RESUMEN
OBJECTIVE: To observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility. METHODS: Models of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue. RESULTS: Compared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 106/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 106/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 106/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01). CONCLUSION: By upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Proteína Ligando Fas/efectos de los fármacos , Infertilidad Masculina/tratamiento farmacológico , Semen/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Proteína Ligando Fas/metabolismo , Células Germinativas , Glicósidos , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Análisis de Semen , Transducción de Señal , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Comprimidos , Testículo/efectos de los fármacos , Testículo/metabolismo , TripterygiumRESUMEN
Objective To observe the effect of Longzuan Tongbi Recipe (LTR) on Fas/FasL sys- tems in serum and synovium of collagen-induced arthritis (CIA) rats. Methods Ten rats were randomly selected from 60 male Wistar rats as a normal control group. CIA model was prepared by injecting type II bovine collagen and incomplete Freund's adjuvant mixture in the rest 50 rats. After modeling rats were di- vided into the model group, the methotrexate (MTX) group, high, middle, and low dose LTR groups, 10 in each group. Normal saline was administered to rats in the model group by gastrogavage. MTX solution (0.27 mg/100 g) was administered to rats in the MTX group by gastrogavage, once per week for 4 succes- sive weeks. LTR (4.32, 2.16, 1.08 g/mL) was administered to rats in the 3 LTR groups by gastrogavage, twice per day for 30 successive days. Morphological changes of synovium were observed by HE staining. Expression levels of Fas/FasL in rat serum and synovium were quantitatively detected by ELISA. Results Normal synovium cells could be seen in the normal group. But they were obviously proliferated, fat cells in the lower synovium were reduced or deformed, fibroblasts were increased in the model group, accompa- nied with infiltration of lymphocytes and monocytes. All these changes were more obviously alleviated in the MTX group, and the 3 LTR groups. Compared withI the normal control group, Fas expression level in- creased in rat serum and synovium, serum FasL expression level decreased in the model group (P <0. 05, P <0. 01). Compared with the model group, Fas expression level decreased in rat serum and synovium in the MTX group, high and middle dose LTR groups; Fas expression level in rat serum increased in the MTX group and 3 LTR groups; Fas expression level in synovium increased in the MTX group, high and middle dose LTR groups (P <0. 05, P <0. 01). Compared with the MTX group, Fas expression level in serum of the low dose LTR group, and Fas expression level in synovium of low and middle dose LTR groups was elevat- ed; Fas expression level in serum and synovium of the high dose LTR group was reduced; FasL expres- sion level in serum and synovium of low and middle dose LTR groups was reduced; FasL expression level in serum and synovium increased of the high dose LTR group (P <0. 05, P <0. 01). Conclusion LTR could control and treat rheumatoid arthritis, and its mechanism might lie in regulating. Fas/FasL systems media- ted cell apoptosis, and relieving pathological reaction of rheumatoid arthritis.
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Artritis Experimental , Medicamentos Herbarios Chinos , Membrana Sinovial , Animales , Artritis Experimental/tratamiento farmacológico , Bovinos , Colágeno Tipo II , Medicamentos Herbarios Chinos/farmacología , Proteína Ligando Fas/efectos de los fármacos , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Membrana Sinovial/efectos de los fármacos , Receptor fas/efectos de los fármacosRESUMEN
Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted much attention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5, 6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted, analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cells HepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilical vein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 was the most sensitive to AHL treatment, a very low dose (0.8µg/ml) significantly inhibiting proliferation . The non- tumor cell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored. We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interrupt polymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1, was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 was observed as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis of HepG-2 cells.
Asunto(s)
Alcaloides/farmacología , Apoptosis/efectos de los fármacos , Proteína Ligando Fas/efectos de los fármacos , Liliaceae , Transducción de Señal/efectos de los fármacos , Apoptosis/genética , Western Blotting , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Proteína Ligando Fas/genética , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Células Hep G2/citología , Células Hep G2/efectos de los fármacos , Humanos , Extractos Vegetales , Valores de Referencia , Sensibilidad y Especificidad , Transducción de Señal/genética , Células Tumorales CultivadasRESUMEN
Alcohol consumption produces a variety of metabolic alterations in liver cells, associated with ethanol oxidation and with nonoxidative metabolism of ethanol, among others apoptosis of hepatocytes. As zinc is known as a potent antioxidant and an inhibitor of cell apoptosis, the aim of this paper was to investigate whether zinc supplementation could inhibit ethanol-induced HepG2 apoptosis, and whether this inhibition was connected with attenuation of oxidative stress and modulation of FasR/FasL system expression. The results indicated that zinc supplementation significantly inhibited ethanol-induced HepG2 cell apoptosis (measured by cytochrome c release from mitochondria and caspase-3 activation) by attenuation of reactive oxygen species (ROS) production, increase in the cellular level of GSH, inhibition of ethanol-induced sFasR and FasL overexpression and caspase-8 activation. These results indicate that zinc can inhibit ethanol-induced hepatocyte apoptosis by several independent mechanisms, among others by an indirect antioxidative effect and probably by inhibition of caspase-8 and caspase-9 activation.