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ABSTRACT: Eight new cycloartane triterpenoids (1-8), named carinatins A-H, and the known compounds secaubryolide (9) and dikamaliartane D (10) were isolated from the leaves and twigs of Gardenia carinata. Their structures were determined on the basis of spectroscopic methods. Cytotoxic, antitopoisomerase IIα, and anti-HIV-1 activities of compounds 1-7, 9, and 10 were investigated.
Journal of Natural Products 04/2013; · 3.13 Impact Factor
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ABSTRACT: PhSCF(2)SiMe(3) () underwent fluoride-catalyzed nucleophilic addition to the carbonyl group of anhydrides to provide the corresponding γ-difluoro(phenylsulfanyl)methyl γ-lactols, which were employed for the synthesis of γ-difluoromethylated γ-lactams.
Organic & Biomolecular Chemistry 02/2013; · 3.70 Impact Factor
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ABSTRACT: Periodontal disease is caused by microorganisms and host-derived inflammation involving increased cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production. We previously demonstrated that human β-defensin-3 induces COX-2 and PGE(2) in human gingival fibroblasts (HGFs). We, therefore, aimed to examine the inducible effects of LL-37, the only cathelicidin expressed in humans, on COX-2 expression and PGE(2) synthesis in HGFs and to elucidate the relevant signaling pathways. The COX-2 expression was upregulated by LL-37 in dose- and time-dependent manners. Accordingly, the synthesis of PGE(2) in cell-free culture supernatants was raised by LL-37 (p < 0.01) and blocked by NS-398, a specific COX-2 inhibitor (p < 0.01). P2X inhibitors and a neutralizing antibody against P2X(7) purinergic receptor significantly abrogated COX-2 induction and PGE(2) production by LL-37 (p < 0.01). LL-37 upregulated COX-2 expression and PGE(2) synthesis via activation of extracellular signal-regulated kinase (ERK) and p46 c-Jun N-terminal kinase (JNK), while interleukin-1β did so via nuclear factor-ĸB and all three mitogen-activated protein kinases. In summary, LL-37 can control arachidonic acid metabolism by induction of COX-2 expression and PGE(2) synthesis via the P2X(7) receptor, ERK, and p46 JNK. The pro-inflammatory effects of LL-37 may be essential for initiating oral mucosal inflammation in periodontal disease.
Journal of Innate Immunity 10/2012; · 4.21 Impact Factor
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ABSTRACT: An asymmetric synthesis of gem-difluoromethylenated dihydroxypyrrolizidines and indolizidines is described. The fluoride-catalyzed nucleophilic addition of PhSCF(2)SiMe(3) (1) to chiral imides was achieved in satisfactory yields to provide mixtures of syn- and anti-isomers 6-9 with moderate to good diastereoselectivities. Reductive cleavage of the phenylsulfanyl group followed by intramolecular radical cyclization of the syn-isomers 6-9 occurred under refluxing conditions to afford the corresponding gem-difluoromethylenated 1-azabicyclic compounds 10-13 in moderate yields as a separable mixture of cis- and trans-isomers. The cis-isomers of compounds 10 and 12 and trans-13 were readily transformed to gem-difluoromethylenated dihydroxypyrrolizidines 20 and 27 and indolizidine 28, respectively, by reductive cleavage of the hydroxyl group and organometallic addition followed by hydrogenolysis.
The Journal of Organic Chemistry 09/2012; 77(19):8465-79. · 4.45 Impact Factor
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ABSTRACT: 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.
Biological & Pharmaceutical Bulletin 08/2012; · 1.66 Impact Factor
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ABSTRACT: OBJECTIVE: To examine CD99 expression and its functional role in ICAM-1 induction in human gingival fibroblasts (HGFs) and human gingival epithelial cells (HGECs) by activating cells with anti-CD99 monoclonal antibody, MT99/3. BACKGROUND: Engagement of CD99 with agonistic antibodies has been shown to regulate immune responses, cell adhesion and migration, and cell death in several studies. Particularly, this engagement results in transendothelial migration of leukocytes mediated by intercellular adhesion molecule-1 (ICAM-1) induction in endothelial cells. METHODS: Total mRNA and protein were isolated from HGFs and HGECs for analyses of CD99 and ICAM-1 expression. Surface expression of CD99 and ICAM-1 was analysed by flow cytometry, and the detection of soluble ICAM-1 was assayed by immunoprecipitation and ELISA. RESULTS: CD99 surface expression was constitutive on HGFs to a greater extent than that on HGECs. CD99 ligation with MT99/3 induced ICAM-1 mRNA expression in HGFs, but not in HGECs. Interestingly, CD99 ligation led to an increased level of soluble ICAM-1 detected in culture supernatant, whereas interleukin-1β (IL-1β) treatment induced expression of membrane-bound ICAM-1. Furthermore, ICAM-1 induction by CD99 engagement was demonstrated to involve the activation of the p50 subunit of nuclear factor-kappaB (NF-κB), extracellular signal-regulated kinase, and p46 c-Jun N-terminal kinase that differed from that by IL-1β treatment. CONCLUSION: Our study has shown the involvement of CD99 ligation in the up-regulation of ICAM-1 expression and its secretion in gingival fibroblasts, which may be essential for better understanding of the pathogenesis of periodontal disease.
Archives of oral biology 07/2012; · 1.65 Impact Factor
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ABSTRACT: BACKGROUND: Osteoporosisis a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function. METHOD: Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 hour of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 hour of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stain with Alizarin Red S staining. MAPK signaling pathway activation was observed by using western blotting. RESULTS: Sesamin promoted the expression COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19. CONCLUSIONS: The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the MAPK signaling pathway (p38 and ERK) and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for osteoporotic therapy.
BMC Complementary and Alternative Medicine 05/2012; 12(1):71. · 2.24 Impact Factor
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ABSTRACT: Fluoride-catalyzed stereoselective nucleophilic addition of PhSCF(2)SiMe(3) (1) to α-carboethoxycycloalkanones 2 followed by intramolecular radical cyclization of the resulting cis-3 adduct afforded the corresponding gem-difluoromethylenated bicyclic compounds 4, which underwent ring-expansion followed by the Baeyer-Villiger-type oxidation of the resulting macrocyclic ketone intermediates to give gem-difluoromethylenated macrocyclic lactones 5.
Organic Letters 03/2012; 14(7):1820-3. · 5.86 Impact Factor
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ABSTRACT: 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.
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.
This review has been compiled using information from a number of reliable references mainly from major databases including SciFinder, ScienceDirect, and PubMed.
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.
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.
Pharmaceutical Biology 01/2012; 50(1):78-91. · 0.88 Impact Factor
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ABSTRACT: Four new flavones, 5,2'-dihydroxy-7,3',4',5'-tetramethoxyflavone (1), 5,2',5'-trihydroxy-7,3',4'-trimethoxyflavone (2), 5,7,2',5'-tetrahydroxy-6,3',4'-trimethoxyflavone (3) and 5,2',5'-trihydroxy-6,7,3',4'-tetramethoxyflavone (4), along with the known 5,3'-dihydroxy-6,7,4',5'-tetramethoxyflavone (5), 5,7,3',5'-tetrahydroxy-6,4'-dimethoxyflavone (6), syringaldehyde, vanillic acid and scopoletin were isolated from the leaves and twigs of Gardenia carinata (Rubiaceae). Their structures were determined by spectroscopic methods. Flavone 2 exhibited cytotoxic activity against P-388 and MCF-7 cell lines, while 3, 5 and 6 were active only in P-388 cell line. All active compounds were found to inhibit DNA topoisomerase IIα activity, which may be responsible for the observed cytotoxicity. Flavones 1-3, 5 and 6 also exhibited anti-HIV-1 activity in the anti-syncytium assay using (∆Tat/rev)MC99 virus and 1A2 cell line system; 2 was most potent. Only flavones 1 and 6 showed considerably activity against HIV-1 reverse transcriptase.
Fitoterapia 12/2011; 83(2):368-72. · 1.85 Impact Factor
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ABSTRACT: Bioassay-guided fractionation and purification of the aerial parts of Piper submultinerve led to the isolation of a new conjugated amide-dimer, submultinamide A (1), along with 11 known compounds. The structures were determined on the basis of spectroscopic methods. Among the tested compounds, pellitorine (2), guineensine (4), N-benzylcinnamide (6) and aristolactam BII (8) showed significant activities in the anti-syncytium assay using (ΔTat/Rev)MC99 virus and 1A2 cell line system, whereas 2 was most active (EC(50) 35.1 µM and selectivity index 4.7). In the HIV-1 reverse transcriptase assay, only 4 was active with IC(50) 50.8 µM.
Natural product research 11/2011; 26(19):1824-30. · 1.01 Impact Factor
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ABSTRACT: 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.
Fitoterapia 05/2011; 82(7):964-8. · 1.85 Impact Factor
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ABSTRACT: Since the use of Nelumbo nucifera stamens in herbal medicines as well as in cosmetic products are highly prevalent in Thailand and increasing worldwide, acute and subchronic toxicity studies to confirm the safe use of Nelumbo nucifera stamens are warranted.
Acute and subchronic oral toxicity studies of Nelumbo nucifera stamens extract in rats were performed in the present study in order to evaluate its safety.
In acute toxicity study, Nelumbo nucifera stamens extract was administered by oral gavage to Sprague-Dawley rats (5 males and 5 females) at a dose of 5000 mg/kg. In subchronic toxicity study, the extract at doses of 50, 100, and 200mg/kg/day were given orally to groups of rats (6 rats/dose/sex) for 90 consecutive days.
The extract at a dose of 5000 mg/kg produced no treatment-related signs of toxicity or mortality in any of the animals tested during 14 days of the study. In the repeated dose 90-day oral toxicity study, there was no significant difference in body weight between the control and all treatment groups with the exception of the body weight of the female group treated with 200mg/kg/day of the extract which was statistically significantly less than that of its control counterpart on day 90 but the percent weight changes of both groups were almost similar. Some statistically significant differences in hematological and biochemical parameters as well as in some internal organ weights of both male and female rats treated with the extract at the highest dose were observed. However, no abnormality of internal organs was observed in both gross and histopathological examinations.
These results suggest that the oral lethal dose of Nelumbo nucifera stamens extract for male and female rats is in excess of 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 200mg/kg/day.
Journal of ethnopharmacology 02/2011; 134(3):789-95. · 2.32 Impact Factor
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ABSTRACT: A new diarylheptanoid, (3S,5S)-3,5-diacetoxy-1,7-bis(3,4,5-trimethoxyphenyl)heptane (1), together with the known docosyl trans-ferulate (2), (1S,2S,4S)-p-menthan-1,2,4-triol (3), 5αH-eudesmane-4α,11-diol (4), 5αH-eudesmane-4β,11-diol (5), 4α,10β-dihydroxy-1βH,5αH-guaia-6-ene (guaianediol) (6), (+)-galanolactone (7), (E)-labda-8(17),12(13)-dien-15,16-olide (8), labda-8(17),13(14)-dien-15,16-olide (9), 3,5-dihydroxy-7,4'-dimethoxyflavone (10) and 3,5,3'-trihydroxy-7,4'-dimethoxyflavone (11) were isolated from the rhizomes of Zingiber mekongense. Their structures were determined by spectroscopic methods. The stereochemistry of 1 was proved through chemical conversion. Compounds 1, 4-7 and 9-11 exhibited anti-HIV-1 activities in the anti-syncytium assay using (∆Tat/rev)MC99 virus and 1A2 cell line system, while only compounds 7 and 11 were found active in the HIV-1 reverse transcriptase assay.
Fitoterapia 01/2011; 82(4):534-8. · 1.85 Impact Factor
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ABSTRACT: A concise asymmetric synthesis of (+)-swainsonine (ent-1) is described starting from 2, which was readily prepared from commercially available l-glutamic acid. The method features installation of the indolizidine ring via an intramolecular cyclisation of α-sulfinyl carbanion as a key step. (+)-Swainsonine was obtained in 11.8% overall yield in 10 steps.
Organic & Biomolecular Chemistry 10/2010; 9(2):531-7. · 3.70 Impact Factor
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Annalen der Chemie und Pharmacie 08/2010; 2010(29):5633 - 5641. · 3.10 Impact Factor
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ABSTRACT: To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma (CCA) KKU-100 and KKU-M156 cells.
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.
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.
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.
World Journal of Gastroenterology 05/2010; 16(18):2235-43. · 2.47 Impact Factor
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ABSTRACT: Bioassay-guided fractionation and purification of the anti-HIV-1-active MeOH extract from the leaves and twigs of Polyalthia sclerophylla led to the isolation of two new compounds, ENT-kaur-sclerodimer ( 1) and cyclotucanol 3-palmitate ( 2), along with the known ENT-kaur-16-en-19-oic acid ( 3), 15 beta-hydroxy- ENT-kaur-16-en-19-oic acid ( 4), 15 beta-acetoxy- ENT-kaur-16-en-19-oic acid ( 5), 15-oxo- ENT-kaur-16-en-19-oic acid ( 6), 16 alpha,17-dihydroxy- ENT-kauran-19-oic acid ( 7), 16 alpha-hydroxy- ENT-kauran-19-oic acid (xylopic acid) ( 8), a pseudodimer (15 alpha-hydroxy- ENT-kaur-16-en-19-oic acid/17-hydroxy- ENT-kaur-15-en-19-oic acid) ( 9), ermanin, nicotiflorin, and allantoin. Among these isolates, compound 3 was the most active in both anti-syncytium (EC (50) 13.7 microg/mL and selectivity index 3.1) and HIV-1 reverse transcriptase (IC (50) 34.1 microg/mL) assays.
Planta Medica 12/2009; 76(7):721-5. · 2.15 Impact Factor
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Vichai Reutrakul,
Natthinee Anantachoke,
Manat Pohmakotr,
Thaworn Jaipetch,
Chalobon Yoosook,
Jittra Kasisit,
Chanita Napaswa,
Ampai Panthong,
Thawatchai Santisuk,
Samran Prabpai,
Palangpon Kongsaeree,
Patoomratana Tuchinda
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ABSTRACT: 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.
Planta Medica 10/2009; 76(4):368-71. · 2.15 Impact Factor
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ABSTRACT: PhSCF(2)SiMe(3) (1) was found, for the first time, to undergo fluoride-catalyzed nucleophilic difluoro(phenylsulfanyl)methylation reaction to cyclic imides 2, affording the corresponding adducts 3 in moderate to good yields. Reductive cleavage of the phenylsulfanyl group of N-alkylated adducts 3 with Bu(3)SnH/AIBN yielded gem-difluoromethylated products 4. Under the same reduction conditions, N-alkenylated and N-alkynylated adducts 3 afforded the corresponding gem-difluoromethylenated 1-azabicyclic compounds 5 and 6 with trans stereoselectivity. These compounds were employed as precursors for preparing substituted gem-difluoromethylenated pyrrolizidinones and indolizidinones 7 and 8 by treatment with Et(3)SiH/BF(3) x OEt(2), and compounds 9 and 10 by nucleophilic displacement of the hydroxyl group, using organosilanes in the presence of BF(3) x OEt(2). The synthesis of highly substituted gem-difluoromethylenated pyrrolizidines 13 and 14 was also demonstrated.
The Journal of Organic Chemistry 05/2009; 74(10):3798-805. · 4.45 Impact Factor
