Angelica acutiloba (PROSEA)

Plant Resources of South-East Asia Introduction

List of species

1, root; 2, stem with flowers and fruits (Iskak Syamsudin)

Angelica acutiloba (Siebold & Zucc.) Kitagawa

Protologue: Bot. Mag., Tokyo 51: 658 (1937).

Family: Umbelliferae

Chromosome number: 2n= 22

Synonym

• Ligusticum acutilobum Siebold & Zucc. (1845).

Vernacular names

• Thailand: tang kui.

Origin and geographic distribution

Angelica comprises about 110 species, widely distributed in the temperate regions of the northern hemisphere. A. acutiloba is indigenous in Japan and was introduced for cultivation in mountainous regions in West Java in the 1970s.

Uses

The root of A. acutiloba ("Angelica Radix") is traditionally used in Japan and China as a general tonic and prescribed in the treatment of dysmenorrhoea, phthisis and haemorrhage. Furthermore, it is used as an emmenagogue, a remedy for anaemia, to alleviate pain during parturition and, in Indo-China, as a carminative and galactagogue. Two other Angelica species with a long history of medicinal use have been successfully introduced in Vietnam: A. dahurica (Fisch. ex Hoffm.) Benth. & Hook.f. ex Franchet & Savat. and A. polymorpha Maxim. (synonym: A. sinensis (Oliv.) Diels). In Western Europe various parts of A. archangelica L. have been used since ancient times as a vegetable and medicinal plant (to treat dyspeptic syndromes and as appetite stimulant).

Production and international trade

Although there is a long tradition of trade of A. acutiloba from Japan to China and Indo-China, no trade figures are available.

Properties

Extensive chemical studies on A. acutiloba have revealed a wide array of compounds including polysaccharides, lactones and alkynes, some of which are medicinally active. The roots of A. acutiloba contain two anticholinergic compounds: ligustilide and butylidenephthalide. They also contain seven analgesic compounds: falcarinol, falcarindiol and falcarinolone (polyacetylenes), and choline, scopoletin, umbelliferone and vanillic acid. The latter compounds inhibit writhing in mice induced by acetic acid. The three polyacetylenes were the most active in the writhing test. Falcarindiol and choline also showed anti-nociceptive activities in the retrograde injection test of bradykinin into a carotid artery on rats. The polysaccharide fraction of a hot water extract of the roots of A. acutiloba showed a mitogenic activity on B-lymphocytes, polyclonal B cell activator activity, antitumour activity against Erhlich ascites cells, interferon-inducing activity and anticomplementary activity. These biological activities are caused by different water-soluble fractions. The action of Angelica immunostimulating polysaccharide (AIP) fraction on murine lymphocytes participating in antibody responses has been investigated. When AIP fraction was injected concomitantly into mice immunized with antigens, immunoglobulins G and M (IgG, IgM), antibody responses against sheep erythrocytes increased significantly, but IgM response against specific T-independent antigens did not augment. Furthermore, murine B lymphocytes were polyclonally activated in vitro and in vivo by AIP fraction to differentiate into antibody-forming cells as functionally matured cells. The differentiation of B lymphocytes to an intermediate stage capable of responding to helper T-lymphocytes was also stimulated by administering AIP fraction to CDF1 and C3H/HeJ mice. Stimulation of T-lymphocytes was also found.

An anticomplementary active arabinogalactan IIb-1 (AGIIb-1) and an inactive arabinogalactan IIb-2 (AGIIb-2) were isolated from an extract of the root of A. acutiloba. AGIIb-1 mainly consisted of arabinose, galactose, rhamnose and galacturonic acid in a molar ratio of 2.2:1.0:0.3:0.4. AGIIb-1 was found to form molecular self aggregation, caused by hydrogen bonding and ionic interaction. However, it was independent of Ca²⁺ ions. The anticomplementary activity of AGIIb-1 seemed to be dependent upon the degree of molecular aggregation; the aggregate in water showed the greatest activity. Further separations of AGIIb-1 revealed that it constisted of one neutral unit (N-I), one neutral arabinan unit (N-II) and two acidic arabinogalactan (A-I and A-II) units. N-I showed the most potent anticomplementary activity. AGIIb-1, A-I, and A-II had similar moderate activities, but N-II had weak activity. Digestion products prepared from the latter fractions by treatment with purified enzymes yielded several polysaccharides that also showed (modified) anticomplementary activity. In general, the anticomplementary activity of AGIIb-1 was expressed mainly through the classical pathway, whereas some modified polysaccharides had markedly increased activity through the alternative pathway.

The crude polysaccharide fraction (AR-1), prepared by ethanol precipitation and dialysis of the hot water extract from the root of A. acutiloba showed a potent antitumour activity against ascitic forms of sarcoma-180, IMC carcinoma and Meth A fibrosarcoma, as well as the solid form of MM-46 tumour. AR-1 was further fractionated into a pectic (AR-2) and a arabinogalactan (AR-4) fraction. An antitumour active component from AR-4 was identified as polysaccharide AR-4E-2, which consisted of arabinose, galactose and rhamnose in the molar ratio of 3.3:1.0:0.7. It also contains a rhamno-galacturonan moiety in which 2,4-di-substituted rhamnose residues are attached to 4-substituted galacturonic acid through position 2 of rhamnose. Furthermore, four pectic polysaccharides with anticomplementary activity were isolated from fraction AR-2. These compounds have been named AR-2 IIa-IId.

A root extract of A. acutiloba showed potent inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate stimulated ³²P incorporation into phospholipids of cultured cells. The hot water extract of roots also exhibited antipyretic, central nervous system depressant, cardiac depressant, and hypotensive, antispasmodic and radioprotective activities.

Description

• A medium-sized perennial herb up to 70(-100) cm tall, tuberous root short with a few thickened secondary roots; stems glabrous, striate, solid.
• Leaves alternate, long-petiolate in lower part of stem, 1-2 ternately pinnate, deltoid in outline, 10-25 cm long, glabrous, leaf sheaths present, stipules absent; leaflets trifid, 5-10 cm × 1-2.5 cm, cuneate, truncate or rounded at base, ultimate segments lanceolate, long-acuminate, margin dentate, reticulate venation prominent.
• Inflorescence a compound many-flowered umbel, papillate, rays 30-40, 3-8 cm long, secondary rays (pedicels) 0.7--1.8 cm long; involucre consisting of a few filiform-linear bracts.
• Flowers with obsolete calys, petals unobtrusive white, ovary inferior, styles 2.
• Fruit consisting of two 1-seeds mericarps, oblong, 4-5 mm long, slightly compressed, narrowed towards the base, mericarps with slender ribs, lateral ribs slightly winged, vittae 3-4 in the intervals, 4 on the commissure.

Other botanical information

Several subspecies and varieties have been distinguished within A. acutiloba. This variation can be partly attributed to geographical origin, but also the long tradition of cultivation has resulted in selections that can be morphologically distinguished. The differences are to some extent supported by karyological research.

Ecology

A. acutiloba occurs naturally at higher elevations in mountainous regions. It is cultivated under similar conditions in Java.

Propagation and planting

A. acutiloba can be propagated by seed as well as by somatic embryogenesis from hypocotyl and cotyledon material in Murashige and Skoog medium with 3% sucrose supplemented with 2,4-D (0.5-2 ppm) and kinetin (0.5-1 ppm). Regenerated plants can be obtained from the embryoids in Murashige and Skoog medium with 2% sucrose. Seedlings are usually transplanted. The spacing in experimental plantings in Java is 40 cm × 40 cm.

Harvesting

Whole plants are uprooted, the tuberous roots separated, small rootlets removed, and finally the tuberous roots are washed and dried in the sun or shade.

Yield

Intercropping A. acutiloba planted at 40 cm × 40 cm with maize and cabbage did not affect the yield of Angelica tuberous roots. In a field experiment in West Java, plantings of cultivar "Siguyama Hikino" were harvested 6, 8, 10, 12, 14 and 16 months after transplanting. Root yields were 65-70% greater after 10 months than after 6-8 months.

Handling after harvest

Roots of A. acutiloba were experimentally dried to a moisture content of about 11% and extracted with ethanol. The quality of the roots harvested after 10 months was of export grade with an ethanol extract percentage of 42%.

Genetic resources and breeding

Breeding efforts in A. acutiloba are aimed at increasing the yield of tuberous roots and the concentration of active compounds. Experimental crosses between the cultivars "Yamato Toki" (var. acutiloba) and "Ibuki Toki" (var. iwatenis (Kitagawa) Hikino) showed a heterosis effect in the F-1 with respect to yield of tuberous roots and their sucrose content. However, the concentration of pharmacologically important compounds was intermediate between those of the parents. For industrial processing, breeding efforts should focus on obtaining plant material with a uniform concentration of pharmacologically important compounds in the roots. Somatic embryogenesis appears to be a successful method for this purpose. Breeding programmes in Vietnam to promote the cropping of Angelica at lower elevations through adapted cultivars have been successful with A. dahurica and A. polymorpha.

Prospects

The polysaccharides from A. acutiloba show promise in antitumour activity and immunology (anticomplementary activity). Research on their actions thus deserves further attention.

Literature

• Kiyohara, H., Cyong, J.C. & Yamada, H., 1988. Structure and anticomplementary activity of pectic polysaccharides isolated from the root of Angelica acutiloba Kitagawa. Carbohydrate Research 182(2): 259-275.
• Kumazawa, Y., Nakatsuru, Y., Fujisawa, H., Nishimura, C., Mizunoe, K., Otsuka, Y. & Nomoto, K., 1985. Lymphocyte activation by a polysaccharide fraction separated from hot water extracts of Angelica acutiloba Kitagawa. Journal of Pharmacobiodynamics 8(6): 417-424.
• Nguyen Van Duong, 1993. Medicinal plants of Vietnam, Cambodia and Laos. Mekong Printing, Santa Ana, California, United States. pp. 412-413, 418.
• Ohwi, J., 1965. Flora of Japan. Smithsonian Institution, Washington D.C., United States. pp. 680-682.
• Okuyama, T., Takata, M., Nishino, H., Nishino, A., Takayasu, J. & Iwashima, A., 1990. Studies on the antitumor-promoting activity of naturally occurring substances. II. Inhibition of tumor-promoter-enhanced phospholipid metabolism by umbelliferous materials. Chemical and Pharmaceutical Bulletin 38(4): 1084-1086.
• Perry, L.M., 1980. Medicinal plants of East and Southeast Asia. Attributed properties and uses. The MIT Press, Cambridge, Massachusetts, United States & London, United Kingdom. pp. 410-411.
• Sada, Y., Tanaka, S., Tabata, M., Ozaki, K. & Komiya, T., 1993. Evaluation of intervarietal F-1 hybrids of the medicinal plant, Angelica acutiloba, clonally propagated by somatic embryogenesis. Shoyakugaku Zasshi 47(3): 235-242 (in Japanese).
• Sudiarto, 1990. Effect of harvesting time on root yield of touki (Angelica acutiloba) in West Java. Industrial Crops Research Journal 2(2): 9-12.
• Tanaka, S., Ikeshiro, Y., Tabata, M. & Konoshima, M., 1977. Anti-nociceptive substances from the roots of Angelica acutiloba. Arzneimittelforschung 27(11): 2039-2045.
• Yamada, H., Komiyama, K., Kiyohara, H., Cyong, J.C., Hirakawa, Y. & Otsuka, Y., 1990. Structural characterization and antitumor activity of a pectic polysaccharide from the roots of Angelica acutiloba. Planta Medica 56: 182-186, 420.

Other selected sources

• Arano, H. & Saito, H., 1979. Cytological studies in family Umbelliferae 4. Karyotypes in genus Angelica 2. Kromosomo (Tokyo) 2(15-16): 417-426.
• Doan Thi Nhu, Nguyen Thuong Thuc, Do Huy Bich & Vu Thuy Huyen (Editors), 1991. Les plantes médicinales au Vietnam. Livre 1. Médicine traditionelle et pharmacopée [The medicinal plants of Vietnam. Volume 1. Traditional medicine and pharmacopoeia]. Agence de coopération Culturelle et Technique, Paris, France. 201 pp.
• Emmyzar, Karawati, E. & Taryono, 1989. Pola tanam tumpang sari Angelica acutiloba dan sayuran [Intercropping Angelica acutiloba with vegetables]. Buletin Penelitian Tanaman Rempah dan Obat 4(2): 70-74.
• Kiyohara, H., Cyong, J.C. & Yamada, H., 1989. Relationship between structure and activity of an anti complementary arabinogalactan from the roots of Angelica acutiloba Kitagawa. Carbohydrate Research 31(193): 193-200.
• Kiyohara, H., Yamada, H., Cyong, J.C. & Otsuka, Y., 1986. Studies on polysaccharides from Angelica acutiloba. V. Molecular aggregation and anti complementary activity of arabinogalactan from Angelica acutiloba. Journal of Pharmacobiodynamics 9(4): 339-346.
• Kosuge, T., Ishida, H., Yamazaki, H. & Ishii, M., 1984. Studies on active substances in the herbs used for oketsu, blood coagulation, in Chinese medicine. I. On antiagulative activities of the herbs for oketsu. Yakugaku Zasshi 104(10): 1050-1053. (in Japanese)
• Mabberley, D.J., 1997. The Plant Book. A portable dictionary of the vascular plants. 2nd Edition. Cambridge University Press, Cambridge, United Kingdom. 858 pp.
• Miura, Y., Fukui, H. & Tabata, M., 1988. Reduced inhomogeneity of Angelica acutiloba plants propagated clonally through somatic embryoids. Planta Medica 54(1): 79-81.
• Ohga, Y., Ono, M. & Furuno, K., 1989. The multiplication method of medical crops by tissue culture: Embryoid formation and plant regeneration. Bulletin of the Fukuoka Agricultural Research Center, Series A. Crop (Japan) 9: 75-78.
• Pételot, A., 1952-1954. Les plantes médicinales du Cambodge, du Laos et du Vietnam [The medicinal plants of Cambodia, Laos and Vietnam]. 4 volumes. Centre National de Recherches Scientifiques et Techniques, Saigon, Vietnam.
• Sakai, W., 1916. Pharmacological action of Ligusticum acutilobum Sieb. & Zucc. Tokyo Igakukai Zasshi 30(24): 19-52. (in Japanese)
• Sheu, S.J., Ho, Y.S., Chen, Y.P. & Hsu, H.Y., 1987. Analysis and processing of Chinese herbal drugs. VI. The study of Angelicae Radix. Planta Medica 53(4): 377-378.
• Toriizuka, K., Nishiyama, P., Adachi, I., Kawashiri, N., Ueno, M., Terasawa, K., & Horikoshi, I., 1986. Isolation of a platelet aggregation inhibitor from Angelicae Radix. Chemical and Pharmaceutical Bulletin 34(12): 5011-5015.
• Yonizawa, M., 1993. Radioprotective activity in some medicinal herbs. Shoyakugaku Zasshi 47(3): 338-341. (in Japanese)

Authors

• N. Bunyapraphatsara & J.L.C.H. van Valkenburg