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Ionized magnesium (iMg) is considered to be the biologically active fraction of circulating total serum Mg (tMg). However, only the relationship between tMg and postoperative shivering has been studied. To our knowledge, hitherto no clinical studies have investigated the association between serum ionized magnesium concentration ([iMg]) and postoperative shivering. Therefore, we aimed to retrospectively examine this association, focusing on hypomagnesemia and depletion of [iMg]. This retrospective study involved 421 patients who underwent pancreaticoduodenectomy under general anesthesia at our center from December 2012 to September 2019. Logistic regression analysis was performed to estimate the odds ratio (OR) for the incidence of postoperative shivering. Postoperative shivering developed in 111 out of 421 patients. The post-surgical concentration of [iMg] was significantly associated with postoperative shivering in the non-adjusted model, but not in the multivariable-adjusted model. In multivariable-adjusted analysis, progressive decrease of [iMg] by 0.1 mmol/L significantly increased the risk of postoperative shivering (OR: 1.64, 95% CI 1.02–2.64, p = 0.04). The multivariable-adjusted OR for postoperative shivering was 3.65 (95% CI 1.25–13.55, p = 0.02) in subjects with post-surgical [iMg] less than 0.6 mmol/L and decrease in [iMg] during surgery compared with those with post-surgical [iMg] more than 0.6 mmol/L and constant or increased of [iMg] during surgery. A decrease in the [iMg] during surgery was significantly associated with postoperative shivering. Subjects who had an [iMg] lower than 0.6 mmol/L post-surgery and decreased [iMg] during surgery had a significantly higher risk of postoperative shivering. Intraoperative depletion of [iMg] was significantly associated with shivering.

Postreperfusion syndrome (PRS) after portal vein reperfusion during liver transplantation (LT) has been reported to cause rapid hemodynamic changes and is associated with a prolonged postoperative hospital stay, renal failure, and increased mortality. Although there are some reports on risk factors for PRS in brain-dead donor LT, there are a few reports on those in living donor LT. Therefore, we retrospectively reviewed the factors associated with PRS to contribute to the anesthetic management so as to reduce PRS during living donor LT.After approval by the ethics committee of our institution, 250 patients aged ≥20 years who underwent living donor LT at our institution between January 2013 and September 2018 were included in the study. A decrease in mean arterial pressure of ≥30% within 5 minutes after portal vein reperfusion was defined as PRS, and estimates and odds ratio (OR) for PRS were calculated using logistic regression. The backward method was used for variable selection in the multivariable analysis.Serum calcium ion concentration before reperfusion (per 0.1 mmol/L increase; OR, 0.74; 95% confidence interval (CI), 0.60-0.95; P.001), preoperative echocardiographic left ventricular end-diastolic diameter (per 1-mm increase: OR, 0.90; 95% CI, 0.85-0.95; P.001, men [versus women: OR, 2.45; 95% CI, 1.26-4.75; P = .008]), mean pulmonary artery pressure before reperfusion (restricted cubic spline, P = .003), anhepatic period (restricted cubic spline, P = .02), and graft volume to standard liver volume ratio (restricted cubic spline, P = .03) were significantly associated with PRS.In living donor LT, male sex and presence of small left ventricular end-diastolic diameter, large graft volume, and long anhepatic period are associated with PRS, and a high calcium ion concentration and low pulmonary artery pressure before reperfusion are negatively associated with PRS.

We aimed to investigate whether 6% HES 130/0.4 was associated with postoperative reduction of estimated glomerular filtration rate (eGFR) in donor patients who underwent nephrectomy for living kidney transplantation. This retrospective study included 213 living kidney transplant donors treated at Kyushu University Hospital in Japan from April 2014 to March 2018. Patients who were administered 6% HES 130/0.4 were allocated in the HES group (n = 108), and those who were not were allocated in the control group (n = 105). The postoperative decrements in estimated glomerular filtration rates (eGFRs) from preoperative values were calculated on postoperative days (PODs) 1, 3, and 14. Decline in kidney function (DKF) according to the Kidney Disease: Improving Global Outcomes (KDIGO) classification were analyzed by multivariable-adjusted ordinal logistic regression to estimate odds ratios (ORs) for postoperative DKF. In HES group, administration amount of HES was median 9.4 [interquartile range: 8.2–14.3] ml/kg. Postoperative decrements in eGFR were similar in the control and HES groups on POD 1 (control group: mean 32.0 vs. HES group: 33.0 mL/min/1.73 m2), same as POD 3 (21.1 vs. 22.4 mL/min/1.73 m2) and POD 14 (26.0 vs. 25.9 mL/min/1.73 m2), even after adjusting for confounding factors. The multivariable-adjusted ORs for postoperative DKF did not significantly increase in the HES group on POD 1 (OR: 0.88), POD 3 (OR: 0.96), and POD 14 (OR: 0.52) compared with the control group. Six percent HES 130/0.4 is not associated with postoperative renal dysfunction in donor patients undergoing nephrectomy for kidney transplantation.

General anesthetic agents can change the shivering threshold. Sevoflurane and desflurane are widely used as inhalational anesthetics and have also been reported to lower the shivering threshold in a dose-dependent manner. Although the comparison of postoperative shivering (POS) between total intravenous anesthesia and inhalational anesthesia has been reported, there have been no reports on a direct comparison between sevoflurane and desflurane anesthesia and the occurrence of POS in open abdominal surgery. After obtaining approval from the Ethics Review Committee (2020-261), 683 adult patients who underwent open radical surgery for uterine, cervical, or pancreatic cancer under general anesthesia using inhalational anesthetics at Kyushu University hospital between December 2012 and March 2020 were included in this retrospective study. The odds ratio (OR) for the occurrence of POS between the two groups (sevoflurane and desflurane) was calculated. Multivariable-adjusted analysis was performed using possible factors affecting POS. Furthermore, propensity score (PS) matching was conducted using these factors. The multivariable-adjusted OR for the occurrence of shivering in the desflurane group (62 occurrences/356 patients) was 1.06 (95% confidence interval [CI]: 0.69-1.62

Despite its classification as a non-life-threatening disease, increased skin pigmentation adversely affects quality of life and leads to loss of self-confidence. Until now, there are no recommended remedies with high efficacy and human safety for hyperpigmentation. This study aimed to investigate anti-melanogenic activity and underlying mechanism of cajanin, an isoflavonoid extracted from Dalbergia parviflora Roxb. (Leguminosae) in human melanin-producing cells. Culture with 50 μM cajanin for 48–72 h significantly suppressed proliferation in human melanoma MNT1 cells assessed via MTT viability assay. Interestingly, cajanin also efficiently diminished melanin content in MNT1 cells with the half maximum inhibitory concentration (IC50) at 77.47 ± 9.28 μM. Instead of direct inactivating enzymatic function of human tyrosinase, down-regulated mRNA and protein expression levels of MITF and downstream melanogenic enzymes, including tyrosinase, TRP-1 and Dct (TRP-2) were observed in MNT1 cells treated with 50 μM cajanin for 24–72 h. Correspondingly, treatment with cajanin modulated the signaling pathway of CREB and ERK which both regulate MITF expression level. Targeted suppression on MITF-related proteins in human melanin-producing cells strengthens the potential development of cajanin as an effective treatment for human hyperpigmented disorders.

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.

Four cycloartane type triterpenoids and three stigmastane type steroids were isolated from the methanolic extract of stem and root part of Pothos scandens L. (Araceae), a Bangladeshi medicinal plant by high performance liquid chromatographic technique. The compounds were characterized as 24-methylenecycloartanol (1), 24-methylenecycloartenone (2), 24-en-cycloartenone (3), 24-methylenecycloartanyl ferulate (4), stigmast-4-en-3-one (5), stigmast-4,22-diene-3-one (6) and β-sitosterol glucoside (7) through extensive 1D and 2D NMR spectroscopic studies. All the isolates were evaluated for their estrogenic/antiestrogenic activity using the estrogen-responsive breast cancer cell lines, MCF-7 and T47D. The results showed that all the compounds possess mild to strong antiestrogenic activity in both cell lines which was compared to positive control tamoxifen. 24- Methylenecycloartanol (1), which contains a hydroxyl group in its C-3 position, inhibited 90% of estradiol (E2)- induced cell proliferation in MCF-7 and T47D cell lines at a concentration of 0.01 μM only. 24- Methylenecycloartanyl ferulate (4) and stigmast-4,22-diene-3-one (6) showed 90% of estradiol (E2)-induced cell proliferation in T47D cell only at a concentration of 0.01 μM whereas 10.0 μM was required for 24- methylenecycloartanyl ferulate (4) for the same activity in MCF-7 cells. This is the first report of isolation of these compounds from the plant along with their antiestrogenic property. Dhaka Univ. J. Pharm. Sci. 18(1): 93-102, 2019 (June)

An electromyographic (EMG) tube is sometimes used for vagal nerve monitoring during neurosurgery. Some characteristics of an EMG tube are different from those of a normal endotracheal tube. Although postoperative laryngeal edema (PLE) may occur and reintubation may be required in some patients in whom an EMG tube is used, its relevance to these events has not been investigated in detail. Our goal was to determine the relevance of an EMG tube to the development of PLE and the need for reintubation.A retrospective study was conducted in 900 patients after neurosurgery from 2012 to 2018. Severe PLE occurrence or the requirement for postoperative reintubation were compared between the EMG tube (E) group and the Normal tube (N) group, using a propensity score (PS) matching analysis RESULTS: After PS matching, severe PLE incidence (n = 2/20, 10.0%) in the E group was significantly higher than that (0/80, 0%) in the N group. There was no significant difference in the incidence of reintubation between the E group (1/20, 5.0%) and the N group (0/80, 0%).Electromyographic (EMG) tube use was significantly associated with higher incidence of severe PLE.

EtOAc extract from the leaves of Terminalia citrina collected in Bangladesh were separated, and seven previously undescribed α-keto tetrahydrofuran lignan glucosides (terminalosides Q to W) were isolated and characterized. NOESY analysis of 1H NMR spectra and ECD spectroscopic data analysis revealed the absolute stereochemistry of the tetrahydrofuran ring of the isolated constituents as being a (7S,8R,8′S)- configuration in terminalosides Q to U and a (7R,8R,8′S)- configuration in terminalosides V and W. All of the isolated compounds were evaluated for their estrogenic and anti-estrogenic properties using two types of estrogen-responsive human breast cancer cell lines (MCF-7 and T47D). Terminaloside R, which has a dioxymethylene group in its aromatic ring, inhibited 90% of estradiol-enhanced cell proliferation in T47D and MCF-7 cells at concentrations of 0.01 μM and 0.1 μM, respectively. On the other hand, terminaloside T, the analogous compound which has two oxymethyl groups in place of dioxymethylene, suppressed 90% of cell proliferation selectively in T47D cells at a concentration of 0.01 μM. However, terminaloside W, the 7R-stereoisomer of terminaloside R, only showed moderate activity.

Estrogens play undisputedly important physiological roles, but lifetime exposure to estrogens has also been linked to the development of breast cancer. Moreover, imbalanced estrogen levels have been associated with various symptoms such as osteoporosis and menopausal disorders. For the improvement of such estrogen imbalances, estrogenic reagents with regulatory properties have shown promising potential. Herein, we report the construction of a 12-arylbenzoacridine library via a diversity-oriented strategy that furnished non-toxic estrogenic and anti-estrogenic agents. Derivatives with a hydroxy group at the molecular edge exhibit potent binding affinity to the estrogen receptor α (ERα) and ERβ (IC50 < μM), while binding to the estrogen-related receptor γ (ERRγ), i.e., an orphan nuclear receptor on which estrogens often trigger unfavorable events, was not observed. These findings offer valuable insights into 12-arylbenzoacridines as a novel platform for the development of selective estrogen-receptor modulators (SERMs).

BACKGROUND Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.Methods and Results:We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)2D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend

Five new polyalkoxylated furofuranone lignan glucosides, terminalosides L-P (1-5), were isolated from EtOAc extracts of the leaves of Terminalia citrina, a Bangladeshi medicinal plant. The structures of the isolates were deduced primarily by NMR spectroscopy, and four of the isolates were found to contain rare tetraoxygenated aryl groups in their structures. The absolute configurations and conformations of the furofuranone ring were confirmed by ECD spectroscopy. All of the isolates were evaluated for their estrogenic and/or antiestrogenic properties using two estrogen responsive breast cancer cell lines, T47D and MCF-7. At a concentration of 10nM, terminaloside L (1) suppressed E2-enhanced T47D cell proliferation by 90%, while terminaloside M (2) showed 90% antiestrogenic activity against MCF-7 cells. Compared to 2, the antiestrogenic activity of terminaloside O (4) and P (5) was weak, possibly due to the different attachment positions of the sugar moiety that they share in common. This is the first report of furofuranone lignans from any Terminalia species, and also of their antiestrogenic activity.

Extracts from the stem and roots of the Bangladeshi medicinal plant Pothos scandens L. (Araceae) were isolated, and three hemiterpene glucoside aromatic esters, pothobanosides A (1), B (2), and C (3), and a phenylisobutanoid, pothobanol (4), along with 14 known compounds, were characterized. The isolates were tested for their estrogenic/anti-estrogenic activity using the estrogen-responsive human breast cancer cell lines MCF-7 and T47D, and syringoyl derivatives (2, 3, and canthoside B) showed strong inhibitory activity against both cell lines. Their less oxygenated analogs (1, and markhamioside F) were almost inactive. The isolates were also evaluated for hyaluronidase and histamine release inhibitory activities, and pothobanoside A (1) showed significant hyaluronidase inhibitory activity among the isolated compounds, which was similar to that of the positive control rosmarinic acid. Because hyaluronidase produces an angiogenic response that has been implicated in tumor invasiveness and metastasis, 1 could be valuable as an anti-tumor compound with a different mechanism of action from related compounds (2, 3). Pothobanoside C (3) and pothobanol (4) were also found to inhibit histamine release to a similar degree to the positive control epigallocatechin 3-O-(3"-O-methyl)-gallate. The histamine release inhibitory potency of these isolates may support the traditional uses of this plant in folk medicine.

Daily treatment of ovariectomized (OVX) ICR mice with puerarin, a glycosyl isoflavone isolated from the root bark of Pueraria candollei var. mirifica, and 17β-estradiol attenuated ovariectomy-induced depression-like behavior, as indicated by a decrease in immobility times in the tail suspension test (TST) and the forced swimming test (FST), an increase in the uterine weight and volume, a decrease in serum corticosterone levels, and dose-dependently normalized the downregulated transcription of the brain-derived neurotrophic factor (BDNF) and estrogen receptor (Erβ and Erα) mRNAs. Like 17β-estradiol, puerarin also inhibited ovariectomy-induced suppression of neurogenesis in the dentate gyrus of the hippocampus (increased the number of doublecortin (DCX)-immunosuppressive cells). These results suggest that puerarin exerts antidepressant-like effects in OVX animals, possibly by attenuating the OVX-induced hyperactivation of the HPA axis and/or normalizing the downregulated transcription of BDNF and ER mRNA in the brain.

Twenty-seven flavonoids isolated from Dalbergia parviflora with vast structural diversity were screened for inhibitory activity against mushroom and murine tyrosinases using l-DOPA as the substrate. Among the flavonoids tested, only four&mdash, khrinone (5), cajanin (9), (3RS)-3&prime, hydroxy-8-methoxy vestitol (21), and (6aR,11aR)-3,8-dihydroxy-9-methoxy pterocarpan (27)&mdash, reacted with mushroom tyrosinase, with IC50 values of 54.0, 67.9, 67.8, and 16.7 &mu, M, respectively, and only compound 27 showed inhibitory activity against murine tyrosinase. With cell-based assays, only compounds 9 and 27 effectively inhibited melanogenesis in B16-F10 melanoma cells (by 34% and 59%, respectively), at a concentration of 15 &mu, M, without being significantly toxic to the cells. However, the crude extract of D. parviflora and some of the flavonoid constituents appeared to increase melanin production in B16-F10 cells, suggesting that there are flavonoids with both inhibitory and stimulatory melanogenesis in the crude extract. Studies on the correlation between the enzyme-based and cell-based assays showed that only the flavonoids with IC50 values below 50 &mu, M against mushroom tyrosinase could inhibit the mammalian tyrosinase, and thus, reduce melanogenesis in B16-F10. Flavonoids with the IC50 values greater than 50 &mu, M, on the other hand, could not inhibit the mammalian tyrosinase, and had either no effect or enhancement of melanogenesis. In conclusion, the tyrosinase enzyme from mushroom is not as selective as the one from mammalian source for the enzyme-based melanogenesis inhibitory screening, and the mammalian cell-based assay appears to be a more reliable model for screening than the enzyme-based one.

This study evaluated methanol extracts from the leaves and branches of the Thai medicinal plant Diospyros mollis (Ebenaceae). Seven triterpenes and 22 aromatic compounds, including five new compounds, were isolated, and their structures were determined. The new compounds had the following structures: diospyrol glycoside (makluoside A, 1), 8,8'-di-O-6-β-D-apiofuranosyl-β-D-glucopyranosyl-6,6'-dimethyl-2,3'-binaphthalene-1-ol-1',4'- dione (makluoside B, 2), and 3-methyl-1,8- naphthalenediol glycosides (makluosides C-E, 3-5). Makluoside B is the first example of a naphthoquinone glycoside that has both a 3-methyl-1,8-naphthalenediol unit and a 5-hydroxy-7-methyl-1,4-naphthoquinone unit. The hyaluronidase inhibitory activity of the isolates was evaluated, revealing that one of the triterpene derivatives possessed moderate inhibitory activity.

Miroestrol (MR) is a phytoestrogen isolated from Pueraria candollei var. mirifica (KwaoKrueaKhao), a Thai medicinal plant used for rejuvenation. We examined the effects of MR on cognitive function, oxidative brain damage, and the expression of genes encoding brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element-binding protein (CREB), factors implicated in neurogenesis and synaptic plasticity, in ovariectomized (OVX) mice. OVX decreased serum 17β-estradiol level and uterine weight. OVX also impaired object recognition performance in the novel object recognition test and spatial cognitive performance in the Y-maze test and the water maze test. Daily treatment of MR dose-dependently attenuated OVX-induced cognitive dysfunction. Moreover, OVX mice had a significantly increased level of thiobarbituric acid-reactive substances, and down-regulated expression levels of BDNF and CREB mRNAs in the hippocampus and frontal cortex. MR treatment as well as hormone replacement therapy with 17β-estradiol significantly reversed these neurochemical alterations caused by OVX. These results suggest that MR ameliorates cognitive deficits in OVX animals via attenuation of OVX-induced oxidative stress and down-regulation of BDNF and CREB mRNA transcription in the brain. Our findings raise the possibility that MR and Pueraria candollei var. mirifica, the plant of origin of MR, may have a beneficial effect on cognitive deficits like AD in which menopause/ovariectomy are implicated as risk factors.

The antioxidant activities of 24 isoflavonoids that were previously isolated as pure compounds from Dalbergia parviflora were evaluated using three different in vitro antioxidant-based assay systems: xanthine/xanthine oxidase (X/XO), ORAC, and DPPH. The isolates consisted of three subgroups, namely isoflavones, isoflavanones, and isoflavans, each of which appeared to have diversified substituents, and were thus ideal for the study of their structure-activity relationships (SARs). The SAR analysis was performed using the results obtained from both the inter-subgroup isoflavonoids with the same substitution pattern and the intra-subgroup compounds with different substitution patterns. The inter-subgroup comparison showed that the isoflavones exhibited the highest antioxidant activities based on all three assays. The intra-subgroup analysis showed that the additional presence of an OH group in Ring B at either R3' or R5' from the basic common structure of the R7-OH of Ring A and the R4'-OH (or -OMe) of Ring B greatly increased the antioxidant activities of all of the isoflavonoid subgroups and that other positions of OH and OMe substitutions exerted different effects on the activities depending on the subgroup and assay type. Therefore, based on the structural diversity of the isoflavonoids in D. parviflora, the present study provides the first clarification of the detailed antioxidant SARs of isoflavonoids.

Monardic acids A (1) and B (2), which are (7R,8R) diastereomers of lithospermic acid (LA) and lithospermic acid B, respectively, were isolated from Monarda fistulosa. A (7S,8R) isomer (3) of LA was also isolated from this plant, and a (7R,8S) isomer (7) of LA was obtained from Lithospermum erythrorhizon. The absolute configuration of 1 was confirmed by analysis of its hydrolysates, 7-epiblechnic acid and 2R-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid. The configuration in the dihydrobenzofuran moieties of 2, 3, and 7 was extrapolated by using the phenylglycine methyl ester method and a Cotton effect at approximately 250-260 nm in their electronic circular dichroism spectra. Diastereomers (1-3 and 7) displayed moderate hyaluronidase inhibitory and histamine release inhibitory activities.

From mycelia of Lentinus polychrous, a Thai local edible mushroom cultured under solid-state fermentation, a new compound, 6-methylheptane-1,2,3,4,5-pentaol (1), and five ergostanoids, namely (22E,24R)-ergosta-7,22-dien-3β,5α,6β-triol (2), 3β,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (3), ergosta-4,6,8(14),22-tetraen-3-one (4), (3β,5α,8α,22E)-5,8-diepoxy-ergosta-6,22-dien-3-ol (5) and 5,8-epidioxy-(3β,5α,8α,22E)-ergosta-6,9(11),22-trien-3-ol (6), was isolated and characterised. The compounds were determined for their oestrogenic and anti-oestrogenic activities by using human breast cancer T47D cells. All compounds had no oestrogenic activity but exhibited suppressive effect on oestradiol-enhanced cell proliferation. Among these compounds, only 4 significantly competed with oestradiol in the binding to oestrogen receptors (ERs) with higher selectivity to ERα than ERβ. These results may suggest that most compounds suppressed this oestradiol-enhanced T47D proliferation via other mechanisms rather than ER binding.

A polyhydroxyoctane, 6-methylheptane-1,2,3,4,5-pentaol (MHP), was first isolated from mycelia of the Thai edible mushroom Lentinus polychrous. MHP was evaluated for its cytotoxic and immunomodulatory effects in vitro. MHP was slightly cytotoxic to murine splenocytes but not to RAW264.7 cells or peripheral blood mononuclear cells. MHP decreased nitric oxide and intracellular O2 (-) production from lipopolysaccharide- and phorbol-12-myristate-13-acetate-activated RAW264.7 cells at levels of 78.98 ± 4.72 and 78.48 ± 2.41 % of controls, respectively. The mRNA expression of pro-inflammatory mediators, including iNOS, TNF-α, IL-1β, IL-6, COX-1 and COX-2, were significantly suppressed by MHP. In addition, MHP significantly increased the proliferation of phytohemagglutinin and pokeweed mitogen-induced splenocytes. These results indicate that MHP is able to modulate inflammatory responses and the proliferation of both T- and B-lymphocyte cells, suggesting that MHP may be a good natural immunomodulator.

Ethnopharmacological relevance The rhizomes of Dioscorea membrancea Pierre have been used in Thai traditional medicine as an ingredient formula for liver cancer and cholangiocarcinoma treatment. Aim of the study To investigate the cytotoxic activity of ethanolic extract and constituents of D. membrancea to support its traditional use. Materials and methods The SRB assay was used to determine the cytotoxic activity against hepatocellular carcinoma (HepG2), cholangiocarcinoma (KKU-M156) cells and one normal human keratinocyte immortal cells (HaCaT) with its ethanolic extract and isolated compounds. Bioassay guided isolation was used for isolating cytotoxic compounds. Results The ethanolic extract of D . membranacea rhizome showed weak cytotoxic against KKU-M156 and HepG2 (IC 50 at 72 h exposure=30.49±0.82 and 38.97±2.04 µg/mL respectively). A new steroid [epipanthogenin B ( 1 )], a known steroid [panthogenin B ( 2 )], two napthofuranoxepins [dioscorealide A ( 3 ) and dioscorealide B ( 4 )], phenanthraquinone [dioscoreanone ( 5 )] and two phenanthrene [5,6-dihydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene ( 6 ) and 2,5,6-trihydroxy-3,4-dimethoxy, 9, 10-dihydrophenanthrene ( 7 )] were isolated from active chloroform fraction. Compound 4 showed the highest cytotoxicity against HepG2 (IC 50 at 72 h exposure=2.87±0.21 µM) and KKU-M156 (IC 50 at 72 h exposure=1.67±0.10 µM) and less toxicity against normal cell line (HaCaT) (IC 50 at 72 h exposure>100 µM). Compound 5 showed selective cytotoxic activity against KKU-M156 (IC 50 at 72 h exposure=3.46±0.11 µM). Compounds 6 and 7 showed weak cytotoxic activity against HepG2 (IC 50 at 72 h exposure=24.96±2.32 and 51.31±3.52 µM). Compounds ( 1 – 3 ) showed no cytotoxic activity against HepG2 and KKU-M156 cell lines (IC 50 at 72 h exposure>100 µM). Conclusion Seven compounds were isolated from active chloroform fraction of the ethanolic extract of D . membranacea rhizomes. Only dioscorealide B ( 4 ) might be served as a good anticancer agent for liver cancer and cholangiocarcinoma cancer because it can kill cancer cell but not toxic on normal cell. This research support Thai traditional medicine use of D. membranacea for liver cancer and cholangiocarcinoma cancer treatment.

This present study was designed to isolate the compounds of Memecylon edule. The chemical compounds were purified by chromatographic methods and their structures were established on the basis of spectroscopic analyses (UV, MS and NMR). The major isolated compounds were tested for anti-inflammatory activity. The methanolic extracts of M. edule leaves gave a new compound 2-butanone 4-glucopyranoside 6′-O-gallate (1) with eight known compounds, namely, 3,3′-di-O-methylellagic acid 4-O-β-d-glucopyranoside (2), epigallocatechin-3-O-gallate (EGCG) (3), (2R, 3R)–dihydromyricetin-4′-β-d-glucopyranoside (4), myricetin-3-O-α-l-rhamnopyranoside (5), benzyl-(6-O-α-L arabinofuranosyl) O-β-d-glucopyranoside (6), benzyl-(6-O-α-l-rhanmopyranosyl) O-β-d-glucopyranoside (7), 2-phenylethyl-(6-O-β-d-apiofuranosyl)-O-β-d-glucopyranoside (8) and methyl benzoate 2-(6-O-α-l-rhamnosyl)-O-β-d-glucopyranoside (9). All compounds were isolated for the first time from this plant. The major compounds (2, 3 and 5) exhibited significant anti-inflammatory activity. In conclusion, M. edule was recognised to be a good source for phenolic compounds and these compounds may contribute to anti-inflammatory activity of the extract.

The MeOH extract from dried whole Botrychium ternatum plants yielded 33 compounds, including seventeen new flavonoid glycosides and sixteen known compounds. The structures of new compounds were established using NMR spectroscopic analysis and chemical evidence.

From the rhizomes of Smilax corbularia Kunth. (Smilacaceae), 11 compounds, (2R,3R)-2″-acetyl astilbin, (2R,3R)-3″-acetyl astilbin, (2R,3R)-4″-acetyl astilbin, (2R,3R)-3″-acetyl engeletin, (2R,3S)-4″-acetyl isoastilbin, 2-(4-hydroxyphenyl)-3,4,9,10-tetrahydro-3,5-dihydroxy-10-(3,4-dihydroxyphenyl)-(2R,3R,10R)-2H,8H-benzo [1,2-b:3,4-b'] dipyran-8-one, 2-(4-hydroxyphenyl)-3,4,9,10-tetrahydro-3,5-dihydroxy-10-(3,4-dihydroxyphenyl)-(2R,3R,10S)-2H, 8H-benzo [1,2-b:3,4-b'] dipyran-8-one, 3,4-dihydro-7-hydroxy-4-(3,4-dihydroxyphenyl)-5-[(1E)-2-(4-hydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, 3,4-dihydro-7-hydroxy-4-(3,4-dihydroxy-phenyl)-5-[(1E)-2-(3,4-dihydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, 3,4-dihydro-7-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-5-[(1E)-2-(4-hydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, and 5,7,3',4'-tetrahydroxy-3-phenylcoumarin along with 34 known compounds were isolated and characterized as 19 flavonoids, 14 catechin derivatives, 6 stilbene derivatives, and 6 miscellaneous substances. All isolates had their estrogenic and anti-estrogenic activities determined using the estrogen-responsive human breast cancer cell lines MCF-7 and T47D. The major constituents were recognized as flavanonol rhamnosides by the suppressive effect on estradiol induced cell proliferation at a concentration of 1μM. Meanwhile, flavanonol rhamnoside acetates demonstrated estrogenic activity in both MCF-7 and T47D cells at a concentration of 100μM, and they enhanced the effects of co-treated E2 on T47D cell proliferation at concentrations of more than 0.1μM.

From the heartwood of Dalbergia parviflora, eight new compounds, khrinones A (1), B (2), C (3), D (4), and E (5), isodarparvinol B (6), dalparvin (7), and (3S)-sativanone (22), along with 32 known compounds, have been isolated and characterized as 17 isoflavones, nine isoflavanones, five flavanones, six isoflavans, and three miscellaneous substances. Isolates were evaluated for their cell proliferation stimulatory activity against the MCF-7 and T47D human breast cancer cell lines, and their luciferase inductive effects using luciferase transiently transfected MCF-7/luc and T47D/luc cells were also determined. Isoflavones such as genistein (10), biochanin A (11), tectorigenin (12), and 2'-methoxyformononetin (13) stimulated the proliferation of both cells, and concentrations of lower than 1 muM of these compounds showed equivalent activity to 10 pM of estradiol (E2). The new isoflavanone (22) also showed activity against both cell types, although it was weaker than that of the corresponding isoflavone (2'-methoxyformononetin, 13). Two optically active isoflavanones (22 and 24: (3S)-violanone) stimulated the proliferation of both cell lines at lower concentrations than three racemates (21: vestitone, 23: 7,3'-dihydroxy-4'-methoxyisoflavanone, and 25: 3-O-methylviolanone). Bowdichione (20), an isoflavone with a quinone structure in its B-ring, showed activity against only one cell line associated with MCF-7 in these assays.

From the aerial parts of Clinopodium chinense var. parviflorum, nine new phenylpropanoids, clinopodic acids A-I (2-10), were isolated together with a known phenylpropanoid, rosmarinic acid (1). The structures of these new compounds were elucidated on the basis of spectroscopic analysis. Clinopodic acid C (4) showed MMP-2 inhibitory activity (IC(50) 3.26 microM).

From the stem bark of Ekebergia capensis, 10 new triterpenoid compounds, ekeberins A (1), B (2), C1 (3), C2 (4), C3 (5), D1 (6), D2 (7), D3 (8), D4 (9), and D5 (10), were isolated together with 17 known compounds. The structures of these new compounds were elucidated on the basis of the results of spectroscopic analysis, and the absolute configuration of compounds 6-10 were determined by partial synthesis from known compounds and using the Mosher ester method. Several of these compounds were screened in vitro against both chloroquine (CQ)-sensitive and -resistant Plasmodium falciparum isolates and were found to exhibit moderate antiplasmodial activity, with compounds 20 (7-deacetoxy-7-oxogedunin) and 27 (2-hydroxymethyl-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene) showing IC50 values of 6 and 7 microM, respectively. Compound 27 at a dose of 500 mg/kg showed moderate parasitemia suppression of 52.9% against P. berghei NK 65 in a mouse model.

Eleven abietane-type diterpenoids and two known abietanes were isolated from the roots of Caryopteris mongolica, and their structures were characterized. The absolute configurations at C-5 and C-10 were determined from the NMR data, including from the nuclear Overhauser effect and CD spectra, and the absolute configuration of C-16 in the hydroxypropyl group was determined via a modified Mosher’s method. Furthermore, the previously unknown absolute configuration of the C-15 of cyrtophyllone B was determined to be in an R-configuration using X-ray crystallography. To estimate the preventive effects of the isolates for neurodegenerative disease development, their inhibitory activities against acetylcholinesterase (AChE) from human erythrocytes and butyrylcholinesterase (BChE) from horse serum were evaluated.

Hairy root cultures of Pharbitis nil treated with CuSO4 and methyl jasmonate (MeJA) produced umbelliferone (1) and scopoletin (2) in the culture medium, and skimmin (3), a beta-D-glucopyranoside of 1, was isolated from the hairy roots. While 1 in the medium increased and reached a maximal level 16 h after the treatment with CuSO4, the amount of 3 in the hairy roots decreased, reaching a minimal level after 8 h, before recovering to a level higher than the basal level after 24 h and then continuously increasing. These observations suggest that 1 was released by the hydrolysis of 3. Umbelliferone (1) inhibited hairy root growth, while skimmin (3) did not. This result suggests that, after the release of 1 as a phytoalexin, the hairy roots glycosylated 1 for the detoxification and re-use of 3 as a source of phytoalexin.

Eight Thai edible plants were tested for their inhibitory activity against an angiotensin-converting enzyme (ACE) using an in vitro assay. The methanol extract of Apium graveolens exhibited significant ACE inhibitory activity with an IC50 value of 1.7 mg/ml, and was then subjected to an isolation procedure that resulted in identification of a pure active constituent, junipediol A 8-O-β-d-glucoside (1-β-d-glucosyloxy-2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol) (1), which had good ACE inhibitory activity with an IC50 value of 76 μg/ml. Another eight known compounds, isofraxidin-β-d-glucoside (2), roseoside (3), apigenin-7-O-β-d-glucoside (4), luteolin-7-O-β-d-glucoside (5), icariside D2 (6), apiin (7), chrysoeriol-7-O-β-d-apiosylglucoside (8), and 11,21-dioxo-3 β,15 α,24-trihydroxyurs-12-ene-24-O-β-d-glucopyranoside (9) were also identified. Although each of these five constituents (2-6) isolated from the same fraction as 1 showed no activity at concentrations of 500 μM, together, when each was present at 300 μg/ml, they enhanced the inhibitory activity of 500 μM of 1 from 64% to 81%.

The effect of natural and synthetic galloyl esters on glucocorticoid-induced gene expression was evaluated by using rat fibroblast 3Y1 cells stably transfected with a luciferase reporter gene under the transcriptional regulation of the mouse mammary tumor virus promoter. The glucocorticoid-induced gene transcription was strongly suppressed by synthetic alkyl esters; n-dodecyl gallate showed the most potent inhibition (66% inhibition at 10 microM), which was far more potent than that of crude tannic acid. n-Octyl and n-cetyl gallate also showed good inhibition, while gallic acid itself was not so active, suggesting that the presence of hydrophobic side chain is important for the suppressive effect. On the other hand, surprisingly, green tea gallocatechins, (-)-epigallocatechin-3-O-gallate and theasinensin A, potently enhanced the promoter activity (182 and 247% activity at 1 microM, respectively). The regulation of the level of the glucocorticoid-induced gene expression by the antioxidative gallates is of great interest from a therapeutic point of view.

The green tea gallocatechins, (-)-epigallocatechin-3-O-gallate (EGCG) (IC(50) = 0.69 microM), (-)-gallocatechin-3-O-gallate (GCG) (IC(50) = 0.67 microM), (-)-epicatechin-3-O-gallate (ECG) (IC(50) = 1.3 microM), and theasinensin A (IC(50) = 0.13 microM), were found to be potent and selective inhibitors of rat squalene epoxidase (SE), a rate-limiting enzyme of cholesterol biogenesis. On the other hand, flavan-3-ols without galloyl group at C-3 did not show significant enzyme inhibition. It was demonstrated for the first time that the cholesterol lowering effect of green tea may be attributed to their potent SE inhibition activities. Inhibition kinetics revealed that EGCG inhibited SE in noncompetitive (K(I) = 0.74 microM), and non-time-dependent manner. The potent enzyme inhibition would be caused by specific binding to the enzyme, and by scavenging reactive oxygen species required for the monooxygenase reaction.

In the course of screening for cell differentiation inducers from botanical sources, the methanol extract of Withania somnifera L. (DUN.) showed activity. From the aerial parts of the plant, sixteen withanolides, including three new compounds, 14, 15 and 16, were isolated and their structures elucidated to be (20S, 22R)-4β, 5β, 6α, 27-tetrahydroxy-1-oxo-witha-2, 24-dienolide, (20R, 22R, 24S, 25R)-4β, 20β-dihydroxy-5β, 6β-epoxy-3β-methoxy-1-oxo-withanolide and 3-O-[β-D-glucopyranosyl(1→6)-β-D-glucopyranosyl]-(20S, 22R)-1α, 3β-dihydroxywitha-5, 24-di-enolide, respectively, from the spectral data. Of these withanolides, 1, 2, 3 and 4 showed potent cell differentiation inducing activity against M1 cells. The most potent compound, 3, showed more potent activity than dexamethasone, the positive control. These active compounds have the same partial structure of the AB ring part, having a 4β-hydroxy-5β, 6β-epoxy-2-en-1-one moiety.

Five new oleanane-type saponins, polygalasaponins XLII–XLVI, along with two known saponins were isolated from the roots of Polygala glomerata Lour. The structures of polygalasaponins XLII–XLVI were elucidated as 3- O -β- d -glucopyranosyl presenegenin 28- O -β- d -xylopyranosyl-(1 → 4)-α- l -rhamnopyranosyl-(1 → 2)-{4- O -[( E )-3,4-dimethoxycinnamoyl]}-β- d -fucopyranosyl ester, 3- O -β- d -glucopyranosyl presenegenin 28- O -β- d -galactopyranosyl-(1 → 4)-β- d -xylopyranosyl-(1 → 4)-α- l -rhamnopyranosyl-(1 → 2)-[α- l -arabinopyranosyl-(1 → 3)]-[4- O -( E )- p -methoxycinnamoyl]-β- d -fucopyranosyl ester, 3- O -β- d -glucopyranosyl presenegenin 28- O -β- d -galactopyranosyl-(1 → 4)-β- d -xylopyranosyl-(1 → 4)-α- l -rhamnopyranosyl-(1 → 2)-[α- d -glucopyranosyl-(1 → 3)]-{4- O -[( E )-3,4-dimethoxycinnamoyl]}-β- d -fucopyranosyl ester, 3- O -β- d -glucopyranosyl presenegenin 28- O -β- d -galactopyranosyl-(1 → 4)-β- d -xylopyranosyl-(1 → 4)-α- l -rhamnopyranosyl-(1 → 2)-[6- O -acetyl-β- d -glucopyranosyl-(1 → 3)]-{4- O -[( E )-3,4-dimethoxycinnamoyl]}-β- d -fucopyranosyl ester, 3- O -β- d -glucopyranosyl presenegenin 28- O -β- d -galactopyranosyl-(1 → 4)-β- d -xylopyranosyl-(1 → 4)-α- l -rhamnopyranosyl-(1 → 2)-[6- O -acetyl-β- d -glucopyranosyl-(1 → 3)]-{4- O -[( Z )-3,4-dimethoxycinnamoyl]}-β- d -fucopyranosyl ester, respectively, on the basis of spectroscopic and chemical evidence.

Seven new sucrose and oligosaccharide esters, glomeratoses A-G, together with four known compounds, 3-O-[(E)-3,4,5- trimethoxycinnamoyl ]-β- d -fructofuranosyl -(2 → 1)-(6-O- benzoyl )-α- d -glucopyranoside , 3-O-(E)- sinapoyl-β- d -fructofuranosyl -(2 → 1)-[6-O-(E)- sinapoyl ]-α- d -glucopyranoside , tenuifoliside C and reiniose G were isolated from the roots of Polygala glomerata . Glomeratoses A-G were elucidated as 3-O-[(E)-3,4,5- trimethoxycinnamoyl ]-β- d -fructofuranosyl -(2 → 1)-α- d -glucopyranoside , 3-O-(E)- sinapoyl-β- d -fructofuranosyl -(2 → 1)-[6-O-(E)-p- coumaroyl ]-α- d -glucopyranoside , 3-O-[(E)-3,4,5- trimethoxycinnamoyl ]-β- d -fructofuranosyl -(2 → 1)-[6-O-(E)-p- coumaroyl ]-α- d -glucopyranoside , 3-O-[(E)-3,4,5- trimethoxycinnamoyl ]-β- d -fructofuranosyl -(2 → 1)-[6-O-(E)-3,4,5- trimethoxycinnamoyl ]-α- d - glucopyranoside , 1-O-∗6-O-[3-O-(E,E)-(β,β′- bis-sinapoyl )-β- d -fructofuranosyl ]∗-α- d -glucopyranoside intramolecular ester, 1-O-(E)-p- coumaroyl -(3-O- benzoyl )-β- d -fructofuranosyl -(2 → 1)-[β- d -glucopyranosyl -(1 → 2)]-[6-O- acetyl-β- d -glucopyranoysl -(1 → 3)]-[4-O-(E)- feruloyl ]-(6- d -acetyl )-α- d -glucopyranoside , 1-O-(E)-p- coumaroyl -(3-O- benzoyl )-β- d -fructofuranosyl -(2 → 1)-[β- d -glucopyranosyl -(1 → 2)]-[6-O- acetyl-β- d -glucopyranoside -(1 → 3)]-∗4-O-[4-O-β- d -glucopyranosyl -(E)- feruloyl ]∗-[6-O-(E)-p- coumaroyl ]-α- d -glucopyranosyl , respectively, on the basis of chemical and spectral evidence.

Five new oligosaccharide polyesters, fallaxoses A–E, along with four known ones, reiniose D, senegose G, tenuifolioses C and P, were isolated from the roots of Polygala fallax . Fallaxoses A–E were elucidated as 3- O -{4- O -[β- d -glucopyranosyl-(1 → 4 -α- l - rhamnopyranosyl]-feruloyl}-β- d -fructofuranosyl- (2 → 1)-(4,6-di- O -benzoyl-α- d -glucopyranoside, 3- O -{4- O -[β- d -gluocopyranosyl-(1 → 3) -(2- O -acetyl-α- l -rhamnopyranosyl]-feruloyl}-β- d -fructofuranosyl-(2 → 1)-(4,6-di- O - benzoyl-α- d -glucopyranoside, l- O - p -coumaroyl-(3- O -benzoyl-β- d -fructofuranosyl-(2 → 1)-[β- d -glucopyranosyl- (1 → 2)-[6- O -acetyl-β- d -glucopyranosyl-(1 → 3)-(4- O - p -coumaroyl)-α- d -glucopyranoside, l- O - p -coumaroyl- (3- O -benzoyl)-β- d -fructofuranosyl-(2 → 1)-[β- d -glucopyranosyl-(1 → 2)]-[6- O -acetyl-β- d -glucopyranosyl-(1 → 3)]- (4- O -feruloyl)-α- d -glucopyranoside, 1- O -feruloyl-(3- O -benzoyl-β- d -fructofuranosyl-(2 → 1)-[β- d -glucopyranosyl- (1 → 2)]-[β- d -glucopyranosyl-(1 → 3)-(6- O -acetyl)-β- d -glucopyranosyl-(1 → 3)]-(6- O -feruloyl)-α- d -glucopyranoside, respectively, by spectroscopic and chemical means.

The NO-generating abilities of aromatic N-nitroso compounds (nitrosoureas, nitrosamides and nitrosamines), and N-acetyl-S-nitroso-DL-penicillamine at ambient temperature were compared by employing the Griess reaction. 3,3-Dibenzyl-1-(4-tolyl)-1-nitrosourea showed the greatest NO-generating ability among the tested compounds. The NO-generating ability of the aromatic N-nitrosoureas and N-nitrosamides was greater than that of the N-nitrosamines, presumably reflecting differences in electrostatic repulsion between the carbonyl oxygen and nitroso oxygen in these compounds. In addition, a conjugative effect between the aromatic ring carbon and neighboring nitrogen influences the NO-generating ability; the conjugative effect in the case of N-nitrosoureas and N-nitrosamides having an ortho-alkyl substituted aromatic ring, or N-nitrosamines having a bulky N-group, such as tert-butyl, is decreased by an increase in steric hindrance around the nitroso group. The N-NO bond then becomes more stable. The NO-generating ability was related to the reciprocal of the ID50 value for growth inhibition of cultured L-5178 Y cells by the aromatic N-nitroso compounds. On the other hand, NO production from the aliphatic N-nitroso compounds was not observed under our conditions, and these N-nitroso compounds did not show effective cytotoxic activity.