Effects of 8-Hydroxyisocapnolactone-2-3-diol and friedelin on mast cell degranulation

Objective To investigate the effects of friedelin (terpenoid) and 8-hydroxyisocapnolactone-2-3-diol (coumarin) with concentration 10 μM, 30 μM, and 100 μM on inhibiting mast cells (MCs) degranulation. Methods The investigation was performed in vitro by administering each compound into rat peritoneal MCs and rat basophilic leukemia-2H3 cells followed by activation with 50 μg/mL of compound 48/80 or 1 μM of ionomycin. The concentration of histamine released from each group was measured by a high-performance liquid chromatography-fluorometry system with post-column derivatization using o-phthalaldehyde. Results 8-Hydroxyisocapnolactone-2-3-diol inhibited degranulation of compound 48/80 activated-rat peritoneal MCs with the histamine release percentages of 74.57%, 72.21% and 51.79% when the 10 μM, 30 μM and 100 μM concentrations were used, respectively. Where as about 81% histamine was released by the control group. Degranulation inhibition ability was also observed in ionomycin-activated rat basophilic leukemia-2H3 cells. In contrast, friedelin failed to inhibit degranulation in either cell type. The inhibition of 8-hydroxyisocapnolactone-2-3-diol was not related to the depletion of histamine synthesis as implied by the total histamine measurement. Conclusions These results exhibit the promising of 8-hydroxyisocapnolactone-2-3-diol is a potential parent structure for developing a MCs stabilizer.

Effects of 8-Hydroxyisocapnolactone-2-3-diol and friedelin on mast cell degranulation

OBJECTIVE@#To investigate the effects of friedelin (terpenoid) and 8-hydroxyisocapnolactone-2-3-diol (coumarin) with concentration 10 μM, 30 μM, and 100 μM on inhibiting mast cells (MCs) degranulation.@*METHODS@#The investigation was performed in vitro by administering each compound into rat peritoneal MCs and rat basophilic leukemia-2H3 cells followed by activation with 50 μg/mL of compound 48/80 or 1 μM of ionomycin. The concentration of histamine released from each group was measured by a high-performance liquid chromatography-fluorometry system with post-column derivatization using o-phthalaldehyde.@*RESULTS@#8-Hydroxyisocapnolactone-2-3-diol inhibited degranulation of compound 48/80 activated-rat peritoneal MCs with the histamine release percentages of 74.57%, 72.21% and 51.79% when the 10 μM, 30 μM and 100 μM concentrations were used, respectively. Where as about 81% histamine was released by the control group. Degranulation inhibition ability was also observed in ionomycin-activated rat basophilic leukemia-2H3 cells. In contrast, friedelin failed to inhibit degranulation in either cell type. The inhibition of 8-hydroxyisocapnolactone-2-3-diol was not related to the depletion of histamine synthesis as implied by the total histamine measurement.@*CONCLUSIONS@#These results exhibit the promising of 8-hydroxyisocapnolactone-2-3-diol is a potential parent structure for developing a MCs stabilizer.

Gastroprotective effects of combination of hot water extracts of turmeric (Curcuma domestica L.), cardamom pods (Ammomum compactum S.) and sembung leaf (Blumea balsamifera DC.) against aspirin-induced gastric ulcer model in rats

<p><b>OBJECTIVE</b>To investigate the protective effect of the combination of turmeric (Curcuma domestica), cardamom pods (Amomum compactum) and sembung leaf (Blumea balsamifera) on gastric mucosa in aspirin-induced gastric ulcer model rats.</p><p><b>METHODS</b>Thirty male Wistar rats weighing 150-200 g were divided into 6 groups. Four groups were administered with the hot water extracts combination consisted of cardamom pods 36.6 mg/200 g body weight and sembung leaf 91.5 mg/200 g body weight (fixed doses). The herbal extracts combination were also consisted of turmeric in various doses i.e. 10 mg/200 g body weight in the second group, 30 mg/200 g body weight in the first and third groups, and 50 mg/200 g body weight in the fourth group. The fifth group rats received sucralfate 72 mg /200 g body weight. Ten minutes after receiving herbal extracts combinations or sucralfate, the rats were induced with aspirin 90 mg/200 g body weight except the first group. Another group (sixth group) only received aspirin without any protective agent. All treatments were adsministered orally for seven days. The number and area of the gastric ulcers were counted and measured macroscopically. Score of mucosal damage and the number of eosinophils as well as the number of mast cells were observed in paraffin sections stained with hematoxylin eosin and toluidine blue, respectively.</p><p><b>RESULTS</b>The groups receiving herbal infuse combination exhibited less number and smaller area of gastric ulcers as well as smaller score of mucosal damage in comparison to those of aspirin group (P<0.05). The number of mast cells and eosinophil of herbal groups were also smaller than that of aspirin group.</p><p><b>CONCLUSIONS</b>The herbal extracts combination of turmeric (Curcuma domestica), cardamom pods (Amomum compactum) and sembung leaf (Blumea balsamifera) has potential gastroprotective effects.</p>

Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin

<p><b>OBJECTIVE</b>To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells (MCF-7/Dox) in cytotoxicity apoptosis and P-glycoprotein (Pgp) expression in combination with doxorubicin.</p><p><b>METHODS</b>The cytotoxic properties, 50% inhibition concentration (IC50) and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin (MCF-7/Dox) cells were determined using MTT assay. Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange. Immunocytochemistry assay was performed to determine the level and localization of Pgp.</p><p><b>RESULTS</b>Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC50 value of 11 µmol/L. Thus, combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect (CI>1.0). Hesperidin did not increase the apoptotic induction, but decreased the Pgp expressions level when combined with doxorubicin in low concentration.</p><p><b>CONCLUSIONS</b>Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC50 of 11 µmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.</p>

Combinational effects of hexane insoluble fraction of Ficus septica Burm. F. and doxorubicin chemotherapy on T47D breast cancer cells

<p><b>OBJECTIVE</b>To evaluate the effects of n-hexane insoluble fraction (HIF) of Ficus septica leaves in combination with doxorubicin on cytotoxicity, cell cycle and apoptosis induction of breast cancer T47D cell lines.</p><p><b>METHODS</b>The in vitro drugs-stimulated cytotoxic effects were determined using MTT assay. Analysis of cell cycle distribution was performed using flowcytometer and the data was analyzed using ModFit LT 3.0 program. Apoptosis assay was carried out by double staining method using ethydium bromide-acridin orange. The expression of cleaved-poly (ADP-ribose) polymerase (PARP) on T47D cell lines was identified using immunocytochemistry.</p><p><b>RESULTS</b>The combination exhibited higher inhibitory effect on cell growth than the single treatment of doxorubicin in T47D cells. In addition, combination of doxorubicin and HIF increased the incidence of cells undergoing apoptosis. HIF could improve doxorubicin cytotoxic effect by changing the accumulation of cell cycle phase from G2/M to G1 phase. The combination also exhibited upregulation of cleaved-PARP in T47D cells.</p><p><b>CONCLUSIONS</b>Based on this results, HIF is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.</p>

Effects of marmin, a compound isolated from Aegle marmelos Correa, on contraction of the guinea pig-isolated trachea

Marmin or 7-[6', 7'-dihydroxygeranyl-oxy] coumarin is a compound isolated from Aegle marmelos Correa. In the study, we examined the effects of marmin on the contraction of guinea pig-isolated trachea stimulated by several inducers, namely histamine, metacholine, compound 48/80. We also evaluated its action against contraction induced by extracellular or intracellular calcium ion. The possibility of marmin to potentiate the

elaxation effect of isoprenaline was also studied. Marmin added in the organ bath at 10 min prior to the agonist inhibited the contraction elicited by histamine and metacholine in a concentration-dependent manner. Moreover, marmin antagonized the histamine-induced contraction in competitive manner. Marmin mildly potentiated the relaxation effect of isoprenaline. In the study, marmin abrogated the contraction of tracheal smooth muscle induced by compound 48/80, an inducer of histamine release. Besides, marmin successfully inhibited CaCl[2-]-induced contraction in Ca[2+] -free Krebs solution. Marmin also inhibited two phases of contraction which were consecutively induced by metacholine and CaCl[2] in Ca[2+]-free Krebs solution. Based on the results we concluded that marmin could inhibit contraction of the guinea-pig tracheal smooth muscle, especially by interfering histamine receptor, inhibiting the histamine release from mast, inhibiting intracellular Ca[2+] release from the intracellular store and the Ca[2+] influx through voltage-dependent Ca[2+] channels

Effects of aegeline, a main alkaloid of aegle marmelos correa leaves, on the histamine release from mast cells

Aegeline or 7V-[2-hydroxy-2[4-methoxyphenyl] ethyl]-3-phenyl-2-propenamide is a main alkaloid isolated from Aegle marmelos Correa collected in Yogyakarta Indonesia. In our study, we investigated the effects of aegeline on the histamine release from mast cell. The study was performed by using [1] rat basophilic leukemia [RBL-2H3] cell line, and [2] rat peritoneal mast cells [RPMCs]. DNP[2]4-BSA, thapsigargin, ionomycin, compound 48/80 and PMA were used as inducers for histamine release from mast cell. In our study, aegeline inhibited the histamine release from RBL-2H3 cells induced by DNP24-BSA. Indeed, aegeline showed strong inhibition when RBL-2H3 cells induced by Ca[2+] stimulants such as thapsigargin and ionomycin. Aegeline is suggested to influence the intracellular Ca[2+] pool only since could not inhibit the [45]Ca[2+] influx into RBL-2H3 cells. Aegeline showed weak inhibitory effects on the histamine release from RPMCs, even though still succeed to inhibit when the histamine release induced by thapsigargin. These findings indicate that aegeline altered the signaling pathway related to the intracellular Ca[2+] pool in which thapsigargin acts. Based on the results, the inhibitory effects ofaegeYme on the histamine release from mast cells depended on the type of mast cell and also involved some mechanisms related to intracellular Ca[2+] signaling events via the same target of the action of thapsigargin or downstream process of intracellular Ca[2+] signaling in mast cells

Effects of skimmianine, a quinoline alkaloid of aegle marmelos correa roots, on the histamine release from rat mast cells

Skimmianine is a quinoline alkaloid isolated from the roots of Aegle marmelos Correa. In the study, we studied the effects of skimmianine on the histamine release from rat mast cells. The study was performed by using two cell lines, rat basophilic leukemia [RBL-2H3] cell line, and rat peritoneal mast cells [RPMCs]. DNP[24]-BSA, thapsigargin, ionomycin, compound 48/80 and PMA were used as inducers for histamine release from rat mast cell. Skimmianine markedly inhibited the histamine release from RBL-2H3 cells induced by DNP[24]-BSA, thapsigargin and ionomycin. The effect suggested is related to Ca[2+] signaling since skimmianine showed strong effects when the histamine release induced by Ca[2+] signal stimulants [thapsigargin and ionomycin]. It is supported that skimmianine altered the influx of [45] Ca[2+] into the cells. In RPMCs experiment, skimmianine also suppressed the histamine release induced by Ca[2+] stimulants, and phorbol myristate acetate [PMA]. However, skimmianine had no effect on the histamine release induced by compound 48/80. Based on the results, the inhibitory effects of skimmianine on the histamine release from mast cells might involve some mechanisms related to intracellular Ca[2+] signaling events and protein kinase C signaling possessing a main role in granule exocytotic processes