Hypericum (PROSEA)

Plant Resources of South-East Asia Introduction

List of species

Hypericum L.

Protologue: Sp. pl. 2: 783 (1753); Gen. pl. ed. 5: 341 (1754).

Family: Guttiferae

Chromosome number: x= (6), 7, 8, 9, 10, 11, 12

Major species

• Hypericum japonicum Thunb. ex Murray,
• H. monogynum L.

Vernacular names

• St John's wort (En).
• Millepertuis (Fr).

Origin and geographic distribution

Hypericum comprises about 400 species and can be considered cosmopolitan, occurring in all continents except for arctic and desert areas and most of the lowland tropics. There are 15 species of Hypericum in Malesia, but the genus is absent from the Moluccas. The genus is also present in Indo-China and Thailand and rare in Australia, with only 2 species.

Uses

All Hypericum species are said to yield essential oils and to be medicinally interesting to some extent. Their medicinal use has been basically the same throughout the world, as they have been used internally against rheumatism, jaundice, oedema and gastric catarrh, and externally to treat wounds and bruises. These effects of Hypericum species are regarded as based on their astringent, diuretic, and haemostatic activities. Though there are 15 Malesian species, specific reports of medicinal use are only found for H. gramineum, H. japonicum, H. monogynum, H. papuanum and H. uralum.

Reports of medicinal use also exist for the non-Malesian H. ascyron L., H. patulum Thunb. ex Murray and H. sampsonii Hance. In Indo-China, the seeds of H. patulum are applied to treat dog bites and bee stings. H. sampsonii is reported to be used as a vulnerary in northern Vietnam. The fruits and seeds of H. ascyron are applied to treat skin problems, gonorrhoea and dysmenorrhoea in Indo-China and China. In Chinese medicine, H. ascyron, H. japonicum and H. sampsonii are mentioned as antihaemorrhagic, and the latter two as vulneraries in the treatment of scrofula and contusions.

A well-known medicinal species in Europe is H. perforatum L., which does not occur in South-East Asia. H. perforatum was already recognized as a medicinal plant by the ancient Greek writers Dioscorides and Hippocrates. Nowadays, drugs based on the plant are used to treat skin and mouth problems and as an antidepressant.

Hypericum species are often grown as ornamentals.

Properties

The most characteristic compounds of Hypericum are xanthonoid pigments and anthraquinonoids (naphthodianthrones, hydroxyanthraquinones), such as hypericin and pseudohypericin. Also present is an essential oil containing considerable amounts of aliphatic compounds such as 2-methyloctane, nonane, undecane, octanal and decanal. Other constituents include some common phenolic components (catechins, leucoanthocyanins, chlorogenic acids, condensed tannins) and flavonoids (quercetin glycosides: rutin, quercitrin, hyperin).

Hypericin and pseudohypericin are present in H. perforatum and many other species, but are not found in the South-East Asian H. ascyron, H. japonicum and H. monogynum, while results are not clear for H. patulum. The pharmacology of hypericin and pseudohypericin has been well investigated. Strong antiviral properties against retroviruses, such as the HIV-1, influenza and cytomegalo viruses has been shown, with no toxic side-effects at therapeutic doses. In this respect, hypericin seems to be more potent than pseudohypericin and clinical trials have been initiated on this compound. At molecular level, hypericin and pseudohypericin specifically inhibit protein kinase C (PKC), having IC₅₀levels of respectively 1.7 μg/ml and 15 μg/ml. Thus, the anti-retroviral activity could be attributable to phosphorylation reactions being inhibited by the PKC occurring during viral infection of cells. In addition to the antiviral activity, antiproliferative activity against mammalian cells (possibly due to PKC inhibition) has been reported in the literature.

The ingestion of hypericin or pseudohypericin (or their biosynthetic precursors proto-hypericin/proto-pseudohypericin) and subsequent exposure to UV light (λ 320 nm) may cause photodermatitis. Therefore, exposure to the sun must be avoided after using Hypericum-based drugs. In animals, this syndrome is called "hypericism". Symptoms are swelling of the face, itches, loss of hair, appearance of sores and eventually apoplexy and death.

In Europe, extracts of H. perforatum are well known as an antidepressant. In several clinical trials of mild and moderate depressions they have been reported to be as effective as standard medications (e.g. using tricyclic antidepressants), but with far fewer side-effects. An antidepressant activity of H. patulum has also been reported in the literature. It remains unclear whether the antidepressant activity is related to the content of hypericin/pseudohypericin. Experiments with purified substances have not given unambiguous results, and tentative investigations of the extracts indicate that other compounds (e.g. flavones) might also play a role.

Several antimicrobial phloroglucinol derivatives (saroaspidin A, B and C, sarothralen A, B, C and D, sarothralin, and sarothralin G) have been isolated from H. japonicum. Of these compounds, sarothralin and sarothralin G have the strongest activity against gram-positive bacteria e.g. Staphylococcus aureus, Bacillus cereus, and Nocardia gardneri. In addition to the phloroglucinols, lactones and flavonoids have also been isolated. Furthermore, the phloroglucinol derivative japonicine A (from H. japonicum) is reported to show anti-malarial activity in mice. Acetone extracts of the leaves of H. papuanum showed antibacterial activity against Staphylococcus aureus.

Aqueous plant extracts of H. japonicum (10 mg/ml) have been found to have strong in vitro antiviral activity against the herpes simplex virus HSV-II, whether administered simultaneously (simultaneous addition of extract and virus to the cell bottle) or therapeutically (virus inoculated into the cell bottle, later followed by addition of the extract). Methanolic plant extracts of H. uralum have shown antiviral activity against 3 mammalian viruses: herpes simplex, Sindbis and polio. The activity was not enhanced by UV light, which suggests that antiviral compounds other than the naphthodianthrones (hypericin, pseudohypericin) are present.

Description

• Herbs or shrubs, sometimes small trees, usually glabrous; branchlets terete or 2-4-lined or -angled.
• Leaves opposite or rarely whorled, simple and entire, with translucent glands and/or black or red glands, sessile or shortly petiolate.
• Inflorescence a terminal dichasium or monochasium.
• Flowers bisexual, (4-)5-merous; sepals quincuncial or rarely decussate, coriaceous to chartaceous, glandular; petals yellow to orange, sometimes tinged or veined red, glandular, glabrous, persistent or deciduous; stamens in epipetalous fascicles, free or variously united, glabrous, persistent or deciduous, each fascicle with up to 70 stamens, filaments yellow, slender, anthers short, oblong, yellow or reddish, dorsifixed or apparently basifixed; ovary superior, 3-5-celled or 1-celled with (2-)3-5 parietal or axile placentas, ovules 2-many on each placenta, styles (2-)3-5, free to united, slender, stigmas small.
• Fruit a (2-)3-5-valved capsule.
• Seeds 1-many on each placenta, curved cylindrical to ellipsoid, sometimes carinate or winged; embryo cylindrical, straight or curved, with cotyledons usually shorter than hypocotyl.
• Seedling with epigeal germination; cotyledons leafy, sessile, glabrous; hypocotyl short, epicotyl very short.

Growth and development

Hypericum includes species with very different habits, from herbs to small trees. The arrangement of stamens in the flowers, with the innermost shorter and not attaining the level of the stigmas favours cross-pollination. The flowers are typically visited by less-specialized insects such as Diptera. Usually seeds are shed by septical dehiscence of the capsule. Seed from Hypericum growing in damp or marshy locations may possibly adhere to the feet and feathers of wading birds and waterfowl and be dispersed thus.

Other botanical information

Hypericum is closely related to Cratoxylum (from a different tribe). The tribes Vismieae, Cratoxyleae and Hypericeae together constitute the subfamily Hypericoideae. As this subfamily forms a natural group, in the past it was often given family ranking (Hypericaceae), but nowadays it is usually classified within the large family Guttiferae (Clusiaceae). Hypericum has been further divided into no fewer than 30 sections.

Ecology

In the tropics, Hypericum is generally a high-altitude genus, though some species are sometimes found at low elevations. In temperate regions, it is found in widely varying conditions, but never in very arid habitats. In South-East Asia, Hypericum is found in forest margins, grassland, marshes or among rocks. It occurs from sea-level in Sumatra up to 3400 m in New Guinea, but is rarely found in the lowlands.

Propagation and planting

Hypericum can be propagated by seed, cuttings, division or suckers. H. monogynum is propagated by division. Light is essential for germination of seed.

Handling after harvest

Whole plants can be used fresh or dried.

Genetic resources and breeding

Wild Hypericum hybrids have been found, but only between closely related species. Artificial hybrids are always sterile and usually weak, though some crosses have thrived.

Prospects

Hypericum extracts have shown strong antiviral, antidepressant and antimicrobial activity, with limited toxic side-effects. Because of these promising medicinal properties, Hypericum may become important in the future. However, chemical and medicinal properties vary between species and there is very little information on the presence of active compounds in South-East Asian Hypericum species.

Literature

• Baureithel, K.H., Buter, K.B., Engesser, A., Burkard, W. & Schaffner, W., 1997. Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum. Pharmaceutical Acta Helvetica 72(3): 153-157.
• Hegnauer, R., 1966. Chemotaxonomie der Pflanzen: eine Übersicht über die Verbreitung und die systematische Bedeutung der Pflanzenstoffe [Chemotaxonomy of plants: an overview of the distribution and the systematic importance of plant substances]. Vol. 4. Birkhäuser Verlag, Basel, Switzerland. pp. 223-226.
• Ishiguro, K., Nagata, S., Fukumoto, H., Yamaki, M. & Isoi, K., 1994. Phloroglucinol derivatives from Hypericum japonicum. Phytochemistry 35(2): 469-471.
• Ishiguro, K., Yamaki, M., Kashihara, M., Takagi, S. & Isoi, K., 1990. Sarothralin G: a new antimicrobial compound from Hypericum japonicum. Planta Medica 56(3): 274-276.
• Mathis, C. & Ourisson, G., 1963. Étude chimio-taxonomique du genre Hypericum. I. Répartition de l'hypéricine [Chemo-taxonomical study of the genus Hypericum. I. Distribution of hypericine]. Phytochemistry 2: 157-171.
• Meruelo, D., Lavie, G. & Lavie, D, 1988. Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. Proceedings of the National Academy of Science, United States 85(14): 5230-5234.
• Robson, N.K.B., 1974. Hypericum. In: van Steenis, C.G.G.J. (General editor): Flora Malesiana. Series 1, Vol. 8. Sijthoff & Noordhoff International Publishers, Alphen aan den Rijn, the Netherlands. pp. 14-29.
• Robson, N.K.B., 1980. Hypericum L. In: Townsend, C.C. & Guest, E.R. (Editors): Flora of Iraq. Vol. 4. Ministry of Agriculture and Agrarian Reform, Bagdad, Iraq. pp. 363-381.
• Robson, N.K.B., 1996. Hypericum. In: Huang, T.-C. (Editor): Flora of Taiwan, 2nd edition. Vol. 2. Editorial Committee of the Flora of Taiwan, Taipei, Taiwan, Republic of China. pp. 698-714.
• Taylor, R.S.L., Manandhar, N.P., Hudson, J.B. & Towers, G.H.N., 1996. Antiviral activities of Nepalese medicinal plants. Journal of Ethnopharmacology 52(3): 157-163.

Selection of species

• Hypericum gramineum
• Hypericum japonicum
• Hypericum monogynum
• Hypericum papuanum
• Hypericum uralum

Authors

• M. Brink