Indonesian Medicinal Plants Research Articles

29-Norcucurbitacin Derivatives Isolated from the Indonesian Medicinal Plant,Phaleria macrocarpa(Scheff.) Boerl.

The new 29-norcucurbitacin, desacetylfevicordin A (1), together with three known 29-norcucurbitacin derivatives (2-4) were isolated from seeds of the Indonesian medicinal plant, Phaleria macrocarpa (Scheff.) Boerl. The structures of 1-4 were elucidated on the basis of spectroscopic analyses and chemical transformation. These compounds exhibited toxicity against the brine shrimp (Artemia salina).

Screening of Indonesian Medicinal Plant Extracts for Antibabesial Activity and Isolation of New Quassinoids fromBrucea javanica

Boiled extracts derived from 28 Indonesian medicinal plants were screened for their antibabesial activity against Babesia gibsoni in vitro. Of these extracts, the fruit of Brucea javanica was the most active in inhibiting parasite growth at a concentration of 10 microg/mL. Bioassay-guided fractionation of the fruit extract of Br. javanica led to the isolation of two new quassinoids, bruceantinol B and bruceine J, and the structures of these compounds were elucidated on the basis of their spectroscopic data and by chemical transformation to known compounds. In addition, the known quassinoids bruceines A-D, bruceantinol, and yadanziolide A were isolated. Antibabesial activities were also examined in vitro, and bruceine A and bruceantinol were shown to be more potent than diminazene aceturate, a drug (IC50 = 103 ng/mL) used clinically against B. gibsoni, with IC50 values of 4 and 12 ng/mL, respectively.

Lignan profile of Piper cubeba, an Indonesian medicinal plant

The lignan profile of the aerial part of Piper cubeba L. (Piperaceae) was determined using GC, GC–MS and HPLC. The number of lignans found in the leaves was 15, followed by berries and the stalks with respectively 13 and five lignans. This is the first investigation of lignans from the leaves and the stalks of P. cubeba. Cubebin, hinokinin, yatein, isoyatein are common lignans in the genus Piper and appeared as major components in all parts of P. cubeba investigated.

164 POSTER In vitro and in vivo evaluation of orally available potent and selective small-molecule antagonists of the MDM2-p53 interaction in multiple models of human cancer

Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases.The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death.MDA-MB-231 cells were incubated with PMEAF for 24 h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array.The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G0/G1 and G2/M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆Ψm) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells.The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G0/G1 and G2/M-phases cell cycle arrest by p53-mediated mechanism.

Determination of chemical structure of antioxidant compound benzophenon glycoside from n-butanol extract of the fruits of Mahkota Dewa [Phaleria macrocarpa (Scheff) Boerl.

In continuing of chemical study research on the parts of the fruits of Mahkota dewa, we have done isolated one antioxidant compound benzophenon glycoside from n -butanol extract. Isolation and purification by column chromatography (SiO2, chloroform-methanol) and determination of chemical structure based on interpretation spectra of ultraviolet (UV), infrared (IR) and nuclear magnetic resonance 1 dimension (1H & 13C NMR), 2 dimension (1H-1H COSY, 13C-1H COSY, HMBC). Based on spectrroscopic data, the compound was identified as 6,4’,-dihidroksi-4- metoksibenzofenon-2- O -α-D glucopyranoside. Key words : Mahkota dewa, Phaleria macrocarpa , Thymelaceae, Indonesian medicinal plant, benzophenone glycoside

Uses of plants as medicine by Muna People, Sub District Wakarumba, District Muna, Province of SoutheastSulawesi

North Wakarumba is one of subdistrict lies in the north of Buton Island, close to North Buton Nature Reserve. More than one etnic live in this sub district such as Muna as the biggest ethnic. Muna people have unique behavior in the plant using and environment management including protecting forest and its surrounding area. Study on the plant usage as traditional medicinal plant has been done by interviewing local people. The result of the research was got 61 species of medicinal plants, where 6 species of them have never been published at the Index of Indonesian Medicinal Plants. Thirty-eight plants species could be found wildly and 16 of them occur in North Buton Nature Reserve areas. Bark of 10 species reported as after giving birth medicine. Grinding of Epipremnum pinnatum leaves could be used as wound medicine. Leaf of Terminalia catappa could be used as anti diarrhea.© 2006 Jurusan Biologi FMIPA UNS SurakartaKey words: North Wakarumba, Muna ethnics, medicinal plant, Buton

Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants

Thirty samples of Indonesian medicinal plants were tested for their mechanism-based inhibition on cytochrome P450 3A4 (CYP3A4) and CYP2D6 via erythromycin N-demethylation and dextromethorphan O-demethylation activities in human liver microsomes. From screening with 0 and 20 min preincubation at 0.5 mg/ml of methanol extracts, five plants ( Cinnamomum burmani bark, Foeniculum vulgare seed, Strychnos ligustrina wood, Tinospora crispa stem, and Zingiber cassumunar rhizome) showed more than 30% increase of CYP3A4 inhibition, while three ( Alpinia galanga rhizome, Melaleuca leucadendron leaf, and Piper nigrum fruit) showed more than 30% increase of CYP2D6 inhibition. In these eight plants, Foeniculum vulgare seed, Cinnamomum burmani bark, and Strychnos ligustrina wood showed time-dependent inhibition on CYP3A4 and Piper nigrum fruit and Melaleuca leucadendron leaf on CYP2D6. Among these, four plants other than Melaleuca leucadendron revealed NADPH-dependent inhibition. Thus, Foeniculum vulgare, Cinnamomum burmani, and Strychnos ligustrina should contain mechanism-based inhibitors on CYP3A4 and Piper nigrum contain that on CYP2D6.

Inhibitory Effect of Artocarpanone from <i>Artocarpus heterophyllus</i> on Melanin Biosynthesis

In our previous efforts to find new tyrosinase inhibitory materials, we investigated 44 Indonesian medicinal plants belonging to 24 families. Among those plants, the extract of Artocarpus heterophyllus was one of the strongest inhibitors of tyrosinase activity. By activity-guided fractionation of A. heterophyllus wood extract, we isolated artocarpanone, which inhibited both mushroom tyrosinase activity and melanin production in B16 melanoma cells. This compound is a strong candidate as a remedy for hyperpigmentation in human skin.

CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants

Thirty samples of Indonesian medicinal plants were analyzed for their capacity to inhibit in vitro metabolism by human cytochrome P450 3A4 (CYP3A4) and CYP2D6 with a radiometric assay. The MeOH-soluble fractions of 25 samples, prepared from water extracts, demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, and 21 samples on the metabolism mediated by CYP2D6. Among the MeOH-soluble fractions, Piper nigrum leaf showed the highest inhibitory activity against CYP3A4 (91.7%), and Punica granatum against CYP2D6 (98.1%). The water extracts of which MeOH-soluble fraction showed inhibitory activity more than 70% were fractionated with EtOAc. From the EtOAc-soluble fractions, Curcuma heyneana (67.0%), Pi. cubeba (75.0%), Pi. nigrum fruit (84.0%), Pi. nigrum leaf (85.8%), and Zingiber aromaticum (75.3%) demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, but only Pi. nigrum fruit (72.8%) and Pi. nigrum leaf (69.1%) showed strong inhibitory activity against CYP2D6. For samples that showed more than 70% inhibition, their IC(50) values were determined. The most potent inhibitory activity against CYP3A4 (IC(50) value of 25 microg/ml) was found for the extract of Pi. nigrum leaf, while that of Catharanthus roseus showed the most potent inhibitory effect against CYP2D6 (IC(50) value of 11 microg/ml). These results should indicate once more the possibility of potential medicinal plant-drug interactions.

Screening of Indonesian medicinal plants for inhibitor activity on nitric oxide production of RAW264.7 cells and antioxidant activity

Traditional Indonesian medicinal plants were screened for their inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and for the antioxidant activity through the evaluation of free radical scavenging effect and reducing power. The results of screening indicated that 50 methanolic extracts inhibited (>50%) lipopolysaccharides (LPS)-induced NO release from RAW264.7 cells at 50 μg/ml, with 18 having greater than 100% inhibition. At 200 μg/ml, 61 methanol extracts exhibited inhibitory activity (>50%), with 45 showing greater than 100% inhibition. In addition, the free radical scavenging effects of 6 methanolic extracts were found to be more than 50% for extract concentration of 0.5 μg/ml. The results indicate that the extracts contain active compounds that inhibit NO release and scavenge free radical.

Indonesian medicinal plants. XXV. Cancer cell invasion inhibitory effects of chemical constituents in the parasitic plant Scurrula atropurpurea (Loranthaceae).

Six fatty acids (1-6), two xanthines (7, 8), two flavonol glycosides (9, 10), one monoterpene glucoside (11), one lignan glycoside (12), and four flavanes (13-16) were clarified by a bioassay-guided separation as chemical constituents of Scurrula atropurpurea (Loranthaceae), a parasitic plant of the tea plant Thea sinensis (Theaceae). Among these constituents, it was found that the alkynic fatty acid octadeca-8,10,12-triynoic acid (6) exhibits a more potent inhibitory effect on cancer cell invasion in vitro than flavanes [(+)-catechin (13), (-)-epicatechin (14), (-)-epicatechin-3-O-gallate (15) and (-)-epigallocatechin-3-O-gallate (16)].

Antiviral and cytotoxic activities of some Indonesian plants

Ten methanolic extracts from eight Indonesian medicinal plants were phytochemically screened and evaluated for antiviral (HSV-1 and Poliovirus) and cytotoxic activities on murine and human cancer lines (3LL, L1210, K562, U251, DU145, MCF-7). Besides Melastoma malabathricum (Melastomataceae), the Indonesian Loranthaceae species among which Elytranthe tubaeflora, E. maingayi, E. globosa and Scurrula ferruginea exhibited attractive antiviral and cytotoxic activities. Piper aduncum (Piperaceae) was found active on Poliovirus. S. ferruginea was selected for further studies because of its activity on the U251 glioblastoma cells.

Screening of several Indonesian medicinal plants for their inhibitory effect on histamine release from RBL-2H3 cells

Twelve alcoholic extracts and 12 hexane extracts of plant materials selected on the basis of medicinal folklore for asthma treatment in Indonesia were studied for their activity in inhibiting histamine release from RBL-2H3 cells (rat basophilic leukemia cell line), a tumor analog of mast cells. The results of screening indicated that five alcoholic extracts ( Plantago major leaves, Eucalyptus globulus leaves and fruit, Cinnamomum massoiae cortex, Vitex trifolia leaves) and two hexane extracts ( Eucalyptus globulus leaves, Vitex trifolia leaves) inhibited IgE-dependent histamine release from RBL-2H3 cells. The inhibitory effects were found to be more than 80% for extract concentrations of 0.5 mg/ml. The results indicate that the extracts contain active compounds that inhibit mast-cell degranulation, and provide insight into the development of new drugs for treating asthma and/or allergic disease.

Helicterins A - F, Six New Dimeric (7.5′,8.2′)-Neolignans from the Indonesian Medicinal PlantHelicteres isora

During a chemical study of Indonesian medicinal plants, we examined the constituents of fruits of Helicteres isora L. (Sterculiaceae), one of the famous Jamu medicines. From a H2O extract of the fruits, we isolated six new neolignans, the helicterins A – F (1 – 6), and elucidated their structures by spectral analyses. Helicterins A – F (1 – 6) are dimeric (7.5′,8.2′)-neolignans with a bicyclo[2.2.2]octene C-framework, and showed mild inhibitory activity against reverse transcriptase from avian myeloblastosis virus.

Indonesian medicinal plants. XXIII. Chemical structures of two new migrated pimarane-type diterpenes, neoorthosiphols A and B, and suppressive effects on rat thoracic aorta of chemical constituents isolated from the leaves of Orthosiphon aristatus (Lamiaceae).

Two novel migrated pimarane-type diterpenes named neoorthosiphols A (1) and B (2) were isolated from the water decoction of the leaves of Orthosiphon aristatus (Lamiaceae), which has been prescribed in Javanese traditional medicine (jamu) for the treatment of hypertension, etc. The absolute chemical structures have been elucidated on the basis of physicochemical properties. It has been found that two migrated pimarane-type diterpenes (1, 2), four isopimarane-type diterpenes (3, 4, 5, 6), three benzochromenes (7, 8, 9) and two flavones (12, 13) exhibit a suppressive effect on contractile responses in rat thoracic aorta, among thirteen chemical constituents (1-13) isolated from the leaves.

Search for pharmacological leads from tropical rainforest plants

Abstract

Helisterculins A and B, Two New (7.5′,8.2′)-Neolignans, and Helisorin, the First (6.4′,7.5′,8.2′)-Neolignan, from the Indonesian Medicinal PlantHelicteres isora

During a chemical study of Indonesian medicinal plants, we examined the constituents of fruits of Helicteres isora L. (Sterculiaceae), one of the famous Jamu medicines. From a water extract of the fruits, we isolated three new neolignans, helisterculins A (1) and B (2) and helisorin (3), and elucidated their structures by spectral analyses. Helisterculins A (1) and B (2) are (7.5′,8.2′)-neolignans with a bicyclo[2.2.2]octene C-framework, while helisorin (3) is a (6.4′,7.5′,8.2′)-neolignan with a very rare 4,4a,9,9a-tetrahydro-3,9-methano-3H-fluorene C-framework. The natural product with the latter C-framework has no literature precedent. The neolignans 1 – 3 showed weak inhibitory activity against reverse transcriptase from avian myeloblastosis virus.

Inhibitory effects of Indonesian medicinal plants on the infection of herpes simplex virus type 1

Water and methanol extracts of 30 traditional medicinal plants, collected in Indonesia, were tested for their anti HSV-1 activity. The extracts of eight plant species showed potent activity on the plaque assay at a concentration of 100 µg/mL. The therapeutic efficacy of seven selected plants was demonstrated by using a mouse HSV-1 infection assay, both the methanol extracts of the fruit of Melaleuca leucadendron (Myrtaceae) and the pericarp of Nephelium lappaceum (Sapindaceae) significantly prolonged the development of skin lesions and reduced the mortality. Copyright © 1999 John Wiley & Sons, Ltd.

Inhibitory effects of Indonesian medicinal plants on the infection of herpes simplex virus type 1.

Water and methanol extracts of 30 traditional medicinal plants, collected in Indonesia, were tested for their anti HSV-1 activity. The extracts of eight plant species showed potent activity on the plaque assay at a concentration of 100 micrograms/mL. The therapeutic efficacy of seven selected plants was demonstrated by using a mouse HSV-1 infection assay, both the methanol extracts of the fruit of Melaleuca leucadendron (Myrtaceae) and the pericarp of Nephelium lappaceum (Sapindaceae) significantly prolonged the development of skin lesions and reduced the mortality.

Studies on Jamu and the medicinal resources in Indonesia. Part 2. Studies on the Constituents of Fruits of Helicteres isora L.

Three new compounds; 4'-O-β-D-glucopyranosyl rosmarinic acid (2), 4, 4'-O-di-β-D-glucopyranosyl rosmarinic acid(3) and 2R-O-(4'-O-β-D-glucopyranosyl caffeoyl)-3-(4-hydroxyphenyl) lactic acid named as 4'-O-β-D-glucopyranosyl isorinic acid (4) were isolated together with rosmarinic acid (1) from the fruit of Helicteres isora L. (Sterculiaceae), an Indonesian medicinal plant. The structures of these compounds, including the absolute stereochemistry of 4, were elucidated by spectroscopic analysis and chemical means. Compound 3 had greater scavenging activity against superoxide anion produced with xanthine and xanthine oxidase (XOD) than rosmarinic acid (1).