RESUMEN

Low-level laser irradiation (LLLI) is a novel approach that shows promise for the treatment of colorectal cancer (CRC). However, the molecular mechanisms underlying its biochemical effects and gene expression remain unclear. Here, LLLI (632.8 nm) was used to treat CRC RKO cells and normal small intestinal NCM460 cells. LLLI showed a significant dose- and time-dependent effect on cell viability, in which a single dose of irradiation at 15 J/cm2 selectively inhibited the growth of RKO cells but largely unaffected the activity of NCM460 cells. And then, LLLI produced an internal response, effectively reducing the level of H2O2 in tumor cells, downregulating the mitochondrial membrane potential, and improving the efficiency of apoptosis in CRC, but no internal response was observed in NCM460 cells under the same conditions. Furthermore, the expression of several important genes in the classical WNT pathway was significantly downregulated, and the pathway was inactivated after LLLI intervention, thereby inhibiting tumor cell growth. Simultaneously, TNF-α was effectively activated to stimulate the caspase family members of the death effector to initiate apoptosis led by the extrinsic pathway. LLLI successfully achieves tumor cell normalization while delivering a potent anticancer effect, expected to be a novel therapeutic modality for CRC.

Asunto(s)

Neoplasias Colorrectales , Peróxido de Hidrógeno , Humanos , Peróxido de Hidrógeno/farmacología , Proliferación Celular/efectos de la radiación , Rayos Láser , Apoptosis , Línea Celular Tumoral

RESUMEN

The androgen receptor (AR) plays a central role in prostate, muscle, bone and adipose tissue. Moreover, dysregulated AR activity is a driving force in prostate cancer (PCa) initiation and progression. Consequently, antagonizing AR signalling cascades via antiandrogenic therapy is a crucial treatment option in PCa management. Besides, very high androgen levels also inhibit PCa cells' growth, so this effect could also be applied in PCa therapy. However, on the molecular and cellular level, these mechanisms have hardly been investigated so far. Therefore, the present study describes the effects of varying androgen concentrations on the viability of PCa cells as well as localization, transactivation, and protein stability of the AR. For this purpose, cell viability was determined via WST1 assay. Alterations in AR transactivity were detected by qPCR analysis of AR target genes. A fluorescent AR fusion protein was used to analyse AR localization microscopically. Changes in AR protein expression were detected by Western blot. Our results showed that high androgen concentrations reduce the cell viability in LNCaP and C4-2 cell lines. In addition, androgens have been reported to increase AR transactivity, AR localization, and AR protein expression levels. However, high androgen levels did not reduce these parameters. Furthermore, this study revealed an androgen-induced increase in AR protein synthesis. In conclusion, inhibitory effects on cell viability by high androgen levels are due to AR downstream signalling or non-genomic AR activity. Moreover, hormonal activation of the AR leads to a self-induced stabilization of the receptor, resulting in increased AR activity. Therefore, in clinical use, a therapeutic reduction in androgen levels represents a clinical target and would lead to a decrease in AR activity and, thus, AR-driven PCa progression.

RESUMEN

There have been many investigations on the negative effects of imidacloprid (IMD) on honey bees. IMD is known to disrupt honey bee physiology and colony health at a relatively low concentration compared to other pesticides. In this study, honey bee colonies were chronically exposed to field-realistic concentrations (5, 20, and 100 ppb) of IMD, and the body weight, flight performance, carbohydrate reserve, and lipid contents of forager bees analyzed. Transcriptome analyses followed by quantitative PCR were also conducted for both nurse and forager bees to elucidate any changes in energy metabolism related to phenotypic disorders. The body weights of newly emerged and nurse bees showed decreasing tendencies as the IMD concentration increased. In forager bees, however, IMD induced a biphasic change in body weight: body weight was decreased at the lower concentrations (5 and 20 ppb) but increased at the higher concentration (100 ppb). Nevertheless, the flight capability of forager bees significantly decreased in a concentration-dependent manner. The effects of IMD on target gene transcription in forager bees showed biphasic patterns between low (5 and 20 ppb) and high (100 ppb) concentrations. Nurse bees showed typical features of premature transition to foragers in a concentration-dependent manner. When exposed to low concentrations, forager bees exhibited downregulation of genes involved in carbohydrate and lipid metabolism and in the insulin/insulin-like growth factor signaling pathway, upregulation of transporter activity, and a dose-dependent body weight reduction, which were similar to insulin resistance and diabetic symptoms. However, increased lipid metabolism and decreased energy metabolism with body weight gain were observed at high IMD concentration. Considered together, these results suggest that field-realistic doses of IMD alter honey bee energy metabolism in distinctly different ways at low and high concentrations, both of which negatively affect honey bee colony health.

Asunto(s)

Insecticidas , Animales , Abejas , Peso Corporal , Carbohidratos , Insecticidas/toxicidad , Neonicotinoides/toxicidad , Nitrocompuestos/toxicidad

RESUMEN

Cytotoxic chemotherapy dominates the field of cancer treatment. Consequently, anticancer phytochemicals are largely screened on the basis of their cytotoxicity towards cancer cells which are achieved at higher doses, leading to various toxic side effects. Some phytochemicals also showed pro-carcinogenic effects at certain doses. The concept of hormesis has taught us to look into biphasic responses of phytochemicals in a more systematic way. Interestingly, the monoterpenoid alcohol, linalool, also has been reported to display both anti-oxidant and pro-oxidant properties, which prompted us to explore a probable biphasic effect on cancer cells. Cytotoxicity of various concentrations of linalool (0.1-4 mM) was tested on B16F10 murine melanoma cell line, and two sub-lethal concentrations (0.4 and 0.8 mM) were selected for further experiments. 0.4 mM linalool inhibited angiogenesis and metastasis, while 0.8 mM increased them. Similarly, B16F10 cell migration, invasion, and epithelial-mesenchymal transition markers also showed inhibition and induction with lower and higher linalool concentrations, respectively. Chorioallantoic membrane assay, scratch wound assay, and Boyden's chamber were used to analyze angiogenesis and metastasis. Expression of molecular markers such as vascular endothelial growth factor (VEGF) and its receptor phosphorylated VEGF receptor II (p-VEGFRII or p-Flk-1), Hypoxia-inducible factor-1 α (HIF-1α), E-cadherin, and vimentin were detected using Western blot, ELISA, PCR, qPCR, and immunofluorescence. Finally, ChIP assay was performed to evaluate HIF-1α association with VEGF promoter. Interestingly, measurement of intracellular reactive oxygen species at the selected concentrations of linalool using DCFDA in a flow cytometer showed that the phytochemical induced significant amount of ROS at 0.8 mM. This work sheds light on bimodal dose-response relationship exhibited by dietary phytochemicals like linalool, and it should be taken into consideration to elicit a desirable therapeutic effect.

Asunto(s)

Monoterpenos Acíclicos/farmacología , Melanoma Experimental , Neovascularización Patológica , Animales , Embrión de Pollo , Células HEK293 , Humanos , Melanoma Experimental/sangre , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Metástasis de la Neoplasia , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología

RESUMEN

Mechanical forces can modulate the immune response, mostly described as promoting the activation of immune cells, but the role and mechanism of pathological levels of mechanical stress in lymphocyte activation have not been focused on before. By an ex vivo experimental approach, we observed that mechanical stressing of murine spleen lymphocytes with 50 mmHg for 3 h induced the nuclear localization of NFAT1, increased C-Jun, and increased the expression of early activation marker CD69 in resting CD8+ cells. Interestingly, 50 mmHg mechanical stressing induced the nuclear localization of NFAT1; but conversely decreased C-Jun and inhibited the expression of CD69 in lymphocytes under lipopolysaccharide or phorbol 12-myristate 13-acetate/ionomycin stimulation. Additionally, we observed similar changes trends when comparing RNA-seq data of hypertensive and normotensive COVID-19 patients. Our results indicate a biphasic effect of mechanical stress on lymphocyte activation, which provides insight into the variety of immune responses in pathologies involving elevated mechanical stress.

Asunto(s)

Activación de Linfocitos/inmunología , Estrés Mecánico , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Biomarcadores/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , COVID-19/complicaciones , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Comorbilidad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Canales Iónicos/metabolismo , Lectinas Tipo C/metabolismo , Lipopolisacáridos/farmacología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/genética , Masculino , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/metabolismo , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/metabolismo , Transducción de Señal/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacología

RESUMEN

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical that interferes with normal steroid hormone production in various species. However, the underlying mechanism of the effect of BPA on steroid production in the human ovary is not well understood. In the present study, we found that BPA, at very low concentrations (10-11 to 10-8 M), significantly increased the expression of FOXL2, a transcriptional factor essential for proper ovarian development and function, in a human ovarian granulosa cell-derived cell line (KGN). Furthermore, BPA enhanced CYP19A1 (aromatase) expression levels and estradiol (E2) production, but these effects were not observed in FOXL2 knockout (KO) cells. In addition, we found that BPA upregulates ß-catenin (CTNNB1) and stimulates nuclear translocation of CTNNB1, leading to transcriptional activation of FOXL2 mRNA. Furthermore, BPA failed to induce CYP19A1 and E2 production in CTNNB1-silenced KGN cells. Thus, we reveal a comprehensive molecular signaling cascade encompassing BPA-CTNNB1-FOXL2-CYP19A1-E2 that contributes to the endocrine-disrupting activities of BPA in human ovarian granulosa cells.

RESUMEN

BACKGROUND: Ocular melanoma is a disorder that is rarely found but is deadly. Four tissues in the eye that can be attacked by melanoma include the uveal tract, conjunctiva, eyelids, and orbit. Uveal melanoma is the most common case, while melanoma conjunctiva is very rare. OBJECTIVE: This study aimed to investigate the effect of giving genistein on cyclin D1 expression in malignant melanoma. METHODS: When confluent, CRL1872 malignant melanoma cells will be divided into treatment groups, the group giving genistein dose 25 µM, the group giving genistein a dose of 50 µM, and the group giving genistein a dose of 100 µM. Cyclin D1 analysis was measured by immunofluorescence using confocal laser scan microscopy. RESULTS: There was a significant increase in the expression of cyclin D1, in the group given genistein 25 µM and 50 µM (p < 0.05). For the administration of the genistein dose of 100 µM, cyclin D1 expression decreased significantly compared to the control group (p < 0.05). CONCLUSION: It was concluded that genistein had a biphasic effect on cyclin D1 expression in malignant melanoma cells. Thus, genistein at the right dose can be a treatment of malignant melanoma.

Asunto(s)

Melanoma , Neoplasias Cutáneas , Neoplasias de la Úvea , Ciclina D1 , Genisteína/farmacología , Humanos , Melanoma/tratamiento farmacológico , Neoplasias de la Úvea/tratamiento farmacológico

RESUMEN

Antidepressants are well-known drugs to treat depression and major depressive disorder for humans. However, the misuse and abuse of antidepressants keep increasing with several side effects reported. The aim of this study was to assess the potential adverse effects of 18 antidepressants by monitoring zebrafish larval locomotor activity performance based on the total distance traveled, burst movement count, and total rotation count at four dark-light intercalated phases. In general, zebrafish larvae displayed sedative effects after antidepressant exposure by showing a significant reduction in all of the locomotor activity-related endpoints. However, three antidepressants i.e., amitriptyline, amoxapine, and sertraline were able to trigger a significantly high locomotor activity in zebrafish larvae during the light cycle. These differences might be due to the pharmacologic differences among the antidepressants. In addition, since each antidepressant possesses a different dosage range from the other, overdoses of these antidepressants might also be the causes of these differences. Furthermore, based on these results, a further study was conducted to observe the effect of these three antidepressants in lower concentrations. From the results, biphasic effects in terms of zebrafish larval locomotor activity were demonstrated by these drugs. Even though further studies are still required to validate the mechanism, these findings indicate that these antidepressants might share a common mechanism responsible for their effects on zebrafish larval locomotor activity although there were some differences in potency of these effects.

Asunto(s)

Amitriptilina/farmacología , Amoxapina/farmacología , Antidepresivos/farmacología , Bioensayo , Evaluación Preclínica de Medicamentos , Locomoción/efectos de los fármacos , Sertralina/farmacología , Pez Cebra/fisiología , Animales , Larva/efectos de los fármacos , Larva/fisiología , Fenómica , Análisis de Componente Principal

RESUMEN

Brassinosteroids (BRs) are known to improve salt tolerance of plants, but not in all situations. Here, we show that a certain concentration of 24-epibrassinolide (EBL), an active BR, can promote the tolerance of canola under high-salt stress, but the same concentration is disadvantageous under low-salt stress. We define this phenomenon as hormonal stress-level-dependent biphasic (SLDB) effects. The SLDB effects of EBL on salt tolerance in canola are closely related to H2 O2 accumulation, which is regulated by polyamine metabolism, especially putrescine (Put) oxidation. The inhibition of EBL on canola under low-salt stress can be ameliorated by repressing Put biosynthesis or diamine oxidase activity to reduce H2 O2 production. Genetic and phenotypic results of bri1-9, bak1, bes1-D, and bzr1-1D mutants and overexpression lines of BRI1 and BAK1 in Arabidopsis indicate that a proper enhancement of BR signaling benefits plants in countering salt stress, whereas excessive enhancement is just as harmful as a deficiency. These results highlight the involvement of crosstalk between BR signaling and Put metabolism in H2 O2 accumulation, which underlies the dual role of BR in plant salt tolerance.

Asunto(s)

Arabidopsis/fisiología , Brassica napus/fisiología , Brasinoesteroides/farmacología , Putrescina/metabolismo , Tolerancia a la Sal/efectos de los fármacos , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Brassica napus/efectos de los fármacos , Germinación/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Oxidación-Reducción , Estrés Salino/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Cloruro de Sodio/toxicidad , Espermidina/metabolismo , Esteroides Heterocíclicos/farmacología

RESUMEN

Curcumin (diferuloylmethane), a component of the yellow powder prepared from the roots of Curcuma longa or Zingiberaceae (known as turmeric) is not only widely used to color and flavor food but also used as a pharmaceutical agent. Curcumin demonstrates anti-inflammatory, anticarcinogenic, antiaging, and antioxidant activity, as well as efficacy in wound healing. Notably, curcumin is a hormetic agent (hormetin), as it is stimulatory at low doses and inhibitory at high doses. Hormesis by curcumin could be also a particular function at low doses (i.e., antioxidant behavior) and another function at high dose (i.e., induction of autophagy and cell death). Recent findings suggest that curcumin exhibits biphasic dose-responses on cells, with low doses having stronger effects than high doses; examples being activation of the mitogen-activated protein kinase signaling pathway or antioxidant activity. This indicates that many effects induced by curcumin are dependent on dose and some effects might be greater at lower doses, indicative of a hormetic response. Despite the consistent occurrence of hormetic responses of curcumin in a wide range of biomedical models, epidemiological and clinical trials are needed to assess the nature of curcumin's dose-response in humans. Fortunately, more than one hundred clinical trials with curcumin and curcumin derivatives are ongoing. In this review, we provide the first comprehensive analysis supportive of the hormetic behavior of curcumin and curcumin derivatives.

Asunto(s)

Curcumina/farmacología , Hormesis/fisiología , Animales , Humanos

RESUMEN

The present study was undertaken to investigate the individual and combined antioxidant or prooxidant effects of genistein, daidzein and quercetin in human erythrocytes and rat microsomes in vitro. Their reducing potential against oxidation of a redox sensitive fluorescent probe, their protective effect against H2O2-induced membrane lipid peroxidation and their inhibitory effect on AAPH-induced hemolysis were evaluated. Genistein and daidzein were prooxidant in erythrocytes but antioxidant in microsomes where their metabolites might have been formed which suggests the importance of metabolic capacity in in vitro models to predict the physiological situation. Quercetin showed antioxidant effects in all models and conditions. Prooxidant effect of 'genistein-daidzein mixture', at their concentrations reflecting the real life, was suppressed by addition of quercetin to the mixture. Our study shows that flavonoids can exert prooxidant effects depending on the conditions, but the mixture effect should be considered while assessing their effects and safety in humans.

Asunto(s)

Antioxidantes/farmacología , Flavonoides/farmacología , Adulto , Animales , Quimioterapia Combinada , Eritrocitos/efectos de los fármacos , Colorantes Fluorescentes/química , Genisteína/farmacología , Hemólisis/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/farmacología , Isoflavonas/farmacología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Oxidantes/farmacología , Oxidación-Reducción , Quercetina/farmacología , Ratas Wistar , Especies Reactivas de Oxígeno

RESUMEN

Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P < 0.001). Sucrose did not affect the lifespan. Glucose reduced lifespan (P < 0.001). Equal amount of G&F or HFCS reduced lifespan (P < 0.0001). Intestinal fat deposition (IFD) was increased at a higher dose of fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated.

Asunto(s)

Caenorhabditis elegans/efectos de los fármacos , Fructosa/farmacología , Edulcorantes/farmacología , Tejido Adiposo/efectos de los fármacos , Animales , Caenorhabditis elegans/fisiología , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Fructosa/administración & dosificación , Glucosa/administración & dosificación , Glucosa/farmacología , Intestinos , Longevidad/efectos de los fármacos , Sacarosa/administración & dosificación , Sacarosa/farmacología , Edulcorantes/administración & dosificación

RESUMEN

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide and the levels of differentiation growth factor midkine (MK) are increased in PCa. Cancer and/or the treatment process itself may lead to psychiatric disorders. Lithium chloride (LiCl) has anti-manic properties and has been used in cancer therapy; however, it has a queried safety profile. In addition, cancer stem cells are responsible for the heterogeneous phenotype of tumor cells; they are involved in progression, metastasis, recurrence and therapy resistance in various cancer types. The aims of the present study were to investigate the effect of different concentrations of LiCl on PCa stem cells (whether a shift from tumorigenic to non-tumorigenic cells occurs) and to determine if these results can be explained through changes in MK levels. Monolayer and spheroid cultures of human prostate stem cells and non-stem cells were incubated with low (1, 10 µM) and high (100, 500 µM) concentrations of LiCl for 72 h. Cell proliferation, apoptotic indices, MK levels and ultrastructure were evaluated. Cells stimulated with low concentrations showed high proliferation, low apoptotic indices, high MK levels and more healthy ultrastructure. Opposite results were obtained at high concentrations. Furthermore, stem cells were more sensitive to stimulation and more resistant to inhibition than non-stem cells. LiCl exhibited concentration-dependent effects on stem cell and non-stem cell groups. MK levels were not involved in the biphasic effect of LiCl; however, they were proportionally affected. To the best of our knowledge, the present study was the first to show the effect of LiCl on PCa stem cells through MK.

RESUMEN

The effect of methanol on the phase and phase-transition properties of a 2×8×8 glycerol-1-monopalmitate bilayer patch is investigated using a series of 239 molecular dynamics simulations on the 180 ns timescale, considering methanol concentrations cM and temperatures T in the ranges 0-12.3M and 302-338 K, respectively. The results in the form of hysteresis-corrected transition temperatures Tm are compatible with the expected features of the biphasic effect, with a reversal concentration crev of about 5.2 M. Below this concentration, the main transition is between the liquid crystal (LC) and gel (GL) phases, and Tm decreases upon increasing cM. Above this concentration, the interdigitated (ID) phase is the stable ordered phase instead, and Tm slightly increases upon increasing T up to about 10 M. The analysis of the structural and dynamical properties also reveals very different sensitivities and responses of the three phases to changes in cM. In particular, the properties of the GL phase are insensitive to cM, whereas those of the LC and ID phases are altered via an increase of the area per lipid. For the LC phase, increasing cM promotes disorder and fluidity. For the ID phase, in contrast, increasing cM up to about 10 M slightly increases the ordering and rigidity. Two side issues are also addressed, concerning: (i) the occurrence tilt-precession motions in the GL and ID phases; (ii) the influence of the pressure coupling scheme employed in the simulations, semi- or fully-anisotropic, on the simulation results.

Asunto(s)

Glicerol/química , Membrana Dobles de Lípidos/química , Metanol/química , Simulación de Dinámica Molecular , Ácido Palmítico/química , Transición de Fase , Enlace de Hidrógeno , Probabilidad , Factores de Tiempo , Temperatura de Transición

RESUMEN

BACKGROUND: The flower buds of Syzygium aromaticum (clove) have been used in indigenous medicines for the treatment of male sexual disorders in Indian subcontinent. OBJECTIVE: To evaluate the effect of Syzygium aromaticum flower bud on male reproduction, using Parkes (P) strain mice as animal model. MATERIALS AND METHODS: Mice were orally administered lipid soluble components of Syzygium aromaticum flower bud in doses of 15, 30, and 60 mg/kg body weight for 35 days, and several male reproductive endpoints were evaluated. RESULTS: Treatment with lower dose (15 mg) of Syzygium increased the motility of sperm and stimulated the secretory activities of epididymis and seminal vesicle, while higher doses (30 and 60 mg) had adverse effects on sperm dynamics of cauda epididymidis and on the secretory activities of epididymis and seminal vesicle. Libido was not affected in treated males; however, a significant decrease in litter in females sired by males treated with higher doses of Syzygium was recorded. CONCLUSION: Treatment with Syzygium aromaticum flower bud causes dose-dependent biphasic effect on male reproductive indices in P mice; lower dose of Syzygium appears stimulatory, while the higher doses have adverse effect on male reproduction. The results suggest that the lower dose of Syzygium may have androgenic effect, but further studies are needed to support this contention.

RESUMEN

The present investigation was aimed at determining the effects of hexane, acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME and ACAQE) on cholinergic and histaminic system using isolated frog rectus abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach response (anticholinesterase like effect) was found with ACAE and ACME at 0.25, 0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20 mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed biphasic effect of Acorus calamus leaves extracts on acetylcholine induced contractile response in isolated frog rectus abdominis muscle preparation (i.e. potentiation effect at lower dose and inhibitory effect at higher dose). Studies on isolated guinea pig ileum demonstrated antihistaminic effect in a dose dependent manner (100-1000 µg/ml) with ACAE, ACME and ACAQE. In addition, the dose dependent inhibition of Ach response (antimuscarinic effect) was observed with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts antinicotinic, anticholinesterase like activities in isolated frog rectus abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum. It has been suggested that these observed activities can be further studied for therapeutic potential of Acorus calamus leaves in the treatment of cognitive disorders and asthma.

Asunto(s)

Acorus , Antagonistas Colinérgicos/farmacología , Inhibidores de la Colinesterasa/farmacología , Antagonistas de los Receptores Histamínicos/farmacología , Íleon/efectos de los fármacos , Extractos Vegetales/farmacología , Recto del Abdomen/efectos de los fármacos , Acetilcolina/metabolismo , Acetilcolina/farmacología , Acetilcolinesterasa/metabolismo , Animales , Anuros , Relación Dosis-Respuesta a Droga , Cobayas , Histamina/metabolismo , Histamina/farmacología , Íleon/metabolismo , Masculino , Contracción Muscular/efectos de los fármacos , Hojas de la Planta , Recto del Abdomen/metabolismo , Recto del Abdomen/fisiología , Rizoma

RESUMEN

Objective: To observe the therapeutic actions of Wenjinghuayu Mixture(Radix Angelicae Sinensis, Rhizoma Chuanxiong, Rhizoma Cyperi, Herba Leonur, etc.) on dysmenorrhea and irregular menstruation. Methods: The uterus and ovary of mice were weighted. The ear edema and writhing and isolated rat uterus were used for experiment models. Results: Wenjinghuayu Mixture could significantly increased the weight of uterus of mice. It had inhibitory effects on mice ear edema and could reduce the writhing of mice and rats. It had biphasic effect on rat's isolated uterine contraction. Conclusion: Wenjinghuayu Mixture has effects of analgesia and anti-inflammation and has biphasic effect on uterine contraction.