                           
      Synthesis of the borneol isomer isoborneol via reduction of camphor

It is aromatic, pungent, bitter, analgesic, expectorant, allays cough with expectoration, appetizer, carminative gastroprotectant and hepatoprotectant.  Though it is anticoagulant, antithrombotic, it does not show anti-platelet activity and does not prevent platelet aggregation. It is frequently used for topical application than for internal use. It has CNS toxicity in mammals. Many of its actions resemble those of camphor. (32)

Caffeic acid
Molecular formula: C9H8O4
Structural formula:
Caffeic acid is the best known anti-oxidant, anti-inflammatory and immunomodulatory agent till date. These properties protect the skin from UV insult and subsequent dermato-carcinogenesis.   
While moderate doses (quantity not mentioned) of oral intake of caffeic acid prevents colonic carcinoma, high intake causes papilloma of the stomach. By altering the structure of DNA, N-nitroso compounds act as carcinogens. By inhibiting the formation of N-nitroso compounds caffeic acid protects the body against carcinogenesis. (33), (34)                         
It is the best known anti-oxidant, anti-inflammatory and immunomodulatory agent till date. These properties protect the skin from UV insult and subsequent dermato-carcinogenesis.   

While moderate doses (quantity not mentioned) of oral intake of caffeic acid prevents colonic carcinoma, high intake causes papilloma of the stomach. By altering the structure of DNA, N-nitroso compounds act as carcinogens. By inhibiting the formation of N-nitroso compounds caffeic acid protects the body against carcinogenesis. (33), (34) 

Caffeic acid protects the liver against CClinsult.
Caffeic acid (4mg/kg) may produce anti-depressive activity via mechanisms other than inhibition of monoamine transporters and monoamine oxidase. (35)

Caffeic acid at the dose of 50mg/kg ameliorated neuronal loss and neurological dysfunction even after 24 hours of the brain ischemia. It also decreased the infarct volume, attenuated the brain atrophy and astrocyte proliferation 14 days after the ischemia. It reduced production of leukotrienes in the ischemic hemisphere from 3 hours to 7 days after the ischemia in rats. Its neuroprotective effects are attributed to inhibition of 5-lipoxygenase. (36)

NO (Nitric Oxide), XO (Xanthine Oxidase) and ADA (Adenosine De-Aminase) play an important role in INH induced oxidative injury to RBCs. Caffeic acid protects the RBCs against INH toxicity. Also CAPE and erdosteine may have protective potential in this process and they may become promising drugs in the prevention of this undesired side effect of INH. (37)

Carbinol
Molecular formula: C9H9NO
Structural formula:
 
Carbinols are chemoprotective and chemopreventive agents. They are anti-mutagenic and anti-carcinogenic. They can induce apoptosis in the breast cancer and prostate cancer (38), (39). 
Carbinols exhibit chemoprotective and anti estrogen activity in the patients of the breast cancer (40) 
Carbinols are anti-oxidants and prevent free radical injury to various tissues; prevent free radical induced hepato-toxicity and lipid peroxidation. (41), (42)


Cineole
Molecular formula: C10H18O
Structural formula:

Cineole is anti-inflammatory, antiseptic, anti-tussive, expectorant, cholagogue, hepatoprotectant, anticholinesterase and anti-nociceptive. 
In mice, subcutaneous injection of 25, 50 and 100 microgram doses induced scratching. This response was diminished by administration of diphenhydramine (H-1 receptor antagonist) and cyproheptadine (Histamine-serotonin receptor antagonist). (43),  (44)   

1, 8 cineole AKA eucalyptol has anti-inflammatory, secretolytic, mucolytic and bronchodilator activity in respiratory disorders. In guinea pigs submitted to antigenic challenge, inhalation of this compound attenuated hyper-reactiveness of the respiratory tract and prevented bronchospasm and excessive bronchial secretions. Levels of pro-inflammatory cytokines TNF alpha and IL-1 beta were lowered. (45) 

 At 100 mg/kg dose, cineole expressed anti-nociceptive action in mice. This action was due to inhibition of formation  of prostaglandin and cytokines. It is therefore anti-inflammatory and analgesic. (46)

Curcumin
Molecular formula: C21H20O5
Structural formula:

                   
                                     Enol form                                   Keto form    (47)

Because of the research on C. longa, Haridraa (Turmeric) has become a popular dietary supplement, but not many are benefited from its use. This is because curcumin is poorly assimilated into the blood stream. While the digestive tract and the liver derive benefit from it, the rest of the body is denied of the benefit. Even after 2 g of intake, very little of it enters the blood stream. However when a small quantity of piperine (an alkaloid from black pepper, Marathi: Miree) is combined with curcumin, its extent of absorption, bioavailability and concentration are markedly increased. (48)

Alcohol dehydrogenase contributes to the formation of curcumin reduction products in the gut and in the liver. Hence curcumin does not show its clinical effects in alcoholics. Even dietary intake of alcohol and use of alcoholic beverages can impair the beneficial effects of curcumin. (49)

Although every chemical ingredient of C. longa contributes to the pharmacological action of the plant; curcumin is their leader. Each pharmacological action of C. longa is predominantly that of curcumin. One can say C. longa and curcumin are ‘pharmacological synonyms’. Hence I describe pharmacological actions of curcumin in detail in the section of ‘Some testimonials from modern research’. 

Guaiacol
Molecular formula: C7H8O2
Structural formula:




Guaiacol is expectorant and local anesthetic. (50)








Limonene
Molecular formula: C10H16                                 
Structural formula:

Limonene inhibits NO and prostaglandin E2 in cells. It also decreases the expression of TNF alpha, IL-1 beta and IL-6 in a dose dependant manner. (51), (52) 
Limonene reduces endogenous and exogenous stress. More research is necessary to establish its role as a potent anti-oxidant which can effectively protect lymphocytes and mitochondrial dysfunction. (53)
Limonene shows CNS sedative and muscle relaxant effects but does not have anxiolytic activity even at higher doses. (54)

Limonene shows anti-nociceptive activity which is probably related with peripheral analgesia but not with stimulation of opioid receptors. (55) 

Limonene is Ache (also written as AchE)-inhibitor.
Limonene not only neutralizes gastric acidity but also exhibits prokinetic activity. It has well established chemoprotective activity against many types of cancers. In one clinical trial it demonstrated partial response in a patient with breast cancer and in three cases of colorectal cancer maintained the patients in stable condition. (56)

Every sane physician, however, shall remember the adage: One swallow does not a summer make!!   

In rats limonene has shown to revert back NASH to restore the normal structure of the liver. It is also an anticancer agent in various models. This anticancer activity is attributed to prevention of protein prenylation (addition of hydrophobic molecule to a protein) at advanced stages of carcinogenesis and increasing levels of glutathione in earlier stages as preventive measure. (57)

Protocatechuic acid (PCA)
Molecular formula: C7H6O4
Structural formula:
      


Protocatechuic acid is anti-oxidant and anti-inflammatory. It induces apoptosis of human leukemia cells, as well as malignant cells taken from human oral cavity. 
Recent studies indicate that antioxidant property of PCA can be useful in preventing cardiovascular diseases and neoplasms.    (58)(59)
PCA inhibits cancer cell metastasis. (60)






Tumerone
Molecular formula:
Structural formula:




Tumerone is anti-inflammatory, anthelmintic and styptic. It shows anti-tumor activity. It acts as anti-lymphocyte agent.(61)









Turpethin 
Molecular formula: C34H56O16
Structural formula:
 Not found
Turpethin is a brownish-yellow, amorphous glucoside analogous to Jalapin. Needless to say then that turpethin is purgative. It stimulates the contractions of the gall bladder. It also stimulates the liver to produce more bile and regulate its viscosity. 

Some Testimonials from Modern Research   
Recent studies validate anti-inflammatory, anti-oxidant, anti-bacterial, anti-viral, anti-fungal, anti-protozoal, anti-fibrotic, anti-venom, anti-ulcer, anti-coagulant, anti-diabetic, hypotensive, hypocholesteremic, anti-fertility, anti-carcinogenic and anti-mutagenic activities of C. longa, i.e. curcumin. 
Its anti-inflammatory, anti-oxidant and anti-cancer roles may be exploited to control RA and other auto-immune osteoarthropathies, carcinogenesis and oxidative stress related pathologies.

Its anticancer effect is mainly mediated through induction of apoptosis.  
Daily intake of Haridraa (Turmeric) in diet does not bring about any chromosomal aberrations or mutations.

 Anti-Inflammatory Activity  
The volatile oil fraction of C. longa and the phenolic compound curcumin are potent anti-inflammatory agents. Curcumin is even more potent in acute inflammation. It is reported to be more potent than ibuprofen. Curcumin mediates this effect through the down regulation of inflammatory transcription factors such as NF kappa-beta,  enzymes such as cyclo-oxygenase-2, lipoxygenase-5 and cytokines such as TNF, interleukin-1 and interleukin-6. At lower doses it inhibits prostaglandins and at higher doses it stimulates the adrenal glands to secrete cortisone. (The quantitative measure of ‘lower doses’ and ‘higher doses’ is not defined in the article)
The early anti-inflammatory activity of curcumin was attributed to anti-histaminic activity while the late effect     may be due to activation of hypothalamo-hypophysio-adrenocortical axis, as the anti-inflammatory response of C. longa is markedly reduced in adrenalectomized animals.
Different analogues contained in C. longa exhibit variable anti-inflammatory and anti-proliferative activity through the mechanism not dependant on ROS (Reactive Oxygen Species) production. (62)

The strength of anti-inflammatory activity of curcumin is comparable to some popular NSAIDs and steroidal drugs. Several clinical studies have shown that 400 to 1200 mg/day of curcumin is as effective as phenylbutazone in treating post operative inflammation, pain and arthritis. At these doses it does not show side effects of NSAIDs and steroids. C. longa does not contain Cox 1 and Cox 2 inhibiting agents.  

Anti-oxidant Activity
C. longa exhibits anti-oxidant activity which was attributed to five anti-oxidative oleoresin compounds detected by  TLC and HPLC. Of these curcumin, demethoxy curcumin and bis-demethoxy curcumin are the major ones. Curcumin markedly antagonizes lipid peroxide in the brain, heart, spleen, liver and kidney of NIH mice. This effect is dose dependant with the range of 0.128 to 20.4 mg/100 ml of curcumin concentration.  
Nitric oxide is implicated in inflammations and cancers. Curcumin is a scavenger of NO and hence a protector against inflammation and cancer. (63)

Tissue hypoxia and hypoxemia markedly increase the free radical activity and endothelial damage. Curcumin antagonizes the free radical insult and protects endothelium. (64)

A test tube study done in 1990s shows that anti-oxidant activity of curcumin is as powerful as vitamin C, vitamin E and beta-carotene.

A recent study shows that anti-inflammatory and anti-oxidant properties of curcumin have neuro-protective effects which arrest neurodegenerative conditions. (65)

Immunomodulatory Activity

Curcumin has been shown to be a potent immnomodulating agent that can modulate the activation of T cells, B cells, macrophages, neutrophils and dendritic cells. Curcumin also down regulates the expression of pro-inflammatory cytokines such as TNF, IL-1, IL-2, IL-6, IL-8 and IL-12. (66)
In experimental studies on Wistar albino rats suffering from arthritis, 30mg/kg of curcumin administered orally showed as powerful anti-inflammatory and analgesic activity as 3mg/kg of indomethacin administered by the same route. (67)

Curcumin inhibits T helper cell cytokine profile in CD4 and T cells by suppressing IL-12 production in macrophages.     It seems therefore that curcumin can be used therapeutically to treat immune mediated diseases. (68)

Anti-microbial Activity
Several clinical and animal studies have shown that C. longa and curcumin extracted from the plant inhibit the    growth of a variety of bacteria, viruses, fungi and parasites. Topical application of curcumin was also effective as an anti-microbial agent. 

The sodium salt of curcumin inhibits Micrococcus pyogenes in 1 in one million and S. aureus in 1 in 640, 000  dilutions (69)

Methyl carbinol and its isomer phenyl ethyl carbinol contained in the volatile oil of the plant have strong action against E. coli. The oil kills S. aureus and S. albus in dilutions 1:5,000. Curcumin and curcuminoids inhibit the growth of S. aureus, S. paratyphi and M. tuberculosis in dilutions varying from 1: 20, 000 to 1: 640, 000. The essential oils show marked anti-bacterial activity against gram positive organisms such as beta hemolytic streptococci and C. diphtheriae and gram negative organisms such as V. cholera, S. typhi, Eenterobacter aerogenes and E. coli.

The essential oils from the rhizome of C. longa show antifungal (fungistatic) activity against Aspergillus niger, Physalospora tucumanesis, Ceratocystis paradoxa, Sclerotium solffii, Curvularia lunata, Helminthosporium   sacchari and Cephalosporium sacchari.

In addition to the antimicrobial activity mentioned above, the aqueous extract of C. longa shows anti-bacterial activity against Klebsiella pneumoniae, Staphyllococcus epidermides. (70)

R-Tumerone, Tumerone and Curlone found in Turmeric oil fraction I and II show anti-bacterial activity against  Bacillus cereus, Bacillus coagulans, Bacillus subtilis, S. aureus, E. coli and Pseudomonas aerugeosa. Fraction II   eluted with 5% ethyl acetate in hexane was found to be the most active fraction. (71)

Anti-fungal activity of C. longa against Candida albicans was reported in the issue 2008 of Records of Natural Products.

The ethyl acetate extract of C. longa (0.125 to 2mg/ml) demonstrated high antibacterial activity against MRSA. (72) 

In the Journal of Ethnopharmacology (Issue 2009) H. J. Kim and his colleagues showed that aqueous extract of            C. longa has a strong antiviral activity against Hepatitis B virus.

Recent studies found that C. longa shows antiviral activity against numerous viruses e. g. HPV (Human Papilloma Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), HSV-1 (Herpes Simplex Virus-1), influenza virus, adenovirus and Coxsackie virus. 
C. longa shows activity against parasites such as Plasmodium falsiparum and Leishmania.
Physician Jennifer Jamison remarks that C. longa can kill round worms. (73)

Mechanism of Anti-viral Activity
Jamison suggests that C. longa strengthens the immune system, increases CD4 and CD8 count and thus restricts the replication of Hepatitis B virus. Kim and his colleagues agree with Jamison but in addition they found that C. longa raises the level of the protein called p53 which hinders the multiplication of Hepatitis B virus.

C. longa suppresses the expression of the protein required for viral replication. Curcumin decreases ROS, restores cell membrane integrity and inhibits apoptosis to protect the neuronal cells. In some studies it was found that curcumin directly inhibits the replication of HCV. (74)

 Beware of the tall rather false claims of cure of AIDS by C. longa!! Curcumin does not inhibit HIV!!   

Hepato-protective Activity
The essential oil found in C. longa has proven stimulating effect on the gallbladder. This effect is attributed to p-tolyl methyl carbinol. It also stimulates the liver to produce more bile. It also regulates the viscosity of the bile.
C. longa (curcumin) protects the liver from adverse effects of acetaminophen, CCl4 and many other chemicals. It can also reverse the biliary hyperplasia, fatty changes and liver necrosis induced by aflatoxin. It prevents and suppresses   the microvascular inflammatory response to lipopolysaccharides in vivo.

Mechanism of Hepato-protective Activity

Several mechanisms may contribute to curcumin’s hepato-protective activity.
1. Its anti-oxidant property prevents lipoperoxidation at sub-cellular level.
2. Anti-oxidation mechanism also protects the liver via inhibition of NF-kappa-B which is implicated in alcoholic liver disease.
3. Curcumin suppresses the expression of cytokines, chemokines, COX-2 in Kupffer cells.

One in vitro study suggests that curcumin may stimulate the conversion of cholesterol into bile acid and therefore increase the excretion of cholesterol. It may reduce the development of fatty streaks in the arteries and therefore prevent the development of atherosclerosis.

Oral administration of curcumin (30 mg/kg) to male Wistar rats reduces the Fe induced hepatic damage by lowering lipid peroxidation. (75)   

C. longa (Curcumin) against Hepatitis Viruses

Curcumin inhibits HBV gene expression and replication of the virus. PGC-1 alpha (Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha) is the protein involved in energy metabolism. During starvation it initiates the gluconeogenesis cascade which co-activates HBV transcription. Curcumin inhibits HBV gene expression and HBV replication via down regulation of PGC-1 alpha. Hence some researchers suggest curcumin should be used as an adjuvant to current virus specific therapies. (76) 

C. longa extract represses the transcription of HBx gene by suppressing HBV enhancer I and X through p53 protein. C. longa extract enhances the accumulation and stability of p53 protein in the hepatocytes. By this mechanism it inhibits HBV replication. C. longa has no adverse effects on hepatocytes. (77)  

Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway. (78) 

C. longa (Curcumin) against HCC 

HCC is characterized by neovascularization activity via VEG-F. Suppression of VEG-F attenuates the tumor growth. Similarly expression of COX-2 increases during hepatocarcinogenesis. Curcumin has been shown to inhibit angiogenic biomarkers VEG-F and COX-2 expression. Some research workers therefore suggest using C. longa (curcumin) as an adjuvant to current virus specific therapies. (79) 

Actions on Metabolism

Recent studies show that cholesterol plays an important role in the development of obesity. By down regulating cholesterol metabolism, curcumin plays an important role in prevention, development, and treatment of obesity and obesity related complications. (80)

Extensive research in the last two decades has revealed that obesity is a proinflammatory state. It is a major risk    factor for type 2 diabetes, atherosclerosis, hypertension, coronary artery disease, cancer and many other obesity  related and inflammation related diseases. Interacting directly with adepocytes, pancreatic cells, hepatic cells, macrophages and muscle cells curcumin suppresses proinflammatory factors and prevents the development of obesity related diseases. (81)

Culinary Uses
In India it is a traditional curry spice. In the West it is used to flavor and color foodstuffs. Oleoresin of Turmeric is used in brine pickles and mayonnaise sauce and relish formulations, non-alcoholic beverages, gelatins, butter and cheese etc.  

Medicinal Actions and Uses
Traditional Uses
In folk traditions it has been used for digestive disorders, jaundice, helminthiasis and to treat insect bite, snake bite etc.

In Ayurveda C. longa has been used internally as stomachic, tonic and blood purifier. For flatulence, dyspepsia, indigestion, jaundice, liver problems and urinary problems it was given in doses of half gram twice a day. It has been used to expel intestinal worms. In chronic catarrh, coryza and cough it was used as lambative (Marathi: Chaatana). Inhalation of the burning Turmeric causes copious mucous discharge and offers instant relief. Traditionally boiled with milk to which a little sugar is added makes a good and effective domestic remedy for cough and cold.

Externally it has been used to improve complexion, as a cosmetic, to dress wounds, treat ulcers and skin conditions  such as allergies, fungal infections of the skin where it is used in the form of dry powder or mixed with oil. For pemphigus and other inflammatory conditions of the skin and shingles a thick coat of mustard oil is smeared    following which Haridraa (Turmeric) powder is applied. Mixed with lime (and alum S. O. S.) it is applied to contusions, sprains and inflammations. In small pox and chicken pox it is used to facilitate the process of scabbing. Turmeric 1 part and alum 20 parts is instilled in the ear in chronic otorrhea.

Decoction of Haridraa (Turmeric) is used as a cooling eye wash for conjunctivitis, trachoma and purulent ophthalmia (Country eye sore). To prepare decoction for this boil 30 grams of Haridraa (Turmeric) powder with 500 ml of water.

In China it has been used for similar ailments mentioned above. In addition it has been used as topical analgesic and to relieve chest pain.
In addition to the conditions mentioned above, in Europe it has been used for hyperacidity, to treat H. pylori infection and uveitis. 

Usages in Ayurvedic Medicine

To treat open wounds Haridraa powder is pressed in the wounds. In case of closed trauma it is applied locally.
It is used as complexion enhancer externally and internally. It is applied to treat boils and pimples
It is used as antitussive. It allays smoker’s cough and bronchial asthma. It is very useful in URTI
It useful in PPH
According to Ashtaanga Sangraha Haridraa is the best Ayurvedic medicine for the treatment of metabolic disorders like diabetes.  (82)

Usages in Modern Medicine

German commission E is an authoritative body that determines which herbs can safely be used for medicinal purpose. The commission has approved C. longa (Curcumin) for a variety of digestive disorders. Curcumin stimulates the contractions of the gall bladder, increases bile flow and helps digest fats. Hence in Germany it is used for dyspepsia, indigestion and bloating. It is used to control hyperchlorhydria, alcoholic gastritis and peptic ulcer. 
Curcumin is an accepted remedy for ulcerative colitis, acid peptic disease, osteoarthritis, to prevent diabetes related complications, atherosclerosis, some viral infections and uveitis in some countries.

Most recently, researchers have focussed their attention to use Curcumin and synthetic Curcumin derivatives to treat OA, RA, some auto-immune conditions, IBS, viral hepatitis, to prevent and cure gall stones, to control dyslipidemia   and prevent and/cure atherosclerosis, to prevent and/cure Alzheimer’s and some neurodegenerative diseases etc.    

Researchers have now focussed their attention to use Curcumin and Curcumin derivatives to treat various cancers and HIV infection.

Toxicity

That Ayurvedic drugs are not toxic, especially the herbal preparations is a myth. They are toxic and do have side effects.
Allergic contact dermatitis can develop in those who handle C. longa powder. It may cause allergic conjunctivitis, running of the nose, sneezing and may even precipitate acute attack of bronchial asthma.  
Though C. longa up to 10 G per day and Curcumin up to 8 G per day taken for 3 months did not show toxicity, at higher doses they show gastro-intestinal disturbances, hepatotoxicity and even carcinogenesis.
By chelating iron and suppressing the protein hepcidin; Curcumin can cause iron deficiency in susceptible subjects.

Although there is little or no evidence suggesting Curcumin ‘safe or unsafe’ during pregnancy; there is still some  concern regarding its use as a ‘drug’ during pregnancy. Curcumin may stimulate uterine contractions especially in  early pregnancy and can cause abortion. Its effects on pregnant rats and guinea pigs were inconclusive. However it    has embryotoxic and terratogenic effects on Zebrafish (Danio rerio) embryos.

Drug Interactions

C. longa powder and Curcumin can increase the risk of bleeding in patients on warfarin, aspirin etc.
Curcumin can interfere with H2 blockers and PPIs.
It can potentiate the effect of hypoglycemic agents.  

Preparations and Dosages

NOTE: Haridraa should be processed well with Ghee, preferably cow ghee (Indian Processed Butter) and should be taken with milk; otherwise the excessive Rooksha (Dryness) guna can aggravate Waata Dosha and can bring some Dosha imbalance in the body. (83)
The dosages of herbal supplements are calculated for an adult weighing 70Kg. Obviously if a child weighs 20-25 Kg the dose should be 1/3 the adult dose.
The standard recommended dose of Curcumin is 250 to 400 mg thrice a day. However some authorities recommend 400 to 600 mg thrice a day dosage. The dosage of Haridraa (Turmeric) for adults is 1.5 to 3G per day. 
Available Forms
Capsules containing powder 1.5 to 3 G per day
Fluid Extract: (1:1) 30 to 90 drops a day
Tincture: (1:2) 15 to 30 drops a day
Cut root: 1.5 to 3 G per day
Dried powdered root: 1.5 to 3 G per day
Standardized powder (Curcumin): 400 to 600 mg thrice a day. (84)

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Comments

Jagdish Thakur said…
Apart from being used for cooking, turmeric is also used for traditional medicine. It has many essential oils including-turmerone, zingiberene,atlantone, and germacrone.In some areas where turmeric is cultivated, its leaves are freshly picked for use in cooking purposes

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