Publications by authors named "Natthinee Anantachoke"

22 Publications

  • Page 1 of 1

Gambogic Acid Inhibits Wnt/β-catenin Signaling and Induces ER Stress-Mediated Apoptosis in Human Cholangiocarcinoma.

Asian Pac J Cancer Prev 2021 Jun 1;22(6):1913-1920. Epub 2021 Jun 1.

Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Objective: Gambogic acid (GA) has been reported to induce apoptosis in cholangiocarcinoma (CCA) cell lines. However, the molecular mechanisms underlying its anti-cancer activity remain poorly understood. This study was aimed to investigate GA's effect on human CCA cell lines, KKU-M213 and HuCCA-1, and its associated mechanisms on Wnt/β-catenin signaling pathway.

Methods: Cell viability, apoptosis, and cell cycle analysis were conducted by MTT and flow cytometry. The effect of GA mediated Wnt/β-catenin and ER stress were determined by luciferase-reporter assay, qRT-PCR, and western blot analysis.

Results: GA exhibited potent cytotoxicity in CCA cells which was associated with significantly inhibited cell proliferation, promoted G1 arrest, and activated caspase 3 mediated-apoptosis. GA attenuated β-catenin transcriptional levels, decreased β-catenin protein, and suppressed the expression of c-Myc, a downstream target gene of Wnt/β-catenin signaling. GA activated genes involved in ER stress mechanism in KKU-M213 and enhanced CCA's sensitivity to gemcitabine.

Conclusion: Our findings reveal that the molecular mechanism underpinning anti-cancer effect of GA is partially mediated through the inhibition of Wnt/β-catenin signaling pathway and induction of ER stress induced-apoptosis. GA may serve as a promising therapeutic modality for amelioration of gemcitabine-induced toxicity in CCA.
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http://dx.doi.org/10.31557/APJCP.2021.22.6.1913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418851PMC
June 2021

Antioxidant and Anticholinesterase Activities of Extracts and Phytochemicals of Leaves.

Molecules 2021 May 30;26(11). Epub 2021 May 30.

Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.

Bioassay-guided separation of young leaves extracts of (Blume) Merr. & L.M. Perry led to the isolation of four triterpenoids (betulinic acid, ursolic acid, jacoumaric acid, corosolic acid) and one sterol glucoside (daucosterol) from the ethyl acetate extract, and three polyphenols (gallic acid, myricitrin, and quercitrin) from the methanol (MeOH) extract. The MeOH extract of and some isolated compounds, ursolic acid and gallic acid potentially exhibited acetylcholinesterase activity evaluated by Ellman's method. The MeOH extract and its isolated compounds, gallic acid, myricitrin, and quercitrin, also strongly elicited DPPH radical scavenging activity. In HEK-293 cells, the MeOH extract possessed cellular antioxidant effects by attenuating hydrogen peroxide (HO)-induced ROS production and increasing catalase, glutathione peroxidase-1 (GPx-1), and glutathione reductase (GRe). Furthermore, myricitrin and quercitrin also suppressed ROS production induced by HO and induced GPx-1 and catalase production in HEK-293 cells. These results indicated that the young leaves of are the potential sources of antioxidant and anticholinesterase agents. Consequently, leaves are one of indigenous vegetables which advantage to promote the health and prevent diseases related to oxidative stress.
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http://dx.doi.org/10.3390/molecules26113295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198064PMC
May 2021

Mass spectral analysis of secondary metabolites from Zingiber montanum rhizome extract using UHPLC-HR-ESI-QTOF-MS/MS.

Phytochem Anal 2021 May 30. Epub 2021 May 30.

Department of Pharmacognosy and Center of Innovative Pharmacy for Pharmaceutical and Herbal Product Development, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Introduction: Zingiber montanum (J.Koenig) Link ex A.Dietr. is a popular medicinal plant in Thailand. Its rhizomes have been used as an ingredient in various Thai traditional medicine formulas. While many reports have focused on the chemical constituents and biological activities of this plant, a comprehensive study on secondary metabolite profiling using tandem mass spectrometry has, to this point, never been documented.

Objective: To analyze the chemical constituents in Z. montanum rhizomes using ultra-high performance liquid chromatography coupled with ultra-high-resolution electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-HR-ESI-QTOF-MS/MS) analyses and to utilize the characteristic fragmentation patterns of these compounds to facilitate their identification.

Methodology: UHPLC-HR-ESI-QTOF-MS/MS in positive ion mode was used for chemical identification of secondary metabolites from the ethanolic extract of the plant material. MS/MS data of some known reference compounds, together with detailed fragmentation pattern information of several compounds obtained from the crude extract, were used to elucidate their chemical structures.

Results: In this work, one benzaldehyde, ten phenylbutenoid monomers, six curcuminoids, and nine phenylbutenoid dimers were assigned based on their characteristic fragment ions. Among these compounds, 2-(3,4-dimethoxystyryl)oxirane was tentatively suggested as a potential new compound. Several characteristic fragment ions from these compounds were assigned and the relative ion abundance of these was also used to differentiate the chemical structures of compounds having the same molecular mass.

Conclusions: The results will benefit future high-throughput screening of bioactive compounds and method development for the quality control of raw materials and herbal drugs derived from Z. montanum rhizome extracts.
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http://dx.doi.org/10.1002/pca.3068DOI Listing
May 2021

Cytotoxic compounds from the leaves and stems of the endemic Thai plant .

Pharm Biol 2020 Dec;58(1):490-497

Department of National Parks, Wildlife and Plant Conservation, Ministry of Natural Resources and Environment, The Forest Herbarium, Bangkok, Thailand.

Weeras., Chalermglin & R.M.K. Saunders (Annonaceae) is a plant endemic to Thailand. Its constituents and their biological activities are unknown. Isolation and identification of the compounds in the leaves and stems of and determination of their cytotoxicity. Methanol extracts of the leaves and stems of were separated by chromatography, and spectroscopic methods were used to determine the structures of the components. The cytotoxicity of the extracts and pure compounds was evaluated using the sulforhodamine B assay with several cell lines. The cells were treated with the compounds at concentrations of 0.16-20 µg/mL for 48 or 72 h. The investigation of the extracts of leaves and stems resulted in the isolation of a new lignan, mitrephoran, and 15 known compounds. Among these compounds, 2-(3,4-dimethoxyphenyl)-6-(3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, ciliaric acid, 6-methoxymarcanine A, and stepharanine were isolated from this genus for the first time. The alkaloids liriodenine and oxoputerine exhibited strong cytotoxicity against all tested cells (IC values of 6.59-11.02 µM). In contrast, magnone A, 3',4--dimethylcedrusin, and 6-methoxymarcanine A inhibited the growth of some of the tested cells (IC values of 2.03-19.73 µM). Magnone A and 6-methoxymarcanine A showed low toxicity for Hek 293 cells (IC >20 µM). is a source of cytotoxic lignans and alkaloids. Among the cytotoxic compounds, magnone A and 6-methoxymarcanine A are potentially useful lead compounds for the further development of anticancer agents because of their selective inhibitory effects on cancer cell lines.
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http://dx.doi.org/10.1080/13880209.2020.1765813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336994PMC
December 2020

Saponins enriched in the epidermal layer of Holothuria leucospilota body wall.

Microsc Res Tech 2018 Oct 8;81(10):1182-1190. Epub 2018 Nov 8.

Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.

Saponins are secondary metabolites that provide medicinal benefits in controlling body homeostasis and metabolic functions. Sea cucumber has been consumed in many Asian countries due to their health benefits. Active chemicals found in sea cucumber include natural source of saponins which are enriched in their tissues, including the Cuvierian tubules and the body wall. Tissue origin of the saponin biosynthesis and accumulation is limitedly known. The present study is to indicate major compositions and distributions of saponins in the body wall of Holothuria leucospilota. Structurally, their body wall consisted of the pigmented layer of the epidermis, the dermal connective tissues, and inner muscular layers. Interestingly, release of the pigmented granules from the epidermis was related to detection of epidermal saponins. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) revealed identical mass spectra in the saponin extracts and compared to the known compounds of holothurians. To investigate the release of epidermal saponins, the epidermis dissolved in either butanol or distilled water were analyzed and presented the saponin masses with two prominent masses of m/z 1,243.3 (holothurin A and scabraside B) and 1,259.3 (holothurin A3). MALDI-IMS also demonstrated strong signals of the known saponins which were only localized in the epidermis of the body wall. Taken together, this study shows that granule release from epidermal pigmented cells is somehow related to the amount of epidermal saponins released to surrounding seawater. Hence, the future research in the sea cucumber better focuses on epidermal cells that are the enriched site of saponins, although several active compounds require further investigation.
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http://dx.doi.org/10.1002/jemt.23115DOI Listing
October 2018

Synergistic Effect of Forbesione From Garcinia hanburyi in Combination with 5-Fluorouracil on Cholangiocarcinoma

Asian Pac J Cancer Prev 2017 Dec 29;18(12):3343-3351. Epub 2017 Dec 29.

Department of Microbiology, Khon Kaen University, Khon Kaen 40002, Thailand.

Background: Chemotherapy for advanced cholangiocarcinoma (CCA) is largely ineffective; thus innovative combinations of chemotherapeutic agents and natural compounds represent a promising strategy. This study aimed to investigate the synergistic effects of forbesione combined with 5-fluorouracil (5-FU) in hamster cholangiocarcinoma (Ham-1) cells both in vitro and in vivo. The anti-tumor effects of 5-FU combined with forbesione in vitro were determined using the Sulforhodamine B (SRB) assay and the effects in vivo were assessed in transplanted Ham-1 allograph models. Using ethidium bromide/acridine orange (EB/AO) staining, the morphological changes of apoptotic cells was investigated. The expressions of apoptosis-related molecules after combined treatment with forbesione and 5-FU were determined using real-time RT-PCR and western blot analysis. Forbesione or 5-FU alone inhibited proliferation of Ham-1 cells in a dose-dependent manner and their combination showed a synergistic proliferation inhibitory effect in vitro. In vivo studies, forbesione in combination with 5-FU exhibited greater inhibition of the tumor in the hamster model compared with treatment using either drug alone. Forbesione combined with 5-FU exerted stronger apoptotic induction in Ham-1 cells than did single drug treatment. The combination of drugs strongly suppressed the expression of B-cell lymphoma 2 (Bcl-2) and procaspase-3 while enhancing the expression of p53, Bcl-2-associated X protein (Bax), apoptotic protease activating factor-1 (Apaf-1), caspase-9 and caspase-3, compared with single drug treatments. These results explained the decreased expression of cytokeratin 19 (CK19) positive cells and proliferation cell nuclear antigen (PCNA) positive cells in Ham-1 cell tumor tissues of the treated hamsters. There was no apparent systemic toxicity observed in the treated animals compared with the control groups. Forbesione combined with 5-FU strongly induced apoptosis in Ham-1 cells. The growth inhibitory effect of combined treatment using these two drugs was much greater than treatment with either drug alone, both in vitro and in vivo.
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http://dx.doi.org/10.22034/APJCP.2017.18.12.3343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980893PMC
December 2017

Antitumor effect of forbesione isolated from on cholangiocarcinoma and .

Oncol Lett 2016 Dec 18;12(6):4685-4698. Epub 2016 Oct 18.

Center of Excellence for Innovation in Chemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Cholangiocarcinoma (CCA) is a malignancy with no effective therapy and poor prognosis. Forbesione, a caged xanthone isolated from , has been reported to inhibit proliferation and to induce apoptosis in human CCA cell lines. The present study aimed to further explore the potential anticancer properties of forbesione by testing its effects against the hamster CCA cell line Ham-1 and . It was observed that forbesione inhibited the growth of Ham-1 cells and suppressed Ham-1 growth as allograft in hamsters by inducing cell cycle arrest at the S phase. This was mediated by decreasing the protein expression of cyclin E, cyclin A and cyclin-dependent kinase 2. In addition, increased expression of p21 and p27 was detected, which could possibly explain the reduced expression of proliferating cell nuclear antigen and of the bile duct cell marker cytokeratin 19 observed in forbesione-treated Ham-1 cells and in tumor tissues of forbesione-treated hamsters. Furthermore, forbesione induced apoptosis through multiple pathways. The death receptor pathway was activated by increased expression of Fas, Fas-associated death domain and activated caspase-3, along with decreased expression of procaspase-8 and procaspase-3. The mitochondrial pathway was driven by increased expression of B-cell lymphoma (Bcl)-2-like protein 4, activated caspase-9 and inhibitor of κB-α, along with decreased expression of Bcl-2, survivin, procaspase-9 and nuclear factor-κB/p65. The endoplasmic reticulum pathway was stimulated by increased expression of activated caspase-12 and decreased expression of procaspase-12. No side effects or toxicity were observed in forbesione-treated hamsters. Thus, forbesione is a potential drug candidate for cancer therapy that deserves further investigation.
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http://dx.doi.org/10.3892/ol.2016.5284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228296PMC
December 2016

Thai Fruits Exhibit Antioxidant Activity and Induction of Antioxidant Enzymes in HEK-293 Cells.

Evid Based Complement Alternat Med 2016 18;2016:6083136. Epub 2016 Dec 18.

Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.

The cellular antioxidant enzymes play the important role of protecting the cells and organisms from the oxidative damage. Natural antioxidants contained in fruits have attracted considerable interest because of their presumed safety and potential nutritional value. Even though antioxidant activities of many fruits have been reported, the effects of phytochemicals contained in fruits on the induction of antioxidant enzymes in the cells have not been fully defined. In this study, we showed that extracts from , , , , and inhibited HO-induced intracellular reactive oxygen species production in HEK-293 cells. Additionally, these Thai fruit extracts increased the mRNA and protein expressions of antioxidant enzymes, catalase, glutathione peroxidase-1, and manganese superoxide dismutase. The consumption of Thai fruits rich in phenolic compounds may reduce the risk of oxidative stress.
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http://dx.doi.org/10.1155/2016/6083136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203924PMC
December 2016

Caged xanthones: Potent inhibitors of global predominant MRSA USA300.

Bioorg Med Chem Lett 2016 07 11;26(13):2980-2983. Epub 2016 May 11.

Department of Chemistry and Center for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.

Total of 22 caged xanthones were subjected to susceptibility testing of global epidemic MRSA USA300. Natural morellic acid showed the strongest potency (MIC of 12.5μM). However, its potent toxicity diminishes MRSA therapeutic potential. We synthetically modified natural morellic acid to yield 13 derivatives (3a-3m). Synthetically modified 3b retained strong potency in MRSA growth inhibition, yet the toxicity was 20-fold less than natural morellic acid, permitting the possibility of using caged xanthones for MRSA therapeutic.
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http://dx.doi.org/10.1016/j.bmcl.2016.05.030DOI Listing
July 2016

Bioactivity-guided Separation of the Active Compounds in Acacia pennata Responsible for the Prevention of Alzheimer's Disease.

Nat Prod Commun 2015 Aug;10(8):1431-4

The objective of this study was to evaluate the health benefits of plants used in Thai food, specifically Acacia pennata Willd., in Alzheimer's prevention. A. pennata twigs strongly inhibited β-amyloid aggregation. Bioactivity-guided separation of the active fractions yielded six known compounds, tetracosane (1), 1-(heptyloxy)-octadecane (2), methyl tridecanoate (3), arborinone (4), confertamide A (5) and 4-hydroxy-1-methyl-pyrrolidin-2-carboxylic acid (6). The structures were determined by spectroscopic analysis. Biological testing revealed that tetracosane (1) was the most potent inhibitor of β-amyloid aggregation, followed by 1-(heptyloxy)-octadecane (2) with IC50 values of 0.4 and 12.3 μM. Methyl tridecanoate (3), arborinone (4) and 4-hydroxy-1-methyl-pyrrolidin-2-carboxylic acid (6) moderately inhibited β-amyloid aggregation. In addition, tetracosane (1) and methyl tridecanoate (3) weakly inhibited acetylcholinesterase (AChE). These results suggested that the effect of A. pennata on Alzheimer's disease was likely due to the inhibition of β-amyloid aggregation. Thus A. pennata may be beneficial for Alzheimer's prevention.
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August 2015

Biological Activity of Dolichandrone serrulata Flowers and Their Active Components.

Nat Prod Commun 2015 Aug;10(8):1387-90

Dolichandrone serrulata (DC.) Seem flowers are widely used as vegetables in northern and eastern Thailand. Biological studies of the methanolic extract of these flowers have shown promising antioxidant activity. Biological-guided separation of D. serrulata flowers yielded six compounds, identified as hallerone, protocatechuic acid, rengyolone, cleroindicin B, ixoside, and isomaltose. This is the first report on hallerone, protocatechuic acid, rengyolone, cleroindicin B, and isomaltose in D. serrulata. Protocatechuic acid was the most potent scavenger of 2,2-diphenyl-l-picrylhydrazyl and hydroxyl radicals with IC50 values of 25.6 +/- 0.6 and 29.6 +/- 0.4 microM, respectively. Hallerone and rengyolone showed moderate scavenging action on superoxide radicals and inhibited H202 induced reactive oxygen species production in HEK-293 cell. In addition, the other isolated compounds showed weak activity.
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August 2015

Polyphenolic compounds and antioxidant activities of the leaves of Glochidion hypoleucum.

Nat Prod Commun 2015 Mar;10(3):479-82

Bioassay-guided fractionation of the methanol extract of Glochidion hypoleucum (Miq.) Boerl leaves led to the isolation of five polyphenolic compounds, methyl gallate, gallic acid, apigenin-8-C-β-D-glucopyranoside (vitexin), luteolin-8-C-β-D-glucopyranoside (orientin), and luteolin-6-C-β-D-glucopyranoside (isoorientin). The chemical structures of the isolated compounds were determined using spectroscopic (NMR, UV-Vis, IR) and mass spectrometric techniques. The antioxidative properties of the methanol extract and isolated polyphenols were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) for radical scavenging activity and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) to measure the level of reactive oxygen species (ROS). With the exception of vitexin, the crude methanol extract and the polyphenolic compounds inhibited DPPH radicals with IC50 values ranging from 2.46 ± 0.05 to 40.0 ± 0.3 μg/mL. In addition, the crude methanol extract attenuated H202-induced intracellular ROS production in a dose-dependent manner in HEK-293 cells. Gallic acid and isoorientin significantly reduced the ROS level in HEK-293 cells at a concentration of 20 μM.
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March 2015

Synergistic effects of isomorellin and forbesione with doxorubicin on apoptosis induction in human cholangiocarcinoma cell lines.

Cancer Cell Int 2014 24;14:68. Epub 2014 Oct 24.

Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, 10400 Thailand.

Background: Chemotherapy for advanced cholangiocarcinoma (CCA) is largely ineffective, but innovative combinations of chemotherapeutic agents and natural compounds represent a promising strategy. In our previous studies, isomorellin and forbesione, caged xanthones isolated from Garcinia hanburyi, were found to induce cell cycle arrest and apoptosis in CCA cell lines. The subject of our inquiry is the synergistic effect(s) of these caged xanthones with doxorubicin on growth inhibition and apoptosis induction in human CCA cell lines.

Methods: KKU-100, KKU-M139 and KKU-M156 cell lines and Chang cells were treated with either isomorellin or forbesione alone or in combination with doxorubicin. Cell viability was determined using the sulforhodamine B assay. The combined effects of plant compounds with doxorubicin were analyzed using the isobologram and combination index method of Chou-Talalay. Apoptosis was determined by ethidium bromide/acridine orange staining. Protein expressions were determined by Western blot analysis.

Results: Isomorellin or forbesione alone inhibited the growth of these CCA cell lines in a dose-dependent manner and showed selective cytotoxicity against CCA cells but not against Chang cells. Isomorellin/doxorubicin combination showed a synergistic growth inhibitory effect on KKU-M139 and KKU-M156 cells, while the forbesione/doxorubicin combination showed a synergistic growth inhibitory effect on KKU-100 and KKU-M139 cells. The percentages of apoptotic cells were significantly higher in the combined treatments than in the respective single drug treatments. The combined treatments strongly enhanced the expression of Bax/Bcl-2, activated caspase-9 and caspase-3, while suppressing the expression of survivin, procaspase-9 and procaspase-3, compared with single drug treatments. The degree of suppression of NF-κB activation mediated by a decrease in the expression of NF-κB/p65, a reduction of the pIκB-α level and an increase in the IκB-α protein level, was significantly higher in the combined treatment groups than in the single drug treatment groups. The degree of suppression of MRP1 protein expression was also significantly higher in the combined treatment than in the single drug treatment groups.

Conclusion: The combinations of isomorellin/doxorubicin and forbesione/doxorubicin showed significant synergistic effects on the growth inhibition and apoptosis induction in KKU-M156 and KKU-100 cells. Caged xanthones may be useful adjunct treatments with chemotherapy for Opisthorchis viverrini (OV)-associated CCA.
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http://dx.doi.org/10.1186/1475-2867-14-68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392878PMC
April 2015

Involvement of p53 and nuclear factor-kappaB signaling pathway for the induction of G1-phase cell cycle arrest of cholangiocarcinoma cell lines by isomorellin.

Biol Pharm Bull 2012 22;35(11):1914-25. Epub 2012 Aug 22.

Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

Cell cycle arrest is closely linked to apoptosis. Isomorellin-a caged xanthone isolated from Garcinia hanburyi-induced apoptosis in cholangiocarcinoma (CCA) cell lines. To elucidate potential anticancer mechanisms, we investigated the effects of isomorellin on the growth, cell cycle progression, cell cycle regulated protein expression and nuclear factor-kappa B (NF-κB) activation of KKU-100 and KKU-M156 CCA cell lines; using sulforhodamine B assay, flow cytometry and Western blot analysis. The growth of both CCA cell lines was significantly inhibited by isomorellin treatment in a time- and dose-dependent manner. The respective IC(50) value of isomorellin for KKU-100 cells was 6.2±0.13, 5.1±0.11 and 3.5±0.25 µM at 24, 48 and 72 h. By comparison, the respective IC(50) value for KKU-M156 cells was 1.9±0.22, 1.7±0.14 and 1.5±0.14 µM at 24, 48 and 72 h. The growth inhibition of CCA cells by isomorellin was through the G0/G1 phase arrest mediated by inhibition of NF-κB activation, up-regulation of p53, p21 and p27 and down-regulation of cyclin D1, cyclin E, Cdk4 and Cdk2 protein levels. Our research suggests that isomorellin induces cell cycle arrest and apoptosis in CCA cell lines through p53 and the NF-κB-signaling pathway. The growth inhibitory potential of isomorellin was comparable to that of gambogic acid. Isomorellin shows potential as a therapeutic agent against human cholangiocarcinoma.
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http://dx.doi.org/10.1248/bpb.b12-00118DOI Listing
April 2013

Chitosan-functionalized poly(methyl methacrylate) particles by spinning disk processing for lipase immobilization.

Carbohydr Polym 2012 Jul 26;89(3):842-8. Epub 2012 Apr 26.

Center of Excellence for Innovation in Chemistry (PERCH-CIC), Department of Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand.

Chitosan-functionalized poly(methyl methacrylate) (PMMA-CH) particles were prepared by complexation between the negatively charged PMMA particles and the positively charged chitosan via a spinning disk processing. Processing parameters; feed rate and spinning speed, were optimized, which were traced by size distribution profiles of the formed PMMA-CH particles. Their sizes and net surface charges were found to be affected by MWs of chitosan (45, 100, and 230 kDa) used. Microscopic evidences were used to confirm their core-shell morphology. Chemical characteristics and thermal stability of such particles were determined by FTIR and TGA, respectively. Then, their ability to immobilize lipase (EC 3.1.1.3) was conducted and followed through zeta potential measurement. The percentage of lipase adsorption capacity increased with increasing lipase content, but the value decreased when the size of PMMA-CH particles increased. Also, the activity of lipase attached on PMMA-CH particles' surface was preserved and increased with lipase loading.
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http://dx.doi.org/10.1016/j.carbpol.2012.04.019DOI Listing
July 2012

Prenylated caged xanthones: chemistry and biology.

Pharm Biol 2012 Jan;50(1):78-91

Department of Pharmacognosy and The Center of Excellence for Innovation in Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Context: Prenylated caged xanthones are "privileged structure" characterized by the presence of the unusual 4-oxo-tricyclo[4.3.1.0(3,7)]dec-8-en-2-one scaffold. The natural sources of these compounds confines mainly in the Garcinia genus in the family of Guttiferae. Gambogic acid is the most abundant substance and most of the studies have been done on this compound, particularly as a new potential antitumor agent. The history, sources, structural diversity, and biological activities of these compounds are covered.

Objective: This review is written with the intention to provide additional aspects from what have been published of prenylated caged xanthones, including history, sources, structural diversity, and biological activities.

Methods: This review has been compiled using information from a number of reliable references mainly from major databases including SciFinder, ScienceDirect, and PubMed.

Results: More than 120 prenylated caged xanthones have been found in the plant genera Garcinia, Cratoxylum, and Dascymaschalon. These compounds exhibited various potentially useful biological activities such as anticancer, anti-HIV-1, antibacterial, anti-inflammatory, and neurotrophic activities.

Conclusions: Prenylated caged xanthones, both naturally occurring and synthetic analogues, have been identified as promising bioactive compounds, especially for anticancer agents. Gambogic acid has been demonstrated to be a highly valuable lead compound for antitumor chemotherapy. The structure activity relationship (SAR) study of its analogues is still the subject of intensive research. Apoptosis cytotoxic mechanism has been identified as the major pathway. Research on the delineation of the in-depth mechanism of action is still on-going. Analogues of gambogic acid had been identified to be effective against a rare and special form of liver cancer, cholangiocarcinoma for which currently there is no chemotherapeutic treatment available.
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http://dx.doi.org/10.3109/13880209.2011.636176DOI Listing
January 2012

Cytotoxic alkaloids from stems, leaves and twigs of Dasymaschalon blumei.

Fitoterapia 2011 Oct 27;82(7):964-8. Epub 2011 May 27.

Department of Chemistry and the Center for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Bangkok, Thailand.

Bioassay-guided fractionation of the cytotoxic ethyl acetate extract from the stems of Dasymaschalon blumei (Annonaceae) led to the isolation of four aristololactam alkaloids, including the hitherto unknown 3,5-dihydroxy-2,4-dimethoxyaristolactam (1), as well as the three known compounds, aristolactam BI, goniopedaline, and griffithinam. Additionally, the cytotoxic extract from the combined leaves and twigs of the same plant yielded three known oxoaporphine alkaloids, oxodiscoguattine, dicentrinone, and duguevalline. The structures of aristolactams and oxoaporphine alkaloids were elucidated on the basis of spectroscopic methods. All isolates were evaluated for cytotoxicity against a panel of mammalian cancer cell lines and a noncancerous human embryonic kidney cell Hek 293.
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http://dx.doi.org/10.1016/j.fitote.2011.05.012DOI Listing
October 2011

Apoptotic activity of caged xanthones from Garcinia hanburyi in cholangiocarcinoma cell lines.

World J Gastroenterol 2010 May;16(18):2235-43

Department of Microbiology, Center of Excellence for Innovation in Chemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

Aim: To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma (CCA) KKU-100 and KKU-M156 cells.

Methods: Four caged xanthones, selected on the basis of their anticancer potency and chemical structure diversities (i.e. isomorellin, isomorellinol, forbesione and gambogic acid) were used in this study. Growth inhibition of these caged xanthones was determined using the sulforhodamine B assay. Induction of apoptosis was assessed by observing cell morphology, ethidium bromide and acridine orange staining and DNA fragmentation assay. Levels of apoptotic-related gene and protein expressions were determined by a real-time reverse transcriptase polymerase chain reaction and Western blotting analysis, respectively.

Results: The compounds were found to inhibit growth of both cell lines in a dose-dependent manner and also showed selective cytotoxicity against the cancer cells when compared with normal peripheral blood mononuclear cells. Growth suppression by these compounds was due to apoptosis, as evidenced by the cell morphological changes, chromatin condensation, nuclear fragmentation, and DNA ladder formation. At the molecular level, these compounds induced down-regulation of Bcl-2 and survivin proteins with up-regulation of Bax and apoptosis-inducing factor proteins, leading to the activation of caspase-9 and -3 and DNA fragmentation. The functional group variations did not appear to affect the anticancer activity with regard to the two CCA cell lines; however, at a mechanistic level, isomorellinol exhibited the highest potency in increasing the Bax/Bcl-2 protein expression ratio (120 and 41.4 for KKU-100 and KKU-M156, respectively) and in decreasing survivin protein expression (0.01 fold as compared to control cells in both cell lines). Other activities at the molecular level indicate that functional groups on the prenyl side chain may be important.

Conclusion: Our findings for the first time demonstrate that four caged xanthones induce apoptosis in CCA cells which is mediated through a mitochondria-dependent signaling pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868216PMC
http://dx.doi.org/10.3748/wjg.v16.i18.2235DOI Listing
May 2010

Anti-HIV-1 and anti-inflammatory lupanes from the leaves, twigs, and resin of Garcinia hanburyi.

Planta Med 2010 Mar 14;76(4):368-71. Epub 2009 Oct 14.

Two new lupanes, 2 alpha-acetoxy-3 beta-hydroxy-19 beta-hydrogen-lup-20(29)-en-28-oic acid (2-acetoxyalphitolic acid) ( 1) and 2 alpha-hydroxy-3 beta-acetoxy-19 beta-hydrogen-lup-20(29)-en-28-oic acid (3-acetoxyalphitolic acid) ( 2), together with the known betulinic acid ( 3), betulin ( 4), and stimasterol-3- O- beta- D-glucopyranoside ( 5), were isolated from the leaves and twigs of GARCINIA HANBURYI. Compounds 1- 3 were also isolated from the resin of this plant. The structure of 2 was confirmed by single-crystal X-ray diffraction analysis. All of the lupanes ( 1- 4) displayed anti-HIV-1 activities in the anti-HIV-1 reverse transcriptase (IC (50) values 16.3-116.9 microg/mL) and syncytium assays (EC (50) 5.6-73.6 microg/mL, SI 1.7-3.3). Moreover compounds 1- 4 exhibited anti-inflammatory activity in an ethyl phenylpropiolate (EPP)-induced ear edema model.
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http://dx.doi.org/10.1055/s-0029-1186193DOI Listing
March 2010

Anti-inflammatory, analgesic and antipyretic activities of the extract of gamboge from Garcinia hanburyi Hook f.

J Ethnopharmacol 2007 May 30;111(2):335-40. Epub 2007 Jan 30.

Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

In Thai folklore medicine, gamboge, the yellow gum-resin secreted from Garcinia hanburyi, is used for infected wound, pain and edema The ethyl acetate extract from Garcinia hanburyi (GH5763) was assessed for anti-inflammatory, analgesic and antipyretic activities using experimental animal models. It was found that GH5763 possessed inhibitory activity on acute phase of inflammation as seen in ethyl phenylpropiolate-induced ear edema and carrageenin-induced hind paw edema in rats. However, GH5763 did not elicit any inhibitory effect on arachidonic acid-induced hind paw edema. In subchronic inflammatory model, GH5763 provoked a significant reduction of both transudative and proliferative phase when tested on cotton pellet-induced granuloma model. GH5763 also reduced the alkaline phosphatase activity in serum of rats in this animal model. In the analgesic test, GH5763 elicited inhibitory activity on acetic acid-induced writhing response and on both the early and the late phase of formalin test. Moreover, GH5763 also possessed an excellent antipyretic effect when tested in yeast-induced hyperthermic rats. It is postulated that the anti-inflammatory, analgesic and antipyretic activities of GH5763 are caused by the inhibition of the prostaglandin biosynthesis.
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http://dx.doi.org/10.1016/j.jep.2006.11.038DOI Listing
May 2007

Cytotoxic and anti-HIV-1 caged xanthones from the resin and fruits of Garcinia hanburyi.

Planta Med 2007 Jan 21;73(1):33-40. Epub 2006 Nov 21.

Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

Three new caged xanthones, 7-methoxydesoxymorellin (1), 2-isoprenylforbesione (2) and 8,8a-epoxymorellic acid (3), together with nine known caged xanthones were isolated from the EtOAc extracts of resin and fruits of Garcinia hanburyi. The structures were determined by spectroscopic methods. Most of the isolated compounds showed significant cytotoxicities against a panel of mammalian cancer cell lines. Compound 3, together with the known compounds desoxymorellin, morellic acid, gambogic acid, hanburin, forbesione and dihydroisomorellin, exhibited anti-HIV-1 activity in the reverse transcriptase (RT) assay while the known compounds desoxygambogenin and dihydroisomorellin were found moderately active in the syncytium assay. This work represents the first report on the anti-HIV-1 activities of caged xanthones.
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http://dx.doi.org/10.1055/s-2006-951748DOI Listing
January 2007

Fine tuning the production of nanosized beta-carotene particles using spinning disk processing.

J Am Chem Soc 2006 Oct;128(42):13847-53

Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Nanoparticles of trans-beta-carotene are accessible using spinning disk processing (SDP), by varying the reaction conditions and the choice of surfactant, macrocyclic amphiphiles, sulfonato-calix[4,5,6,8]arenes, and alpha,beta-cyclodextrins. SDP ensures rapid mixing and fast kinetics, and nanoparticles of the carotene formed in the presence of the calixarenes are stable with respect to extraction of the carotene into an organic solvent, unlike in the presence of the cyclodextrins. Insight into the supramolecular structure of the carotene nanoparticles has also been established. The mean particle sizes (dynamic light scattering, DLS) have been optimized at 40(2) and 56(1) nm and 71.4(6) and 82(1) nm, respectively, for each sulfonato-calix[5,6 and 4,8]arene, whereas the cyclodextrins form nanoparticles with a mean diameter of 71(1) and 68.5(6) nm, respectively. Zeta-potential studies show stability of all the colloidal dispersions at pH > 4 with values below -30 mV. UV-visible spectroscopy shows a blue shift indicative of H-aggregates of the carotene within the nanoparticles. The surface area derived from BET studies is 39.12 m(2)/g corresponding to particles of 76.7(5) nm in diameter, in agreement with sizes obtained from DLS and TEM measurements.
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http://dx.doi.org/10.1021/ja063545nDOI Listing
October 2006
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