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PURPOSE: Prevention of postoperative nausea and vomiting (PONV) is important to achieve DREAM (drinking, eating, mobilization). Ondansetron inhibits PONV, but its effects on postoperative food intake have not been investigated. This study aimed to examine associations between ondansetron and PONV incidence, and postoperative food intake. METHODS: This retrospective study included adult patients (n = 632) who underwent laparoscopic gynecological surgery at Kyushu University Hospital between January 2017 and June 2023. Outcomes were PONV on the day of surgery, PONV up to the day after surgery, and food intake, which was assessed for breakfast and lunch on the day after surgery. Odds ratios (ORs) for PONV incidence and postoperative no-food intake were calculated between those with and without ondansetron during surgery. Multivariable-adjusted analysis was performed using possible confounding factors for PONV. Synergistic effects of combining ondansetron with dexamethasone or total intravenous anesthesia (TIVA) were assessed. RESULTS: Multivariable-adjusted ORs for PONV on the day of surgery and up to the day after surgery were 0.56 (95% confidence interval, 0.32-0.99, p = 0.04) and 0.52 (0.30-0.93, p = 0.03), respectively, in the ondansetron group (n = 84) compared with the non-ondansetron group (n = 548). In contrast, multivariable-adjusted ORs for no-food intake of breakfast and lunch the day after surgery in the ondansetron group compared with the non-ondansetron group were not significant. Analysis of synergistic effects on PONV showed no significant interaction between ondansetron and dexamethasone or ondansetron and TIVA combinations. CONCLUSION: Ondansetron administration during surgery was significantly associated with decreased PONV risk but was not associated with food intake the day after surgery.
Assuntos
Antieméticos , Laparoscopia , Adulto , Humanos , Feminino , Ondansetron/efeitos adversos , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Antieméticos/efeitos adversos , Estudos Retrospectivos , Incidência , Japão/epidemiologia , Dexametasona , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Ingestão de Alimentos , Método Duplo-CegoRESUMO
The management of skin wound healing problems is a public health issue in which traditional herbal medicines could play a determining role. Kampo medicine, with three traditionally used ointments, provides interesting solutions for these dermatological issues. These ointments named Shiunko, Chuoko, and Shinsen taitsuko all have in common a lipophilic base of sesame oil and beeswax from which herbal crude drugs are extracted according to several possible manufacturing protocols. This review article brings together existing data on metabolites involved in the complex wound healing process. Among them are representatives of the botanical genera Angelica, Lithospermum, Curcuma, Phellodendron, Paeonia, Rheum, Rehmannia, Scrophularia, or Cinnamomum. Kampo provides numerous metabolites of interest, whose content in crude drugs is very sensitive to different biotic and abiotic factors and to the different extraction protocols used for these ointments. If Kampo medicine is known for its singular standardization, ointments are not well known, and research on these lipophilic formulas has not been developed due to the analytical difficulties encountered in biological and metabolomic analysis. Further research considering the complexities of these unique herbal ointments could contribute to a rationalization of Kampo's therapeutic uses for wound healing.
RESUMO
Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17ß-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERß) is expressed in the brain, and activation of ERß ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.
Assuntos
Agaricales , Fármacos Neuroprotetores , Animais , Estradiol/farmacologia , Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Feminino , Genisteína , Hericium , Humanos , Metanol , Ovariectomia , Fitoestrógenos , Ratos , Aumento de PesoRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Cálcio , Feminino , Humanos , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Complicações Pós-Operatórias/etiologia , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , SíndromeRESUMO
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, p = 0.79) compared with the sevoflurane group (77/327, reference). Similarly, after PS matching, the crude OR for the occurrence of shivering in the desflurane group (47/210) was 1.09 (95% CI: 0.68-1.75, p = 0.72) compared with the sevoflurane group (44/210, reference). Similar results were obtained in the stratified analysis by sex and age. The occurrence of POS is not different between sevoflurane and desflurane anesthesia.
Assuntos
Anestésicos Inalatórios , Hipotermia Induzida , Isoflurano , Éteres Metílicos , Adulto , Período de Recuperação da Anestesia , Anestesia por Inalação/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Desflurano/efeitos adversos , Humanos , Isoflurano/efeitos adversos , Éteres Metílicos/efeitos adversos , Estudos Retrospectivos , Sevoflurano/efeitos adversos , EstremecimentoRESUMO
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.
Assuntos
Isoflavonas/farmacologia , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Fator de Transcrição Associado à Microftalmia/efeitos dos fármacos , Fator de Transcrição Associado à Microftalmia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dalbergia/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Hiperpigmentação/tratamento farmacológico , Interferon Tipo I/metabolismo , Oxirredutases Intramoleculares/metabolismo , Isoflavonas/química , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Melanócitos/enzimologia , Melanócitos/metabolismo , Melanoma/enzimologia , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/farmacologia , Proteínas da Gravidez/metabolismo , Qualidade de VidaRESUMO
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 17ß-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 17ß-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-1ß, 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.
Assuntos
Disfunção Cognitiva/tratamento farmacológico , Hipocampo/metabolismo , Ovariectomia/efeitos adversos , Fitoestrógenos/administração & dosagem , Pueraria/química , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Malondialdeído/sangue , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fitoestrógenos/química , Fitoestrógenos/farmacologiaRESUMO
PURPOSE: 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. METHODS: 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%). CONCLUSION: Electromyographic (EMG) tube use was significantly associated with higher incidence of severe PLE.
Assuntos
Edema Laríngeo , Neurocirurgia , Eletromiografia , Humanos , Intubação Intratraqueal/efeitos adversos , Edema Laríngeo/diagnóstico , Edema Laríngeo/etiologia , Estudos RetrospectivosRESUMO
Two-pore channel 2 (TPC2) resides in endolysosomal membranes but also in lysosome-related organelles such as the melanin producing melanosomes. Gain-of-function polymorphisms in hTPC2 are associated with decreased melanin production and blond hair color. Vice versa genetic ablation of TPC2 increases melanin production. We show here an inverse correlation between melanin production and melanoma proliferation, migration, and invasion due to the dual activity of TPC2 in endolysosomes and melanosomes. Our results are supported by both genetic ablation and pharmacological inhibition of TPC2. Mechanistically, our data show that loss/block of TPC2 results in reduced protein levels of MITF, a major regulator of melanoma progression, but an increased activity of the melanin-generating enzyme tyrosinase. TPC2 inhibition thus provides a twofold benefit in melanoma prevention and treatment by increasing, through interference with tyrosinase activity, the synthesis of UV blocking melanin in melanosomes and by decreasing MITF-driven melanoma progression by increased GSK3ß-mediated MITF degradation.
Assuntos
Canais de Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Flavonoides/farmacologia , Melaninas/metabolismo , Melanoma/tratamento farmacológico , Melanossomas/efeitos dos fármacos , Linhagem Celular Tumoral , Endossomos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Células HEK293 , Cor de Cabelo/efeitos dos fármacos , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Melanoma/metabolismo , Melanossomas/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Pigmentação/efeitos dos fármacosRESUMO
PURPOSE: 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]. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Assuntos
Magnésio , Estremecimento , Eletrólitos , Humanos , Período Pós-Operatório , Estudos RetrospectivosRESUMO
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Six percent HES 130/0.4 is not associated with postoperative renal dysfunction in donor patients undergoing nephrectomy for kidney transplantation.
Assuntos
Rim , Doadores Vivos , Taxa de Filtração Glomerular , Humanos , Derivados de Hidroxietil Amido/efeitos adversos , Japão , Nefrectomia/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVES: The incidence of postoperative shivering is known to be inversely associated with core body temperature. However, previous studies have pointed out that the threshold of shivering could be affected by peripheral temperature or anesthetic agents. These reports pointed specific drugs, though, anesthesia techniques have since advanced considerably. This study aimed to investigate factors associated with postoperative shivering in the context of the current body warming practice. METHODS: The institutional clinical research ethics committee of Kyushu University approved the study protocol (IRB Clinical Research number 2019-233). This retrospective study involved 340 patients who had undergone radical surgery for gynecological cancer treatment under general anesthesia at our center from December 2012 to June 2019. Logistic regression analysis was performed to estimate the odds ratio (OR) for the incidence of postoperative shivering. RESULTS: Postoperative shivering developed in 109 out of 340 patients. After multivariate-adjusted logistic regression, the incidences of postoperative shivering decreased significantly with increasing patient age (OR = 0.96; 95%CI: 0.93-0.98; p = 0.0004). Volatile anesthesia technique was less inclined to shiver after surgery than TIVA (OR = 0.55; 95%CI: 0.30-0.99; p = 0.04). Acetaminophen was much less used in the shivering group than in the non-shivering group (OR = 0.49; 95%CI: 0.25-0.94; p = 0.03). CONCLUSIONS: This study indicated that the development of shivering in patients receiving the anesthetic technique currently used in our hospital was associated with use of acetaminophen or volatile agents, and patient age.
Assuntos
Acetaminofen , Estremecimento , Acetaminofen/efeitos adversos , Humanos , Incidência , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos RetrospectivosRESUMO
Daily treatment of ovariectomized (OVX) ICR mice with puerarin, a glycosyl isoflavone isolated from the root bark of Pueraria candollei var. mirifica, and 17ß-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 (Erß and Erα) mRNAs. Like 17ß-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.
Assuntos
Depressão/tratamento farmacológico , Estradiol/administração & dosagem , Isoflavonas/administração & dosagem , Ovariectomia/efeitos adversos , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Corticosterona/sangue , Depressão/etiologia , Depressão/genética , Depressão/metabolismo , Modelos Animais de Doenças , Proteína Duplacortina , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Isoflavonas/farmacologia , Camundongos , Camundongos Endogâmicos ICRAssuntos
Neoplasias , Vitamina D/sangue , Humanos , Incidência , Estudos Prospectivos , Vitamina D/análogos & derivadosRESUMO
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 fourkhrinone (5), cajanin (9), (3RS)-3'-hydroxy-8-methoxy vestitol (21), and (6aR,11aR)-3,8-dihydroxy-9-methoxy pterocarpan (27)reacted with mushroom tyrosinase, with IC50 values of 54.0, 67.9, 67.8, and 16.7 µM, 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 µM, 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 µM against mushroom tyrosinase could inhibit the mammalian tyrosinase, and thus, reduce melanogenesis in B16-F10. Flavonoids with the IC50 values greater than 50 µM, 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.
Assuntos
Agaricales/enzimologia , Flavonoides/farmacologia , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Melanócitos/metabolismoRESUMO
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-ß-D-apiofuranosyl-ß-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.
Assuntos
Diospyros/química , Glicosídeos/química , Naftalenos/química , Extratos Vegetais/química , Folhas de Planta/química , Plantas Medicinais/química , TailândiaRESUMO
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.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Furanos/farmacologia , Glucosídeos/farmacologia , Lignanas/farmacologia , Plantas Medicinais/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Bangladesh , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Estradiol/farmacologia , Furanos/química , Furanos/isolamento & purificação , Glucosídeos/química , Glucosídeos/isolamento & purificação , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Folhas de Planta/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
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 ERß (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).
Assuntos
Acridinas/farmacologia , Antineoplásicos/farmacologia , Desenho de Fármacos , Antagonistas de Estrogênios/farmacologia , Estrogênios/metabolismo , Acridinas/síntese química , Acridinas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Ligação Competitiva/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Antagonistas de Estrogênios/síntese química , Antagonistas de Estrogênios/química , Células HeLa , Humanos , Células MCF-7 , Estrutura Molecular , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
BACKGROUND: Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.MethodsâandâResults: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 <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH)2D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2than in those with eGFR ≥60 mL/min/1.73 m2; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04). CONCLUSIONS: The findings suggested that a lower serum 1,25(OH)2D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.