The ethnomedicinal, phytochemical and pharmacological properties of Phaleria macrocarpa (Scheff). Boerl.
The ethnomedicinal, phytochemical and pharmacological properties of Phaleria macrocarpa (Scheff). Boerl.
TANG. 2014. Nov, 4(4): 22-22
Copyright © 2014, Association of Humanitas Medicine
This is an open access article under the CC BY-NC license. (
  • Received : April 14, 2014
  • Accepted : October 31, 2014
  • Published : November 30, 2014
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About the Authors
Siti Nur Atiqah Md Othman
Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia
Satyajit Dey Sarker
Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, England, UK
Lutfun Nahar
Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, England, UK
Norazah Basar
Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, England, UK

Phaleria macrocarpa (Scheff.) Boerl. is a dense evergreen tree of the family Thymelaeceae. This plant is popular with the name of Mahkota dewa, which is literally translated as God’s Crown. All parts of this plant including fruits, seeds, stem, and leaves have well known therapeutic properties and have been extensively used in traditional medicine for the treatment of various diseases such as cancer, diabetes mellitus, allergies, kidney disorders, blood diseases, stroke, and acne with satisfactory results. Scientific findings on bioactivities of P. macrocarpa also demonstrated different pharmacological properties of various parts of this plant including cytotoxic, antidiabetic, antioxidant, anti-inflammatory, antibacterial, and antihypertensive activities. Phytochemicals studies of P. macrocarpa revealed the presence of several classes of compounds such as benzophenones, terpenoids, xanthones, lignans, acids, and sugars. This review aims to provide a critical overview on botanical description, traditional usage, phytochemicals, and pharmacological activities of P. macrocarpa .
Nature plays an important role in providing the basic needs of human in the production of food-stuffs, shelters, clothing, means of transportation, fertilizers, flavours and fragrances, and, not the least, medicines for the treatment of various diseases ( Cragg and Newmann, 2013 ; Gordaliza, 2007 ). Mineral, animal and plant products were utilized as the main sources of drugs, and the use of natural products with therapeutic properties is as ancient as human civilization ( De Pasquale, 1984 ; Rates, 2001 ; Samuelsson, 2004 ). Most of the plant compounds that have been found to be medicinally useful and interesting tend to be secondary metabolites including alkaloids, phenolics, acetogenins and terpenoids. Secondary metabolites represent features that can be expressed in terms of ecological, taxonomic and biochemical differentiation and diversity. The wide chemical diversity of secondary metabolites throughout the plant kingdom represents an extremely rich biogenic resource for the discovery of novel drugs and for developing innovative remedies ( Gurib-Fakim, 2006 ). To date, natural products and their derivatives represent more than 50% of all the drugs in clinical use in the world. Higher plants contribute no less than 25% of the total. During the last 40 years, at least a dozen potent drugs were reported from flowering plants ( Gurib-Fakim, 2006 ).
The Thymelaeaceae family is a cosmopolitan family of flowering plants, which is established by Hanus-Fajerska et al. (2012) . This family consists of 45 genera and 700 - 800 species, and is widely distributed in both hemispheres ( Herber, 2002 ; 2003 ). Nine genera and 89 species of the Thymelaeaceae plants are endemic to China (Zheng et al., 1999). In the other large genera of the Thymelaeaceae are Gnidia with approximate number of species 160, Pimelea (110), Daphne (95), Wikstroemia (70), Daphnopsis (65), Struthiola (35), Lachnaea (30), Thymelaea (30), Phaleria (30), and Gonystylus (25) ( Kubitzki and Bayer, 2003 ). The species of this family include mostly shrubs or small trees, rarely herbs, evergreen or deciduous. Most species are toxic but some have medicinal properties. The phloem contains strong fibers, which make the bark of many species beneficial in manufacturing of high quality paper especially bank notes. The stems have characteristics of supple and are difficult to break, and used as a substitute for string (Zheng et al., 1999). One of the plants within the Thymelaeceae is Phaleria macrocarpa (Scheff.) Boerl. which was first described by Scheffer as Drimyspermum macrocarpum based on fruiting specimens collected by Teysmann near Doré, in western New Guinea ( Angiosperm Phylogeny Group, 2003 ). The other botanical name of this plant is Phaleria papuana Warb var. Wichanii (Val) Back ( Hou, 1960 ). This plant is popular with the name of ‘ Mahkota dewa ’, which is literally translated as God’s Crown. It is locally known as ‘ Simalakama ’ in Sumatra (Malay) and Depok (West Java) and ‘ Makutadewa ’, ‘ Makuto rajo ’, ‘ Makuto ratu ’ or ‘ Makuto mewo ’ in Java (Harmanto, 2005).
- Botanical descriptions ofP. macrocarpa(Scheff.) Boerl.
P. macrocarpa is a shrub or small tree that grows throughout the year. This plant usually reaches the height of 5 m but sometimes its height could also reach up to 18 m ( Harmanto, 2003 ; Stevens, 1974 ; Winarto, 2003). It grows in areas of 10 – 1,200 m above the sea level and the most productive age of this plant is in between 10 – 20 years ( Saufi, 2007 ). The plant of P. macrocarpa has features of many-branched crown with 1-metre long straight root exuding sap, a brownish green bark and white wood. The leaves are green, sharp edge and tapering from 10 - 15 cm in length and 3 – 5 cm in wide ( Fig. 1A ). Its flowers appear in white colour with trumpet-like shape and produce pleasant smell. The fruits have an eclipse shape; occur in various sizes with diameter ranging from 3 – 5 cm. Its fruits have smooth surface and changing their colour from green when young into red or maroon when ripening ( Fig. 1B ). The pit is round, white and poisonous ( Fig. 1C ) ( Altaf et al., 2013 ; Hendra et al., 2011 ; Saufi, 2007 )
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The (A) leaves, (B) fruit and (C) pit of P. macrocarpa
- Traditional usage of various parts ofP. macrocarpa(Scheff.) Boerl.
P. macrocarpa is frequently used as a therapeutic healing alternative in health system of the Indonesians and lower course of Malaysia ( Ali et al., 2012 ). All parts of this plant including fruits, seeds, stems and leaves have well known therapeutic properties and have been extensively used in traditional medicine ( Tjandrawinata et al., 2010 Winarto, 2003). Specifically, the fruits of P. macrocarpa are used to treat flu, rheumatism, heart diseases and cancer; the leaves are used to treat dysentery, allergy, tumour and impotency while the stems are beneficial in the treatment of bone cancer. The eggshells of seeds are used to counter breast cancer, cervix cancer, lung disease, liver, and heart diseases. This plant especially the seed part cannot be consumed directly due to its high toxicity which can cause swelling, numbness and unconsciousness. However, the seeds can be used as an external medicine for the treatment of skin conditions and for ornamental cultivation purposes, which act as a traditional biopesticide ( De Padua et al., 1999 ; Harmanto, 2003 ).
- Phytochemical studies
Several research groups especially from Indonesia and China had extensively carried out studies to find chemical constituents from P. macrocarpa . The studies resulted in the isolation of several classes of compounds such as benzophenones, terpenoids, xanthones, lignans, acids and sugars. Chemical investigation on the fruits, leaves and bark of P. macrocarpa afforded eight benzophenone derivatives, identified as phalerin (1) ( Altaf et al., 2013 ; Oshimi et al., 2008 ), isophalerin A (2), isophalerin B (3) ( Susilawati, 2012 ), Mahkoside A (4) ( Zhang et al., 2006 ), Mahkoside B (5) ( Zhang et al., 2012 ), 6,4'-dihydroxy-4-methoxybenzophenone-2-O-α-D-glucopyranoside (6) ( Tambunan and Simanjutak, 2006 ), 6,4'-dihydroxy-4-methoxybenzophenone-2-O-β-D-glucopyranoside (7) ( Susilawati, 2012 ; Winarno and Katrin, 2009 ) and 2,6,4'-trihydroxy-4-methoxybenzophenone (8) ( Simanjutak, 2008 ; Susilawati et al., 2011 ). Several triterpenoids derivatives known as icariside C3 (9) ( Oshimi et al., 2008 ), phalerielide (10) ( Susilawati, 2012 ), β-sitosterol (11), stigmasterol (12) and cyloargetanol (13) ( Simanjutak, 2008 ) were successfully isolated from the fruits of P. macrocarpa . Phytochemical studies on the fruits by Kurnia et al. (2008) reported a new 29-norcucurbitacin derivative named as desacetyl-fevicordin A (14), together with fevicordin A (15), fevicordin A glucoside (16) and fevicordin D glucoside (17).
In addition, studies on chemical constituents from the fruits of P. macrocarpa revealed the isolation of an ester compound, ethyl stearate (18) ( Zhang, 2006 ) and acid derivatives including palmitic acid (19) ( Simanjutak, 2008 ; Zhang et al., 2006 ), oleic acid (20), linoleic acid (21), linolineic acid (22), dodecanoic acid (23) ( Simanjutak, 2008 ), naphtoic acid (24) ( Susilawati, 2012 ) and gallic acid (25) ( Faried et al., 2007 ). A novel lignan named as macronone (26) ( Susilawati et al., 2012 ) and a known lignan, syringaresinol (27) ( Lisdawati et al., 2007 ) were obtained from the ethyl acetate extract of the bark and mesocarp of P. macrocarpa , respectively. The investigation on the chemical constituents of this plant yielded a xanthone and flavonoid compound identified as mangiferin (28) ( Kim et al., 2010 ; Oshimi et al., 2008 ; Zhang et al., 2006 ) and kaempferol- 3-O-β-D-glucoside (29) ( Zhang et al., 2006 ). Moreover, two sugar molecules known as glucose (30) and sucrose (31) ( Simanjutak, 2008 ; Zhang et al., 2006 ) were isolated from the aqueous extract of P. macrocarpa fruits. Furthermore, the quantitative analysis on various parts of P. macrocarpa fruits revealed the presence of five major flavonoids named as kaempferol (32), myricetin (33), quercetin (34), naringin (35), and rutin (36). Qualitative analysis of the flavonoids was carried out by reversed-phased high performance liquid chromatography (RP-HPLC) using an analytical column C18 60Å 4μm, 3.9 × 150 mm, Waters, NANPA, MA (USA). The flavonoids were detected at 365 nm of UV-Vis photodiode array (DAD) detector ( Hendra et al., 2011 ).
- Pharmacological activities
Empirically, Indonesian people have as often utilized the fruits bark and leave of P. macrocarpa for the treatment of various diseases such as cancer, diabetes mellitus, allergies, kidney disorders, blood diseases, stroke and acne with satisfactory results. Therefore, many scientific evaluations on bioactivities of P. macrocarpa have been conducted in order to prove the traditional claims on the medicinal values of this plant.
- Anticancer activity
Cytotoxic activities of the methanolic extract from different parts of P. macrocarpa fruits were evaluated against the human colon adenocarcinoma cell line (HT-29), human breast adenocarcinoma cell line (MCF-7), human cervical cell line (HeLa) and normal human hepatocytes cell line (Chang liver cell). The viability of cells was measured using the MTT assay. The fruits were divided into pericarp, mesocarp and seed. Results obtained indicated that all parts had potential cytotoxic activity against the MCF-7 and HeLa cancer cell lines with IC 50 values ranging from 25.5 – 40.8 μg/ml. The results also showed that the seeds exhibited potential cytotoxic effect against HT-29 with an IC 50 value of 29.5 μg/ml while the pericarp and mesocarp exhibited mild cytotoxicity with IC 50 values between 63.8 – 70.1 μg/ml ( Hendra et al., 2011 ).
An in vitro study on the cytotoxic effect of fruit extract was carried out against the human uterine cervical carcinoma cell line (HeLa) ( Rahmawati et al., 2006 ). Various concentrations of fruit extract were used to determine the inhibition activity against the HeLa cell line after 24, 72 and 120 h of incubation. The results showed good inhibitory activity against the HeLa cell after 72 h of incubation with an IC 50 value of 5.09 ppm ( Pertamawati, 2007 ). Another investigation on the anticancer activity of the ethanol extract of the fruit pulps of P. macrocarpa against mouse mammary tumour was induced by transplantation. This study concluded that the ethanol extract did not inhibit the mouse mammary tumour growth at doses of 20, 40 and 80 fold human doses given orally after tumour transplantation for 30 days. However, the results demonstrated the significant increase of apoptosis atthe dose of 80 time human dose ( Rahmawati et al., 2006 ).
Phytochemicals ofP. macrocarpaaccording to its part and types of extract used
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Phytochemicals of P. macrocarpa according to its part and types of extract used
Previous cytotoxic study on the fruits of P. macrocarpa reported the non-toxic effect of the ethanol extract from the seeds and fruits flesh towards human mononuclear peripheral normal cell but slightly toxic to the vero cell line. The extract also did not increase p53 and decrease bcl-2 gene expression that suggested the mechanism of dying cell was caused by necrosis and not by apoptosis ( Altaf R et al., 2013 ). Bioactivity study of irradiated P. macrocarpa leaves showed that the n-hexane, ethyl acetate and methanol extracts exhibited strong cytotoxic effect against the mouse leukaemia L1210 cell line with IC 50 values of 12.4 10.3 and 24.1 μg/ml, respectively ( Katrin et al., 2011 ). In addition, cytotoxic activity of the n-hexane, chloroform, ethyl acetate and methanol extracts from the leaves of P. macrocarpa plant were investigated against the human hepatoma cell lines (HepG2). The ethyl acetate and methanol extracts were found to have mild cytotoxic effect (IC 50 32.5 and 40 μg/ml, respectively) ( Yosie et al., 2011 ).
The investigations on cytotoxic effects of isolated compounds were conducted against several cancer cell lines. Study on cytotoxic activity of phalerin (1) from the methanolic extract of P. macrocarpa leaves was investigated against the myeloma cell line (NS-1). Phalerin (1) was non-toxic towards NS-1 cell line (IC 50 83μg/ml) ( Altaf et al., 2013 ). Two benzophenone glucosides, mahkoside A (4) and mahkoside B (5) were found to have low cytotoxic effect towards several human cancer cell lines including the prostate cancer cell line (PC-3), stomach cancer cell line (MGC-803) and esophageal cancer cell lines (EC109 and EC9706), with IC 50 values exceeding 100 μM/L ( Zhang et al., 2012 ). However, the inhibitory activity of another benzophenone glucoside named as 6,4'-dihydroxy-4-methoxybenzophenone-2-O-β-D-gluco pyranoside (7) displayed that this compound had strong cytotoxic properties against the mouse leukaemia cell line (L1210) (IC 50 5.1 μg/ml) ( Winarno and Katrin, 2009 ). Additionally, fevicordin A (15) demonstrated strong anticancer properties against the murine leukaemia cell line (P388) and cervix cancer cell line (HeLa) (IC 50 0.01 and 1.16 μg/ml, respectively). This compound also exhibited moderate anticancer activity against another cervix cancer cell line (CasKi) and oesophagus cancer cell line (TE-8) with IC 50 values of 12 and 14.6 μg/ml, respectively ( Diantini et al., 2012 ).
Faried et al. (2007) studied the anticancer properties of gallic acid (25), isolated from the fruits of P. macrocarpa . The cell proliferation activity was performed using the MTT assay against the human esophageal cancer cell line (TE-2), gastric cancer cell line (MKN-28), colon cancer cell lines (HT-29 and Colo201), breast cancer cell line (MCF-7), cervix cancer cellline (CaSki), mouse colon cancer cell line (colon 26) with one normal human esophageal cell line (CHEK-1). Interestingly, gallic acid (25) showed significant anticancer properties towards all tested cancer cell lines and induced apoptosis in TE-2 cell line. Apart from the cytotoxic screening activities, the study on molecular mechanism of the extract from this plant on human breast cancer cell line (MDA-MB-231) was performed using a bioactivity-guided DLBS1425. In a previous study, DLBS1425 was found to confer antiproliferative and proapoptosis effects via eicosanoid pathway ( Tjandrawinata et al., 2010 ). DLBS1425 was shown as a potent anticancer agent that targets genes involved in cell survival and apoptosis in the MDA-MB-231 cell line ( Tandrasasmita et al., 2010 ).
Summary of pharmacological activities of chemical constituent fromP. macrocarpa
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Summary of pharmacological activities of chemical constituent from P. macrocarpa
- Antidiabetic activities
The investigation on the α-glucosidase inhibitory activity and hypoglycemic effect by oral administration of fruit extracts from P. macrocarpa in rats were evaluated ( Sugiwati et al., 2006 ). The highest α-glucosidase inhibitory activity was displayed by the n-butanol extract of young and ripe fruits followed by the ethyl acetate and methanol extracts. The boiled water and n-butanol extracts also displayed hypoglycemic effect by reducing the blood glucose concentration of rats with effective dose ranging between 1.0 × 10 -3 – 6.5 × 10 -3 mg/g. The results suggested that this plant could be suitable as a traditional antidiabetic drug ( Sugiwati et al., 2006 ). The hypoglycemic activity of this plant was further investigated by evaluating the effect of the fruits powder on blood glucose levels in glucose loading healthy volunteers. The effective dose of mesocarp fruit powder to decrease the blood glucose level in healthy volunteers was significantly found at the concentration of 500 mg ( Meiyanti et al., 2006 ).
Another study revealed the potential of the ethyl acetate extract of fruits to improve insulin sensitivity in hyperglycemic rats by decreasing the blood glucose level. The highest activity of insulin activity was 18.3%, 9 min after the rats being injected with glucose and exogenous insulin ( Muhtadi et al., 2008 ). The in vitro mechanism study demonstrated the antidiabetic properties of the ethanol extract of the fruits as α-glucosidase inhibitor and as insulin secretagog in clonal glucose responsive insulin secreting cell (BRIN-BD11). In the same study, the qualitative analysis of phytochemicals from the ethanol extract revealed the presence of flavonoid, alkaloid, tannin and steroid. Among these classes of compounds, flavonoid was suggested to be responsible for the antidiabetic properties of the extract in that study ( Suparto et al., 2008 ). In addition, the methanol extract from the fruits pericarp was found to have potential anti-hyperglycemic effect by lowering blood glucose at 56.3% and 58.3% after 12 days of treatment.
Summary of pharmacological activities of extracts fromP. macrocarpa
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Summary of pharmacological activities of extracts from P. macrocarpa
This finding led to phytochemical screening, revealing the presence of flavonoids, terpenoids, and tannins in the methanol extract. These classes of compounds were suggested to be the major contributors to its antidiabetic properties ( Ali et al., 2012 ).
Sulistyoningrum et al. (2013) discovered the protective effect of the methanol and water extracts of P. macrocarpa on renal histological changes of alloxan-induced diabetes. The results concluded that both extracts were able to restore glomerular hypertrophy and improved glomeruloscierosis in alloxan-induced diabetes. Bioassay-guided antidiabetic study on the extract from the fruits successfully identified the active sub-fraction that had flavonoids in abundance. The sub-fraction was proved to have potent antidiabetic activity by inhibiting rat intestinal glucose transportation and absorption. ( Atangwho et al., 2012 ).
- Anti-inflammatory activities
Different parts of the fruits of P. macrocarpa were screened for their anti-inflammatory activity using the nitric oxide (NO) synthesis in macrophage RAW 264.7 cell lines induced by the LPS/IFN-γ assay. Extracts from the pericarp and mesocarp showed notable anti-inflammatory effect with percentage of inhibition of 63.4% and 69.5%, respectively ( Hendra et al., 2011 ). Study on anti-inflammatory activity was performed on the major compound from the fruits identified as phalerin (1). This compound showed low inflammatory effect since it decreased the inflammation twice lower than the standard, Napoxen at dose of 22.5 mg/kg body weight ( Mariani et al., 2010 ). Anti-inflammatory activity of phalerin (1) was also determined by using the lipoxygenase (LOX), hyaluronidase (HYA) and xanthine oxidase (XO) assays. The results showed that phalerin (1) had mild anti-inflammatory properties in the XO and LOX assays with percentage of inhibition 34.8% and 23.5%, respectively. Meanwhile, phalerin (1) did not exhibit any inflammatory effect in the HYA assay ( Fariza et al., 2012 ).
- Antioxidant activities
Antioxidant activity of the methanol and ethanol extracts from different parts of young and old fruits of P. macrocarpa was evaluated using the free-radical-scavenging method (DPPH). Most of the parts from young and old fruits showed potent antioxidant activity with scavenging inhibition ranging between 38.4 - 48.1%. Further fractionation of the active extracts was carried out to give ethyl acetate, n -butanol and water extracts. The highest antioxidant activity was observed in the n-butanol extract of the young fruits with IC 50 of 41.07 ppm ( Soeksmanto et al., 2007 ). The same DPPH method was also performed to determine the antioxidant activity of different polarity of extracts from the leaves of P. macrocarpa . Ethyl acetate and methanol extracts exhibited strong antioxidant activity with 76% and 79% inhibitions, respectively. Meanwhile, the n-hexane and chloroform extracts displayed moderate antioxidant properties with 59% and 69% inhibitions, respectively ( Yosie et al., 2011 ).
Various in vitro model systems such as ferric thiocyanate, thiobarbituric acid, DPPH, ferric-reducing antioxidant power (FRAP) and nitric oxide (NO) scavenging method were used to characterize the antioxidant properties of different parts of the fruits. The results revealed the strong antioxidant properties of the pericarp and mesocarp in the FRAP assays with percentage inhibition of 92.35% and 78.78%, respectively ( Hendra et al., 2011 ). In addition, antioxidant study of 2,6,4'-trihydroxy-4-methoxybenzophenone (8) and macronone (26) performed using the DPPH method. Interestingly, compound (8) displayed strong antioxidant properties (IC 50 10.57 μg/ml) while macronone (26) had weak activity (IC 50 240.14 μg/ml) ( Susilawati et al., 2011 ; 2012 ).
- Antimicrobial activities
Antibacterial activity of various parts of P. macrocarpa fruits was studied using the disc diffusion method against eight bacterial strains, i.e., Bacillus cereus , Bacillus subtilis , Enterobacter aerogenes , Escherichia coli , Klebsiela pneumonie , Micrococcus luteus , Pseodomonas aeruginosa and Staphylococcus aureus . All parts including the pericarp, mesocarp and seeds exhibited weak to moderate antibacterial activity against all pathogenic bacteria strains with inhibition zones ranging from 9.3 – 23.3 mm ( Hendra et al., 2011 ). In the same study, the antifungal activity was evaluated using the agar well diffusion assay against Aspergillus niger , Fusarium oxysporum , Ganoderma lucidum and Mucor indicus . The results showed that only seed extract was active against A. niger at a concentration of 0.3 mg/well ( Hendra et al., 2011 ).
Different polarities of extracts from the leaves of P. macrocarpa including the n-hexane, chloroform, ethyl acetate and methanol extracts were evaluated for their antibacterial activity against E. coli , K. pneumonia , P. aeruginosa , Streptococcus ubellis , Streptococcus aureus and B. cereus . Mueller Hinton agar well diffusion method was used to determine the susceptibility of bacteria tests. The highest activity was shown by ethyl acetate and methanol extracts against B. cereus and S. aureus with inhibition zone diameter ranging between 1527 mm ( Yosie et al., 2011 ).
- Toxicity
The general toxicity of 29-norcucurbitacin derivatives; desacetyl-fevicordin A (14), fevicordin A (15), fevicordin A glucoside (16) and fevicordin D glucoside (17), isolated from this plant was evaluated by the brine shrimp ( Artemia salina ) lethality assay. All compounds showed variable general toxicity with LD 50 values ranging from 3 – 12 ppm ( Kurnia et al., 2008 ).
- Vasorelaxant activity
The vasorelaxant activity of the extracts and compounds (1, 9, 28) isolated from the fruits of P. macrocarpa was evaluated against noradrenaline-induced contraction of isolated rat aorta. The results demonstrated the moderate vasorelaxant activity of the chloroform extract, while icariside C3 (9) showed a slow vasorelaxant activity. Phalerin (1) and mangiferin (28) did not show any vasorelaxant effect ( Oshimi et al., 2008 ).
- Antihypertensive activity
Study on the antihypertensive activity of nine medicinal plants from Indonesia was conducted against angiotensin converting enzyme. The nine tested plants were Scurulla artopurpurea , catharanthus roseus , Swietenia mahogany , Persea Americana , Oxalis corniculata , P. macrocarpa , Gynura procumbens , Melia azedarach and Hisbiscus rosasinensisi . Interestingly, all extracts from the fruits and leaves of P. macrocarpa displayed the highest level of inhibitory activity against acetylcholine esterase with IC 50 ranging between 102 – 189 μg/ml ( Rinayanti et al., 2013 ).
In this review, we have reviewed the relevant literature to assemble the ethnomedicinal, phytochemical and pharmacological properties of P. macrocarpa (Scheff). Boerl. This plant is used as folk remedies in both traditional as well as modern system of medicine to treat various diseases and illnesses. Various types of compounds with diverse chemical structures present in this plant are responsible for varied pharmacological and medicinal properties. Reported data show that the plant possesses promising anticancer, antidiabetic, antiinflammatory, antioxidant, antimicrobial, antihypertensive, toxicity and vasorelaxant activities. However, in view of the wide range of medicinal uses of P. macrocarpa , it is necessary to conduct further clinical and pharmacological studies at molecular level to investigate the potential of this plant, because most of the activity reported is based only on their in vitro assays. Similarly, additional studies have to be carried out in order to establish the potential of the extracts of P. macrocarpa in the development of new therapeutic drugs and to provide the basis for future research on the application of medicinal plants.
CONFLICT OF INTEREST The authors declare no conflict of interest.
The authors acknowledge Ministry of Higher Education (MOHE), Malaysia for the financial support under Research University Grant (RUG) vote number Q.J130000.2626.08J14 and the Faculty of Science, Universiti Teknologi Malaysia for providing the necessary support for this study.
Ali RB , Atangwho IJ , Kuar N , Mohamed EAH , Mohamed AJ , Asmawi MZ , Mahmud R 2012 Hypoglycemic and antihyperglycemic study of Phaleria macrocarpa fruits pericarp J Med Plants Res 6 1982 - 1990
Altaf R , Asmawi MZ , Dewa A , Sadikun A , Umar MI 2013 Phytochemistry and medicinal properties of Phaleria macrocarpa (Scheff.) Boerl. extracts Pharmacogn Rev 7 73 - 80    DOI : 10.4103/0973-7847.112853
2003 An update of the angiosperm phylogeny group classification for the orders and families of flowering plants: APG II Botanical J Linnean Society 141 399 - 436    DOI : 10.1046/j.1095-8339.2003.t01-1-00158.x
Atangwho IJ , Ali RB , Kuar N , Asmawi MZ , Mahmud R , Ahmad M 2012 Bioassay-guided antidiabetic study of Phaleria macrocarpa fruit extract Molecules 17 4986 - 5002    DOI : 10.3390/molecules17054986
Cragg GM , Newmann DJ 2013 Natural products: A continuing source of novel drug leads Biochim Biophys Acta 1830 3670 - 3695    DOI : 10.1016/j.bbagen.2013.02.008
De Padua LS , Bunyapraphatsara N , Lemmens RHMS 1999 Plant resources of South East Asia, Medical and poisonous plants 1 (PROSEA) Backhuys Publishers Leiden, Netherlands 36 - 38
De Pasquale A 1984 Pharmacognosy: the oldest modern science J Ethnopharmacol 11 1 - 16    DOI : 10.1016/0378-8741(84)90092-8
Diantini A , Subarnas A , Supriyatna Levita J , Abdulah R , Achmad TH , Faried A , Faried LS , Julaeha E , Kurnia D , Wardhani SR , Koyama H 2012 Cytotoxicity of fevicordin-A from Phaleria macrocarpa (Scheff.) Boerl. on P388, HeLa, Caski, TE-2, TE-8 and Prepuce’s Fibroblast cells J Med Res 1 1 - 5
Faried A , Kurnia D , Faried LS , Usman N , Miyazaki T , Kato H , Kuwano H 2007 Anticancer effects of gallic acid isolated from Indonesia herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines Int J Oncol 30 605 - 613
Fariza IN , Fadzureena J , Zunoliza A , Chuah AL , Pin KY , Adawiyah I 2012 Anti-inflammatory activity of the major compound from methanol extract of Phaleria macrocarpa leaves J Appl Sci 12 1195 - 1198    DOI : 10.3923/jas.2012.1195.1198
Gordaliza M 2007 Natural products as leads to anticancer drugs Clin Transl Oncol 9 767 - 776    DOI : 10.1007/s12094-007-0138-9
Gurib-Fakim A 2006 Medicinal plants: Traditions of yesterday and drugs of tomorrow Mol Aspects Med 27 1 - 93    DOI : 10.1016/j.mam.2005.07.008
Hanus-Fajerska E , Wiszniewska A , Czaicki P 2012 Effectiveness of Daphne L. (Thymelaeaceae) In vitro propagation, rooting of microshoots and acclimatization of Plants Acta Agrobotanica 65 21 - 28
Harmanto N 2003 Conquering disease in unison with mahkota dewa, Phaleria macrocarpa 1st ed. Mahkotadewa Indonesia North Jakarta, Indonesia 14 -
Hendra R , Ahmad S , Sukari A , Shukor MY , Oskoueian E 2011 Antioxidant, anti-inflammatory and cytotoxicity of Phaleria macrocarpa (Boerl.)Scheff fruit BMC Complement Altern Med 11 1 - 10    DOI : 10.1186/1472-6882-11-1
Hendra R , Ahmad S , Sukari A , Shukor MY , Oskoueian E 2011 Flavanoid analyses and antimicrobial activity of various parts of Phaleria macrocarpa (Scheff.) Boerl fruit Int J Mol Sci 12 3422 - 3431    DOI : 10.3390/ijms12063422
Herber BE 2002 Pollen morphology of the Thymelaeaceae in relation to its taxonomy Plant Sys Evol 232 107 - 121    DOI : 10.1007/s006060200030
Herber BE , Bayer C , Kubitzki K 2003 The families and genera of vascular plants Springer Berlin Heidelberg New York, USA Flowering plants dicotyledons 373 - 396
Hou D. , Van Steenis C.G.G.J. 1960 Thymelaeaceae;Flora malesiana series I Wolter-Noordhoff Publishing Groningen, Netherlands 1 - 15
Katrin E , Winarno H 2011 Chromatogram profiles and cytotoxic activity of irradiated mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) leaves Atom Indones 37 17 - 23
Kim WJ , Veriansyah B , Lee YW , Kim J , Kim JD 2010 Extraction of mangiferin from mahkota dewa (Phaleria macrocarpa) using subcritical water J Ind Eng Chem 16 425 - 430    DOI : 10.1016/j.jiec.2009.08.008
Kubitzki K , Bayer C 2003 The families and genera of vascular plants: Flowering plants dicotyledons Springer Berlin Heidelberg 5 383 -
Kurnia D , Akiyama K , Hayashi H 2008 29-Norcucurbitacin derivatives isolated from the Indonesian medicinal plant, Phaleria macrocarpa (Scheff.) Boerl Biosci Biotechnol Biochem 72 618 - 620    DOI : 10.1271/bbb.70627
Lisdawati V , Wiryowidagdo S , Kardono L , Broto S 2007 Isolasi dan elusidasi struktur senyawa lignin dan asam lemak dari ekstrak daging buah Phaleria macrocarpa Bul Penel Kesehatan 35 115 - 124
Mariani R , Wirasutisna K R , Nawawi A , Adnyana IK 2010 Antiinflammatory activity of dominant compound of mahkota dewa fruit Phaleria macrocarpa (Scheff.) Boerl Indonesian J Pharm 21 129 - 133
Dewoto HR , Suyatna FD 2006 Hypoglycemic effect of mahkota dewa mesocarp fruit (Phaleria macrocarpa (Scheff.) Boerl.) on glucose blood level in glucose loading healthy volunteers Universa Medicina 25 114 - 120
Muhtadi A , Susilawati Y , Zakaria AD 2008 The activity of isolate from ethyl acetate fraction of mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) fruits on insulin sensitivity in hyperglycaemic mouse Proceeding Int Seminar on Chemistry Jatinangor, Indonesia 527 - 530
Oshimi S , Zaima K , Matsuno Y , Hirasawa Y , Izuka T , Studiawan H , Indrayanto G , Zaini NC , Morita H 2008 Studies on the constituents from the fruits of Phaleria macrocarpa J Nat Med 62 207 - 210    DOI : 10.1007/s11418-007-0209-9
2007 Pengaruh sitotoksik ekstrak buah mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) terhadap sel kanker lestari HeLa J Sains dan Teknologi Indones 9 39 - 43
Rahmawati E , Dewoto HR , Wuyung PE 2006 Anticancer activity study of ethanol extract of Mahkota dewa fruit pulp (Phaleria macrocarpa (Scheff.) Boerl.) in C3H mouse mammary tumor induced by transplantation Med J Indones 15 217 - 222
Rates SMK 2001 Plants as source of drugs Toxicon 39 603 - 613    DOI : 10.1016/S0041-0101(00)00154-9
Rinayanti A , Radji M , Mun’im A , Suyatna FD 2013 Screening angiotensin converting enzyme (ACE) inhibitor activity of antihypertensive medicinal plants from Indonesia International Journal of Pharmacy Teaching and Practices 4 527 - 532
Samuelsson G 2004 A textbook of pharmacognosy;Drugs of natural origin Swedish Pharmaceutical Press Stockholm, Sweden 473 - 575
Saufi A. 2007 Lignans in Phaleria macrocarpa (Scheff.) Boerl. and in Linum flavum var. compactum L Shaker Verlag GmbH Maastricht, Germany 13 - 14
Simanjutak P 2008 Identifikasi senyawa kimia dalam buah Mahkota dewa (Phaleria macrocarpa), Thymelaceae J Ilmu Kefarmasian Indones 6 23 - 28
Soeksmanto A , Hapsari Y , Simanjuntak P 2007 Antioxidant content of parts of mahkota dewa, Phaleria macrocarpa [Scheff] Boerl. (Thymelaceace) Biodivertas 8 92 - 95
Stevens PF 1974 Three new species of Phaleria (Thymelaeaceae) from Papuasia J Arnold Arboretum 55 264 - 268
Sugiwati S , Kardono LBS , Bintang M 2006 α-Glucosidase inhibitory activity and hypoglycemic effect of Phaleria macrocarpa fruit pericarp extracts by oral administration to rats J Appl Sci 6 2312 - 2316    DOI : 10.3923/jas.2006.2312.2316
Sulistyoningrum E Setiawati , Ismaulidiya FR 2013 Phaleria macrocarpa (Scheff.) Boerl. improved renal histological changes in alloxan-induced diabetic rats Int J Med Plants Alt Med 1 87 - 92
Suparto IH , Arfianti N , Septiawati T , Triwahyuni W , Iskandriati D 2008 Ethanol extract of mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) fruit with in-vitro antidiabetic activities Proceeding. International Seminar on Chemistry Jatinangor, Indonesia 285 - 288
2012 Isolasi metabolit sekunder dari buah, kulit batang dan daun Mahkota Dewa (Phaleria macrocarpa (Scheff.) Boerl.) serta uji antioksidannya. PhD dissertation Universitas Gadja Mada Yogyakarta, Indonesia
Susilawati Matsjeh S , Pranowo HD , Anwar C 2011 Antioxidant activity of 2,6,4'-trihydroxy-4-methoxybenzophenone from ethyl acetate extract of leaves of mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) Indo J Chem 11 180 - 185
Susilawati Matsjeh S , Pranowo HD , Anwar C 2012 Macronone, a novel diepoxylignan from bark of mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) and its antioxidant activity Indo J Chem 12 62 - 69
Tambunan RM , Simanjutak P 2006 Determination of chemical structure of antioxidant compound benzophenone glycoside from n-butanol extract of the fruits of mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) Majalah Farmasi Indones 17 184 - 189
Tandrasasmita OM , Lee JS , Baek SH , Tjandrawinata R 2010 Induction of cellular apoptosis in human breast cancer by DLBS1425, a Phaleria macrocarpa compound extract, via downregulation of P13-kinase/AKT pathway Cancer Biol Ther 10 814 - 823    DOI : 10.4161/cbt.10.8.13085
Tjandrawinata RR , Arifin PF , Tandrasasmita OM , Rahmi D , Aripin A 2010 DLBS1425, a Phaleria macrocarpa (Scheff.) Boerl. extract confers antiproliferative and proapoptosis effects via eicosanoid pathway J Exp Ther Oncol 8 187 - 201
Wang Y , Gilbert MG , Mathew B , Brickell CD , Nevling LI , Wu ZY , Raven PH , Hong DY 2007 Flora of China In Thymelaeaceae Science Press Beijing, China 213 - 250
Winarno H , Katrin WE 2009 Benzophenone glucoside isolated from the ethyl acetate of the bark of mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) and its inhibitory activity on leukemia L1210 cell line Indo J Chem 9 142 - 145
Yosie A , Effendy MAW , Sifzizul TMT , Habsah M 2011 Antibacterial, radical-scavenging activities and cytotoxicity properties of Phaleria macrocarpa (Scheff.) Boerl leaves in HEPG2 cell lines Int J Pharm Sci Res 2 1700 - 1706
Zhang YB , Xu XJ , Liu HM 2006 Chemical constituents from mahkota dewa J Asian Nat Prod Res 8 119 - 123    DOI : 10.1080/10286020500480472
Zhang SY , Zhang QH , Zhao W , Zhang X , Zhang Q , Bi YF , Zhang YB 2012 Isolation, characterization and cytotoxic activity of benzophenone glucopyranoside from mahkota dewa (Phaleria macrocarpa (Scheff.) Boerl.) Bioorg Med Chem Lett 22 6862 - 6866    DOI : 10.1016/j.bmcl.2012.09.038