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  1. Jalil J, Sabandar CW, Ahmat N, Jamal JA, Jantan I, Aladdin NA, et al.
    Molecules, 2015 Feb 16;20(2):3206-20.
    PMID: 25690285 DOI: 10.3390/molecules20023206
    The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E2 (PGE2) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated from the root bark of the plant, koetjapic (1), 3-oxoolean-12-en-30-oic (2), and betulinic (3) acids, exhibited significant concentration-dependent inhibitory effects on PGE2 production with IC50 values of 1.05, 1.54, and 2.59 μM, respectively, as compared with the positive control, indomethacin (IC50 = 0.45 μM). Quantification of compounds 1 and 3 in the methanol extracts and fractions were carried out by using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method. The ethyl acetate fraction of the stem bark showed the highest content of both compound 1 (15.1%) and compound 3 (52.8%). The strong inhibition of the extracts and fractions on cyclooxygenase-2 (COX-2) enzymatic activity was due to the presence of their major constituents, especially koetjapic and betulinic acids.
    Matched MeSH terms: Dilleniaceae/chemistry*
  2. Saiful Yazan L, Armania N
    Pharm Biol, 2014 Jul;52(7):890-7.
    PMID: 24766363 DOI: 10.3109/13880209.2013.872672
    Dillenia (Dilleniaceae) is a genus of about 100 species of flowering plants in tropical and subtropical trees of Southern Asia, Australasia, and the Indian Ocean Islands. Until now, only eight Dillenia species have been reported to be used traditionally in different countries for various medical purposes. Out of eight species, D. pentagyna (Roxb), D. indica (Linn.) and D. suffruticosa (Griffith Ex. Hook. F. & Thomsom Martelli) have been reported to be used to treat cancerous growth.
    Matched MeSH terms: Dilleniaceae/chemistry*
  3. Armania N, Yazan LS, Ismail IS, Foo JB, Tor YS, Ishak N, et al.
    Molecules, 2013;18(11):13320-39.
    PMID: 24172241 DOI: 10.3390/molecules181113320
    The present research was designed to evaluate the anticancer properties of Dillenia suffruticosa extract. Our focus was on the mode of cell death and cell cycle arrest induced in breast cancer cells by the active fractions (designated as D/F4, D/F5 and EA/P2) derived from chromatographic fractionation of D. suffruticosa extracts. The results showed that the active fractions are more cytotoxic towards MCF-7 (estrogen positive breast cancer cells) and MDA-MB-231 (estrogen negative breast cancer cells) as compared to other selected cancer cell lines that included HeLa, A459 and CaOV3. The induction of cell death through apoptosis by the active fractions on the breast cancer cells was confirmed by Annexin V-FITC and PI staining. Cell cycle analysis revealed that D/F4 and EA/P2 induced G2/M phase cell cycle arrest in MCF-7 cells. On the other hand, MDA-MB-231 cells treated with D/F4 and D/F5 accumulated in the sub-G1 phase without cell cycle arrest, suggesting the induction of cell death through apoptosis. The data suggest that the active fractions of D. suffruticosa extract eliminated breast cancer cells through induction of apoptosis and cell cycle arrest. The reason why MCF-7 was more sensitive towards the treatment than MDA-MB-231 remains unclear. This warrants further work, especially on the role of hormones in response towards cytotoxic agents. In addition, more studies on the mechanisms underlying the induction of apoptosis and cell cycle arrest by the plant extract also need to be carried out.
    Matched MeSH terms: Dilleniaceae/chemistry*
  4. Abubakar S, Al-Mansoub MA, Murugaiyah V, Chan KL
    Phytother Res, 2019 Mar;33(3):660-675.
    PMID: 30653753 DOI: 10.1002/ptr.6255
    The Dillenia suffruticosa leaves (Dilleniaceae), a folk medicine recommended in Southeast Asia for treating inflammation, were phytochemically studied for the first time and assessed for suppression of λ-carrageenan-induced paw oedema in rats. The crude methanolic extract orally administered at 5,000 mg/kg, displayed no toxicity and at 250 to 1,000 mg/kg significantly suppressed the paw oedema. Two-isolated triterpenoids, betulinic acid (1) and koetjapic acid (2) orally administered at 50 mg/kg, significantly reduced the paw oedema, (p 
    Matched MeSH terms: Dilleniaceae/chemistry*
  5. Alhassan AM, Ahmed QU, Latip J, Shah SAA
    Nat Prod Res, 2019 Jan;33(1):1-8.
    PMID: 29417849 DOI: 10.1080/14786419.2018.1437427
    The bioactivity guided fractionation of Tetracera indica leaves crude ethanolic extract has afforded the isolation and characterization of six compounds including a new natural product viz., 5,7-dihydroxyflavone-O-8-sulphate (1) and five known flavonoids (2-6). The structures of the compounds were elucidated using 1D and 2D NMR and HRESIMS spectroscopic analyses. All the isolated compounds were evaluated for their in vitro inhibitory activity against alpha-glucosidase. Compound 1, 5 and 6 showed strong alpha-glucosidase inhibitory activity, 3 and 4 displayed weak activity while compound 2 was inactive. The interactions of the active compounds with alpha-glucosidase were further investigated using molecular docking to confirm their antidiabetic potential.
    Matched MeSH terms: Dilleniaceae/chemistry*
  6. Sabandar CW, Jalil J, Ahmat N, Aladdin NA
    Phytochemistry, 2017 Feb;134:6-25.
    PMID: 27889244 DOI: 10.1016/j.phytochem.2016.11.010
    The genus Dillenia is comprised of about 100 species of evergreen and deciduous trees or shrubs of disjunct distribution in the seasonal tropics of Madagascar through South and South East Asia, Malaysia, North Australia, and Fiji. Species from this genus have been widely used in medicinal folklore to treat cancers, wounds, jaundice, fever, cough, diabetes mellitus, and diarrhea as well as hair tonics. The plants of the genus also produce edible fruits and are cultivated as ornamental plants. Flavonoids, triterpenoids, and miscellaneous compounds have been identified in the genus. Their extracts and pure compounds have been reported for their antimicrobial, anti-inflammatory, cytotoxic, antidiabetes, antioxidant, antidiarrheal, and antiprotozoal activities. Mucilage from their fruits is used in drug formulations.
    Matched MeSH terms: Dilleniaceae/chemistry*
  7. Shah MD, Gnanaraj C, Khan MS, Iqbal M
    J Environ Pathol Toxicol Oncol, 2015;34(2):133-52.
    PMID: 26081032
    Dillenia suffruticosa L. (Dilleniaceae) is used in traditional medicine for protection against various diseases. The current study was designed to investigate the bioactive compounds and hepatoprotective potential of methanol leaves extract of D. suffruticosa against carbon tetrachloride (CCl4)-induced hepatic oxidative injury. Sprague Dawley rats were pretreated with methanol extract of D. suffruticosa leaves (200, 300, and 400 mg/kg body weight [bwt]) once daily for 14 days followed by two doses of CCl4 (1.0 mL/kg bwt). After 2 weeks the rats were sacrificed and hepatoprotective analysis was performed. The identified bioactive compounds include phenol (1.39%); benzyl alcohol (2.04%); 2H-pyran-2-one, 4,6-dimethyl (1.19%); phenol, 2,4-bis(1,1-dimethylethyl) (0.83%); dodecanoic acid (0.84%); hexadecanoic acid, methyl ester (2.66%); n-hexadecanoic acid (0.96%); and phytol (2.13%). The administration of D. suffruticosa significantly depleted the elevation of enzymatic levels of alanine transaminase and aspartate transaminase (4% to 59% recovery), reduced the extent of malondialdehyde production (13% to 79% recovery), elevated the level of reduced glutathione (5% to 21% recovery), and increased the activities of antioxidant enzymes (0.43% to 35% recovery). Histopathological analyses by light and electron microscopy revealed that the plant extract protects the liver from the toxic effects of CCl4 and cured lesions such as necrosis and fatty degeneration. It also decreased hepatocyte injuries such as irregular lamellar organization and dilations in endoplasmic reticulum. Immunohistochemical studies indicate the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxyl-2-nonenal (HNE)-modified protein adducts. In addition, the overexpression of the inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) are reduced. Hence, we find D. suffruticosa to be a good source of bioactive compounds with hepatoprotective effects against CCl4-induced oxidative damage.
    Matched MeSH terms: Dilleniaceae/chemistry*
  8. Hasan MM, Ahmed QU, Soad SZM, Latip J, Taher M, Syafiq TMF, et al.
    BMC Complement Altern Med, 2017 Aug 30;17(1):431.
    PMID: 28854906 DOI: 10.1186/s12906-017-1929-3
    BACKGROUND: Tetracera indica Merr. (Family: Dilleniaceae), known to the Malay as 'Mempelas paya', is one of the medicinal plants used in the treatment of diabetes in Malaysia. However, no proper scientific study has been carried out to verify the traditional claim of T. indica as an antidiabetic agent. Hence, the aims of the present study were to determine the in vitro antidiabetic potential of the T. indica stems ethanol extract, subfractions and isolated compounds.

    METHODS: The ethanol extract and its subfractions, and isolated compounds from T. indica stems were subjected to cytotoxicity test using MTT viability assay on 3T3-L1 pre-adipocytes. Then, the test groups were subjected to the in vitro antidiabetic investigation using 3T3-L1 pre-adipocytes and differentiated adipocytes to determine the insulin-like and insulin sensitizing activities. Rosiglitazone was used as a standard antidiabetic agent. All compounds were also subjected to fluorescence glucose (2-NBDG) uptake test on differentiated adipocytes. Test solutions were introduced to the cells in different safe concentrations as well as in different adipogenic cocktails, which were modified by the addition of compounds to be investigated and in the presence or absence of insulin. Isolation of bioactive compounds from the most effective subfraction (ethyl acetate) was performed through repeated silica gel and sephadex LH-20 column chromatographies and their structures were elucidated through (1)H-and (13)C-NMR spectroscopy.

    RESULTS: Four monoflavonoids, namely, wogonin, norwogonin, quercetin and techtochrysin were isolated from the T. indica stems ethanol extract. Wogonin, norwogonin and techtochrysin induced significant (P 

    Matched MeSH terms: Dilleniaceae/chemistry*
  9. Foo JB, Yazan LS, Tor YS, Armania N, Ismail N, Imam MU, et al.
    PMID: 24947113 DOI: 10.1186/1472-6882-14-197
    Dillenia suffruticosa root dichloromethane extract (DCM-DS) has been reported to exhibit strong cytotoxicity towards breast cancer cells. The present study was designed to investigate the cell cycle profile, mode of cell death and signalling pathways of DCM-DS-treated human caspase-3 deficient MCF-7 breast cancer cells.
    Matched MeSH terms: Dilleniaceae/chemistry*
  10. Nokhala A, Siddiqui MJ, Ahmed QU, Ahamad Bustamam MS, Zakaria AZA
    Biomolecules, 2020 02 12;10(2).
    PMID: 32059529 DOI: 10.3390/biom10020287
    Stone leaf (Tetracera scandens) is a Southeast Asian medicinal plant that has been traditionally used for the management of diabetes mellitus. The underlying mechanisms of the antidiabetic activity have not been fully explored yet. Hence, this study aimed to evaluate the α-glucosidase inhibitory potential of the hydromethanolic extracts of T. scandens leaves and to characterize the metabolites responsible for such activity through gas chromatography-mass spectrometry (GC-MS) metabolomics. Crude hydromethanolic extracts of different strengths were prepared and in vitro assayed for α-glucosidase inhibition. GC-MS analysis was further carried out and the mass spectral data were correlated to the corresponding α-glucosidase inhibitory IC50 values via an orthogonal partial least squares (OPLS) model. The 100%, 80%, 60% and 40% methanol extracts displayed potent α-glucosidase inhibitory potentials. Moreover, the established model identified 16 metabolites to be responsible for the α-glucosidase inhibitory activity of T. scandens. The putative α-glucosidase inhibitory metabolites showed moderate to high affinities (binding energies of -5.9 to -9.8 kcal/mol) upon docking into the active site of Saccharomyces cerevisiae isomaltase. To sum up, an OPLS model was developed as a rapid method to characterize the α-glucosidase inhibitory metabolites existing in the hydromethanolic extracts of T. scandens leaves based on GC-MS metabolite profiling.
    Matched MeSH terms: Dilleniaceae/chemistry*
  11. Foo JB, Saiful Yazan L, Tor YS, Wibowo A, Ismail N, How CW, et al.
    J Ethnopharmacol, 2015 May 26;166:270-8.
    PMID: 25797115 DOI: 10.1016/j.jep.2015.03.039
    Dillenia suffruticosa (Family: Dilleniaceae) or commonly known as "Simpoh air" in Malaysia, is traditionally used for treatment of cancerous growth including breast cancer.
    Matched MeSH terms: Dilleniaceae/chemistry*
  12. Tor YS, Yazan LS, Foo JB, Wibowo A, Ismail N, Cheah YK, et al.
    PLoS One, 2015;10(6):e0127441.
    PMID: 26047480 DOI: 10.1371/journal.pone.0127441
    Dillenia suffruticosa, which is locally known as Simpoh air, has been traditionally used to treat cancerous growth. The ethyl acetate extract of D. suffruticosa (EADs) has been shown to induce apoptosis in MCF-7 breast cancer cells in our previous study. The present study aimed to elucidate the molecular mechanisms involved in EADs-induced apoptosis and to identify the major compounds in the extract. EADs was found to promote oxidative stress in MCF-7 cells that led to cell death because the pre-treatment with antioxidants α-tocopherol and ascorbic acid significantly reduced the cytotoxicity of the extract (P<0.05). DCFH-DA assay revealed that treatment with EADs attenuated the generation of intracellular ROS. Apoptosis induced by EADs was not inhibited by the use of caspase-inhibitor Z-VAD-FMK, suggesting that the cell death is caspase-independent. The use of JC-1 dye reflected that EADs caused disruption in the mitochondrial membrane potential. The related molecular pathways involved in EADs-induced apoptosis were determined by GeXP multiplex system and Western blot analysis. EADs is postulated to induce cell cycle arrest that is p53- and p21-dependent based on the upregulated expression of p53 and p21 (P<0.05). The expression of Bax was upregulated with downregulation of Bcl-2 following treatment with EADs. The elevated Bax/Bcl-2 ratio and the depolarization of mitochondrial membrane potential suggest that EADs-induced apoptosis is mitochondria-dependent. The expression of oxidative stress-related AKT, p-AKT, ERK, and p-ERK was downregulated with upregulation of JNK and p-JNK. The data indicate that induction of oxidative-stress related apoptosis by EADs was mediated by inhibition of AKT and ERK, and activation of JNK. The isolation of compounds in EADs was carried out using column chromatography and elucidated using the nuclear resonance magnetic analysis producing a total of six compounds including 3-epimaslinic acid, kaempferol, kaempferide, protocatechuic acid, gallic acid and β-sitosterol-3-O-β-D-glucopyranoside. The cytotoxicity of the isolated compounds was determined using MTT assay. Gallic acid was found to be most cytotoxic against MCF-7 cell line compared to others, with IC50 of 36 ± 1.7 μg/mL (P<0.05). In summary, EADs generated oxidative stress, induced cell cycle arrest and apoptosis in MCF-7 cells by regulating numerous genes and proteins that are involved in the apoptotic signal transduction pathway. Therefore, EADs has the potential to be developed as an anti-cancer agent against breast cancer.
    Matched MeSH terms: Dilleniaceae/chemistry*
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