Andrographis paniculata

Nomenclature:

Botanical Name: Andrographis paniculata (Burm. f.) Wall. ex Nees

Common Name : Kalmegh

Sanskrit: Bhunimba, kirata;
Hindi: Kalmegh, kirayat, mahatita;
Eng :The Creat;
Beng:Kalimegh;
Guj: Kariyatu;
Gondi:Bhuilimb;
Kan:Nelaberu;
Mal.:Kiriyattu,nelaveppu;
Mar:Olikiryata;
Mundari:Bhuinim.
Oriya:Bhuinimba;
Tam.:Nilavembu;
Tel:.Neelaveemu;.

Family: Acanthaceae   

Habitat: An erect annual herb, chiefly found throughout the Indian plains from Himachal Pradesh to Assam and Mizoram and all over South India. The plant is gregarious and grows abundantly in moist, shady waste grounds and sometimes in dry forests.

Morphology

An erect annual herb, stem dark green, 0.3-1.0 m in height, 2- 6 mm in dia., quadrangular with longitudinal furrows and wings on the angles of the younger parts, slightly enlarged at the nodes. Leaves glabrous, up to 8.0 cm Iong and 2.5 cm broad, lanceolate, pinnate; flowers small, in lax spreading axillary and terminal racemes or panicles; capsules linear-oblong, acute at both ends, 1.9 cm x 0.3 cm long; seeds numerous, subquadrate and yellowish brown in colour.

Part used as crude drug

The crude drug consists of dried or fresh leaves or the aerial portions of the plant. Sometimes, the whole plant, including the roots, is used. The drug is sometimes mixed with the genuine chirata (Swertia chirayita Karst.) but can be distinguished from the latter easily by the green colour of its stems, numerous erect, slender, opposite branches and its lanceolate, green leaves. The drug normally should not contain more than two per cent of foreign organic matter.

Morphological characteristics of drug
Drug consists of dried leaves and tender shoots; yields not less than 1% of andrographolide on dry wt. basis. Normally powdered drug is used.

Cultivars (including improved Varieties)

Comparative studies of plants from different localities have shown variation in the total alkaloids content. Local clones are generally cultivated as there is no named variety available.

However, based on plant height, leaf length, leaf width, leaf stem ratio, leaf biomass ratio and dry biomass (herbage) yield /plant and chlorophyll content, morphogenetically diverse genotypes have been reported from Bhuvneshwar, Lucknow, Kakori and Assam.

Cultivation

The plant is also cultivated as a Kharif season crop. It prefers a sunny situation. Propagation is generally done through seeds, however, it can also be propagated by inducing rooting in cuttings. The seeds are sown during May-June. The seedlings are transplanted at a distance of 60 cm x 30 cm in the last week of July. Two or three irrigations may be required during the dry periods. It flowers during Aug – Nov. Fertiliser requirements for this crop are – poultry manure or FYM @ 10 tons /ha, castor cake 2 tons/ha, 75 Kg N and 75 Kg P₂ O_{5 .}

The plant is collected at maturity i.e. after complete flowering and fruiting. Depending upon area of cultivation harvesting is done in Oct.- Nov. However, in Andhra Pradesh, it is collected from wild populations from Nov-Jan. The whole plant is dried in shade by spreading on the floor for 7-8 days. During this period, it is protected from dew at nights.

Traditional Knowledge (Ethnobotanical / Folk-lores / House hold remedies / Self help mode)

Powdered plant mixed with sarson oil, applied in itching. Plant used in spleen complaints, colic, strangulation of intestine, constipation, diarrhoea, cholera, pathisis, consumption and bite of rabid jackal.

The macerated leaves and juice together with certain spices, such as cardamom, clove and cinnamon, are made into pills and prescribed for relief from gripe and other stomach ailments in infants and also used as domestic medicine for flatulence and diarrhoea of children. Used in tropidity of liver, neuralgia and convalescence after fever.

The herb is the well-known drug kalmegh or 'green chiretta', and forms the principal ingredient of a reputed household medicine, used as a bitter tonic and febrifuge. The herb is reported to possess astringent, anodyne, tonic and alexipharmic properties and is helpful in dysentery, cholera, diabetes, consumption, influenza, bronchitis, swellings and itches, piles and gonorrhoea. It is also used as a cure for torpid liver and jaundice. It is also used as curative or preventive in snake venom poisoning.

Chemistry

Analysis of the whole plant gave the following lactones (dry basis): andrographolide,0.6%; 14-deoxy-11-oxoandrographolide (C₂₀ H ₂₈ O₅), 0.12%;14-deoxy -11, 12-ldehydroandrographohde (C₂₀,H₃₀O₄), 0.06%; 14- deoxyandrographolide (C₂₀H₃₀O₄), 0.02% and a non-bitter constituent, neoandrographolide (C₂₆ H₄₀ O₈),0.005%.

The leaves contain andrographolide (yield, 1%). From the petroleum ether extract of the leaves from Bangladesh, the following compounds have been isolated: a , b -unsaturated lactone, homo-andrographolide (C₂₂ H₃₂ O₃). andrographosterol (C₂₃ H₃₈ O), andrographane (C₄₀ H₈₂), andrographone (C₃₂H₆₄0 ), a wax, and two esters containing, hydroxyl groups.

The roots gave apigenin-7,4'-di-0-methyl ether, andrographolide and a new natural flavone, 5-hydroxy-7,8,2',3'-tetramethoxyflavone (C₁₉H₁₈0₇ );yield, 0.006%). They also contain a monohydroxy-trimethylflavone, andrographin (C₁₈H₁₆0₆ )and a dihydroxy-di-methoxyflavone, panicolin (C₁₇H₁₄O₆ ). The presence of a - sitosterol is also reported.

Chemical markers

Andrographolide, a diterpene lactone is the major constituents of the drug and its minimum quantity is prescribed as 0.5-0.9% in the appropriate drug.

Molecular Markers (Protein, DNA)

No information available

Isozymes

No information available

Pharmacology

(a) Bioactivity

Neither leaf and stem extract of kalmegh administered orally nor andro-grapholide given s.c. or orally changed blood sugar level of normal or diabetic rats. kalmegh increased biliary flow and liver weight in rat and decreased hexobarbital-induced sleeping time. It is less potent than phenobarbital.

Apigenin-7,4-di,O-methyl either produced significant dose- dependent antiulcer activity in Shay rats, histamine- induced ulcer in guinea pigs and aspirin –induced ulcers in rats. Pre-treatment with a single does of Kalmegh leaf (500mg/ kg, p.o)or and androgrpholide (5 mg/kg, p.o) prevented carbon tetrachloride –induced increase of serum glutamate- oxaloacetate transaminase (SGOT)and glutamate-pyruvate transaminase(SGPT)but decreased liver levels of these enzymes in dog. These changes were not observed by simultaneous treatment with either of the drugs. Pre-treatment of rats with Kalmegh leaf or androgropholide, however, failed to arrest carbon tetrachloride –induced change of (SGOT) and SGPT in blood serum and liver.

Total root flavonoids effective against experimental myocardial ischemic necrosis induced by isoprenaline in rats and by ligation of left descending coronary artery in rabbits; decreased infarction size, and pathological changes in ST segment and Q wave inhibited; LD50 of flavonoids in mice have been reported as 1.15 g/kg by intravenous application.

Andrographolide (5.0 mg/kg and 10.0 mg/kg) or single dose of leaf extract (0.5 g/kg and 1.0 g/kg) given orally to adult male rats produced dose-related and time-dependent characteristic activation of brush-border membrane-bound hydrolyses, lactase, maltase and sucrose in duodenum, jejunum and ileum.

(b) Toxicity

Within the prescribed limits under ISM, no toxicity is reported from Kalmegh

Formulation

A decoction of the plant is a blood-purifier. It forms the major constituent of the Ayurvedic drug SG-1 Switradilepa which is effective in treating vitiligo-a dermatological disease. It is also used in certain homoeopathic preparations.

General usage

A constituent of ayurvedic formulations used for curing debility, chronic malaria, jaundice, anemia and loss of apetite.

Dose

1.5 to3.0 g of the dried crude drug is generally given for antipyretic and anti-infective activities. Fresh herb is used in doses of 25 to 75g as antidiarrhoeal. However, as a bitter , 0.5 to 1.0 ml of kalmegh liquid extract is used.

Commercial aspects

(a) Production

No figures for its production from cultivated sources are available. From the wild sources the total annual production is about 5000 tonnes mainly from the states of Madhya Pradesh, Uttar Pradesh and Bihar.

(b) Demand

Estimated demand of this drug in India is 1000 tonnes per year.

(c) Market Trends (price)

Rate in Indian market is Rs. 1800 per quinta

Herbal drug dealers at Amritsar, Delhi and Nimach Mandi in Madhya Pradesh are the major suppliers of this drug.

Major Users

Ayurvedic and Homoeopathic drug manufacturers.

Patents

1.Babish and Ma, Anti-Cancer Effects of Andrographolide and Its Synergistic Use with Ah Receptor Antagonists and/or Agonists; Use of Andrographolide Compounds To Treat or Prevent Pathogenicity of Disease, s/n PCT/US95/15915.

2. Mehrotra, Raj., Katiyar, Chandra Kant., Gupta, Ajaya Prakash.Assignee: Dabur Research Foundation (Ghaziabad, IN) Hepatoprotective compositions and composition for treatment of conditions related to hepatitis B and E infection United States Patent 6,136,316 October 24, 2000

3. Wheelock,Geoffrey D.,Rininger, Joseph., Babish,John G., Chigurupati, Padmasree ., Assignee: Paracelsian, Inc. (Ithaca, NY) Use of the AH receptor and AH receptor ligands to treat or prevent cytopathicityof viral infection United States Patent 5,833,994 November 10, 1998

4. Wheelock; Geoffrey, D., Rininger; Joseph; Babish,John G., Chigurupati, Padmasree. Assignee:Paracelsian, Inc. (Ithaca, NY)

In vitro screening assay for identification of compounds that inhibit cytopathicity of viral infection United States Patent 6,140,063 October 31, 2000

5. Tsai, Hsiu-Hsien., Hwang, Shie-Ming., Kung, Pai-Chu.Assignee: Sage R&D (Columbus, OH) Use of plant extracts for treatment of HIV, HCV and HBV infections United States Patent 5,837,257 ;November 17, 1998.

6. Zhang Wenying. Anti-infectious, antipyretic and analgesic medicine. (People Rep. China ). Assignee: Faming Zhuanli Shenqing Gongkai Shuomingshu CN 1266699 A 20 September 2000, 9 pp. (Chinese). APPLICATION: CN,2000-112661 28 Jan 2000.

7. Oshima, Koichi; Fujimiya, Yoshiaki; Soda, Makoto; Takano, Fumie; Fushitani, Shinji .Inducible nitric oxide synthase (NOS) formation inhibitors containing compounds extracted from plants in Indonesia. Assignee: Jpn. Kokai Tokkyo Koho JP 2001058969 A2 6 Mar 2001, 11 pp. (Japanese). (Japan).

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