1104

12(2): Medicinal and poisonous plants 2

Goniothalamus Hook.f. & Thomson

Fl. ind. 1: 105 (1855).

ANNONACEAE

x = unknown; Goniothalamus macrophyllus: 2n = 16

Major species Goniothalamus amuyon (Blanco) Merr., Goniothalamus giganteus Hook.f. & Thomson, Goniothalamus macrophyllus (Blume) Hook.f. & Thomson, Goniothalamus tapis Miq., Goniothalamus velutinus Airy Shaw.

Indonesia: pisang-pisang (used for most Annonaceae). Malaysia: mempisang (used for most Annonaceae). Vietnam: gi[as]c d[ees].

Goniothalamus is an Old World genus comprising 50—115 species; it is found from India eastward to the Philippines, throughout South-East Asia to New Guinea and Australia (Queensland).

In traditional Malay medicine, Goniothalamus is used in connection with childbirth (e.g. Goniothalamus macrophyllus, Goniothalamus tapis, Goniothalamus fulvus Hook.f. & Thoms. and Goniothalamus scortechinii King). Uses vary from an ingredient of an abortifacient in early pregnancy to a post-partum medicine. The leaves of several species have also been recommended as a hot poultice for swellings. Leaves of some fragrant species such as Goniothalamus malayanus Hook.f. & Thomson, Goniothalamus macrophyllus and Goniothalamus scortechinii when burned are effective as mosquito repellent. In Sarawak, a number of closely resembling species known in Malay as lim panas, hujan panas or in Iban as selokai (Goniothalamus longistipites Mat Salleh ined., Goniothalamus sinclairianus Mat Salleh ined., Goniothalamus tapisoides Mat Salleh ined., Goniothalamus velutinus) or selokai ladah (G. moniliformis Mat Salleh ined., Goniothalamus uvariodes King) are used more or less indiscriminately. The bark is smoked to scare off bees while collecting honey, but also to scare away evil spirits. The leaf stalks are used as a medicine for stomach-ache. The Kelabit in Sarawak drink a decoction of the roots of Goniothalamus tapis and Goniothalamus dolichocarpus Merr. to ease stomach-ache. The bark of several species is used for rope of varying quality and durability (e.g. Goniothalamus punctilatus Boerl. & Koord., Goniothalamus sumatranus Miq.) The species with a trunk of reasonable size are locally used for timber, e.g. Goniothalamus malayanus.

Goniothalamus is only used on a local scale. Wood of Goniothalamus velutinus is traded in local markets in Sabah and Sarawak at US$ 2 a stick. Fragrant flowers of Goniothalamus tapis are on sale in local markets like those of Cananga odorata (Lamk) Hook.f. & Thomson.

Phytochemical studies of Goniothalamus have led to the isolation and characterization of a large number of styryl lactones and acetogenins, which were found to possess significant cytotoxic activities against several human tumour cell lines.
For instance, a methanolic extract from the stem bark of Goniothalamus macranii Craib, from Thailand and Peninsular Malaysia, revealed strong toxicity in the brine shrimp lethality test with LD₅₀ values of 3.1 µg/ml and also showed cytotoxity against the human tumour cell lines A-549 (lung carcinoma), HT-29 (colon adenocarcinoma), MCF7 (breast carcinoma), RPMI (melanoma) and U251 (brain carcinoma) with ED₅₀ values of about 1 µg/ml. Activity-directed fractionation resulted in the isolation of the following cytotoxic compounds: marcanine A, B, C, D and dielsiquinone, which are all azo-anthraquinones, together with 5-hydroxy-3-amino-2-aceto-1,4-naphthoquinone. They exhibited cytotoxic activities against the human tumour cell lines A-549, HT-29, MCF7, RPMI and U251 with the ED₅₀ values in the range of 0.04—3.03 µg/ml.
Furthermore, activity-guided fractionation using the brine shrimp lethality test also identified 2 bioactive acetogenins in the bark of Goniothalamus giganteus: goniotriocin and a mixture of (2,4-cis and -trans)-xylomaticinones. The two compounds showed significant and selective cytotoxicity towards 6 human solid tumour cell lines in a seven-day MTT test panel. Both compounds exhibited potent and selective cytotoxicities against MCF-7 (breast adenocarcinoma) and HT-29 (colon adenocarcinoma) cell lines with 10—10 000 times the potency of adriamycin as reference. In addition, goniotriocin was quite active in the yellow fever mosquito (Aedes aegypti) larvae microtitre assay, with an ED₅₀ value of 3.5 µg/ml. Mono-tetrahydrofuran acetogenins such as 4-deoxyannomontacin, a mixture of (2,4-cis and -trans)-annomontacinone isolated from the bark of Goniothalamus giganteus showed selective and potent cytotoxicity to certain human tumour cell lines and furthermore were comparable to the activity of rotenone against yellow fever mosquito larvae. Bis-tetrahydrofuran acetogenins (e.g. 4-deoxygigantecin, a mixture of (2,4-cis and -trans)-gigantecinone) were more potent than rotenone in pesticidal activity, and the compound showed selective and potent cytotoxicity against PC-3 human prostrate adenocarcinoma cell line with an ED₅₀ value of 1.08 10^-3 µg/ml. The acetogenins pyranicin, pyragonicin and goniotrionin, isolated from the stem bark of Goniothalamus giganteus show an unusual hydroxylated-allylic moiety. In addition to goniotrionin, also pyranicin and pyragonicin are selectively cytotoxic against the pancreatic cell line (PACA-2) in a panel of six human solid tumour cell lines, pyranicin showing 10 times the potency of the adriamycin control. Goniotrionin showed more potent selectivity against the breast cell line (MCF-7).
The styryl lactone goniodiol isolated from the stem bark of Goniothalamus giganteus showed significant and selective toxicity against human lung tumour cells (A-549). Furthermore, 2 other cytotoxic acetogenins were isolated from the ethanol extract of the bark: gigantetronenin and gigantrionenin. They exhibited selective and potent cytotoxicity against A-549, MCF-7 and HT-29 human tumour cell lines, with ED₅₀ values of 2.92 10^-3—8.06 µg/ml.
The styrylpyrone, goniodiol-7-monoacetate, isolated from Goniothalamus amuyon, showed potent cytotoxicities against KB, P-388, RPMI and TE671 tumour cell lines, with ED₅₀ values of less than 0.1 µg/ml; it lacked cytotoxicity against A-549 and HCT-8 tumour cell lines when tested at 4.0 µg/ml. Finally, goniodiol-8-monoacetate isolated from the methanol extract of the leaves showed potent cytotoxicities against KB, P-388, A-549, HT-29 and Hl-60 tumour cell lines, with an ED₅₀ value of 4.85, 1.68, 4,79, 3,99 and 1.85 µg/ml, respectively.
Extracts of Goniothalamus dolichocarpus and Goniothalamus tapis showed strong antibacterial activity against Bacillus subtilis, Escherichia coli, Micrococcus luteus, Pseudomonas aeruginosa, Staphyllococcus aureus and Staphyllococcus faecalis. Extracts of various parts of Goniothalamus grandiflorus (Warb.) Boerl., from New Guinea, show antibacterial activity against Escherichia coli and Staphyllococcus aureus.
The styrylpyrone derivative goniothalamin has been isolated from roots, wood, bark and fruits of Goniothalamus tapis, Goniothalamus scortechinii, Goniothalamus malayanus, Goniothalamus macrophyllus, Goniothalamus fulvus Hook.f. & Thomson and Goniothalamus andersonii J. Sinclair. The antifertility effect of goniothalamin, isolated from Goniothalamus tapis, was studied in mice during the early stage of pregnancy. Treatment with goniothalamin, intraperitoneally at the dose of 138.9 mg/kg body weight from day 1 to day 7 of gestation, prevented the normal maintenance of pregnancy. Serum level of progesterone in goniothalamin-treated mice was found to be significantly (p < 0.01) lower than the control group while the luteinising hormone levels were significantly (p < 0.001) higher on days 5 and 6. The uterus wet weight was also significantly (p < 0.001) lower than the control, an indication that the animals were not pregnant. Thus, the failure to maintain pregnancy could be attributed to a direct or indirect effect on the corpus luteum, which may result in the inhibition of the synthesis and/or the secretion of progesterone by the corpus luteum.
Finally, several alkaloids have been isolated from Goniothalamus velutinus, e.g. velutinam I and aristolactam B-II which showed cytotoxicity against HeLa and L-1210 cells in culture. The aporphine alkaloid, oxostaphanine has been isolated from Goniothalamus scortechinii and Goniothalamus tapis.

Shrubs or small trees with simple hairs. Leaves alternate, simple, entire; petioles short; stipules absent. Flowers bisexual, usually axillary, solitary or in few-flowered fascicles, often on the trunk. Sepals 3, valvate; petals 6, valvate, coriaceous, in 2 whorls, inner much shorter than outer ones, shortly clawed, cohering above the reproductive organs; stamens numerous, connective with a truncate dilated or conical apex, anther cells frequently transversely septate; carpels numerous; ovules 1—2(—5), basal or lateral; pedicel with several imbricate, distichous bracts at the base. Fruit a monocarp, globose to oblong, stipitate or sessile.

Many Goniothalamus species flower and fruit throughout the year e.g. Goniothalamus macrophyllus, whereas others have a more strictly defined flowering period, e.g. Goniothalamus amuyon in Taiwan flowers in May, and fruits are mature in October. Goniothalamus velutinus in Borneo flowers and fruits from June—August. Goniothalamus has cleistogamous; flowers and seems to be completely autogamous, to date no pollinators have been observed. In Sarawak, however, beetles (Carpophilus spp., Endaenidius spp and Endaeus spp.) were observed feeding on stigmatic secretions.

Goniothalamus is badly in need of revision. According to a classification based on both flower and fruit characters of Annonaceae from all over the world, Goniothalamus is placed in an informal group which also includes the Asian genera Anomianthus, Fissistigma, Friesodielsia, Melodorum, Mitrella, Mitrephora, Neo-uvaria, Oreomitra, Papualthia, Petalolophus, Phaeanthus, Popowia, Pseuduvaria, Pyramidanthe, Richella, Schefferomitra and Trivalvaria.

Goniothalamus species are usually confined to forests at low elevations, although some montane species exist.

Some trials with low survival rates have been carried out with wildings transplanted into the open.

Sticks about 1—1.5 m long are cut from Goniothalamus tapis treelets and traded in the market.

Goniothalamus comprises numerous endemic species and some widespread ones, mostly in the understorey of primary forest, some also are common in secondary vegetation. The narrow endemics from primary forest habitats in particular are potentially threatened by forest degradation.

The annonaceous acetogenins and styrylpyrones as found in Goniothalamus are relatively new classes of promising anticancer and pesticidal natural compounds for which a potent inhibition of ATP production via blocking of the plasma membrane bound NADH oxidase leading to apoptosis (programmed cell death) is at least in part, involved in their mechanism of action. This unique mechanism of action for cancer chemotherapy will certainly merit further research, in order to fully evaluate the potential of the compounds in future medicine.

Alali, F.Q., Rogers, L., Zhang, Y. & McLaughlin, J.L., 1999. Goniotriocin and (2,4-cis- and -trans)-xylomaticinones, bioactive annonaceous acetogenins from Goniothalamus giganteus. Journal of Natural Products 62(1): 31—34.
Alali, F.Q., Zhang, Y., Rogers, L. & McLaughlin, J.L., 1998. Mono-tetrahydrofuran acetogenins from Goniothalamus giganteus. Phytochemistry 49(3): 761—768.
Fang, X.P., Anderson, J.E., Smith, D.L., McLaughlin, J.L. & Wood, K.V., 1992. Gigantetronenin and gigantrionenin: novel cytotoxic acetogenins from Goniothalamus giganteus. Journal of Natural Products 55(11): 1655—1663.
Hawariah, L.P.A., Munawer, M. & Din, L.B., 1994. Antifertility effect of goniothalamin: A styrylpyrone isolated from Goniothalamus tapis Miq. Asia Pacific Journal of Pharmacology 9(4): 273—277.
Soonthornchareonnon, N., Suwanborirux, K., Bavovada, R., Patarapanich, C. & Cassady, J.M., 1999. New cytotoxic 1-azaanthraquinones and 3-aminonaphthoquinone from the stem bark of Goniothalamus marcanii. Journal of Natural Products 62(10): 1390—1394.
Wu, Y.C., Chang, F.R., Duh, C.Y., Wang, S.K. & Wu, T.S., 1992. Cytotoxic styrylpyrones of Goniothalamus amuyon. Phytochemistry 31(8): 2851—2853.

Khozirah Shaari

Goniothalamus amuyon
Goniothalamus giganteus
Goniothalamus macrophyllus
Goniothalamus tapis
Goniothalamus velutinus

Shaari, K., 2001. Goniothalamus Hook.f. & Thomson. 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:
Goniothalamus amuyon
Goniothalamus giganteus
Goniothalamus macrophyllus
Goniothalamus tapis
Goniothalamus velutinus