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Holarrhena pubescens Wall. ex G.Don

Protologue
Gen. hist. 4: 78 (1837).
Family
Apocynaceae
Chromosome number
2n = 22
Synonyms
Holarrhena antidysenterica (L.) Wall. ex A.DC. (1844) p.p., Holarrhena febrifuga Klotzsch (1862).
Vernacular names
Conessi, fever pod, holarrhena, kurchi bark, tellichery bark (En). Ecorce de conessie (Fr). Quina, erva do Malabar (Po). Mti mweupe, mkwale (Sw).
Origin and geographic distribution
Holarrhena pubescens is indigenous in the eastern part of tropical Africa and in tropical Asia (from India to Vietnam). In Africa, it occurs from eastern DR Congo and Kenya south to northern South Africa. It is planted in botanical gardens in Africa, India and the Indian Ocean Islands.
Uses
The stem bark and root bark of Holarrhena pubescens are used throughout its distribution area in the treatment of amoebic dysentery. The stem bark is listed in the Pharmacopoeia of India. Although slow in action compared with emetine, it is less toxic and can be administered orally. The bark has astringent, anthelminthic, stomachic, febrifugal and tonic properties. In Kenya the pounded leaves in water are taken to cure stomach-ache. An infusion of the roots is furthermore taken to stimulate milk production. In southern Africa an infusion of the powdered root is taken to treat constipation, asthma, abdominal pains and infertility. It is also taken as an abortifacient and aphrodisiac. The root boiled in milk is applied against snakebites and is used in the treatment of venereal diseases. A hot decoction of the stem bark is used as a gargle to treat toothache. Juice from the fruit is taken to treat cough. In India the bark and leaves are externally applied to cure scabies, boils, ulcers and haemorrhoids. A powder prepared from the roots and leaves is administered to stop haemorrhages after childbirth and nose bleeding. The oil from the seeds is considered to possess similar properties as the bark.
The wood is popular for turning and carving. It is used to make small articles such as combs, picture frames, carved boxes, toys, spoons, knives, walking sticks and beads, and sometimes for furniture and ploughs. It has been used to make paper. Holarrhena pubescens may prove useful for the reforestation of deforested land in comparatively dry regions, also because it is not readily browsed even by goats. A dye similar to henna is extracted from the leaves, while the wood ash is used as a mordant. The floss from the seeds is used for stuffing pillows. Holarrhena pubescens is also cultivated in India as an ornamental for its attractive flowers.
Production and international trade
Although Holarrhena pubescens has been known as a medicinal plant since historic times, data on its production and international trade are scarce. It is mainly grown or collected for domestic or local use, and the root bark is sold in local markets for medicinal purposes, e.g. in Zimbabwe and South Africa. There is some trade through internet, mainly from India.
Properties
The stem bark, root bark and seeds of Holarrhena pubescens yield more than 40 alkaloids. The highest concentration is found in the stem bark and root bark, up to 4.3%, but only 0.4% has been reported for flowering plants. The leaves contain 1–1.5% and the seeds 0.6–1.8%. According to the Pharmacopoeia of India, the bark should contain about 2% alkaloids. Most of the alkaloids of the stem bark and root bark are steroid alkaloids derived from conanine or the closely related conamine, which also occur in other Holarrhena species. The main alkaloid of the stem bark and root bark is conessine; other compounds are norconessine (kurchine), conessimine, kurchamine, kurchessine, kurcholessine, conimine, conamine and holarrhenine. The leaves contain mainly steroid alkaloids derived from pregnane, such as holarrhimine, holaphyllamine, holamine and holaphylline, as well as the alkaloid triacanthine (an adenine derivative). Various amino-glycosteroids are also present in the leaves. These substances contain an amino-sugar and in some of them, e.g. holarosine and holacurtine, the steroidal part of the molecule is a cardenolide. The seeds contain conessine, norconessine, conamine and conarrhimine.
Conessine has sedative, central nervous system depressant, cardiac depressant, antipyretic and analgesic activities. It also has significant anti-amoebic activity, but it needs to be used with caution because it can produce neurological problems such as vertigo, tremors, insomnia, agitation or anxiety. Conessine also shows antibacterial and antifungal activities against a range of human pathogens in vitro. Several other steroidal alkaloids also show antibacterial and antifungal activities. The steroid alkaloids present in the stem bark and root bark have hypotensive activity and are simultaneously local anaesthetic and spasmolytic, but they are also cardiotoxic. Triacanthine also has hypotensive activity, but is also cardiotonic, antispasmodic and a respiratory analeptic. In addition, triacanthine stimulates the development of mature red blood cells and acts on experimental anaemia in rabbits. Many of the pregnane derivatives can be used as a starting material for the partial synthesis of pharmaceutical steroids, such as adrenocortical hormones (corticosteroids) and sex hormones (e.g. oestrogens, progestrogens and androgens). Holamine, holaphyllamine and holaphylline show significant anti-inflammatory properties. Aqueous extracts of the root bark, stem bark or leaves have relatively low toxicity. The alcoholic extract of the fruit showed anticancer activity against human epidermoid carcinoma of the nasopharynx in tissue culture. The aqueous extract of the fruits exhibited hypoglycaemic effects in rats.
Different extracts of Holarrhena pubescens seed or bark showed significant antibacterial and antifungal activities against a wide range of human pathogens, including several antibiotic-resistant strains. The bark extract also shows antiplasmodial activity. A stem bark decoction showed anti-ulcerogenic effects in different models of gastroduodenal ulcers in rats. It also showed antimicrobial activity against enterohaemorrhagic Escherichia coli strains. Conessine was found to possess a wide range of disruptive activities against 4 insect species, and showed potential as a larval growth inhibitor, sterilant and antifeedant in laboratory tests.
Callus cultures of Holarrhena pubescens yielded a maximum of 300 mg alkaloids per 100 g dry cells in 40 days; a suspension culture reached 130 mg per 100 g dry cells in 8 days. The alkaloid production can be boosted by adding cholesterol as a precursor. About 90% of the total alkaloids produced in the cell cultures were conessine. In later experiments, also aminopregnane and other conanine type alkaloids were obtained.
The wood of Holarrhena pubescens is moderately soft and white, with straight grain and fine and even texture; there is no distinction between sapwood and heartwood. The wood turns yellowish or pinkish with age. The timber seasons well and develops few end splits and surface cracks with little tendency to warping, but is liable to damage by insects. Air drying as log reduces surface cracking, whereas kiln drying improves the colour of the timber and reduces liability to insect attack. The wood is easy to saw and machine and fairly durable under cover.
Adulterations and substitutes
In India the seeds or bark of Holarrhena pubescens are sometimes adulterated with those of Wrightia tinctoria R.Br., which do not have the same medicinal properties, although both show antibacterial activity. The seeds of Holarrhena pubescens are intensely bitter, while those of Wrightia tinctoria are tasteless. The stem bark of Funtumia africana (Benth.) Stapf also contains steroid alkaloids of the conanine-type, with similar pharmacological activities as extracts of the stem bark of Holarrhena pubescens.
Description
Shrub or small tree up to 9(–18) m tall, with abundant white latex in all parts; bole up to 25 cm in diameter; bark in young trees nearly smooth, later corky, longitudinally fissured, pale to dark grey; branchlets shortly hairy. Leaves opposite, simple and entire; stipules obscure; petiole up to 1 cm long, shortly hairy, glandular at base; blade almost circular to ovate or elliptical, 1.5–20 cm Χ 1.5–11 cm, base cuneate to rounded, apex acuminate to acute, shortly hairy to glabrous, pinnately veined with 5–25 pairs of lateral veins. Inflorescence a seemingly axillary cyme, rather lax, many-flowered; peduncle 1–1.5 cm long, shortly hairy; bracts linear, 1–2 mm long, shortly hairy. Flowers bisexual, regular, 5-merous, fragrant; pedicel 0.5–1 mm long; sepals elliptical to linear, 2–12 mm long, free or fused at base, shortly hairy; corolla tube cylindrical, 9–19 mm Χ 0.5–2 mm, shortly hairy outside and inside from the throat to the insertion of the stamens, lobes elliptical, 10–24(–30) mm Χ 3–8 mm, spreading to recurved, shortly hairy to glabrous, white; stamens inserted 1.5–2.5 mm from the corolla base, included; ovary superior, ovoid, consisting of 2 carpels connate at extreme base, style cylindrical, c. 1 mm long, pistil head ovoid, stigma 2-lobed. Fruit composed of 2 long and slender follicles 20–38 cm Χ 2–9 mm, pendulous, dehiscent, pale grey to dark brown, many-seeded. Seeds narrowly oblong, 9–16 mm long, grooved, glabrous, with a dense tuft of 2.5–4.5 cm long hairs at apex. Seedling with epigeal germination; cotyledons 2–3 mm long.
Other botanical information
Holarrhena comprises 4 species, 2 of which occur in tropical Africa (one of these also in Asia) and 2 of which are restricted to tropical Asia. Holarrhena pubescens and Holarrhena floribunda (G.Don) T.Durand & Schinz differ in flower size and fruit size, the flowers of Holarrhena pubescens being larger and its fruits smaller. The distribution areas of the two species only overlap in eastern DR Congo. Holarrhena congolensis Stapf from western DR Congo and Cabinda (Angola) is considered a hybrid between Holarrhena pubescens, introduced from Mozambique, and Holarrhena floribunda.
Growth and development
Holarrhena pubescens sheds its leaves at the end of the dry season and new leaves appear at the beginning of the rainy season. The flowers appear shortly after the leaves; the flowering period is short. Fruits mature a few months after flowering, but do not dehisce until 3–4 months later. Holarrhena pubescens coppices well and can survive bush fires by producing sucker shoots from burned-down stumps. Juvenile plants are more susceptible to damage by fire than older ones. Though sensitive to frost, the plant recovers easily from damage. It can stand slight shade but develops best in full light and it is drought-hardy. Natural reproduction is abundant owing to regular and copious seeding from an early age, comparative immunity of the plant to damage by animals and its power of recovery from injury. Seeds, that are dispersed by wind germinate during the early rains, and seedlings attain 10–15 cm by the end of the first year. In subsequent years, growth is more rapid, the mean annual diameter increment being 7–8 mm. In India, early height increment of Holarrhena pubescens is low, only 10–15 cm/year under natural conditions.
Ecology
Holarrhena pubescens occurs in dry evergreen to dry deciduous forest, scrub woodland, savanna, or in rocky localities, often near watercourses, up to 1500 m altitude. It is a pioneer species that quickly invades open spaces.
Propagation and planting
Holarrhena pubescens can be propagated by seed, either by direct sowing or by raising seedlings in a nursery. Fresh seeds have a high percentage of germination, but in seeds more than one year old the viability is low. There are 32,000–35,000 seeds/kg. The seed usually germinates in 2–3 weeks. In India the species is successfully intercropped with field crops.
Tissue culture of Holarrhena pubescens through nodal and shoot-segment explants has been successful.
Management
As far as is known, Holarrhena pubescens is not cultivated on a large scale. In India it is used in reclaiming wasteland. Weeding, periodic thinning and loosening of soil are beneficial. Established plants are fast growing and require little or no management. For ornamental purposes shrubs are pruned to improve their appearance. To maintain vigorous growth, pruning should start as early as 12 months after planting and should be repeated at least once a year. The degree of pruning depends on the management objectives: severe pruning favours stem diameter growth and bark production; denser stands are needed for rapid leaf production.
Harvesting
Stem bark, root bark, leaves and seeds are collected for medicinal purposes from the wild. The root bark and stem bark are also harvested from cultivated trees. The stem bark is mainly collected from 8–12 year-old trees. The alkaloid content varies with the age of the tree and the season.
Handling after harvest
The bark needs to be freed from attached wood, and is cut into small pieces of 1–6 cm long and 1–7 mm thick. The dried stem bark and root bark should be stored in dry, well-closed containers.
Genetic resources
Holarrhena pubescens is widely distributed in tropical Africa and continental Asia and is found in open anthropogenic habitats. Therefore the risk of genetic erosion seems limited.
Prospects
Holarrhena pubescens is an important medicinal plant in the tropics. Its steroid alkaloids may be useful for synthesis of pharmaceutical products. Conessine is a possibly valuable alternative for well-known drugs like emetine in the treatment of amoebic dysentery. Outside India there is no commercial production, and this deserves more attention, given the easy propagation and management of Holarrhena pubescens. Development of sustainable collection methods is recommended and the possibilities for using leaves or seed instead of stem and root bark deserve investigation.
Major references
• de Kruif, A.P.M., 1981. A revision of Holarrhena R.Br. (Apocynaceae). Mededelingen Landbouwhogeschool Wageningen 81–2, Wageningen, Netherlands. pp. 1–36.
• Jolly, C.I. & Mechery, N.R., 1996. Comparative pharmacognostical, physicochemical and antibacterial studies on seeds of Holarrhena antidysenterica Wall. and Wrightia tinctoria R.Br. Indian Journal of Pharmaceutical Sciences 58(2): 51–54.
• Kaul, M.K. & Atal, C.K., 1983. Studies on Holarrhena antidysenterica Wall. 1. Botany, medico-ethnobotany and distribution. Journal of Ethnopharmacology 8(3): 349–356.
• Kumar, R., Sharma, K. & Agrawal, V., 2005. In vitro clonal propagation of Holarrhena antidysenterica (L.) Wall. through nodal explants from mature trees. In Vitro Cellular and Developmental Biology, Plant 41(2): 137–144.
• Neuwinger, H.D., 2000. African traditional medicine: a dictionary of plant use and applications. Medpharm Scientific, Stuttgart, Germany. 589 pp.
• Raha, S. & Roy, S.C., 2001. In vitro plant regeneration in Holarrhena antidysenterica Wall., through high-frequency axillary shoot proliferation. In Vitro Cellular and Developmental Biology, Plant 37(2): 232–236.
• Williamson, J., 1955. Useful plants of Nyasaland. The Government Printer, Zomba, Nyasaland. 168 pp.
• Wongsatit Chuakul, Noppamas Soonthornchareonnon & Promjit Saralamp, 1999. Holarrhena R.Br. In: de Padua, L.S., Bunyapraphatsara, N. & Lemmens, R.H.M.J. (Editors). Plant Resources of South-East Asia No 12(1). Medicinal and poisonous plants 1. Backhuys Publishers, Leiden, Netherlands. pp. 296–298.
Other references
• Aqil, F., Khan, M.S., Owais, M. & Ahmad, I., 2005. Effect of certain bioactive plant extracts on clinical isolates of beta-lactamase producing methicillin resistant Staphylococcus aureus. Journal of Basic Microbiology 45(2): 106–114.
• Begum, S., Usmani, S.B., Siddiqui, B.S. & Siddiqui, S., 1994. Alkaloids from the bark of Holarrhena pubescens. Phytochemistry 29(10): 1537–1541.
• Bhutani, K.K., Vaid, R.M., Ali, M., Kapoor, R., Soodan, S.R. & Kumar, D., 1990. Steroidal alkaloids from Holarrhena antidysenterica. Phytochemistry 29(3): 969–972.
• Bisset, N.G., 1981. Phytochemistry of Holarrhena R.Br. Mededelingen Landbouwhogeschool Wageningen 81–2, Wageningen, Netherlands. p. 37.
• Chakraborty, A. & Brantner, A.H., 1999. Antibacterial steroid alkaloids from the stem bark of Holarrhena pubescens. Journal of Ethnopharmacology 68(1–3): 339–344.
• Coates Palgrave, K., 1983. Trees of southern Africa. 2nd Edition. Struik Publishers, Cape Town, South Africa. 959 pp.
• Endress, M.E., Hesse, M., Nilsson, S., Guggisberg, A. & Zhu, J.-P., 1990. The systematic position of the Holarrheninae (Apocynaceae). Plant Systematics and Evolution 171: 157–185.
• Gelfand, M., Mavi, S., Drummond, R.B. & Ndemera, B., 1985. The traditional medical practitioner in Zimbabwe: his principles of practice and pharmacopoeia. Mambo Press, Gweru, Zimbabwe. 411 pp.
• Jayaswal, S.B., 1977. Wrightia tomentosa, a substitute for Holarrhena antidysenterica. Indian Journal of Pharmacy 39(2): 37–39.
• Kavitha, D., Shilpa, P.N. & Devaraj, S.N., 2003. Antibacterial effect of conessine, an alkaloid from Holarrhena antidysenterica, against enteropathogenic Escherichia coli. Biomedicine 23(1–2): 66–71.
• Khan, P.S.H., 1987. Comparative seed structure of medicinally important Holarrhena antidysenterica (Roth.) A.DC. and its adulterant, Wrightia tinctoria R.Br. (Apocynaceae). International Journal of Crude Drug Research 25(2): 81–86.
• Kokwaro, J.O., 1993. Medicinal plants of East Africa. 2nd Edition. Kenya Literature Bureau, Nairobi, Kenya. 401 pp.
• Omino, E.A. & Kokwaro, J.O., 1993. Ethnobotany of Apocynaceae species in Kenya. Journal of Ethnopharmacology 40: 167–180.
• Omino, E.A., 1996. A contribution to the leaf anatomy and taxonomy of Apocynaceae in Africa. Wageningen Agricultural University Papers 96–1. Wageningen Agricultural University, Wageningen, Netherlands. 178 pp.
• Panda, A.K., Bisaria, V.S., Mishra, S. & Bhojwani, S.S., 1991. Cell Structure of Holarrhena antidysenterica: growth and alkaloid production. Phytochemistry 30(3): 833–836.
• Panda, A.K., Mishra, S. & Bisaria, V.S., 1992. Alkaloid production by plant cell suspension culture of Holarrhena antidysenterica: I. Effect of major nutrients. Biotechnology and Bioengineering 39(10): 1043–1051.
• Raha, S. & Roy, S.C., 2003. Efficient plant regeneration in Holarrhena antidysenterica Wall., from shoot segment-derived callus. In Vitro Cellular and Developmental Biology, Plant 39(2): 151–155.
• Raman, M.S, Sultana, N. & Anwar, M.N., 2004. In vitro antimicrobial activity of holarrifine-24ol isolated from the stem bark of Holarrhena antidysenterica. International Journal of Agriculture and Biology 6(4): 698–700.
• Rani, P. & Khullar, N., 2004. Antimicrobial evaluation of some medicinal plants for their anti-enteric potential against multi-drug resistant Salmonella typhi. Phytotherapy Research 18(8): 670–673.
• Simonsen, H.T., Nordskjold, J.B., Smitt, U.W., Nyman, U., Pushpangadan, P., Prabhakar, J. & Varughese, G., 2001. In vitro screening of Indian medicinal plants for antiplasmodial activity. Journal of Ethnopharmacology 74(2): 195–204.
Sources of illustration
• Wongsatit Chuakul, Noppamas Soonthornchareonnon & Promjit Saralamp, 1999. Holarrhena R.Br. In: de Padua, L.S., Bunyapraphatsara, N. & Lemmens, R.H.M.J. (Editors). Plant Resources of South-East Asia No 12(1). Medicinal and poisonous plants 1. Backhuys Publishers, Leiden, Netherlands. pp. 296–298.
Author(s)
• A. Maroyi
Department of Biological Sciences, Bindura University of Science Education, P.O. Bag 1020, Bindura, Zimbabwe


Editors
• G.H. Schmelzer
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
• A. Gurib-Fakim
Faculty of Science, University of Mauritius, Rιduit, Mauritius
Associate editors
• C.H. Bosch
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
• M.S.J. Simmonds
Royal Botanic Gardens, Kew, Richmond, Surrey TW9 3AB, United Kingdom
• R. Arroo
Leicester School of Pharmacy, Natural Products Research, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom
• A. de Ruijter
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
General editors
• R.H.M.J. Lemmens
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
• L.P.A. Oyen
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
Photo editor
• A. de Ruijter
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands

Correct citation of this article:
Maroyi, A., 2006. Holarrhena pubescens Wall. ex G.Don. In: Schmelzer, G.H. & Gurib-Fakim, A. (Editors). Prota 11(1): Medicinal plants/Plantes mιdicinales 1. [CD-Rom]. PROTA, Wageningen, Netherlands.
Distribution Map wild


1, tree habit; 2, flowering twig; 3, opened flower; 4, fruit; 5, seed.
Source: PROSEA



flowering plant in pot