Andrographis paniculata (PROSEA)

Plant Resources of South-East Asia
Introduction

1, flowering stem; 2, flower; 3, flower with detail of style and stamen arrangement; 4, dehisced fruit; 5, seed (Iskak Syamsudin)

Andrographis paniculata (Burm.f.) Wallich ex Nees

Protologue: Wallich, Pl. asiat. rar. 3: 116 (1832).

Family: Acanthaceae

Chromosome number: 2n= 50

Synonym

Andrographis subspathulata C.B. Clarke (1884).

Vernacular names

Creat, green chireta (En).
Roi des amers (Fr)
Indonesia: ki oray (Sundanese), sambilata (Javanese), ampadu (Padang)
Philippines: aluy, lekha (Tagalog), sinta (Bikol)
Thailand: fa thalaai (Bangkok), khee-pang-hee (Chinese), yaa kannguu (Songkhla)
Vietnam: công cộng, khổ diệp, xuyên tâm liên.

Origin and geographic distribution

A. paniculata is probably native to India, but has been introduced and cultivated as a medicinal plant in many parts of Asia including Indo-China, China, Thailand, Peninsular Malaysia, Indonesia, the Philippines and Australia. It is now widely naturalized in most of these regions. It has also been introduced, possibly for its ornamental value, in the West Indies and Central America.

Uses

The roots and leaves of A. paniculata have a well-known application in traditional medicine in India, various parts of South-East Asia, Central America and the Caribbean. It used to be considered an effective remedy against snake bites; in India, it is locally still used for this. It has also been reported as useful to treat insect bites and, in combination with Orthosiphon aristatus (Blume) Miq., as a remedy for diabetes. An infusion or sap from the crushed leaves has been recommended for the treatment of fever, as a tonic, and for itching skin eruptions. A decoction of the leaves or roots is used against stomach-ache, dysentery, typhus, cholera, influenza and bronchitis, as a vermifuge, and is considered a diuretic. Another use is as a poultice on swollen legs or feet, vitiligo and piles. Pills or infusions are also recommended to treat female disorders, dyspepsia, hypertension, rheumatism, gonorrhoea, amenorrhoea, torpid liver and jaundice. Furthermore, A. paniculata is considered to be anti-inflammatory and immunosuppressive, but reports on antibacterial activity are contradictory.

Properties

Phytochemical studies on A. paniculata have resulted in the isolation of a number of diterpenes from the aerial parts, of which the most important are:

Diterpenoids of the ent-labdane type, e.g. andrographolide, 14-epi-andrographolide, isoandrographolide, 14-deoxyandrographolide, 14-deoxy-12-methoxyandrographolide, 12-epi-14-deoxy-12-methoxyandrographolide, 14-deoxy-12-hydroxyandrographolide, 14-deoxy-11-hydroxyandrographolide, 14-deoxy-11,12-dihydroandrographolide, ent-14β-hydroxy-8(17),12-labdadien-15,16-olide-3β,19-oxide.

Diterpene glucosides, e.g. andrographiside, deoxyandrographiside, 14-deoxy-11,12-dihydroandrographiside, neoandrographolide, 6'-acetylneoandrographolide.

Bis-andrographolides A, B, C, and D.

The presence of flavones in the root has also been reported. Extracts and purified diterpenes and flavonoids have been investigated for a multitude of pharmacological effects.

In a placebo-controlled double-blind study, performed as a pilot trial in 50 patients, the effect of a standardized A. paniculata extract was evaluated in the initial treatment of the common cold and sinusitis. Patients were advised to take 4 tablets (containing 85 mg of the extract, or placebo) 3 times daily. Furthermore, they were given a self-monitoring form, and were assessed at the clinic after 5 days. In the A. paniculata group the subjective symptoms and symptom duration were both significantly reduced. In another double-blind study, patients with common cold were treated with A. paniculata extract (dose 1200 mg powdered leaves/day) or placebo. A significant reduction in clinical symptoms was observed in the treated group on day 4 of administration. It was concluded that powdered A. paniculata leaves have the capacity to significantly shorten the duration of common colds. When the efficacy of a high dose of powdered A. paniculata leaves (6 g/day) was compared with either a low dose of powdered leaves (3 g/day) or paracetamol (acetaminophen, 3 g/day) in a randomized double blind design in patients with pharyngotonsilitis, the paracetamol and the high dose of the powdered leaves produced significantly better effects than the low dose of A. paniculata on day 3, in terms of relief of fever and sore throat. On day 7 the clinical effects were no longer different. Furthermore, minimal, self-limiting side effects were found in about 20% of each of the groups.

The anti-inflammatory effect (carrageenin-induced oedema model) of an orally administered infusion of leaves at 51.4 mg/100 g bodyweight has been tested in mice; it was similar to 10 mg phenylbutazon/100 g. Andrographolide at 100 or 300 mg/kg also shows anti-inflammatory activity and significantly inhibits hind paw oedema induced by carrageenin, kaolin and nystatin. Furthermore, an ethanol extract stimulates both antigen-specific and nonspecific immune responses in mice more than the purified andrographolides.

An ethanolic extract of A. paniculata administered orally to rats with yeast-induced fever showed significant antipyretic activity. Andrographolide at 100 or 300 mg/kg also exhibits significant antipyretic properties in rats. Evaluated for its analgesic effects in mice, a dose of 8 mg/kg of a 10% infusion of the herb, applied intraperitoneally, is comparable with 48 mg/kg phenylbutazon. At a per oral dose of 300 mg/kg, purified andrographolide shows significant analgesic activity in the acetic acid-induced writhing test in mice and in Randall Selitt's test in rats.

The crude water extract of A. paniculata as well as the semi-purified n-butanol and aqueous fractions produced a significant fall in mean arterial blood pressure in anaesthetized Sprague-Dawly rats; the ED₅₀ values were respectively 11.4 mg/kg, 5.0 mg/kg and 8.6 mg/kg. The aqueous extract exhibits a dose-dependent hypotensive activity on the systolic blood pressure in spontaneously hypertensive rats, when chronic intraperitoneal infusions are administered by osmotic pumps. Mechanistic studies indicate that the effect might be due to a reduction of circulating angiotensin-converting enzyme levels, as well as to a reduction of numbers of free radicals in the kidneys. Furthermore, a 10% infusion of the herb applied intravenously to rabbits at 1 ml/kg bodyweight reduced the blood pressure by 6-10 mm Hg in 10-20 seconds.

An A. paniculata extract was found to significantly alleviate atherosclerotic iliac artery stenosis induced by both de-endothelialization and high cholesterol diet in rabbits. It may therefore play an important role in preventing restenosis after coronary angioplasty, which normally can be 30-40%. Observations in dogs with experimentally induced myocardium infarction indicate that an aqueous extract may also limit the expansion of localized anaemia of the myocardium and exert a marked protective effect on reversibly ischemic myocardium. In these experiments, antithrombotic effects were also observed in the animals, e.g. inhibition of thromboxane (TBX2) synthesis and of platelet aggregation. It is believed that these effects might be at least partially due to flavones present in the extract.

When administered intraperitoneally (100 mg/kg) in mice, andrographiside and neoandrographolide have a significant protective effect on hepatotoxicity induced by carbontetrachloride or tert-butylhydroperoxide. Andrographolide is also hepatoprotective against galactosamine and paracetamol induced liver damage in rats. An extract of A. paniculata showed antidiarrhoeal activity in rabbit and guinea-pig ileal loop models. The diterpenes andrographolide and neoandrographolide isolated from the alcoholic extract showed potent antisecretory activity against Escherichia coli enterotoxin induced secretions. Andrographolide at 100 or 300 mg/kg is also known to exhibit significant anti-ulcer properties in rats. Furthermore, apigenin 7,4'-di-o-methyl-ether (a flavonoid) shows anti-ulcer effects in experimentally induced ulcers in guinea-pigs and rats. It is suggested that this effect is due to the antisecretory activity and protective effect on the gastric mucosa.

Other pharmacological effects reported in literature include:

The water extract administered at 10 mg/kg can significantly prevent glucose-induced hyperglycaemia in rabbits, but has no effect on adrenaline-induced hyperglycaemia. Furthermore, a hypoglycaemic effect in rabbits was observed when a 20% infusion was administered orally at doses of 12.5 and 37.5 ml/kg.

The chloroform extract administered orally in rats at a dose of 8 mg/kg has a diuretic effect similar to 25 mg furosemide/kg.

Platelet aggregation in humans was significantly reduced by A. paniculata extracts.

Oral administration of 20 mg of the dry leaf powder for 60 days has an antifertility effect (antispermatogenic and/or anti-androgenic) in male albino rats.

The alcoholic extract of the rhizomes of A. paniculata exhibits good in vitro anthelmintic activity against Ascaris lumbricoides.

Andrographolide exhibits a strong choleretic action when administered intraperitoneally to albino rats.

Neoandrographolide isolated from A. paniculata exhibits significant antimalarial activity against Plasmodium berghei NK 65 in the mouse Mastomys natalensis.

Dehydroandrographolide succinic acid monoester, derived from andrographolide, has been found to inhibit the human immunodeficiency virus (HIV) in vitro.

Several of the ent-labdane type diterpenoids (e.g. andrographolide, 14-epi-andrographolide, isoandrographolide, 12-epi-14-deoxy-12-methoxyandrographolide) show potent induction of cell differentiation towards M1 cells. In general, the activity of the dimers (bis-andrographolides A, B, C) is even more potent in this model system; the glucosides are only weakly active.

It has also been found that the ether extract of A. paniculata leaves has a fairly high anti-alkylating effect against ethyl-methane sulphonate. In general, anti-alkylating substances are associated with anti-carcinogenicity.

A leaf infusion administered intraperitoneally in mice, has an LD₅₀ at 71.1 mg/10 g body weight (acute toxicity). At a concentration of 1 mg/kg it lowers the body temperature at least 2 °C. In guinea-pigs, a leaf infusion of 5%, 10% and 15% at a dose of 8 ml/kg lowers the body temperature by 0.9-1.1 °C. The possible testicular toxicity of a dried extract of A. paniculata was investigated in male Sprague Dawley rats. No testicular toxicity was found with the treatments of 20, 200 and 1000 mg/kg during 60 days as evaluated by reproductive organ weight, testicular histology, ultrastructural analysis of leydig cells and testosterone levels after 60 days of treatment. It was concluded that A. paniculata extract did not produce subchronic testicular toxicity in male rats.

Finally, A. paniculata extract is reported to have antifeedant and anti-oviposition activity against a number of crop pests like Callosobrunchus chinensis, Darcus dorsalis, Nephotettix cincticeps, Plutella xylostella, Sitophilus oryzae and Spodoptera litura.

Description

A perennial herb 30-100 cm tall; stems distinctly 4-angular, glabrous apart from a few hairs at the nodes.
Leaves opposite, simple, narrowly ovate to lanceolate, 5-10 cm × 1.2-2.5 cm, base long attenuate, apex long acuminate, margin entire, glabrous but often gland-dotted; petiole short, up to 6 mm long, connected with the opposite one by transverse ridges.
Flowers in lax, axillary and terminal racemes or panicles combined into a pyramidal inflorescence, with 2 small bracteoles at base of the 1-7 mm long pedicel, bisexual, zygomorphic; calyx segments 5, jointed at base, with glandular and aglandular hairs; corolla bilabiate, white or rose with purple markings on the upper lip, tube 5-6 mm long, slightly enlarged below the limb, lower lip 4-6 mm long, oblong, 2-toothed at the apex, upper lip deeply 3-lobed, as long as the lower; stamens 2, inserted at the corolla tube apex and exserted, filaments hairy, anthers inserted at equal level, basally connate, bearded at base, deep purple to black; ovary superior, 2-locular with 3-7 ovules in each cell, style curved upwards, stigma entire.
Fruit an erect, loculicidal, narrowly ellipsoidal, glandular hairy capsule, 14-20 mm × 3-3.5 mm, many-seeded.
Seeds held up on well-developed hooks (retinaculae), almost rectangular, rugosely furrowed, with 2 deep furrows.

Growth and development

In India, leaves of A. paniculata start to redden in October and are shed in December, after which the plants dry from the top down, leaving only a small portion of the stem green. New flushes emerge towards the end of the dry season. There are two distinct flowering periods: in India October and March-May, although plants growing under shaded conditions flower from October through to May. In Java, flowers and fruits of A. paniculata have been observed throughout the year. In northern Australia, flowering and fruiting specimens have been collected from November to June.

Other botanical information

Andrographis comprises about 18 species occurring originally from India to China and western Malesia. It belongs to the small tribe Andrographideae of the subfamily Acanthoideae. This tribe is characterized by its articulated shoots and epidermis with cystoliths in combination with a 2-lipped corolla with ascending lobes and many ovules per locule. The pollen shows a unique structure as well.

Within various populations of A. paniculata in India and Bangladesh 9 different cytotypes have been identified. These proved to be related to the environment, particularly to soil conditions.

Ecology

A. paniculata is locally common and often gregarious. It exhibits weedy characteristics and occurs from sea-level up to 1600 m altitude in village groves, roadsides, waste places, open sandy locations and fields, but also in monsoon and teak forest receiving only 10-20% of full light.

Propagation and planting

Propagation of A. paniculata by seed is possible. Seed should be soaked during 24 hours and dried before being sown. Germination starts after 1 week and the mean germination rate is about 80%. Cuttings consisting of 3 nodes taken from the upper third of 1-year-old plants have given the best results in vegetative propagation, with 80-90% rooting. In India, seed is sown in May-June, and seedlings are transplanted at 60 cm × 30 cm.

In vitro production of active compounds

A distinct cell line from callus culture of A. paniculata proved capable of synthesizing andrographolide in greater quantity than in the intact plant. Plantlets differentiated from this line were also high-yielding.

Husbandry

In shading experiments with A. paniculata the optimal proved to be 20% shade with average dry-matter production of 13.2 g per 5-month-old plant. In India, irrigation may be necessary during dry periods.

Diseases and pests

Sclerotium sp. occasionally causes wilt disease in A. paniculata during the rainy season. Eugenol at 200 ppm or clove powder containing 0.2 % eugenol could inhibit the growth and development of Sclerotium myceliae; its establishment is inhibited by eugenol at a concentration of 300 ppm or by clove powder containing 0.3% eugenol.

Harvesting

Leaves of A. paniculata should be harvested when the inflorescence axis starts to grow, because the maximum accumulation of andrographolide is at that stage. In India, harvesting is in February-March, i.e. 9 months after planting. In Vietnam, where the crop is grown as an annual, the leaves are hand picked before flowering and roots are harvested when leaves start discolouring or wilting.

Yield

Yields of 1-1.5 kg fresh weight/plant are obtained from 7-month-old A. paniculata.

Handling after harvest

In general, harvested plant parts of A. paniculata are used fresh and consumed within a few days after collection. However, leaves and roots should be washed and dried in the sun or artificially before storage.

Genetic resources and breeding

A. paniculata is relatively widespread and has a tendency to naturalize in areas where it has been introduced. Locally it is cultivated both for its ornamental and medicinal value. Therefore, the risk of genetic erosion seems rather limited. Selection should be directed to plant material with a higher content of medicinally important constituents. Preliminary results from callus culture techniques show considerable potential for improvement.

Prospects

Extracts of A. paniculata as well as isolated compounds show a broad range of interesting pharmacological effects. In particular, the treatments for the common cold, the anti-inflammatory effects and the prevention of restenosis after coronary angioplasty deserve further attention. Furthermore, A. paniculata preparations may remain of local importance as a general tonic.

Literature

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Authors

Sri Sugati Sjamsuhidajat, Sudjaswadi Wiryowidagdo, Rini Sasanti & Wien Winarno