Alkaloids from the Genus Dehaasia: Phytochemistry and Biological Activities

Article history: Received on: 29/12/2016 Accepted on: 27/01/2017 Available online: 30/03/2017 The genus Dehaasia is one of the genera of evergreen trees or shrubs belong to Lauraceae, and comprise about 35 species of tree that are distributed worldwide. The purpose of this review is to provide an update and comprehensive information on the phytochemistry and pharmacological research of Dehaasia species in order to explore their therapeutic potential and evaluate future research opportunities. All the available information on Dehaasia species was actualized systematically by searching the scientific literatures databases such as PubMed, SciFinder, Web of Science, and Google Scholar. From the data collected in this review, the genus Dehaasia has attracted much attention due to their richness in alkaloids with various bioactivities, and it comprises a wide range of therapeutically promising plants. Therefore, a detailed study and clinical evaluation of Dehaasia species should be carried out in future for the safety approval of therapeutic applications.


INTRODUCTION
Dehaasia is a member of the Lauraceae family. It is an evergreen tree of moderate size, with large leaves, found growing in the western parts of Malaysia, China, and the Philipines (Burkill, 1935). About 35 species of Dehaasia are spread out worldwide and nine species are found in Malaysia. According to the current listing reported in the taxonomical internet database lead by the Royal Botanical Gardens at Kew and the Missouri Botanical Garden (www.theplantlist.org-accessed 25 December 2016), the genus Dehaasia encompasses the following 38 accepted (65.5%) taxons, as listed in Table 1.
Dehaasia is locally known as 'gajus hutan' or 'pekan', and its timber is durable and used for building houses (Hsuen, 1969). This genus presents several alkaloids, with isoquinolines as the main class reported in the literature.
The isoquinoline alkaloids are formed from the amino acid tyrosine by consecutive reactions forming the tetrahydroisoquinoline core and are of great importance due to several pharmacological activities described to the benzyltetrahydroisoquinoline, aporphine and pavine skeletons (Houlihan, 1972). This review aims to examine the phytochemical and pharmacological perspectives of the Dehaasia species reported in the literature.

PHYTOCHEMISTRY STUDIES
A substructure search is performed using the SciFinder Scholar database and keywords research in PubMed, Medline, and Scopus. A bibliographic search carried out from the year 1986 to 2014 of the genus Dehaasia revealed that only six species were investigated at chemical or biological level.   Lu and co-workers (1986) have investigated this species collected from Orchid Islands, Taiwan. In this study, they have successfully isolated two new bisbenzylisoquinoline alkaloids, dehatridine 1 and dehatrine 2, together with six known alkaloids, isocorydine 3, corytuberine 4, atheroline 5, nantenine 6, obaberine 7, and xanthoplanine 8. Except for 6 and 8 which were obtained from the trunk, the other six alkaloids were obtained from the leaves. Seven years later, Lee et al., (1996) have reinvestigated this species, in which his reinvestigation resulted in the isolation of three novel alkaloids, isocorydione (9), norisocorydione 10, and dehatriphine 11, besides the most abundant aporphine, isocorydine 3 from the leaves extract. In the same year,they also managed to find another five additional new alkaloids, secoxanthoplanine 12, dehydroisocorydione 13, (8,8′-R)-bisisocorydine 14, (8,8′-S)-bisisocorydine15, and 11,8′-O-bisisocorydine 16 from the leaves of D. triandra. Compound 14and 15 are the first C-C linked bisaporphines at C-8, while 16is the first bisaporphine with a diphenyl ether-linkage at C-8 and C-11. The structures of 12, 14, . and 15 were further confirmed by semisynthesis as reported by the authors. In addition,  have reported that the species contained nine alkaloids, identified as aromoline 17, obamegine 18, berbamine 19, homoaromoline 20, colorflammine 21, thalrugosine 22, norobaberine 23, tetrandrine 24, and isotetrandrine 25. Furthermore, Sun and co-workers (2000) have also reported that isolation of these alkaloids by high-performance liquid chromatography determines the content of such alkaloids present in the stem woods of D. triandra. Continuing the investigation of the phytochemicals of this species, Chen and coworkers (2003) have also managed to isolate eleven bisbenzylisoquinoline alkaloids, homoaromoline20, daphnandrine 26, aromoline 17, daphnoline 27, pangkorimine 28, colorflammine 21, thalrugosine 22, obamegine 18, 2-norobamegine 29, dehatridine 1 and 1,2-dehydroapateline 30 from the leaves extract.

D. longipedicellata (Ridl.) Kosterm
D. longipedicellata is a small tree with 12 m tall and 30 cm girth. Its leaves are apex pointed; blade softy hairy on the undersurface, broadly elliptic to obovate, 13-27.5 cm × 6.5-13.5 cm and stalk is about 1.0-2.5 cm long. The leaves also have 10-14 pairs of secondary nerves, raised below; faint above and tertiary nerves scalar form. They are also having reticulations visible on both surfaces. The fruit of this species is globosely with depressed or flattened apex, 5.5 cm across on 3.5 cm long swollen stalks According to the Sakai of the Tapah Hills, the fruit is very poisonous (Ng, 1989). Three studies have been reported on the phytochemical studies of D. longipedicellata. Mukhtar and coworkers (2004)

D. hainanensis Kosterm
D. hainanensislocally known as 'liangui' in China. It is a shrub or small tree and up to 5 m tall. Its' leaves are alternate, petiole brown, concave-convex, and glabrous, whereas its' flowers are small and glabrous up to 1.5 mm (Xiwen et al., 1836). Only one study has been reported in the literature about this species in 2007 when Chen and co-workers (2007)

D. candolleana (Meisn.) Kosterm
D. candolleanais a small tree with 8 m tall and 10 cm in diameter. Its bark is whitish grey; inner bark is white and grey twigs with large leaf-scars; leaves spirally simple, crowded at the end of the twigs, elliptic, apex shortly acuminate or acute, base obtuse, 17.5-25.0 cm × 5.5-13.5 cm, bright green and rugose above, paler below, nerves 8-11 pairs, distinct below; petioles 2.5 cm long; in fluorescence in axillary panicles, dark red flowers and densely hairy (Ng, 1989). Only one report on this species appeared in the literature in 2008 when Hadi and co-workers (2008) described the isolation from the bark extract and structural characterization of (+)-sebiferine 37, (-)-O,O-dimethylgrisabine 41, and grisabine 51.

D. incrassata (Jack) Kosterm
D. incrassata known as 'yaoguo nan' is a small tree with 5 m tall and 10 cm in diameter. The bark is grey-brown, smooth, and lenticellate while the inner bark is yellow. Its leaves are spirally simple, leathery from elliptic-oblong to oblanceolate or obovate, apex acuminate, base 8.0-15.0×5.5-10.0 cm, bright green above, polar below, nerves 8-11 pairs, crving and joining near the margin; petiole 3 cm long, grooved above; fruit terminal, oblong, 5×2 cm, bright green, ripening shyny purplish black; stalks 3 cm long (Ng, 1989). The first phytochemical study of this species appeared in the literature in 1991 when Said and co-workers isolated and structurally characterizediscorydine 3, norisocorydine 52, and oxyacanthine 53 from the leaves extracts.

D. kurzii King ex Hook. f.
D. kurzii is locally known as 'mojar', 'mostapata' or 'modonbocchu' in Bangladesh. Its leaves and roots are used to treat leucorrhoea (Hasan et al., 1987). Only two brief reports on this species appeared in the literature in 1988 when Rahman and co-workers described the isolation of boldine 38 from the stem bark extract (Rahman et al., 1988a;1988b).

Antibacterial activity
The alkaloids extract of D. kurzii exhibited a strong in vitro antibacterial activity against Shigella flexneri and moderate activity against Vibrio cholera, Staphylococcus aureus, Proteus, Pseudomonas spp., and Shigella dysenteriay type-I. The isolated compound from this extract, boldine 38 has shown a strong and specific cytotoxic activity towards human epidermoid carcinoma of larynx (Hep-2 cells). It showed complete inhibition of cultured HEp-2 cells at a concentration of 0.3 mg/mL and partial inhibition at 0.7 mg/mL (Hasan et al., 1987).

Antimalarial activity
The leaves extract of D. incrassata was also screened for antimalarial activity and found to be active at 0.31 μg/mL (Said et al., 1991).

CONCLUSION
According to the presented data, it can be seen that the Dehaasia genus presents a great number of alkaloids with isoquinoline alkaloids as the major class. The overall biological investigations of Dehaasia are far from deep, except for some preliminary works regarding in vitro screenings, in which the isolated compounds showed various biological activities such as antioxidant, antiplasmodial, antimicrobial and cytotoxic activities. Alkaloids are among the most thoroughly investigated ingredients, exhibiting anti-inflammatory activity, antitumor activity, and endotoxemia and vasoconstrictor effects (Cao et al., 2015). Therefore, they represent valuable potential constituents for drug development. In conclusion, further investigations of Dehaasia, especially in-depth in vivo and in vitro pharmacological evaluations of alkaloids, are valuable and encouraging.