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Record Number

449

PROSEA Handbook Number

12(1): Medicinal and poisonous plants 1

Taxon

Stephania Lour.

Protologue

Fl. cochinch.: 608 (1790).

Family

MENISPERMACEAE

Chromosome Numbers

x = 11, 12, 13; Stephania japonica: 2n = 22, 24

Major Taxa and Synonyms

Major species Stephania japonica (Thunb.) Miers, Stephania sinica Diels.

Vernacular Names

Vietnam: b[if]nh v[oo]i (general).

Origin and Geographic Distribution

Stephania consists of approximately 45 species and occurs in tropical and subtropical regions and in the warmer parts of temperate regions of the Old World. In Malesia, 12 or perhaps 13 species have been found, some of which have very wide distribution, particularly Stephania japonica.

Uses

Many Stephania species are used in local medicine against a variety of complaints. In the Philippines, Stephania japonica is known as a cure for itches; in Papua New Guinea, Stephania roots and juice are applied to sores, cuts and stings. In India, the roots are used in the treatment of diarrhoea, dyspepsia, urinary diseases and heart ailments. Roots of Stephania spp. are employed in India and Indo-China in the treatment of pulmonary tuberculosis, asthma, dysentery, fever, hypoglycaemia and intestinal complaints (decoction, reported dose 4-5 g/day). Stems are used to treat ascariasis and dysmenorrhoea, leaves to treat indigestion, wounds, headache, sore breasts, dysuria, oliguria and oedema (decoction, reported dose 6-12 g/day), and flowers to treat leprosy.
Root extracts of Stephania glabra (Roxb.) Miers have a long-standing reputation in India as an antidysenteric, antipyretic and antiasthmatic. In Thailand, Stephania venosa is commonly known as 'blood-soap', due to the red colour of its latex. The plant is often employed as a bitter tonic. The roots of Stephania pierrei Diels are used in Thai folk medicine as a skeletal muscle relaxant and also as an analgesic and tonic. A number of Stephania species are well known in traditional Chinese medicine; the most important are Stephania tetrandra S. Moore (analgesic, diuretic and antihypertensive) and Stephania cepharantha Hayata (analgesic, diuretic and tuberculostatic). In Africa (e.g. in Nigeria), Stephania extracts are also used medicinally.
Drugs from the tuberous roots are usually administered in the form of a decoction, as tincture or as a tablet with high alkaloid content. In Vietnam, for instance, (-)-tetrahydropalmatine is prescribed to treat neurasthenia and psychoses in the form of a 0.05 g tablet with a daily dose of 1-3 tablets. Stephania tetrandra has been used in slimming regimens because it eliminates oedema and 'stress-related water retention' but some cases of rapidly progressive fibrosing interstitial nephritis have been recorded in young women following this slimming regimen. However, the renal failure was not caused by the Stephania ingredient, since thorough investigations showed that Stephania had been confused with a species of Aristolochia, but these cases demonstrate how important it is to properly identify natural products to be used as medicines.
The leafy branches of Stephania japonica are sometimes used as forage.

Production and International Trade

Stephania species are only used on a local scale. However, recently the use of tuberous Stephania has gained importance, and in Vietnam they are much traded and also exported unregistered.

Properties

Numerous alkaloids have been isolated from the tuberous roots and stems of Stephania japonica. Epistephanine and hypoepistephanine (major components), stepholine, stebisimine and insularine are alkaloids of the bisbenzylisoquinoline type. Stepinonine is a related alkaloid with a benzazepine structural element. A series of alkaloids derived from hasubanan (a structural isomer of morphinan) have also been isolated from the roots and stems of Stephania japonica: hasubanonine, metaphanine, homostephanoline, prometaphanine, stephamiersine, epistephamiersine, oxostephamiersine, stephasunoline, oxoprometaphanine, oxohasubanonine, oxoepistephamiersine and oxostephasunoline. Various other alkaloids have been isolated from the roots and/or stems, including stephadiamine (norhasubanan type), oxostephanine, lanuginosine and magnoflorine (aporphine type), cyclanoline and steponine (tetrahydroprotoberberine type), and protostephanine (bibenz[d,f]azonine type). The composition of alkaloid constituents seems to differ somewhat between plants collected in different habitats. The alkaloids oxostephamiersine and oxoprometaphanine (hasubanan type) and stebisimine (bisbenzylisoquinoline type) have been isolated from the leaves of Stephania japonica, and stephabenine, oxostephabenine and prostephanaberrine (all hasubanan type) from the fruits. Oxostephabenine can be converted by alkaline hydrolysis into N,O-dimethyloxostephine, whereas prostephanaberrine is converted into stephanaberrine upon treatment with aqueous HCl.
Four alkaloids have been isolated from the aerial parts of Stephania japonica var. discolor: (+)-epistephanine (bisbenzylisoquinoline type), magnoflorine (aporphine type), aknadinine (= 4-demethylhasubanonine) and hernandifoline (hasubanan type). (+)-Epistephanine possesses significant adrenergic neurone blocking activity. The compound acts like guanethidine, by selectively blocking the responses to sympathic nerve stimulation without affecting the responses to the receptor agonist adrenaline. Parallel dose response curves suggest that both components act by the same mechanism, although (+)-epistephanine is approximately one tenth as potent as guanethidine, and the onset of action was slower and duration shorter than that of the latter. Finally, the bisbenzylisoquinoline alkaloid insularine is reported to have a curare-like activity.
Four isoquinoline alkaloids with (-)-tetrahydropalmatine (tetrahydroprotoberberine type) as the major alkaloid have been isolated from the tuberous roots of plants identified as Stephania rotunda Lour. (its status is uncertain); cepharamine, a hasubanan alkaloid, has been isolated from the leaves and stems. The alkaloidal content of the aerial parts of the plant was found to be quite different from that of the tuberous roots.
Investigations of the roots of Stephania glabra resulted in the isolation of two bisbenzylisoquinoline alkaloids ((-)-cycleanine and (-)-N-desmethylcycleanine), five tetrahydroprotoberberine alkaloids ((-)-capaurine, (-)-corynoxidine, (-)-tetrahydropalmatine, (-)-corydalmine and (-)-stepholidine), two aporphine alkaloids ((+)-stepharine and (+)-pronuciferine), and five quaternary protoberberine alkaloids (palmatine, palmatrubine, dehydrocorydalmine, jatrorrhizine and stepharanine).
Several alkaloids isolated from plants identified as Stephania rotunda or Stephania glabra possess pharmacological activity. (-)-Cycleanine has shown significant inhibition of nitric oxide production in vitro, and reduced the level of tumour necrosis factor in vivo, using a mouse model for fulminant hepatitis.
(-)-Stepholidine has shown sedative and antispastic effects in experiments with animals. Detailed pharmacological investigations revealed the compound to be a dopamine (DA2-subtype) antagonist in normal rats. Under certain experimental conditions (in 6-hydroxydopamine lesioned rats), however, dopamine (DA1-subtype) agonistic effects could be demonstrated. Further investigations on the calcium metabolism suggest that (-)-stepholidine may modulate its pharmacological actions by altering Ca2+ regulating processes in the central dopaminergic nervous system.
(-)-Tetrahydropalmatine has been found to show antispasmodic (especially on the gastro-intestinal tract), sedative and cardiotonic activity. Investigations indicate the component to be a dopamine (DA2-subtype) antagonist. The interaction also has stereoselectivity; (-)-tetrahydropalmatine is a DA2 antagonist whereas (+)-tetrahydropalmatine seems not to be.
The identity of Stephania erecta Craib is somewhat controversial; it is usually considered a synonym of Stephania pierrei. Comparison of the alkaloid content of both species indicated that different types of isoquinoline alkaloids were produced. Bisbenzylisoquinolines were the major alkaloids of Stephania erecta, whereas aporphine and tetrahydroprotoberberine type alkaloids represented the major constituents of Stephania pierrei. Isolation procedures guided by biological activity resulted in the isolation and identification of 23 isoquinolines from the latter species, which were subsequently tested for antimalarial and cytotoxic effects. Only the aporphine type alkaloid (-)-asimilobine demonstrated appreciable antimalarial activity together with a lack of cytotoxicity and may thus provide a good starting point for further development of more potent analogues. However, (-)-cycleanine also showed selective antiplasmodial activity.
At least 23 alkaloids have been identified in Stephania venosa, belonging to the protoberberine or (oxo-)aporphine type. The major alkaloids found in the roots were (+)-stepharine (aporphine type) and (-)-crebanine (aporphine type), each about 5% by weight.
Stephania tetrandra and Stephania cepharantha are well known in traditional Chinese medicine. The roots of Stephania tetrandra are a rich source of bisbenzylisoquinolines, in which S,S-tetrandrine is the predominant (0.7-1.3%) alkaloid. S,S-Tetrandrine has interesting pharmacological properties, including Ca2+ channel blocking, anti-inflammatory and immunosuppressive activities (See under Cyclea for more detailed information). Cepharanthine, a bisbenzylisoquinoline alkaloid found in the roots of Stephania cepharantha, has been found to decrease leucopenia due to the use of antineoplastic agents, to inhibit collagen-induced blood platelet aggregation and to counteract the development of experimental silicosis. Cepharanthine has also been reported from dried roots of Stephania pierrei (about 1%); it is considered to be an immunostimulant and to decrease effectively the side effects of anti-cancer drugs, as well as to inhibit the growth of tuberculous bacteria. In in vitro experiments, cepharantine inhibited proliferation of cancer cells by inducing apoptosis, and it was a highly potent inhibitor of HIV-1 replication.
Extracts from the leaves of Stephania japonica showed mild insecticidal properties against fruit flies in Thailand.

Adulterations and Substitutes

Other plants that contain isoquinoline alkaloids and are used in Chinese medicine include Berberis, Coptis, Corydalis and Cyclea species and several Menispermaceae not mentioned here.

Description

Mostly slender dioecious climbers up to 20 m long; stem herbaceous or woody, usually glabrous but sometimes puberulous; roots often tuberous. Leaves arranged spirally, simple and entire, peltate, palmately veined, petiole usually geniculate at base; stipules absent. Inflorescence axillary or cauliflorous, usually composed of peduncled umbelliform, solitary or racemose cymes, sometimes flowers in capitula. Flowers unisexual, calyx with 1-8 free imbricate sepals, corolla with 2-4 free petals; male flowers with stamens fused into a peltate synandrium with 4-8 anther cells; female flowers with 1 carpel having a short-lobed or divaricately laciniate stigma. Fruit an obovoid drupe with style scar near base; endocarp bony, dorsally ornamented with a horseshoe-shaped band of 2 or 4 longitudinal rows of processes or transverse ridges. Seed horseshoe-shaped; embryo with cotyledons equalling the radicle, embedded in endosperm.

Growth and Development

Some Stephania species can develop 2-3 tuberous roots under favourable conditions, but usually there is only one. Several species are deciduous in the dry or cold season. Flowers are pollinated by small flies, bees, and possibly also small beetles and moths. The leaves of Stephania japonica produce a fragrance and may also play a role in attracting insects. The fruits may be dispersed by water.

Other Botanical Information

Stephania belongs to the tribe Menispermeae and is most closely related to Cissampelos and Cyclea. It can be recognized by the inflorescences composed of umbelliform cymes or disciform capitula.
The taxonomy and nomenclature of the Asian Stephania species is still very complex. In Vietnam many species are exploited under a single common name b[if]nh v[oo]i. The correctness of the name Stephania rotunda Lour. is still being debated; this name has often been applied to e.g. Stephania glabra (Roxb.) Miers, Stephania venosa (Blume) Sprengel and Stephania pierrei Diels. On nomenclatural grounds, these couplings are difficult to approve, since the Stephania rotunda Lour. is the oldest name. A large number of species not occurring in the Malesian region are used in Chinese and Indo-Chinese medicine, e.g. Stephania cepharantha, Stephania kwangsiensis H.S. Lo, Stephania longa Lour., Stephania pierrei and Stephania tetrandra.

Ecology

Stephania species occur in primary and secondary forest, regrowths, hedges, thickets and on river banks, sometimes on limestone and along the seashore, up to 2000(-2700) m altitude. Most species are slightly ombrophilous and hygrophilous, especially during the seedling period.

Propagation and planting

Stephania is rarely planted. Cultivation trials have been conducted in Vietnam (1983-1984) and Georgia (1965-1969). Plants were propagated from root cuttings and seed, and planted in the fields at a spacing of 70 cm x 20 cm.

In Vitro Production of Active Compounds

Cell suspension cultures of Stephania glabra have been studied in Russia, using a Murashige and Skoog medium supplemented with saccharose (30 g/l), vitamins, mezoinozite, 2,4-D (1 mg/l) and kinetine (0.1 mg/l). Eleven alkaloids were found in the culture, with no less than 0.3-0.8% stepharine, which was not detectable in plants grown in Georgia. (-)-Tetrahydropalmatine, which is the main alkaloid in the roots, was not detectable in the culture.

Husbandry

In trials in Georgia, a combination of organic and chemical fertilizers (5 t of organic fertilizer, 150 kg N, 200 kg P and 120 kg K per ha) increased yields of tuberous roots by 27%.

Diseases and Pests

Three nematode species have been isolated from Stephania japonica in India.

Harvesting

In Vietnam, it is recommended to harvest only tuberous roots in the weight class of 800-1000 g. This ensures a good quality of the product and a fair rate of regeneration.

Yield

The yield per ha of fresh tuberous roots in Georgia was 11-13 t for 1-year-old plants, 28-35 t for 2-year-old plants and 42-44 t at the age of 3 years.

Handling After Harvest

The harvested roots are sliced and dried in the sun or in ovens at not too high temperature. The quality of the product varies considerably; for instance, the content of (-)-tetrahydropalmatine may vary from 0.3-3.6% of the dry tuberous root in Stephania glabra.

Genetic Resources and Breeding

The Stephania species described here are widely distributed, locally rather common, and occur particularly in disturbed forest. They seem to be not very liable to genetic erosion. However, several species are rare and threatened in Indo-China and China, partly because of overcollecting. Conservation and planting of these species is essential to counteract genetic erosion which is serious, since the drugs have become popular in recent years.

Prospects

The alkaloids which are particularly present in the tuberous roots of Stephania have interesting properties, as is the case in many other Menispermaceae. The roots are used in traditional medicine in different parts of the world for similar purposes, which also seems to confirm their effectiveness.

Literature

Bruneton, J., 1995. Pharmacognosy, phytochemistry, medicinal plants. Lavoisier Publishing, Paris, France. p. 748.
Forman, L.L., 1986. Menispermaceae. In: van Steenis, C.G.G.J. & de Wilde, W.J.J.O. (General editors): Flora Malesiana. Series 1, Vol. 10. Kluwer Academic Publishers, Dordrecht,the Netherlands. pp. 243-253.
Forman, L.L., 1991. Menispermaceae. In: Smitinand, T. & Larsen, K. (Editors): Flora of Thailand. Vol. 5(3). The Forest Herbarium, Royal Forest Department, Bangkok, Thailand. pp. 311-323.
Kozuka, M., Miyaji, K., Sawada, T. & Tomita, M., 1985. A major alkaloid of the leaves and stems of Stephania rotunda. Journal of Natural Products 48(2): 341-342.
Matsui, M., Kabashima, T., Ishida, K., Takebayashi, T. & Watanabe, Y., 1982. Alkaloids of the leaves of Stephania japonica (Japan). Journal of Natural Products 45(4): 497-500.
Matsui, M. & Yamamura, Y., 1986. Alkaloids from the fruits of Stephania japonica, part 3. Structures of prostephanaberrine and stephanaberrine, two new hasubanan alkaloids. Journal of Natural Products 49(4): 588-592.
Nguyen Van Duong, 1993. Medicinal plants of Vietnam, Cambodia and Laos. Mekong Printing, Santa Ana, California, United States. pp. 260-261.
Patra, A., Ghosh, A. & Mitra, A.K., 1980. Alkaloids of Stephania glabra. Planta Medica 40(4): 333-336.
Taga, T., Akimoto, N. & Ibuka, T., 1984. Stephadiamine, a new skeletal alkaloid from Stephania japonica: the first example of a C-norhasubanan alkaloid. Chemical and Pharmaceutical Bulletin 32(10): 4223-4225.
Vanherweghem, J.L. et al., 1993. Rapidly progressive interstitial renal fibrosis in young women and association with slimming regimen including Chinese herbs. Lancet (North American Edition) 341 (8842): 387-391.

Selected Sources

[1031] Nguyen Tien Ban, 1995. The family Menispermaceae in the flora of Vietnam. Journal of Biology 17(4): 61-67. (in Vietnamese)
[1130] Pham Hoang Ho, 1991-1993. An illustrated flora of Vietnam. 3 volumes. Mekong Publisher, Montreal, Canada.

Author(s)

Nguyen Tien Ban, Bui Thi Bang, Nguyen Tap & Nguyen Chieu

Stephania capitata
Stephania japonica
Stephania sinica
Stephania venosa

Correct Citation of this Article

Nguyen Tien Ban, Bui Thi Bang, Nguyen Tap & Nguyen Chieu, 1999. Stephania Lour.. In: de Padua, L.S., Bunyapraphatsara, N. and Lemmens, R.H.M.J. (Editors): Plant Resources of South-East Asia No 12(1): Medicinal and poisonous plants 1. PROSEA Foundation, Bogor, Indonesia. Database record: prota4u.org/prosea

Selection of Species

The following species in this genus are important in this commodity group and are treated separatedly in this database:
Stephania capitata
Stephania japonica
Stephania sinica
Stephania venosa

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