Dipterocarpol in Oleoresin of Dipterocarpus alatus Attributed to Cytotoxicity and Apoptosis-Inducing Effect.

Dipterocarpus alatus Roxb. ex G. Don is widely found in Southeast Asia. Its oleo-resin has reportedly been used in biodiesel production. Two different biodiesel production processes produce resinous byproducts, namely degumming (DG) and distillation (DT). Gas chromatography-mass spectrometry identified sesquiterpenes and triterpenes in oleo-resin, DG, and DT; and long-chain hydrocarbons in oleo-resin. High-performance liquid chromatography detected dipterocarpol as a marker compound, with the highest to lowest amounts detected in DG, DT, and oleo-resin, respectively. Oleo-resin, DG, and DT exerted more cytotoxicity than dipterocarpol, and melphalan, a chemotherapeutic drug. Oleo-resin, DG, and DT exerted cytotoxicity to a different degree in T cell leukemia (Jurkat), cervical adenocarcinoma (HeLa), and human hepatocellular carcinoma (HepG2) cells, while the highest selectivity was found in the Jurkat cells compared to the non-cancer Vero cells. Dipterocarpol exhibited the highest cytotoxicity in HepG2 cells and the lowest cytotoxicity in Jurkat cells. Oleo-resin, DG, and DT induced apoptosis in Jurkat cells. In oleo-resin, DG, and DT, dipterocarpol and other compounds may act in synergy leading to cytotoxicity and an apoptosis-inducing effect. Oleo-resin, DG, and DT could be potential sources for anticancer agents. Dipterocarpol could serve as a biomarker for follow ups on the anticancer activity of a sample from D. alatus.

Antinociceptive, Anti-Hyperalgesia and Antiallodynic Activities of Polyphenol Rich Extract from Shorea roxburghii against Cyclophosphamide Induced Peripheral Neuropathy.

Cyclophosphamide (CYP) is a widely used antineoplastic and immunosuppressive drug, however, despite its efficacy, it has shown extensive multiple organ toxicities, including peripheral neuropathy which significantly affects the quality of life of cancer patients. This study elucidated the protective properties of Shorea roxburghii polyphenol extract (SLPE) in CYP-induced peripheral neuropathy. Rats were treated with SLPE (100 and 400 mg/kg) for five weeks plus CYP once a week from the second week of SLPE treatment. Using UHPLC-QTOF-MS, 54 polyphenolic compounds were identified in SLPE extract. After the treatment period the antinociceptive, anti-hyperalgesia and antiallodynic effects was evaluated using formalin paw edema, acetic acid abdominal writhing, hot plate, tail immersion and von Frey filament tests. While the locomotive and motor coordination effects were evaluated by open field and rotarod tests. The administration of CYP led to significant increases in mechanical and thermal hyperalgesia, in addition to hyper-nociceptive responses in the formalin and acetic acid writhing tests. CYP also significantly reduced locomotive activity and motor coordination. SLPE significantly protected against CYP-induced mechanical and thermal hyperalgesia. Furthermore, SLPE displayed robust antinociceptive effect by counteracting formalin and acetic acid induced hyper-nociception. In addition, SLPE increased the locomotive activity as well as the grip and motor coordination of the CYP treated rats. In conclusion, these results revealed the protective effects of SLPE against CYP-induced peripheral neuropathy and could be an effective therapeutic remedy for chemotherapy induced peripheral neuropathy.

Niosome-encapsulated balanocarpol: compound isolation, characterisation, and cytotoxicity evaluation against human breast and ovarian cancer cell lines.

Natural products have been successfully used to treat various ailments since ancient times and currently several anticancer agents based on natural products are used as the main therapy to treat cancer patients, or as a complimentary treatment to chemotherapy or radiation. Balanocarpol, which is a promising natural product that has been isolated from Hopea dryobalanoides, has been studied as a potential anticancer agent but its application is limited due to its high toxicity, low water solubility, and poor bioavailability. Therefore, the aim of this study is to improve the characteristics of balanocarpol and increase its anticancer activity through its encapsulation in a bilayer structure of a lipid-based nanoparticle drug delivery system where the application of nanotechnology can help improve the limitations of balanocarpol. The compound was first extracted and isolated from H. dryobalanoides. Niosome nanoparticles composed of Span 80 (SP80) and cholesterol were formulated through an innovative microfluidic mixing method for the encapsulation and delivery of balanocarpol. The prepared particles were spherical, small, and uniform with an average particles size and polydispersity index ∼175 nm and 0.088, respectively. The encapsulation of balanocarpol into the SP80 niosomes resulted in an encapsulation efficiency of ∼40%. The niosomes formulation loaded with balanocarpol showed a superior anticancer effect over the free compound when tested in vitro on human ovarian carcinoma (A2780) and human breast carcinoma (ZR-75-1). This is the first study to report the use of SP80 niosomes for the successful encapsulation and delivery of balanocarpol into cancer cells.

Hopea odorata Extract Can Efficiently Kill Breast Cancer Cells and Cancer Stem-Like Cells in Three-Dimensional Culture More Than in Monolayer Cell Culture.

INTRODUCTION: The breast cancer cells with CD44+CD24- phenotype are known to play an important role in tumorigenesis, drug resistance, and cancer recurrence. Breast cancer cells with CD44+CD24- phenotype are cultured in three-dimensional (3D) stereotype showing the recapitulation of tumors in vivo such as cell differentiation, heterogeneity, and microenvironment. Using this 3D model in anti-cancer compound research results in a more accurate reflection than conventional monolayer cell culture. This study aimed to identify the antitumor activity of Hopea odorata methanol extract (HO-MeOH-E) on breast cancer cells and cancer stem-like cells in both models of three-dimensional culture (3D) and monolayer cell culture (2D). METHODS: HO-MeOH-E was produced from Hopea odorata plant. The VN9 breast cancer cells (VN9) were collected and expanded from the previous study. The breast cancer stem-like cells (VN9CSC) were sorted from the VN9 based on phenotype CD44+CD24-. Both VN9 and VN9CSC were used to culture in monolayer culture (2D) and organoids (3D) before they were used to treat with HO-MeOH-E. Two other anticancer drugs, doxorubicin and tirapazamine, were used as references. The antitumor activities of extracts and drugs were determined via two assays: antiproliferation using the Alamar blue assay and cell cycle assay. RESULTS: The results showed that HO-MeOH-E was sensitive to both VN9 and VN9CSC in 3D more than 2D culture (IC50 on 3D organoids 144.8 ± 2.172 µg/mL and on 2D 340.2 ± 17.01 µg/mL for VN9CSC (p < 0.001); IC50 on 3D organoids 2055 ± 82.2 µg/mL and on 2D 430.6 ± 8.612 µg/mL for VN9 (p < 0.0001), respectively). HO-MeOH-E inhibits VN9CSC proliferation by blocking S phase and increasing the populations of apoptotic cells; this is consensus to the effect of tirapazamine (TPZ) which is used in hypoxia-activated chemotherapy. CONCLUSION: Taken these results, HO-MeOH-E has the potential effect in hypoxia-activated chemotherapy specifically on breast cancer stem-like cells with CD44+CD24- phenotype.

Shorea roxburghii Leaf Extract Ameliorates Hyperglycemia Induced Abnormalities in High Fat/Fructose and Streptozotocin Induced Diabetic Rats.

This study investigated the hypoglycemic effect of the methanol extract of Shorea roxburghii leaves (SRL) in high fat diet/high fructose solution (HFDHF) and streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) in rats as well as evaluating its ameliorative potentials in altered biochemical and hematological parameters in the treated rats. T2DM was induced in Sprague Dawley (SD) rats by feeding with HFDHF for 4 weeks and administering STZ (35 mg/kg, i. p.). Diabetic rats were given SRL extract at doses of 100 and 400 mg/kg for 30 days. The food and water intake were monitored on a daily basis, while the fasting blood glucose (FBG) levels and body weight were measured weekly. Biochemical and hematological parameters as well as histopathological studies of the pancreas were also evaluated. SRL significantly decreased FBG and improved the body weight, food and water intake of treated diabetic rats. Furthermore, biochemical and hematological parameters including liver and kidney function enzymes, lipid profiles, white blood and red blood cells parameters were markedly ameliorated by SRL. Histopathological analyses of the pancreas indicated reconstitution of ß-cells architecture in SRL treated rats. The results of this study suggest that SRL has antidiabetic potential and can be considered for the treatment of T2DM.

Metals Uptake from Particulate Matter Through Foliar Transfer and Their Impact on Antioxidant Enzymes Activity of S. robusta in a Tropical Forest, West Bengal, India.

Particulate matters deposition on the leaves of S. robusta were investigated during three different seasons in two tropical forests: Barjora forest, situated adjacent to heavy pollution sources, and the control, Ballavpur Wildlife Sanctuary, West Bengal, India. The purpose of this study is to measure the dust fall and foliar transfer of heavy metals (viz., Pb, Cd, Cu, Cr, Fe, Ni, Zn, and Mn) and antioxidant enzyme activities (peroxidase, catalase) in S. robusta, including the measurement of heavy metals present in the suspended particulate matter in ambient air. Dust fall on leaves and the total metal accumulation capacity of the plant were the highest during winter season with metal accumulation index of 9.82. Based on two-way ANOVA, it has been shown that there is a statistically significant difference in dust fall between the two forests and in different seasons. From cluster analysis, correlation results, and principal component analysis, it was suggested that heavy metals in Barjora may be due to the traffic emission and various industrial activities. Increased levels of peroxidase and catalase activities and the presence of high levels of reactive oxygen species in the leaves of the Barjora forest was an indication of stress state in this forest. On the basis of these findings, controlling the emission of pollutants from industrial and vehicular activities in that area is highly encouraged.

Chemical Composition, Antioxidant and Cytotoxicity Activities of Leaves, Bark, Twigs and Oleo-Resin of Dipterocarpus alatus.

Dipterocarpus alatus (Dipterocarpaceae) is a medicinal plant whose use is well known for the treatment of genito-urinary diseases. However, there is no report of its cytotoxic potential. In this study, the chemical composition, antioxidant and cytotoxic activities of extracts of the leaves, bark, twigs and oleo-resin from D. alatus are investigated. Cytotoxicity was measured by the neutral red (NR) assay against HCT116, SKLU1, SK-MEL2, SiHa and U937 cancer cell lines and antioxidant capacity was evaluated by DPPH, ABTS radical scavenging, and ferric reducing antioxidant power (FRAP) assays. The chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). Leaf, bark and twig extracts exhibited stronger antioxidant activity than oleo-resin, with bark extract showing the highest antioxidant activity and the highest total phenolic content. All samples showed more cytotoxic activity against the U937 cell line than HCT116, SKLU1, SK-MEL2 and SiHa cells with oleo-resin being more cytotoxic than melphalan against U937 cells. Chemical composition analysis of oleo-resin by GC-MS showed that the major components were sesquiterpenes, namely α-gurjunene (30.31%), (-)-isoledene (13.69%), alloaromadendrene (3.28%), ß-caryophyllene (3.14%), γ-gurjunene (3.14%) and spathulenol (1.11%). The cytotoxic activity of oleo-resin can be attributed to the sesquiterpene content, whereas the cytotoxic and antioxidant activities of leaf, bark and twig extracts correlated to total phenolic content.

Ampelopsin E Reduces the Invasiveness of the Triple Negative Breast Cancer Cell Line, MDA-MB-231.

Breast cancer is the most common and the second leading cause of cancer-related deaths in women. It has two distinctive hallmarks: rapid abnormal growth and the ability to invade and metastasize. During metastasis, cancer cells are thought to form actin-rich protrusions, called invadopodia, which degrade the extracellular matrix. Current breast cancer treatments, particularly chemotherapy, comes with adverse effects like immunosuppression, resistance development and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, a natural oligostilbene extracted from Dryobalanops species, has exhibited various pharmacological properties, including anticancer and anti-inflammatory activities. However, there is yet no scientific evidence of the effects of ampelopsin E towards metastasis. Scratch assay, transwell migration and invasion assays, invadopodia and gelatin degradation assays, and ELISA were used to determine the effects of ampelopsin E towards the invasiveness of MDA-MB-231 cells. Strikingly in this study, ampelopsin E was able to halt migration, transmigration and invasion in MDA-MB-231 cells by reducing formation of invadopodia and its degradation capability through significant reduction (p < 0.05) in expression levels of PDGF, MMP2, MMP9 and MMP14. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC.

Effects of the Ethanol Extract of Dipterocarpus alatus Leaf on the Unpredictable Chronic Mild Stress-Induced Depression in ICR Mice and Its Possible Mechanism of Action.

Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.

A Bioactive Resveratrol Trimer from the Stem Bark of the Sri Lankan Endemic Plant Vateria copallifera.

A new resveratrol trimer, vateriferol (1), having four cis-oriented methine protons and constituting four contiguous stereocenters, was isolated from the bark extract of Vateria copallifera by bioassay-guided fractionation using a combination of normal, reversed phase, and size exclusion column chromatography. The structure was established based on its spectroscopic data. Vateriferol (1) was evaluated in vitro for its antioxidant capacity, enzyme inhibitory activity, growth inhibitory activity on a number of cancer cell lines, neuroprotective activity, and anti-inflammatory activity. Vateriferol (1) exhibited AChE inhibitory activity (IC50 8.4 ± 0.2 µM), ORAC activity (2079 ± 0.20 TE/g), and neuroprotective activity at 1.5 µM using PC12 cells deprived of oxygen and glucose and lowered NO levels in lipopolysaccharide-stimulated SIM-A9 microglial cells at 14.7 and 73.6 µM. Vateriferol (1) exhibited weak cytotoxic potency (<50% growth inhibition) against the tested cell lines at 147.2 µM.

4'-Methoxyresveratrol Alleviated AGE-Induced Inflammation via RAGE-Mediated NF-κB and NLRP3 Inflammasome Pathway.

Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4'-methoxyresveratrol (4'MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4'MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4'MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Besides, 4'MR significantly decreased oxidative stress, demonstrated by levels of ROS production, protein carbonyl and advanced oxidation protein product via down-regulation of NADPH oxidase. Further analysis showed that 4'MR attenuated the RAGE overexpression induced by MGO-BSA. It also blocked the downstream signal of AGE-RAGE, particularly, MAPKs including p38 and JNK, and subsequently reduced NF-κB activation. Additionally, 4'MR significantly abated the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome including NLRP3 and cleaved caspase-1 and reduced the secretion of mature IL-1ß. Taken together, our results suggest that the anti-inflammatory effect of 4'MR is mainly through suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. 4'MR could be a novel therapeutic agent for inflammation-related diseases.

Effects of selected Indonesian plant extracts on E. cuniculi infection in vivo.

The present study was conducted to evaluate the methanolic extracts from several plant leaves widely used in traditional medicine to cure digestive tract disorders and in the self-medication of wild animals such as non-human primates, namely Archidendron fagifolium, Diospyros sumatrana, Shorea sumatrana, and Piper betle leaves, with regard to their antimicrosporidial activity against Encephalitozoon cuniculi in immunocompetent BALB/c mice determined using molecular detection of microsporidial DNA (qPCR) in various tissues and body fluids of infected, treated mice. Of the plant extracts tested, Diospyros sumatrana provided the most promising results, reducing spore shedding by 88% compared to untreated controls. Moreover, total burden per 1 g of tissue in the D. sumatrana extract-treated group reached 87% reduction compared to untreated controls, which was comparable to the effect of the standard drug, Albendazole. This data represents the baseline necessary for further research focused on determining the structure, activity and modes of action of the active compounds, mainly of D. sumatrana, enabling subsequent development of antimicrosporidial remedies.

Quantitative Determination of Stilbenoids and Dihydroisocoumarins in Shorea roxburghii and Evaluation of Their Hepatoprotective Activity.

A simultaneous quantitative analytical method for 13 stilbenoids including (-)-hopeaphenol (1), (+)-isohopeaphenol (2), hemsleyanol D (3), (-)-ampelopsin H (4), vaticanols A (5), E (6), and G (7), (+)-α-viniferin (8), pauciflorol A (9), hopeafuran (10), (-)-balanocarpol (11), (-)-ampelopsin A (12), and trans-resveratrol 10-C-ß-d-glucopyranoside (13), and two dihydroisocoumarins, phayomphenols A1 (14) and A2 (15) in the extract of Shorea roxburghii (dipterocarpaceae) was developed. According to the established protocol, distributions of these 15 polyphenols (1-15) in the bark and wood parts of S. roxburghii and a related plant Cotylelobium melanoxylon were evaluated. In addition, the principal polyphenols (1, 2, 8, 13-15) exhibited hepatoprotective effects against d-galactosamine (d-galN)/lipopolysaccharide (LPS)-induced liver injury in mice at a dose of 100 or 200 mg/kg, p.o. To characterize the mechanisms of action, the isolates were examined in in vitro studies assessing their effects on (i) d-GalN-induced cytotoxicity in primary cultured mouse hepatocytes; (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages; and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. The mechanisms of action of these polyphenols (1, 2, and 8) were suggested to be dependent on the inhibition of LPS-induced macrophage activation and reduction of sensitivity of hepatocytes to TNF-α. However, none of the isolates reduced the cytotoxicity caused by d-GalN.

Induction of apoptosis and G2/M arrest by ampelopsin E from Dryobalanops towards triple negative breast cancer cells, MDA-MB-231.

BACKGROUND: Several compounds isolated from Dryobalanops have been reported to exhibit cytotoxic effects to several cancer cell lines. This study investigated the cytotoxic effects, cell cycle arrest and mode of cell death in ampelopsin E-treated triple negative cells, MDA-MB-231. METHODS: Cytotoxicity of ampelopsin E, ampelopsin F, flexuosol A, laevifonol, Malaysianol A, Malaysianol D and nepalensinol E isolated from Dryobalanops towards human colon cancer HT-29, breast cancer MDA-MB-231 and MCF-7, alveolar carcinoma HeLa and mouse embryonic fibroblast NIH/3 T3 cells were determined by MTT assay. The cells were treated with the compounds (0.94-30 µM) for 72 h. The mode of cell death was evaluated by using an inverted light microscope and annexin V/PI analysis. Cell cycle analysis was performed by using a flow cytometer. RESULTS: Data showed that ampelopsin E was most cytotoxic toward MDA-MB-231 with the IC50 (50 % inhibition of cell viability compared to control) of 14.5 ± 0.71 µM at 72 h. Cell shrinkage, membrane blebbing and formation apoptotic bodies characteristic of apoptosis were observed following treatment with ampelopsin E. The annexin V/PI flow cytometric analysis further confirmed that ampelopsin E induced apoptosis in MDA-MB-231 cells. Cell cycle analysis revealed that ampelopsin E induced G2/M phase cell cycle arrest in the cells. CONCLUSION: Ampelopsin E induced apoptosis and cell cycle arrest in MDA-MB-231 cells. Therefore, ampelopsin E has the potential to be developed into an anticancer agent for treatment of triple negative breast cancer.

Antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of organic and aqueous extracts of Hopea odorata leaves and in silico PASS prediction of its isolated compounds.

BACKGROUND: Hopea Odorata, locally known as Telsur (Bangladesh), has some traditional uses as folk medicine. This study aims to investigate the antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of H. odorata leaf extracts as new therapeutic prospects predicting the activity of some of the isolated compounds of this plant. METHODS: Leaves of Hopea odorata was extracted with pure methanol (MEHO), ethanol (EEHO) and water (AEHO). The extract was tested for antioxidant activity by using reducing power and H2O2 scavenging assay. Antidiarrheal effects were assayed by three standard methods of bioassay: Castor oil-induced diarrhea, Castor oil induced enteropooling and gastrointestinal transit test. Hypoglycemic effect was determined by normoglycemic model of mice. Thrombolytic activity was evaluated by clot lyses test for human and mice blood. In silico PASS prediction was applied for phytoconstituents namely Balanocarpol, Hopeaphenol and Ampelopsin H isolated from this plant. RESULT: Among the all extracts, MEHO exhibited strong antioxidant activity in both reducing power and H2O2 scavenging assay. Phenol content of MEHO was 297.22 ± 0.78 mg/g and flavonol content was 91.53 ± 1.82 mg/g. All the experiment of extracts at dose of 200 and 400 mg/kg and the standard drug loperamide (5 mg/kg) showed significant (p < 0.001) inhibition against castor oil induced diarrhea and castor oil induced enteropooling in mice. There were also significant (p < 0.01) reduction in gastrointestinal motility in the charcoal meal test. Leaf extract showed no significant (P < 0.01) decrease of blood glucose compared to Glibenclamide in normoglycemic mice. Using an in vitro thrombolytic model, MEHO showed the highest and significant clot lysis of human and mice blood compared to Streptokinase. PASS predicted the wide range of antioxidant, free radical scavenger, Nitric oxide scavenger, cardioprotectant, hepatoprotectant, thrombolytic, fibrinolytic, antibacterial, antifungal, anticarcinogenic, anthelmintic and anti-inflammatory activity of examined phytoconstituents. CONCLUSION: These findings suggest that the plant may be a potential source of new antidiarrheal, thrombolytic and antioxidative agents but it is found to have no antidiabetic capability. PASS prediction matched with present study for the extracts. Further study needs to identify the PASS predicted biological actions of the phytoconstituents.

Synergistic effect of fragrant herbs in Japanese scent sachets.

The sedative activity of eight aromatic natural medicines that are traditionally used in Japanese scent sachets was examined using an open field test with mice. Galangal (Kaempferia galanga), patchouli (Pogostemon cablin), sandalwood (Santalum album), spikenard (Nardostachys chinensis), cinnamon (Cinnamomum cassia), clove (Syzygium aromaticum), star anise (Illicium verum), and borneol (Dryobalanops aromatica) distilled oils were used. These natural medicines have various pharmacological effects. For example, galangal has insecticidal activity and clove extracts possess strong total antioxidant activity. Aromatherapy, a well-known complementary medicine system that uses inhalation, has recently attracted much attention. The sedative activity of inhaled aromatic compounds or essential oils has been examined by measuring the spontaneous motor activity of mice in an open field test. The galangal, patchouli, sandalwood, spikenard, and borneol oils showed significant sedative effects. The effect was stronger for a mixture of the five oils than for any of the single oils. This suggests that the oil mixture may have synergistic activity. Sedative activity was not observed when inactive oils (cinnamon, clove, and star anise) were added to the mixture of the five active oils.

Oligostilbenoids with acetylcholinesterase inhibitory activity from Dipterocarpus alatus.

Phytochemical investigation of the stem wood of Dipterocarpus alatus led to the isolation and characterization of four new oligostilbenoids, dipterocarpols A-D (1-4), together with two known resveratrol oligomers, hopeahainol (5) and hopeafuran (6). The structures of the new compounds were determined by comprehensive spectral analysis including 1D and 2D NMR, and high-resolution MS. The absolute configurations were determined by NOESY and CD spectra. Dipterocarpol A (1) and hopeahainol A (5) showed moderate acetylcholinesterase inhibitory activity with IC50 values of 8.28 µM and 11.28 µM, respectively. Furthermore, the discovery of compound 3 gave the first evidence that the biosynthetic origin of resveratrol aneuploids is related to the loss of a half resveratrol unit by oxidative cleavage.

A new symmetrical tetramer oligostilbenoid containing tetrahydrofuran ring from the stem bark of Dryobalanops lanceolata.

A new tetramer oligostilbenoid possessing tetrahydrofuran ring, malaysianol C (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata, together with four known oligostilbenoids nepalensinol E (2), ϵ-viniferin (3), laevifonol (4), and ampelopsin F (5). The structures of isolated compounds were elucidated on the basis of spectral evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay, whereas the cytotoxic activity was tested using MTT assay. The plausible biogenetic routes of the isolated compounds are also discussed.

Dipterocarpus tuberculatus as a promising anti-obesity treatment in Lep knockout mice.

Introduction: The therapeutic effects and mechanisms of Dipterocarpus tuberculatus (D. tuberculatus) extracts have been examined concerning inflammation, photoaging, and gastritis; however, their effect on obesity is still being investigated. Methods: We administered a methanol extract of D. tuberculatus (MED) orally to Lep knockout (KO) mice for 4 weeks to investigate the therapeutic effects on obesity, weight gain, fat accumulation, lipid metabolism, inflammatory response, and ß-oxidation. Results: In Lep KO mice, MED significantly reduced weight gains, food intake, and total cholesterol and glyceride levels. Similar reductions in fat weights and adipocyte sizes were also observed. Furthermore, MED treatment reduced liver weight, lipid droplet numbers, the expressions of adipogenesis and lipogenesis-related genes, and the expressions of lipolysis regulators in liver tissues. Moreover, the iNOS-mediated COX-2 induction pathway, the inflammasome pathway, and inflammatory cytokine levels were reduced, but ß-oxidation was increased, in the livers of MED-treated Lep KO mice. Conclusion: The results of this study suggest that MED ameliorates obesity and has considerable potential as an anti-obesity treatment.

Antidiabetogenic oligostilbenoids and 3-ethyl-4-phenyl-3,4-dihydroisocoumarins from the bark of Shorea roxburghii.

A methanol extract of the bark of Shorea roxburghii (Dipterocarpaceae) was found to inhibit plasma glucose elevation in sucrose-loaded mice. From the extract, three new 3-ethyl-4-phenyl-3,4-dihydroisocoumarins, 1'S-dihydrophayomphenol A(2) (1) and phayomphenols B(1) (2) and B(2) (3), were isolated together with 24 known compounds including 20 stilbenoids and oligostilbenoids. The structures of 1-3 were determined on the basis of their spectroscopic properties as well as of chemical evidences. Among the isolates, (-)-hopeaphenol (6), hemsleyanol D (8), (+)-α-viniferin (15), and (-)-balanocarpol (18) showed inhibitory activity against plasma glucose elevation in sucrose-loaded rats at doses of 100-200mg/kg, p.o. To clarify the mode of action of the antihyperglycemic property, effects of these oligostilbenoids on gastric emptying in mice, those on glucose uptake in isolated intestinal tissues as well as inhibitory activities against rat intestinal α-glucosidase and rat lens aldose reductase were examined.