Arcangelisia flava (PROSEA)

Plant Resources of South-East Asia Introduction

List of species

1, intertwining flowering and fruiting stems; 2, closed male flower; 3, opened male flower; 4, part of woody stem; 5, detail of stem in cross and longitudinal section (P. Verheij-Hayes)

Arcangelisia flava (L.) Merr.

Protologue: Interpr. Herb. amboin.: 222 (1917).

Family: Menispermaceae

Chromosome number: 2n= unknown

Synonyms

• Arcangelisia lemniscata (Miers) Becc. (1877),
• Arcangelisia loureiri (Pierre) Diels (1910).

Vernacular names

• Yellow-fruited moonseed (En)
• Indonesia: areuy ki koneng (Sundanese), sirawan (Javanese), daun bulan (Moluccas)
• Malaysia: mengkunyit
• Philippines: abutra (Ilokano, Bisaya), suma (Tagalog, Pampango)
• Thailand: khamin khruea (Chanthaburi), kamphaeng jedchunum
• Vietnam: vảy dắng.

Origin and geographic distribution

Arcangelisia consists of only 2 species. Yellow-fruited moonseed is widely distributed from Hainan (China), Indo-China, southern peninsular Thailand, Peninsular Malaysia, Sumatra, Java, Borneo, the Philippines, Sulawesi, the northern Moluccas to New Guinea.

Uses

Yellow-fruited moonseed is mainly used medicinally. In Peninsular Malaysia, a decoction of the stem is taken internally for jaundice, worms, indigestion and other intestinal complaints. The smoke from the burning wood is inhaled for troubles of the mucous membrane of the nose and mouth. In the Philippines, yellow-fruited moonseed is a popular antiseptic: a decoction of the wood is used to clean wounds, ulcers and other skin irritations. Traditional applications include the use of a decoction or infusion of the stem as a stomachic, febrifuge, expectorant, tonic, and emmenagogue or abortivum (depending on the quantity administered). In Indonesia, the stems are sold as "kayu seriawan", meaning "wood against sprue". The sap which flows abundantly from cut stems is drunk against fever and sprue. In Thailand, the stems are used against indigestion, as a tonic and emmenagogue; the flowers are used to treat dysentery. In the Philippines, the Moluccas and New Guinea a yellow dye is extracted from the woody stem. The use of the fruits as a fish poison is questionable.

Properties

Menispermaceae species are well-known to contain mixtures of (bis-)benzylisoquinoline-type alkaloids, which are biosynthetically derived from the amino acids phenylalanine or tyrosine. Alkaloids found in A. flava are: berberine, 8-hydroxyberberine, columbamine, jatrorrhizine, palmatine, thalifendine, dehydrocorydalmine, shobakunine (all of the quaternary protoberberine type), and (-)R,R-limacine, (+)R,S-homoaromaline and pycnarrhine (of the bisbenzylisoquinoline type). The pharmacological effects and the yellow colour of the dye extracted from the plant, are largely attributable to berberine, which is present in concentrations of up to 5% in the stem (dry weight).

The pharmacological effects of berberine have been fairly well investigated. Berberine (as the chloride) has been found to be active against a number of gram-positive as well as gram-negative bacteria, such as Diplococcus pneumoniae, Escherichia coli, Neisseria gonorrhoeae, Salmonella typhosa, Shigella dysenteriae, Staphylococcus aureus, S. hemolyticus and S. paradysenteria in different media. It had about the same antibacterial activity as some sulphonamides; berberine also had an effect in broth supplemented with serum, whereas the sulphonamides were antagonized. However, it was found possible for the microorganisms to acquire resistance when left in contact with berberine for a long time.

Berberine (as the sulphate) has been shown to be bactericidal to Vibrio cholerae at a concentration of 35 μg/ml and bacteriostatic to Staphylococcus aureus at a concentration of 50 μg/ml. In both these organisms berberine at the concentrations mentioned inhibited RNA and protein synthesis almost immediately after addition. Cell-free preparations made from vibrios pretreated with berberine did not produce choleraic symptoms in infant rabbits, suggesting that the toxin was either inactivated or neutralized. Oral administration of berberine to infant rabbits 18-24 h before a single fatal intra-intestinal dose of choleragenic toxin prevented toxin-induced diarrhoea and consequently prolonged survival when compared with untreated choleragenic animals. The quaternary ammonium group in berberine seems necessary for its antibacterial activity. Derivatives without the quaternary ammonium group, such as tetrahydroberberine, showed only little antibacterial effect. Berberine (sulphate) in concentrations of 10-25 mg/ml inhibited the growth of the fungi Alternaria spp., Aspergillus flavus, A. fumigatus, Candida albicans, Curvularia spp., Drechslera spp., Fusarium spp., Mucor spp., Penicillium spp., Rhizopus oryzae and Scopulariopsis spp. Oral administration of berberine sulphate at doses of 350-700 mg/kg was effective in treating Candica albicans infections of the intestine in mice.

Berberine (sulphate) administered to rats at doses of 100 mg/kg body weight, 10 days after experimentally induced intestinal amoebiasis was effective in 80% of the animals. It completely inhibited the growth to trophozoites of Entamoeba histolytica at concentrations of 0.5-1 mg/ml in vitro, and was active in vivo against infections with E. histolytica in hamsters and rats. Berberine has also been found to be trypanocidal against Trypanosoma brucei rhodesiense. In vitro activities with IC₅₀ values of 0.4 μg/ml were determined.

Both berberine sulphate (50 μg/ml) and berberine chloride (25 μg/ml) showed growth inhibition of Ehrlich and lymphoma ascites tumour cells. The presence of berberine in granules inside the cells was detected by its fluorescence. The cytotoxic ED₅₀ values in HeLa cell cultures were 3.5-30 μg/ml, and in KB cells a 70% inhibition of protein synthesis was found at a concentration of 1 μg/ml. Berberine chloride inhibited the formation of DNA, RNA, proteins and lipids, as well as the oxidation of [¹⁴C] glucose to ¹⁴CO₂ when incubated with S180 (Swiss mouse ascites sarcoma) cells in vitro. Protein and RNA syntheses were most sensitive to berberine. However, berberine failed to inhibit the growth of S180 ascites tumours in mice, which may be explained by the effect of different glucose levels in biological fluids. The binding of the alkaloid to DNA was investigated by means of spectroscopy. Calf thymus DNA produced systematic changes in the absorption spectrum of berberine, which suggests that berberine forms a complex with DNA and binds to the extent of one alkaloid molecule per two base pairs. These binding properties seem te be influenced by the presence of charge and the position and type of substituents in the molecule. From other experiments it was also concluded that berberine is a potent activator for macrophages, to induce inhibition of tumour cells in vitro.

Intravenous infusion of berberine sulphate to rats was found to lower the blood pressure in a dose-dependent manner. A significant hypotensive effect was followed by bradycardia. These effects were also observed in bilaterally vagotomized rats. Berberine chloride at doses of 0.5-5.0 mg/kg administered to rabbits anaesthetized with urethane produced a long lasting, dose-related decrease in blood pressure. The berberine induced hypotension seems attributable to α-adrenoceptor blockade, and not to a direct relaxant effect on vascular smooth muscle. Berberine had no direct vasodilatory effects on isolated rabbit pulmonary and cat coronary arteries either, however, the alkaloid reversed vasoconstriction mediated by α-adrenergic agents in both preparations.

Both berberine and palmatine inhibited specific cholinesterase in rabbit spleen and pseudocholinesterase in normal horse serum. Both compounds were less effective inhibitory agents than neostigmine, but palmatine exhibited lower toxicity than berberine. Tetrahydropalmatine and tetrahydroberberine had no anticholinesterase effect, suggesting that the quaternary ammonium group is crucial for the effect of isoquinoline alkaloids on this enzyme.

Some metabolic and toxicological data on berberine are available from experiments on rats. The blood level of orally administered [³H] berberine chloride plateaued after 4-24 h, and maximal levels in the liver and muscles were achieved at 12 h. Urinary berberine excretion reached a maximum at 12-24 h. Excretion in the urine and faeces at 48 h amounted to respectively 2.7% and 86% of the administered dose. Faecal elimination as the main excretion route indicates that berberine is not readily absorbed by the gastro-intestinal tract. The biological half-life of berberine chloride was 5.2 h after intraperitoneal administration and 5.4 h after oral administration. Perfusion experiments (in dogs and rabbits) indicated oxidation of berberine chloride in the liver. The LD₅₀ value of berberine sulphate was more than 1 g/kg after oral administration in the rat and about 90 mg/kg after intraperitoneal administration. Histopathological examinations revealed no changes in tissues and organs, even in cases when berberine sulphate had been given for 6 weeks at daily doses of 500 mg/kg.

Of the bisbenzylisoquinoline alkaloids investigated, (+)-homoaromaline showed inhibition of the histamine production by RBL-2H3 cells in vitro, and both (+)-homoaromaline and (-)-limacine were capable of inhibiting the growth of cultured Plasmodium falciparum strains and tumour cell lines. However, their "selectivity index" (activity against mammalian cells / activity against cultured P. falciparum strains) typically ranges from 2-100; a selectivity index of > 1000 appears to indicate that a component merits further investigation as an anti-malarial.

Crude aqueous extracts of A. flava showed slight insecticidal activity against cotton bollworm (Helicoverpa armigera) in the Philippines. Bollworms fed with treated cotton bolls were significantly smaller and shorter than their controls.

Adulterations and substitutes

Several Menispermaceae, e.g. Coscinium fenestratum (Gaertner) Colebr., Fibraurea tinctoria Lour., Limacia spp. and Tinospora spp. contain berberine or related compounds and are used for similar purposes. Coptis teeta Wallich (Ranunculaceae) is another species containing berberine and with similar uses. Berberine has been named after the genus Berberis (Berberidaceae) in which the compound was found first. In India and Vietnam, for example, Berberis spp. are used against similar diseases as A. flava.

Description

• A large, woody, glabrous, dioecious liana, up to 20 m long; stem up to 5 cm in diameter, wood yellow, exuding yellow sap when cut.
• Leaves usually ovate, (10-)12-25 cm × (5.5-)8-19 cm, coriaceous, palmately 5-veined at the base; petiole (4-)7-15(-20) cm long, swollen at both ends; stipules absent.
• Inflorescence axillary or cauliflorous, paniculate, slender, 10-50 cm long, lateral branches spicate to subspicate.
• Flowers unisexual, with 3-4 minute outer sepals and 6 larger inner sepals, petals absent; male flower subsessile, with a sessile, globose cluster of 9-12 anthers; female flower with 3 carpels and a number of staminodes.
• Fruit a slightly laterally compressed drupe, transversely subovoid, 2-3 cm in diameter, yellow, with a club-shaped stalk; endocarp woody, covered with a dense mat of radial fibres.
• Seed broadly ellipsoidal, with ruminate endosperm, cotyledons much folded.

Growth and development

The fruits are eaten and dispersed by primates such as macaques, gibbons and orang-utans, and probably other arboreal mammals.

Other botanical information

Some confusion exists in the literature between Arcangelisia flava and Anamirta cocculus (L.) Wight & Arnott. A. flava has yellow wood and is used predominantly as a medicine, Anamirta cocculus has white wood and the fruits are used as a fish poison and an insecticide, while its bark is used as rope. The second Arcangelisia species (A. tympanoda (Lauterb. & K. Schumann) Diels) is apparently endemic to New Guinea and is poorly known.

Ecology

A. flava occurs in forests at altitudes up to 1000 m, sometimes near river banks. In Sulawesi, it is reported on limestone.

In vitro production of active compounds

In vitro production of berberine is possible. Callus cultures of A. flava have been established in Thailand, using revised tobacco medium supplemented with phytohormones (naphtalene acetic acid at 2 mg/l, indole-butyric acid at 2 mg/l and kinetin at 1 mg/l). The production can be increased on media containing coconut milk, casein hydrolysate, tyrosine (a berberine precursor), manganese sulphate and aluminium sulphate. The intensity of the yellow colouration of the callus is an indication of the amount of alkaloid produced.

Harvesting

In Indonesia, the stems are cut in the early morning to obtain the sap which is drunk to cure fever and sprue.

Yield

In the Philippines, it has been reported that as much as 1 kg of berberine can be obtained from a single plant.

Genetic resources and breeding

Yellow-fruited moonseed is widespread and seems not to be easily liable to genetic erosion. There are no known germplasm collections or breeding programmes. Future breeding work may focus on the selection of types with high alkaloid content.

Prospects

Yellow-fruited moonseed is considered an interesting medicinal plant and may become important in cancer control. The development of proper biotechnological methods to produce alkaloids in tissue culture might provide the tools for large-scale production of alkaloids from A. flava.

Literature

• Brown, W.H., 1951. Useful plants of the Philippines. Vol. 1. Technical Bulletin 10. Department of Agriculture and Natural Resources. Bureau of Printing, Manila, the Philippines. pp. 530-531.
• Burkill, I.H., 1966. A dictionary of the economic products of the Malay Peninsula. 2nd edition, Vol. 1. Ministry of Agriculture and Co-operatives, Kuala Lumpur, Malaysia. pp. 215-217.
• Chi, C.W., Chang, Y.F., Chao, T.W., Chiang, S.H., P'Eng, F.K., Lui, W.Y. & Liu, T.Y., 1994. Flowcytometric analysis of the effect of berberine on the expression of glucocorticoid receptors in human hepatoma HepG2 cells. Life Sciences 54(26): 2099-2107.
• Creasey, W.A., 1979. Biochemical effects of berberine. Biochemical Pharmacology 28(7): 1081-1084.
• de Padua, L.S., Lugod, G.C. & Pancho, J.V., 1977. Handbook on Philippine medicinal plants. Vol. 1. Documentation and Information Section, Office of the Director of Research, University of the Philippines, Los Baños, the Philippines. p. 43.
• Forman, L.L., 1986. Menispermaceae. In: van Steenis, C.G.G.J. & de Wilde, W.J.J.O. (Editors): Flora Malesiana. Series 1, Vol. 10. Kluwer Academic Publishers, Dordrecht, Boston, London. pp. 209-211.
• Heyne, K., 1927. De nuttige planten van Nederlandsch Indië [The useful plants of the Dutch East Indies]. 2nd edition. Vol. 1. Departement van Landbouw, Nijverheid & Handel in Nederlandsch-Indië. p. 621.
• Quisumbing, E., 1978. Medicinal plants of the Philippines. Katha Publishing Co., Quezon City, the Philippines. pp. 293-294.
• Tang, W. & Eisenbrand, G., 1992. Chinese drugs of plant origin. Springer Verlag, Berlin, Heidelberg, New York. pp. 361-371.
• Yanpaisan, W., 1989. The effect of phytohormones and some additives on tissue culture establishment and in vitro production of alkaloids from Arcangelisia flava Merr. Journal of the National Research Council of Thailand 21(1): 1-27.

Other selected sources

• Freiburghaus, F., Kaminsky, R., Nkunya, M.H.H. & Brun, R., 1996. Evaluation of African medicinal plants for their in vitro trypanocidal activity. Journal of Ethnopharmacology 55: 1-11.
• Gutierrez, H.G., 1980-1982. An illustrated manual of Philippine materia medica. 2 volumes. Natural Research Council of the Philippines, Tagig, Metro Manila, the Philippines. Vol. 1 (1980) pp. 1-234, Vol. 2 (1982) pp. 235-485.
• Kloppenburg Versteegh, J., 1934. Wenken en raadgevingen betreffende het gebruik van Indische planten, vruchten, enz. [Hints and recommendations on the use of East Indies plants, fruits etc.] G.T.C. van Dorp, Semarang, Surabaya, Bandung, Dutch East Indies. (5th Edition. 1978. Servire, Katwijk aan Zee, the Netherlands). 364 pp.
• Likhitwitayawuid, K., Angerhofer, C., Cordell, G.A. & Pezzuto, J.M., 1993. Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Stephania erecta. Journal of Natural Products 56: 30-38.
• Lim Sylianco, C.Y., Concha, J.A., San Augustin, J., Panizares, I. & Pablo, C., 1980. Mutagenicity and clastogenicity potential of decoctions and infusions from Philippine medicinal plants. Bulletin of the Philippine Biochemical Society 3: 54-65.
• Lin, L.Z., Shieh, H.L., Angerhofer, C.K., Pezzuto, J.M., Cordell, G.A., Xue, L., Johnson, M.E. & Ruangrungsi, N., 1993. Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Cyclea barbata. Journal of Natural Products 56: 22-29.
• Nakamura, K., Tsuchiya, S., Sugimoto, Y., Sugimura, Y. & Yamada, Y., 1992. Histamine release inhibition activity of bisbenzylisoquinoline alkaloids. Planta Medica 58: 505-508.
• Saralamp, P., Temsiririrkkul, R., Chuakul, W., Riewpaiboon, A., Prathanturarug, S., Suthisisang, C. & Pongcharoensuk, P. (Editors), 1996. Medicinal plants in the Siri Ruckhachati Garden. 2nd Edition. Siambooks and Publications Co., Bangkok, Thailand. 263 pp.
• Solsoloy, A.D., Dumlao, N.A. & Solsoloy, T.S., 1987. Insecticidal activity of indigenous plant extracts against bollworms (Helicoverpa armigera Hubn.). Technical Report calendar year 1985-86, Cotton Research and Development Institute, Batac, Ilocos Norte, the Philippines. pp. 175-184.

Authors

• E.H. Mandia, C.E. Ridsdale, S.F.A.J. Horsten & A.M. Aguinaldo