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1.
Molecules ; 28(2)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36677541

RESUMEN

The stem of Tinospora cordifolia has been traditionally used in traditional Indian systems of medicine for blood sugar control, without the knowledge of the underlying mechanism and chemical constitution responsible for the observed anti-diabetic effect. In the present study, Tinosporaside, a diterpenoid isolated from the stem of T. cordifolia, was investigated for its effects on glucose utilization in skeletal muscle cells, which was followed by determining the anti-hyperglycemic efficacy in our diabetic db/db mice model. We found that tinosporaside augmented glucose uptake by increasing the translocation of GLUT4 to the plasma membrane in L6 myotubes, upon prolonged exposure for 16 h. Moreover, tinosporaside treatment significantly increased the phosphorylation of protein kinase B/AKT (Ser-473) and 5' AMP-activated protein kinase (AMPK, Thr-172). These effects were abolished in the presence of the wortmannin and compound C. Administration of tinosporaside to db/db mice improved glucose tolerance and peripheral insulin sensitivity associated with increased gene expression and phosphorylation of the markers of phosphoinositide 3-kinases (PI3Ks) and AMPK signaling in skeletal muscle tissue. The findings revealed that tinosporaside exerted its antidiabetic efficacy by enhancing the rate of glucose utilization in skeletal muscle, mediated by PI3K- and AMPK-dependent signaling mechanisms.


Asunto(s)
Fosfatidilinositol 3-Quinasas , Tinospora , Ratones , Animales , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Músculo Esquelético/metabolismo , Glucosa/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fibras Musculares Esqueléticas , Fosforilación , Transportador de Glucosa de Tipo 4/metabolismo
2.
Omega (Westport) ; : 302228221108544, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-35686845

RESUMEN

Death awareness and near-death experiences initiate shifts in awareness, priorities, and relationships. This narrative inquiry explored the stories of four individuals who had near-death experiences. Participants shared their experiences before and after the experiences. Findings include considerations of how mortality awareness connects with life experiences. Resonant threads across narratives included Interactions with Death, Life after Death, and Meaning in Life after Death. Specifically, findings explore near-death experiences, how life was changed following interactions with death, and the meaning-making process through death awareness. Findings and discussion explore the impact of death awareness as well as considerations for those in death and trauma-related fields.

3.
Molecules ; 26(11)2021 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-34073781

RESUMEN

Estrogenic molecules have been reported to regulate glucose homeostasis and may be beneficial for diabetes management. Here, we investigated the estrogenic effect of ß-sitosterol-3-O-D-glucopyranoside (BSD), isolated from the fruits of Cupressus sempervirens and monitored its ability to regulate glucose utilization in skeletal muscle cells. BSD stimulated ERE-mediated luciferase activity in both ERα and ERß-ERE luc expression system with greater response through ERß in HEK-293T cells, and induced the expression of estrogen-regulated genes in estrogen responsive MCF-7 cells. In silico docking and molecular interaction studies revealed the affinity and interaction of BSD with ERß through hydrophobic interaction and hydrogen bond pairing. Furthermore, prolonged exposure of L6-GLUT4myc myotubes to BSD raised the glucose uptake under basal conditions without affecting the insulin-stimulated glucose uptake, the effect associated with enhanced translocation of GLUT4 to the cell periphery. The BSD-mediated biological response to increase GLUT4 translocation was obliterated by PI-3-K inhibitor wortmannin, and BSD significantly increased the phosphorylation of AKT (Ser-473). Moreover, BSD-induced GLUT4 translocation was prevented in the presence of fulvestrant. Our findings reveal the estrogenic activity of BSD to stimulate glucose utilization in skeletal muscle cells via PI-3K/AKT-dependent mechanism.


Asunto(s)
Glucosa/metabolismo , Imitación Molecular , Músculo Esquelético/metabolismo , Fitoestrógenos/farmacología , Sitoesteroles/farmacología , Transportador de Glucosa de Tipo 4/metabolismo , Células HEK293 , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Músculo Esquelético/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Sitoesteroles/química
4.
BMC Complement Altern Med ; 18(1): 69, 2018 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-29463254

RESUMEN

BACKGROUND: Spinacia oleracea is an important dietary vegetable in India and throughout the world and has many beneficial effects. It is cultivated globally. However, its effect on osteoarthritis that mainly targets the cartilage cells remains unknown. In this study we aimed to evaluate the anti-osteoarthritic and chondro-protective effects of SOE on chemically induced osteoarthritis (OA). METHODS: OA was induced by intra-patellar injection of monosodium iodoacetate (MIA) at the knee joint in rats. SOE was then given orally at 250 and 500 mg.kg- 1 day- 1 doses for 28 days to these rats. Anti-osteoarthritic potential of SOE was evaluated by micro-CT, mRNA and protein expression of pro-inflammatory and chondrogenic genes, clinically relevant biomarker's and behavioural experiments. RESULTS: In vitro cell free and cell based assays indicated that SOE acts as a strong anti-oxidant and an anti-inflammatory agent. Histological analysis of knee joints at the end of the experiment by safranin-o and toluidine blue staining established its protective effect. Radiological data corroborated the findings with improvement in the joint space and irregularity of the articular and atrophied femoral condyles and tibial plateau. Micro-CT analysis of sub-chondral bone indicated that SOE had the ability to mitigate OA effects by increasing bone volume to tissue volume (BV/TV) which resulted in decrease of trabecular pattern factor (Tb.Pf) by more than 200%. SOE stimulated chondrogenic marker gene expression with reduction in pro-inflammatory markers. Purified compounds isolated from SOE exhibited increased Sox-9 and Col-II protein expression in articular chondrocytes. Serum and urine analysis indicated that SOE had the potential to down-regulate glutathione S-transferase (GST) activity, clinical markers of osteoarthritis like cartilage oligometric matrix protein (COMP) and CTX-II. Overall, this led to a significant improvement in locomotion and balancing activity in rats as assessed by Open-field and Rota rod test. CONCLUSION: On the basis of in vitro and in vivo experiments performed with Spinacea oleracea extract we can deduce that SOE has the ability to alleviate the MIA induced deleterious effects.


Asunto(s)
Osteoartritis/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Spinacia oleracea/química , Animales , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , India , Yodoacetatos/efectos adversos , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Osteoartritis/inducido químicamente , Osteoartritis/genética , Osteoartritis/metabolismo , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Tibia/efectos de los fármacos , Tibia/metabolismo , Tibia/patología
5.
Toxicol Appl Pharmacol ; 316: 63-73, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28017615

RESUMEN

Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuated the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress.


Asunto(s)
Aldehído Deshidrogenasa Mitocondrial/metabolismo , Benzamidas/farmacología , Benzodioxoles/farmacología , Proteína Morfogenética Ósea 2/biosíntesis , Regeneración Ósea/fisiología , Diferenciación Celular/fisiología , Osteoblastos/metabolismo , Animales , Proteína Morfogenética Ósea 2/agonistas , Regeneración Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Activadores de Enzimas/farmacología , Femenino , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Ratas , Ratas Sprague-Dawley
6.
Br J Nutr ; 117(11): 1511-1522, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28689509

RESUMEN

The bone regeneration and healing effect of formononetin was evaluated in a cortical bone defect model that predominantly heals by intramembranous ossification. For this study, female Balb/c mice were ovariectomised (OVx) and a drill-hole injury was generated in the midfemoral bones of all animals. Treatment with formononetin commenced the day after and continued for 21 d. Parathyroid hormone (PTH1-34) was used as a reference standard. Animals were killed at days 10 and 21. Femur bones were collected at the injury site for histomorphometry studies using microcomputed tomography (µCT) and confocal microscopy. RNA and protein were harvested from the region surrounding the drill-hole injury. For immunohistochemistry, 5 µm sections of decalcified femur bone adjoining the drill-hole site were cut. µCT analysis showed that formononetin promoted bone healing at days 10 and 21 and the healing effect observed was significantly better than in Ovx mice and equal to PTH treatment in many aspects. Formononetin also significantly enhanced bone regeneration as assessed by calcein-labelling studies. In addition, formononetin enhanced the expression of osteogenic markers at the injury site in a manner similar to PTH. Formononetin treatment also led to predominant runt-related transcription factor 2 and osteocalcin localisation at the injury site. These results support the potential of formononetin to be a bone-healing agent and are suggestive of its promising role in the fracture-repair process.


Asunto(s)
Regeneración Ósea/efectos de los fármacos , Hueso Cortical/efectos de los fármacos , Fabaceae/química , Fracturas Óseas/metabolismo , Isoflavonas/farmacología , Osteogénesis/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Hueso Cortical/patología , Modelos Animales de Enfermedad , Fémur/efectos de los fármacos , Fémur/patología , Fracturas Óseas/tratamiento farmacológico , Isoflavonas/uso terapéutico , Ratones Endogámicos BALB C , Osteocalcina/metabolismo , Ovariectomía , Hormona Paratiroidea/farmacología , Hormona Paratiroidea/uso terapéutico , Fitoestrógenos/farmacología , Fitoestrógenos/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos
7.
Br J Nutr ; 117(5): 645-661, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28367764

RESUMEN

Balance between adipocyte and osteoblast differentiation is the key link of disease progression in obesity and osteoporosis. We have previously reported that formononetin (FNT), an isoflavone extracted from Butea monosperma, stimulates osteoblast formation and protects against postmenopausal bone loss. The inverse relationship between osteoblasts and adipocytes prompted us to analyse the effect of FNT on adipogenesis and in vivo bone loss, triggered by high-fat diet (HFD)-induced obesity. The anti-obesity effect and mechanism of action of FNT was determined in 3T3-L1 cells and HFD-induced obese male mice. Our findings show that FNT suppresses the adipogenic differentiation of 3T3-L1 fibroblasts, through down-regulation of key adipogenic markers such as PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding protein (SREBP) and inhibits intracellular TAG accumulation. Increased intracellular reactive oxygen species levels and AMP-activated protein kinase (AMPK) activation accompanied by stabilisation of ß-catenin were attributed to the anti-adipogenic action of FNT. In vivo, 12 weeks of FNT treatment inhibited the development of obesity in mice by attenuating HFD-induced body weight gain and visceral fat accumulation. The anti-obesity effect of FNT results from increased energy expenditure. FNT also protects against HFD-induced dyslipidaemia and rescues deterioration of trabecular bone volume by increasing bone formation and decreasing bone resorbtion caused by HFD. FNT's rescuing action against obesity-induced osteoporosis commenced at the level of progenitors, as bone marrow progenitor cells, obtained from the HFD mice group supplemented with FNT, showed increased osteogenic and decreased adipogenic potentials. Our findings suggest that FNT inhibits adipogenesis through AMPK/ß-catenin signal transduction pathways and protects against HFD-induced obesity and bone loss.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Adipogénesis/efectos de los fármacos , Isoflavonas/farmacología , Obesidad/prevención & control , Osteoporosis/prevención & control , beta Catenina/metabolismo , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Resorción Ósea/tratamiento farmacológico , Diferenciación Celular/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Osteoporosis/etiología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína Desacopladora 1/genética , Regulación hacia Arriba/efectos de los fármacos
8.
Bioorg Med Chem Lett ; 27(6): 1390-1396, 2017 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-28202325

RESUMEN

The structural modifications of pregnenolone have been described via the introduction of heterocyclic moieties at C-17 position by limiting the acyl group. Novel heterocyclic analogues of pregnenolone have been synthesized by using Friedlander and Claisen-Schmidt reactions, and the synthesized compounds were evaluated for their osteogenic activity. Among the synthesized derivatives, four compounds showed significantly increased ALP activity. Among all four active compounds, the novel compound 3a has shown significant bone matrix mineralization and mRNA expressions of osteogenic marker genes, BMP2, RUNX-2 and OCN at 1pM concentration.


Asunto(s)
Compuestos Heterocíclicos/química , Osteoporosis/tratamiento farmacológico , Pregnenolona/farmacología , Humanos , Pregnenolona/uso terapéutico
9.
Bioorg Med Chem Lett ; 27(8): 1765-1775, 2017 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-28274632

RESUMEN

The chemical modifications of the hydroxyl group of dalbergin have been described via the introduction of cyclic amine, ester and amide groups. Among the twenty-three prepared novel analogues of dalbergin, compound 4d (EC50 2.3µM) showed significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells in vitro. Compound 4d, at a dose of 1.0mg/kg body weight exhibited the significant osteoprotective effect. It showed a significant increase in osteogenic gene expression RunX2 (∼4fold), ALP (∼5fold), OCN (∼4fold) and COL1 (∼4fold) as compared to control group at the same dose in vivo assay.


Asunto(s)
Cumarinas/química , Cumarinas/uso terapéutico , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Animales , Proteína Morfogenética Ósea 2/metabolismo , Calcificación Fisiológica/efectos de los fármacos , Células Cultivadas , Cumarinas/síntesis química , Diseño de Fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ratones Endogámicos BALB C , Osteoblastos/metabolismo , Osteoblastos/patología , Osteoporosis Posmenopáusica/genética , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Cráneo/citología , Cráneo/efectos de los fármacos , Cráneo/metabolismo , Cráneo/patología
10.
Planta Med ; 81(3): 208-14, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25654406

RESUMEN

The present work was undertaken to investigate the effects and the molecular mechanism of the standardized ethanolic extract of Allium cepa (onion) on the glucose transport for controlling diabetes mellitus. A. cepa stimulates glucose uptake by the rat skeletal muscle cells (L6 myotubes) in both time- and dose-dependent manners. This effect was shown to be mediated by the increased translocation of glucose transporter typ 4 protein from the cytoplasm to the plasma membrane as well as the synthesis of glucose transporter typ 4 protein. The effect of A. cepa extract on glucose transport was stymied by wortmannin, genistein, and AI½. In vitro phosphorylation analysis revealed that, like insulin, A. cepa extract also enhances the tyrosine phosphorylation of the insulin receptor-ß, insulin receptor substrate-1, and the serine phosphorylation of Akt under both basal and insulin-stimulated conditions without affecting the total amount of these proteins. Furthermore, it is also shown that the activation of Akt is indispensable for the A. cepa-induced glucose uptake in L6 myotubes. Taken together, these findings provide ample evidence that the ethanolic extract of A. cepa stimulates glucose transporter typ 4 translocation-mediated glucose uptake by the activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt dependent pathway.


Asunto(s)
Allium , Diabetes Mellitus/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Glucosa/metabolismo , Insulina/metabolismo , Extractos Vegetales/farmacología , Animales , Diabetes Mellitus/tratamiento farmacológico , Proteínas Sustrato del Receptor de Insulina/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Fosforilación , Fitoterapia , Extractos Vegetales/uso terapéutico , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de Señal
11.
Bioorg Med Chem Lett ; 24(12): 2664-8, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24803361

RESUMEN

The present study was undertaken to investigate and rationalize the in vitro antiosteoporotic activity of neoflavonoids, isolated from Dalbergia sissoo heartwood. Neoflavonoids were isolated using extensive column chromatography and identified as dalsissooal (1) a new compound and cearoin (2), dalbergin (3), 4-methoxy dalbergion (4), dalbergiphenol (5), dalbergichromene (6), methyl dalbergin (7) and latinone (8) as known compounds by comparison their spectroscopic data with those reported in the literature. Among the screened compounds, compounds 1, 3, 5-8 significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells.


Asunto(s)
Dalbergia/química , Flavonoides/aislamiento & purificación , Osteoblastos/efectos de los fármacos , Extractos Vegetales/farmacología , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/aislamiento & purificación , Conservadores de la Densidad Ósea/farmacología , Proliferación Celular/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Estructura Molecular , Osteoblastos/citología , Plantas Medicinales/química
12.
Bioorg Med Chem Lett ; 24(12): 2674-9, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24813738

RESUMEN

Structure modifications of lupeol at the isopropylene moiety have been described via allylic oxidation using selenium dioxide. The antidiabetic efficacy of lupeol analogues were evaluated in vitro as glucose uptake stimulatory effect in L6 skeletal muscle cells. From all tested compounds, 2, 3, 4b and 6b showed significant stimulation of glucose uptake with respective percent stimulation of 173.1 (p <0.001), 114.1 (p <0.001), 98.3 (p <0.001) and 107.3 (p <0.001) at 10µM concentration. Stimulation of glucose uptake by these compounds is associated with enhanced translocation of glucose transporter 4 (GLUT4) and activation of IRS-1/PI3-K/AKT-dependent signaling pathway in L6 cells. Structure-activity relationship analysis of these analogues demonstrated that the integrity of α,ß-unsaturated carbonyl and acetyl moieties were important in the retention of glucose uptake stimulatory effect. It is therefore proposed that naturally occurring lupeol and their analogues might reduce blood glucose, at least in part, through stimulating glucose utilization by skeletal muscles.


Asunto(s)
Diseño de Fármacos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacología , Músculo Esquelético/efectos de los fármacos , Triterpenos Pentacíclicos/síntesis química , Triterpenos Pentacíclicos/farmacología , Transporte Biológico , Metabolismo de los Hidratos de Carbono/genética , Células Cultivadas , Relación Dosis-Respuesta a Droga , Glucosa/metabolismo , Humanos , Hipoglucemiantes/química , Estructura Molecular , Triterpenos Pentacíclicos/química , Relación Estructura-Actividad
13.
Phytother Res ; 28(8): 1196-203, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24399792

RESUMEN

Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5 µM (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ß and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity.


Asunto(s)
Andrógenos/metabolismo , Cupressus/química , Diterpenos/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Frutas/química , Humanos , Masculino , Fosforilación , Ratas , Ratas Sprague-Dawley , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo
14.
Bioorg Med Chem ; 21(5): 1116-22, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23357036

RESUMEN

Phytochemical investigation of the n-butanol fraction of Evolvulus alsinoides (Linn.) led to the isolation of three new phenolic glycosides, evolvosides C, D and E (1-3) along with six known compounds (4-9). The structures of the compounds were elucidated on the basis of spectroscopic analysis, viz. 1D and 2D NMR experiments, chemical study, and comparison with literature data. Evolvoside C (1) was characterized as kaempferol 4'-O-ß-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranoside, whereas evolvosides D and E (2-3) were found to be mono and di-O-methyl derivatives of 1. The new compounds (1-3) represent rare triglycoside derivatives of flavonol at C-4'. The isolated compounds (1-6) were screened for acute stress-induced biochemical changes in male Sprague-Dawley rats at a dose of 40 mg/kg body weight. Compounds 1 and 2 displayed anti-stress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 3 and 6 were also found to be effective in normalizing most of these stress parameters, whereas compounds 4 and 5 were ineffective in normalizing most of these effects.


Asunto(s)
Convolvulaceae/química , Flavonoles/química , Glicósidos/química , Quempferoles/química , Trisacáridos/química , Animales , Corticosterona/sangre , Creatina Quinasa/sangre , Glicósidos/farmacología , Glicósidos/uso terapéutico , Hiperglucemia/tratamiento farmacológico , Quempferoles/farmacología , Quempferoles/uso terapéutico , Espectroscopía de Resonancia Magnética , Masculino , Conformación Molecular , Ratas , Ratas Sprague-Dawley , Estrés Fisiológico/efectos de los fármacos , Trisacáridos/farmacología , Trisacáridos/uso terapéutico
15.
Indian J Exp Biol ; 51(5): 363-74, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23821824

RESUMEN

The crude powder, ethanolic extract and aqueous, chloroform, hexane and n-butanol soluble fractions of ethanolic extract of heart wood of P. marsupium showed marked improvement on oral glucose tolerance post sucrose load in normal rats. All these fractions except aqueous fraction showed improvement on oral glucose tolerance post sucrose load on streptozotocin (STZ)-induced diabetic rats. The crude powder, ethanolic extract and hexane and n-butanol fractions showed marked decline in blood glucose level on STZ-induced diabetic rats. The ethanolic extract (100 mg/kg body weight) when given to STZ-induced diabetic rats for 10 consecutive days declined blood glucose, improved OGTT and increased their serum insulin levels. The ethanolic extract also showed marked improvement on oral glucose tolerance on high fat-low dosed STZ-induced diabetic rats and neonatally STZ treated rats. The ethanolic extract of P. marsupium also showed marked antidyslipidemic effects on high fat diet fed Syrian golden hamsters. Altered renal and hepatic function markers and serum insulin levels of high fat diet fed-low dosed STZ-treated diabetic rats were also found towards normalization when these animals were treated with ethanolic extract of P. marsupium for 28 consecutive days. The four out of five phenolic C-glycosides isolated from n-butanol fraction of ethanolic extract of P. marsupium enhanced glucose uptake by skeletal muscle cells (C2C12) in a dose dependent manner. It may primarily be concluded that phenolic-C-glycosides present in P. marsupium heart wood are the phytoconstituents responsible for the antihyperglycemic activity and validate the claim of antidiabetic activity of heart wood of P. marsupium.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Extractos Vegetales/uso terapéutico , Pterocarpus/química , Animales , Relación Dosis-Respuesta a Droga , Etanol/química , Prueba de Tolerancia a la Glucosa , Masculino , Extractos Vegetales/química , Ratas , Estreptozocina
16.
ISA Trans ; 135: 355-368, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37032567

RESUMEN

This paper proposes an intelligent control scheme for a two-stage integrated onboard electric vehicle (EV) battery charger connected to a single-phase household outlet which offers a close to ideal battery charging profile with power factor correction feature. Generally, the front-end AC-DC​ conversion stage is controlled by dual loop proportional-integral (PI) controllers, and tuning their gain constants is a difficult task. Furthermore, to achieve a close to ideal charging profile for an EV battery, the DC-DC conversion stage switches from constant current (CC) and constant voltage (CV) mode after a certain state of charge (SOC) which may lead to discontinuity in the charging current and voltage. This paper attempts to solve these issues by proposing an intelligent control scheme that includes the dynamic estimation of PI controller gain constants as well as provides a seamless mode transfer feature for battery charging. It is achieved by using fuzzy-PI-based control in the AC-DC conversion stage and Bayesian Regularization (BR) algorithm trained artificial neural network (ANN)-based control in the DC-DC conversion stage. The performance of the proposed control scheme is assessed both in steady-state and transient conditions in MATLAB® Simulink environment by comparing it against similar control schemes. The proposed intelligent control approach improves the dynamic response of DC link voltage, offers unity power factor operation and maintains the line current harmonics within IEEE 519 standards even during the switchover from CC to CV charging mode. Also, there is a decrease of 85% in the third harmonic component of the source current, 23.2% improvement in DC link voltage undershoot and 6.5% reduction in DC link voltage overshoot with reduced settling times using the proposed unified control scheme.

17.
Bioorg Med Chem Lett ; 22(14): 4636-9, 2012 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-22726926

RESUMEN

A new class of N-substituted piperazine analogues of imbricatolic acid have been designed and synthesized by using the appropriate synthetic routes in excellent yield. All synthesised compounds were screened for their in vitro glucose uptake stimulatory activity. Among them compounds 4b, 4e, 8b, and 8e triggered L6 skeletal muscle cells for glucose uptake at 54.73%, 40.79%, 40.90%, and 39.55% stimulation, respectively. Compound 4b has emerged as important lead compound showing potential antidiabetic activity. Illustration about their synthesis and in vitro glucose uptake activity is described.


Asunto(s)
Diterpenos/química , Glucosa/metabolismo , Células Musculares/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Piperazinas/química , Animales , Línea Celular , Diterpenos/farmacología , Estructura Molecular , Células Musculares/metabolismo , Músculo Esquelético/metabolismo , Piperazina , Ratas , Relación Estructura-Actividad
18.
Bioorg Med Chem Lett ; 22(2): 890-7, 2012 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-22212722

RESUMEN

One new isoflavone glucoside, caviunin 7-O-[ß-d-apiofuranosyl-(1→6)-ß-d-glucopyranoside] (10) and a new itaconic derivative, (E)-4-methoxy-2-(3,4-dihydroxybenzylidene)-4-oxobutanoic acid (15) along with series of isoflavones and flavonols with their glucosides (1-9 and 11-14) and a lignan glucoside (16) were isolated from the ethanolic extract of Dalbergia sissoo leaves. The structures of these compounds were established on the basis of IR, UV, (1)H and (13)C NMR, DEPT, COSY, HSQC, HMBC and MS data. All compounds (1-16) were assessed for osteogenic activity in primary calvarial osteoblast cultures. Compounds 1-4 and 10 increased alkaline phosphatase activity and mineralization thus resulting in significant osteogenic activity.


Asunto(s)
Dalbergia/química , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estructura Molecular , Osteoblastos/citología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Cultivo Primario de Células , Ratas , Estereoisomerismo , Relación Estructura-Actividad
19.
Indian J Med Res ; 135(4): 548-54, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22664506

RESUMEN

BACKGROUND & OBJECTIVES: Ocimum sanctum (OS) is known to possess various therapeutic properties. We have earlier isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating stress-induced central changes is unexplored. Thus, the present study was aimed to investigate the effect of these OS compounds on restraint stress (RS)-induced changes in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus of rats. METHODS: RS was produced by immobilizing (restraining) the Sprague Dawley rats for a period of 2.5 h inside cylindrical steel tubes. The monoamine levels and the in vivo antioxidant status in brain regions were evaluated by HPLC-EC and spectrophotometric assays, respectively. RESULTS: RS significantly increased the dopamine levels in the frontal cortex and decreased in the striatum and hippocampus, and accompanied with selective increase of dopamine metabolites compared to the NS control group. The serotonin and its metabolite levels were significantly increased, while noradrenaline levels were decreased by RS in the three brain regions studied. The activities of superoxide dismutase and glutathione peroxidase in the frontal cortex and striatum were significantly increased by RS with decreased glutathione levels and increased lipid peroxidation. Pre-treatment with Ocimumoside A and B (40 mg/kg po) for a period of 3 days prevented the RS-induced changes with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg po) and antioxidant (Melatonin; 20 mg/kg ip) drugs, while, Ocimarin failed to modulate these changes. OS compounds per se had no effect on these parameters. INTERPRETATION & CONCLUSIONS: The present findings showed the anti-stress potential of Ocimumoside A and B in relation to their simultaneous modulatory effects on the central monoaminergic and antioxidant systems implicating their therapeutic importance in stress-related disorders. Further studies are required to understand the mechanism of action of these compounds.


Asunto(s)
Cuerpo Estriado/metabolismo , Lóbulo Frontal/metabolismo , Hipocampo/metabolismo , Ocimum , Extractos Vegetales/administración & dosificación , Animales , Antioxidantes/metabolismo , Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Lóbulo Frontal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Norepinefrina/metabolismo , Ocimum/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Estrés Fisiológico/efectos de los fármacos
20.
Environ Sci Pollut Res Int ; 29(11): 15432-15489, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34997510

RESUMEN

Particulate matter (PM) emitted from compression ignition (CI) engines (diesel engines) has a detrimental effect on human health and the environment. The physical and chemical characteristics of PM emitted from CI-engines are influenced by engine operating conditions and fuel properties. The morphology, nanostructure, and chemical composition of PM affect its toxicity and interaction with the environment. From automotive industry perspective, these parameters influence the design of diesel particulate filters. This study presents a review of the physical and chemical characteristics of particulate emissions from the CI-engine. The present study commences with a brief description about the composition of PM emitted from CI-engine and the PM formation mechanism in CI-engine. Later on, the detailed review of PM's physical and chemical characteristics and the effect of engine operating parameters and alternative fuels on the particle number concentration, morphology, nano-structure, and oxidative reactivity of PM is presented. Online and offline methods of diesel particulate characterization and emerging chemical characterization techniques such as X-ray photoelectron spectroscopy and X-ray absorption fine structure (EXAFS) are also discussed briefly. Correlation between physical and chemical properties, and oxidative reactivity of PM is also discussed. It was found that engine operating parameters affect the physical and chemical properties of PM. Use of alternative fuels changes the diesel particulate morphology, nanostructure, and chemical composition which enhances the oxidative reactivity of PM.


Asunto(s)
Contaminantes Atmosféricos , Nanoestructuras , Contaminantes Atmosféricos/análisis , Polvo , Gasolina/análisis , Humanos , Material Particulado/análisis , Emisiones de Vehículos/análisis
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