1011

12(2): Medicinal and poisonous plants 2

Clerodendrum L.

Sp. pl. 2: 637 (1753); Gen. pl. ed. 5: 285 (1754).

VERBENACEAE

x = 12, 23; Clerodendrum indicum: 2n = 40, 48, 52, Clerodendrum inerme: 2n = 46, 48, Clerodendrum philippinum: 2n = 46, 52, Clerodendrum phlomidis: 2n = 48, 52, Clerodendrum serratum 2n = 48

Major species Clerodendrum inerme (L.) Gaertner, Clerodendrum serratum (L.) Moon, Clerodendrum viscosum Vent.

Clerodendrum (excluding Kalaharia and Rotheca) comprises some 400 species and is most abundant in tropical and subtropical Asia and Africa, poorly represented in the Americas except where cultivated and naturalized. A few species extend into temperate zones.

A wide range of Clerodendrum species is used throughout South-East Asia. The use of individual species is often very restricted as a result of their often very local distribution or because species may well be mutually exchangeable for a given use. Despite their medicinal use several species are much more connected with magic than medicine. A considerable number of species are considered to be febrifuge. Some have both internal and external uses, others only external, such as washes and poultices for sores, boils and skin diseases; they have perhaps depurative, resolvent, and vulnerary properties, or are used as an anodyne to relieve rheumatism or pain. Many of the uses for Indonesia date back to Rhumphius. Great confusion often exists about the actual identity of a given plant and the taxonomical status of that species. In Indonesia, the roots and wood of Clerodendrum phyllomega Steudel (synonym Clerodendrum macrophyllum Blume) are reputed to be highly poisonous. In Malaysia, a decoction of the roots of Clerodendrum umbratile King & Gamble is used for fever in children. Boiled and dried the roots are used to make a powder for rubbing on the face in fever. An extract of the roots of Clerodendrum deflexum Wallich is used for fever and stomach complaints. The leaves of Clerodendrum disparifolium Blume are used to relieve constipation. The roots, pounded and rubbed on the body or the paste placed in a hollow tooth are considered anodyne. In the Philippines, an infusion of the leaves of Clerodendrum bethuneanum Lowe is used as a tonic during pregnancy. The leaves of Clerodendrum cumingianum Schauer are used for stomach-ache. A decoction of the leaves of Clerodendrum brachyanthum Schauer is given as a tonic for stomach problems, and in large doses is considered abortive. The leaves of Clerodendrum macrostegium Schauer in decoction or as a poultice are applied externally to carbuncles. The leaves of Clerodendrum navesianum Vidal (synonym Clerodendrum quadriloculare (Blanco) Merr.) are externally applied for healing wounds and ulcers. They are also used in tonic baths. In India, Clerodendrum phlomidis L.f. (synonym Clerodendrum phlomoides auct.) is used for post-natal complaints in women, and also for dyspepsia, stomach-ache, colic and dysentery. The juice of the leaves and a tonic from the roots are used as an alterative. Externally the leaves are rubbed over the body in cases of oedema and used in poultice on swellings and ulcers. Various parts of Clerodendrum infortunatum L. are used both internally and/or externally in traditional Indian medicine to treat coughs, skin diseases and tumours, and as a vermifuge and expectorant.
Many Clerodendrum are widely cultivated as ornamentals. Some of these have medicinal uses, but their ornamental value far outweighs their medicinal importance. Clerodendrum minahassae Teysm & Binnend. is used in the Philippines as an external remedy for chest and stomach pains. Furthermore, the boiled leaves are used as a poultice for carbuncles. The leaves of Clerodendrum intermedium Cham. are used in the Philippines as a cataplasm to relieve the pains following childbirth, and for rheumatism and neuralgia. They are also used as a plaster to relieve colic in children. Furthermore the roots are considered purgative. In the Moluccas the roots of Clerodendrum rumphianum de Vriese & Teysm. (synonym Clerodendrum squamatum Vahl var. rumphianum (de Vriese & Teysm.) Bakh.) are used to treat dysentery, and a cold infusion of the leaves in vinegar is considered a remedy for gonorrhoea. The leaves enter in prescriptions for afflictions as diverse as oedema, haematuria and rheumatism. Furthermore, leaves are an ingredient of a herbal bath for newborns. In Malaysia, an infusion of Clerodendrum paniculatum L. is drunk as a purgative, and externally a poultice is applied on a distended stomach. In Indonesia, the leaves are used as a poultice for burns, wounds and ulcers. The roots enter in prescriptions for afflictions as diverse as pulmonary problems, oedema, haematuria and rheumatism. In Thailand, various parts are used for their anti-inflammatory properties. The root is used as an antimalarial, carminative and against tuberculosis, and the leaves are used for chest pain in general. In Indo-China, a decoction of the roots of Clerodendrum japonicum (Thunb.) Sweet (synonyms Clerodendrum squamatum auct. non Vahl, Volkameria japonica Thunb., Clerodendrum coccineum Lam) is prescribed in chest complaints. In China, floral bracts are chewed for haematuria and applied as a poultice to painful joints. The very similar Clerodendrum kaempferi (Jacq.) Siebold ex Steudel (synonym Clerodendrum squamatum Vahl, Volkameria kaempferi Jacq.) is also used in folk medicine in Vietnam and Indonesia.
Magical properties ascribed to Clerodendrum in particular refer to Clerodendrum deflexum, Clerodendrum disparifolium, Clerodendrum serratum, Clerodendrum umbratile and Clerodendrum villosum Blume in Malaysia and Clerodendrum viscosum and Clerodendrum rumphianum in Indonesia.

Clerodendrum is only used on a local scale.

Phytochemical investigations of Clerodendrum in general revealed the presence of iridoids (or their glycosides), steroids and flavonoids as important groups of components. For example, of a total of 12 Clerodendrum spp. examined, 8 species contained iridoids. They contained iridoid glycosides such as melittoside, aucubin, 8-O-acetylharpagide, harpagide, ajugoside, 8-O-acetylmioporoside, reptoside, euphroside and plantarenaloside. Leaves of Clerodendrum inerme contained melittoside at 0.1%. Leaves of Clerodendrum tomentosum (Vent.) R.Br. and Clerodendrum indicum contained harpagide at 0.01% and 0.02%, repectively. No iridoid glycosides were found in the leaves of Clerodendrum buchananii (Roxb.) Walp., Clerodendrum bungei Steudel or Clerodendrum paniculatum. The leaves of Clerodendrum serratum, which belongs to the section Cyclonema, contain iridoid glycosides with a C-4 formyl group, plantarenaloside at 0.05% and euphroside at 0.03%. Such compounds are unique in Verbenaceae. Further information is available for Clerodendrum inerme. The presence of a series of iridoid biglycosides is reported: inerminosides A, A1, B, C and D, of which most of them are derivatives of mussaenosidic acid.
Samples from the aerial parts of Clerodendrum fragrans, Clerodendrum inerme, Clerodendrum infortunatum (including seeds) and Clerodendrum indicum, and the seeds of Clerodendrum infortunatum contained 24'BETA'-ethylsterols possessing a 25'DELTA'-bond, clerosterol and 22-dehydroclerosterol as the dominant components. The other 24-ethylsterols lacking a 25'DELTA'-bond, 24-ethyl-22-dehydrocholestanol, 24-ethylcholesterol and 24-ethyl-22-dehydrocholesterol, which were present as minor components, were shown to be mixtures of the 24'ALFA'- and 24'BETA'-epimers, with the 24'ALFA'-epimers predominanting in all cases. Four minor 24-methylsterols, 24-methylcholestanol, 24-methylcholesterol, 24-methyl-22-dehydrocholesterol, and 24-methyllathosterol, were also shown to be C-24 epimeric mixtures, whereas two others, 24-methyl-22,25-bis- dehydrocholesterol and 24-methyl-22-dehydrolathosterol, were found to be present only as the 24'BETA'-epimers.
Most flavonoids reported for Clerodendrum are commonly found in higher plants (apigenin, luteolin, nepetin). However, some Clerodendrum flavonoids are unique. Examples of these include nepetin-7-O-'BETA'-D-glucuronide from Clerodendrum serratum, and the methyl ester of acacetin-7-O-glucuronide from Clerodendrum infortunatum.
Extracts and isolated compounds from selected Clerodendrum species showed antimicrobial activity in several test systems. For instance, the antimicrobial activity of petroleum ether- and fractionated methanol extracts of the leaves of Clerodendrum phlomidis was evaluated in vitro. At 0.1%, the ethyl acetate fraction of a methanol extract produced maximal growth inhibition of Penicillium italicum followed by the hexane fraction of the methanol extract against Trichoderma sp. Subsequent column chromatography of both the fractions resulted in the isolation of 5,7-dihydroxy-6,4'-dimethoxyflavone and pectolinarigenin. From the ethyl acetate fraction furthermore 2 glycosides were isolated, 5,7-dihydroxy-6,4'-dimethoxyflavone-7-0-'BETA'-D-glucuronic acid methyl ester and 5,7-dihydroxy-6,4'-dimethoxyflavone-7-0-'BETA'-D-glucoside. The antifungal activity of the fractions mentioned is thought to be attributable in part to the presence of the flavones, either in their aglycone form or in glycosidic combinations. None of the crude extracts and the pure compounds tested produced any significant inhibition of Xanthomonas campestris, Pseudomonas aeruginosa or Alternaria sp. In addition, cabruvin and quercetin, flavonoids isolated from roots of Clerodendrum infortunatum, showed antifungal activity. Cabruvin at 200, 500 and 1000 mg/ml exhibited good inhibition of spore germination of Alternaria carthami and Helminthosporium oryzae (Cochliobolus miyabeanus). Quercetin at the same concentrations exhibited good inhibition of spore germination of A. alternata and Fusarium lini. The essential oil of Clerodendrum inerme exhibited antifungal activity against several fungi e.g. Aspergillus, Cladosporum and Cunninghamella.
Antiviral activity is reported for both human and plant viruses. An extract of Clerodendrum inerme significantly inhibited the secretion of HbsAg (hepatitis B surface antigen) into the culture medium at non-cytotoxic concentrations by using a hepatitis B expressing hepato-blastoma cell line. However, it had no effect on intracellular extrachromosomal hepatitis B virus DNA levels. Furthermore, in the field of phytopathology, leaf extracts of Clerodendrum inerme sprayed on tobacco early in the season at a dilution of 1:1000 gave good protection against tobacco mosaic virus (TMV). Subsequent partial purification of the antiviral substance indicated that the active principle is a macromolecule (glycoprotein) containing 74% protein and 26% carbohydrate. Its activity was stable for up to 30 days, and it can withstand a temperature of 90EC at a dilution of 1:500. In addition, infection of tobacco plants by (cowpea) chlorotic mottle bromovirus under greenhouse conditions was inhibited (100%) when aqueous leaf extracts of Clerodendrum inerme were mixed with the virus inoculum. Infection of Vigna radiata (L.) Wilczek and V. mungo (L.) Hepper by mung bean yellow mosaic virus under natural conditions was suppressed by aqueous partially clarified leaf extracts of Clerodendrum fragrans. Administered as a foliar spray at 4%, every 3—4 days from the seedling stage, the extract reduced infection by about 60%. Flowering and consequent fruiting was advanced by the treatment which also increased nodulation. The yield in plants treated with Clerodendrum fragrans extract was considerably enhanced.
Other pharmacological activities of Clerodendrum extracts include a general screening on a range of central nervous system related enzyme- and receptor systems in vitro, in which Clerodendrum mandarinorum Diels and Clerodendrum bungei root bark hydroethanolic extracts displayed affinity for 'ALFA'1-, 'ALFA'2-adrenoceptors, 5HT-1, 5HT-1A, 5HT-2, opiate, adenosine-1, dopamine-1, GABA_A and GABA_B receptors via radioligand studies. A methanolic extract of the leaves of Clerodendrum phlomidis was also tested for its antidiarrhoeal potential against several experimental models of diarrhoea in Wistar albino rats. It showed significant inhibitory activity against castor oil-induced diarrhoea and PGE2-induced enteropooling in rats. The extract also showed a significant reduction in gastro-intestinal motility in charcoal meal test in rats. The results obtained establish at least in part the efficacy of the extract as an anti-diarrhoeal agent thus substantiating the folklore claim. In addition, a methanolic extract from the bark of Clerodendrum indicum was found to be a potent inhibitor of lipid peroxidation with an IC₅₀ value of 0.93 #ug/ml using bovine brain phospholipid liposomes as model membranes.
Saponins isolated from Clerodendrum serratum showed spermicidal activity in human semen in both the Spot and IPPF (International Planned Parenthood Federation) tests. Spermicidal activity was associated with the 'BETA'-amyrin C-28 carboxylic acid type of sapogenins linked to a particular sequence of sugar moieties. The aqueous extract of Clerodendrum serratum root bark showed antihistaminic activity when tested on rat ileum and trachea.
Furthermore, the petroleum ether extract of Clerodendrum inerme leaves afforded a compound that matched the clerodane compound (—)-3-epicaryoptin in physical and spectral characteristics. The test compound inhibited the development of larvae of the fly Musca domestica and the mosquito Culex quinquefasciatus. First- and third-instar fly larvae reared on 3-epicaryoptin-treated diet pupariated later and earlier than their respective controls and adult emergence from puparia was inhibited. Apart from larval mortality, exposure of fourth-instar mosquito larvae to 3-epicaryoptin resulted in death at larval-pupal moult and pupal-adult eclosion, indicating inhibition of the moulting process. An equivalent petroleum ether extract of Clerodendrum inerme leaves at 0.5% also gave 93% seed protection against the pulse beetle Callosobrunchus chinensis, with few toxic effects. In addition, a methanol extract of Clerodendrum inerme showed 90% activity against the brown planthopper (Nilaparvata lugens) at a dose of 0.5 #ug/female, using a topical application method, and a crude leaf extract containing 2.5% Clerodendrum infortunatum completely inhibited adult emergence, whilst a 3% extract produced 100% mortality in fourth-instar Anopheles subpictus larvae under laboratory conditions.

Vines, shrubs or small trees, usually unarmed, glabrous or pubescent. Leaves opposite or whorled, simple, sometimes lobed, entire or dentate; petiolate or not; stipules absent. Inflorescence a terminal or axillary cyme, sometimes arranged in panicles or corymbs. Flowers zygomorphic, bisexual, usually large, showy, mostly white, blue, violet or red; calyx campanulate or tubular, truncate or 5-dentate to 5-partite, often accrescent; corolla salverform, tube cylindrical, straight or curved, limb 5-lobed, spreading or reflexed, stamens 4, long-exserted, didynamous, inserted in corolla tube; ovary imperfectly 4-locular, style exserted. Fruit a drupe, obovoid or globose, 4-lobed or 4-sulcate, usually separating in 4 pyrenes. Seed exalbuminous. Seedling with epigeal germination; cotyledons emergent, green, fleshy, hypocotyl elongated (Clerodendrum inerme); or with hypogeal germination; cotyledons not emergent, hypocotyl not elongated (Clerodendrum serratum, Clerodendrum villosum).

Clerodendrum can be found flowering and fruiting throughout the year. Pollination is mostly by butterflies, moths and bees. The fruits are eaten by birds, which disperse the seeds. In many species the calyx provides a contrasting colour. The pseudo-aril present in some species is actually a placental part of the pericarp that acts as an attractant to birds in the fruit dispersal process.

Cladistic analysis of molecular data from both chloroplast and nuclear genomes of Clerodendrum s.l. has demonstrated that the classification systems devised in the past do not adequately reflect the natural grouping within the genus. A thorough revision of Clerodendum is necessary and the same applies to Rotheca. Although some new combinations in Rotheca apply to medicinally used Combretum in South-East Asia, the Clerodendrum name is maintained as such here. All African and Asian species, except for coastal species, form genetically isolated groups. Four species common in cultivation are often confused: C. intermedium, Clerodendrum japonicum, Clerodendrum paniculatum and Clerodendrum speciosissimum Van Geert ex Morren. Clerodendrum japonicum has leaves similar to Clerodendrum intermedium but the flowers are twice as big. Clerodendrum intermedium is also similar to Clerodendrum paniculatum L., but the latter has bigger inflorescences and lobulate leaves. The glabrate leaves of Clerodendrum intermedium may be distinguished from the pubescent leaves of Clerodendrum speciosissimum.

Clerodendrum can be found in many habitats ranging from mangrove, salt marshes and beach forest through grassland thickets up to cloud forest, on soils ranging from saline soils with up to 6.4% salinity, sand dunes to limestone formations. It can be grown in full sun or shade in any well-drained, friable soil. However, Clerodendrum is most abundant at lower elevations.

Clerodendrum is propagated by seed, softwood and semi-ripe cuttings, root cuttings or simply by rooted suckers.

The climbing species of Clerodendrum do better when planted in a bed of soil rather than in pots or tubs. They should be trained along pillars and rafters to show off their full beauty. An annual top dressing of fresh compost is advisable. Pruning in general consists of removing the dead twigs on old bushes.

Leaves of Clerodendrum indicum are often attacked by the fungus Cercoseptoria clerodendri.

The various parts of Clerodendrum are in general simply collected whenever the need arises.

Roots of Clerodendrum are washed and dried either whole or cut in thin slices for future use. Likewise leaves can be dried for future use.

All Clerodendrum species treated here have a large area of distribution, either naturally or as a result of cultivation, and do not seem to be at risk of genetic erosion. There are no known breeding programmes of Clerodendrum for medicinal purposes.

Quite substantial information on biological activities of Clerodendrum is available, especially in the field of antimicrobial, antiviral and insecticidal activities. Little information is found in the literature, however, on the plant constituents which might be involved in these actions. Therefore, research is needed to fill the gap in this respect. Only then will a full evaluation be possible of the future potential of the Clerodendrum species involved.

Akihisa, T., Matsubara, Y., Ghosh, P., Thakur, S., Tamura, T. & Matsumoto, T., 1989. Sterols of some Clerodendrum spp. Verbenaceae. Occurrence of the 24-alpha and 24-beta epimers of 24 ethylsterols lacking a delta-25-bond. Steroids 53(3—5): 625—638.
Jacke, G. & Rimpler, H., 1983. Distribution of iridoid glycosides in Clerodendrum species. Phytochemistry 22(8): 1729—1734.
Mehdi, H., Tan, G.T., Pezzuto, J.M., Fong, H.H.S., Farnsworth, N.R., El-Feraly, F.S., Al-Yahya, M.A., Mossa, J.S., Peeples, M.E., Kernan, M. R. & Rozhon, E.J., 1997. Cell culture assay system for the evaluation of natural product-mediated anti-hepatitis B virus activity. Phytomedicine 3(4): 369—377.
Rani, S., Ahamed, N., Rajaram, S., Saluja, R., Thenmozhi, S. & Murugesan, T., 1999. Anti-diarrhoeal evaluation of Clerodendrum phlomidis Linn. leaf extract in rats. Journal of Ethnopharmacology 68(1—3): 315—319.
Roy, R., Pandey, V.B., Singh, U.P. & Prithiviraj, B., 1996. Antifungal activity of the flavonoids from Clerodendron infortunatum roots. Fitoterapia 67(5): 473—474.
Steane, D.A., Scotland, R.W., Mabberley, D.J. & Olmstead, R.G., 1999. Molecular systematics of Clerodendrum (Lamiaceae): ITS sequences and total evidence. American Journal of Botany 86(1): 98—107.

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

Clerodendrum indicum
Clerodendrum inerme
Clerodendrum philippinum
Clerodendrum serratum
Clerodendrum viscosum

van Valkenburg, J.L.C.H. & Bunyapraphatsara, N., 2001. Clerodendrum L.. In: van Valkenburg, J.L.C.H. and Bunyapraphatsara, N. (Editors): Plant Resources of South-East Asia No 12(2): Medicinal and poisonous plants 2. PROSEA Foundation, Bogor, Indonesia. Database record: prota4u.org/prosea

The following species in this genus are important in this commodity group and are treated separatedly in this database:
Clerodendrum indicum
Clerodendrum inerme
Clerodendrum philippinum
Clerodendrum serratum
Clerodendrum viscosum