RESUMEN
Anaplastic thyroid cancer (ATC) is a highly lethal undifferentiated malignancy without reliable therapies. Retinoic acid (RA) has been employed to promote redifferentiation of thyroid cancers by increasing their I131 uptake and radio-sensitivity, but its effect(s) on ATCs has not yet been ascertained. Likewise, resveratrol induces cancer redifferentiation but, also in this case, its effects on ATCs remain unknown. These issues have been addresses in the current study using three human ATC cell lines (THJ-11T, THJ-16T, and THJ-21T) through multiple experimental approaches. The results reveal that RA exerts a small inhibitory effect on these cell lines. In comparison with normally cultured cells, the total cell number in resveratrol-treated THJ-16T and THJ-21T cultures significantly decreased (p < 0.05), and this effect was accompanied by reduced Cyclin D1 immuno-labeling, increased apoptotic fractions, and distinct caspase-3 activation. Resveratrol failed to inhibit growth but enhanced RA sensitivity of THJ-11T cells, suppressed peroxisome proliferator-activated receptor-ß/δ (PPAR-ß/δ), and upregulated cellular retinoic acid-binding protein 2 (CRABP2) and retinoic acid receptor beta (RAR-ß) expression. Increased thyroglobulin (Tg) and E-cadherin levels and appearance of membranous E-cadherin were evidenced in resveratrol-treated THJ-11T cells. Our results demonstrate for the first time: (1) the therapeutic value of resveratrol by itself or in combination with RA in the management of ATCs, (2) the capacity of resveratrol to overcome RA resistance in ATC cells by reprogramming CRABP2/RAR- and fatty acid-binding protein 5 (FABP5)/PPAR-ß/δ-mediated RA signaling, and (3) the redifferentiating potential of resveratrol in ATC cells.
Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Estilbenos/farmacología , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Tretinoina/farmacología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas de Neoplasias/biosíntesis , Resveratrol , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The importance of signal transducer and activator of transcription 3 (STAT3) signaling in the growth and survival of glioblastoma cells has been well documented, while the reasons leading to STAT3 activation remains to be elucidated. Suppressors of cytokine signaling (SOCS) 1 and SOCS3, SH2 domaincontaining phosphatase (SHP2) and protein inhibitors of activated STAT3 (PIAS3) are known to inhibit STAT3 signal transduction, while their expression statuses in the four grades of astrocytomas and relevance with STAT3 activation remain to be described. The present study aimed to address these issues by tissue microarraybased immunohistochemical profiling the expression levels of phosphorylated (p)STAT3, SOCS1, SOCS3, PIAS3 and pSHP2. The results revealed that pSTAT3 nuclear translocation was rarely observed in noncancerous brain tissues and its frequencies were increased in a tumor gradeassociated manner (65.2, 77.1, 81.8 and 85.7% for grade IIV, respectively). PIAS3, pSHP2, SOCS1 and SOCS3 were expressed in higher levels (++ and +++) in 63.6, 90, 87.5 and 81.8% of tumor surrounding brain tissues, which reduced to 13.1, 47.8, 33.3 and 50% in grade I, 11.4, 65.7, 58.3 and 77.1% in grade II, 9.1, 63.6, 38.1 and 31.8% in grade III and 7.1, 66.7, 30.8 and 7.1% in grade IV astrocytomas. The above results revealed that although the expression levels of SOCS1, SOCS3 and, in particular, pSHP2, tend to decrease in the four types of astrocytomas, PIAS3 downregulation is more negatively correlated with STAT3 activation in the stepwise progress of astrocytomas and would indicate an unfavorable outcome.
Asunto(s)
Astrocitoma/patología , Neoplasias Encefálicas/patología , Encéfalo/patología , Chaperonas Moleculares/análisis , Proteínas Inhibidoras de STAT Activados/análisis , Proteína Tirosina Fosfatasa no Receptora Tipo 11/análisis , Factor de Transcripción STAT3/análisis , Proteína 1 Supresora de la Señalización de Citocinas/análisis , Proteína 3 Supresora de la Señalización de Citocinas/análisis , Astrocitoma/metabolismo , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/patología , Humanos , Inmunohistoquímica , Chaperonas Moleculares/metabolismo , Proteínas Inhibidoras de STAT Activados/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Factor de Transcripción STAT3/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismoRESUMEN
OBJECTIVES: Although it is well accepted that there is a close relationship between hypothyroidism and depression, previous studies provided inconsistent or even opposite results in whether subclinical hypothyroidism (SCH) increased the risk of depression. One possible reason is that the etiology of SCH in these studies was not clearly distinguished. We therefore investigated the relationship between SCH resulting from 131I treatment of Graves' disease and depression. DESIGN AND METHODS: The incidence of depression among 95 patients with SCH and 121 euthyroid patients following 131I treatment of Graves' disease was studied. The risk factors of depression were determined with multivariate logistic regression analysis. Thyroid hormone replacement therapy was performed in patients with thyroid-stimulating hormone (TSH) levels exceeding 10 mIU/L. RESULTS: Patients with SCH had significantly higher Hamilton Depression Scale scores, serum TSH and thyroid peroxidase antibody (TPOAb) levels compared with euthyroid patients. Multivariate logistic regression analysis revealed SCH, Graves' eye syndrome and high serum TPO antibody level as risk factors for depression. L-thyroxine treatment is beneficial for SCH patients with serum TSH levels exceeding 10 mIU/L. CONCLUSIONS: The results of the present study demonstrated that SCH is prevalent among 131I treated Graves' patients. SCH might increase the risk of developing depression. L-thyroxine replacement therapy helps to resolve depressive disorders in SCH patients with TSH > 10mIU/L. These data provide insight into the relationship between SCH and depression.
Asunto(s)
Depresión/etiología , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/radioterapia , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/radioterapia , Radioisótopos de Yodo/uso terapéutico , Tirotropina/uso terapéutico , Adulto , Anciano , Depresión/prevención & control , Femenino , Enfermedad de Graves/complicaciones , Enfermedad de Graves/metabolismo , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/metabolismo , Yoduro Peroxidasa/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Our previous study has showed that co-grafted Schwann cells (SCs) promote proliferation and migration of the grafted oligodendrocyte precursor cells (OPCs). However, how the co-grafted SCs affect OPCs has not been clarified. In the present study, we confirmed that SC-induced proliferation and migration of OPCs were mediated by SC-secreted factors using SC-conditioned medium (SCM). Then, we detected several candidate factors, PDGF-AA, FGF-2, and IGF-1, in SCs and SCM, and their receptors in OPCs. Finally, by using the selective inhibitors, the effects of these candidate factors on proliferation and migration of OPCs were examined. Our results showed that SCM-stimulated proliferation and migration of OPCs could be markedly decreased by both AG1295 (the inhibitor of PDGFR) and PD173074 (the inhibitor of FGFR). Together, our study suggests that SCs affect proliferation and migration of OPCs through secreting PDGF-AA and FGF-2. Identity of these molecules not only contributes to understand the mechanism of SC-induced proliferation and migration of OPCs but also provides possible target for treatment of CNS diseases.
Asunto(s)
Movimiento Celular , Proliferación Celular , Factor 2 de Crecimiento de Fibroblastos/farmacología , Células-Madre Neurales/efectos de los fármacos , Oligodendroglía/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Células de Schwann/metabolismo , Animales , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Femenino , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Células-Madre Neurales/citología , Células-Madre Neurales/fisiología , Oligodendroglía/citología , Oligodendroglía/fisiología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Hypothyroidism leads to somatic, neuropsychological, and psychiatric changes that are similar to depression. The mechanisms underlying the behavioral abnormalities in adult onset hypothyroidism remain ambiguous. Hypothyroidism was induced in adult male Wistar rats by the maintenance of 0.05% propylthiouracil (PTU) in drinking water for 5 weeks (hypothyroid group; HP group); control rats (CON group) received an equivalent amount of water. The open field and sucrose preference tests were employed, and the link between behavioral changes and brain glucose metabolism was evaluated using micro positron emission tomography imaging. The open field test revealed slightly decreased locomotor activity and significantly reduced rearing and defecation in the hypothyroid group. Hypothyroid rats were also characterized by decreased body weight, sucrose preference, and relative sucrose intake compared to control rats. Hypothyroidism induced reduced brain glucose metabolism in the bilateral motor cortex, the caudate putamen, the cortex cingulate, the nucleus accumbens, and the frontal association cortex. A decreased sucrose preference was positively correlated with metabolic glucose changes in the caudate putamen and the nucleus accumbens. The results indicate that the activity pattern in adult onset hypothyroidism is different from the activity pattern when hypothyroidism is induced in the developmental period of the central nervous system. Decreased sucrose preference in hypothyroid rats may be attributed to anhedonia. Furthermore, these findings suggest there may be a common mechanism underlying adult onset hypothyroidism and depression.
Asunto(s)
Encéfalo/metabolismo , Preferencias Alimentarias , Hipotiroidismo/metabolismo , Hipotiroidismo/psicología , Actividad Motora , Tomografía de Emisión de Positrones , Animales , Antitiroideos/administración & dosificación , Antitiroideos/envenenamiento , Peso Corporal , Modelos Animales de Enfermedad , Agua Potable , Glucosa/metabolismo , Hipotiroidismo/inducido químicamente , Locomoción , Masculino , Propiltiouracilo/administración & dosificación , Propiltiouracilo/envenenamiento , Ratas , Ratas Wistar , SacarosaRESUMEN
BACKGROUND: Caspase-3 is a critical apoptosis-promoting element but its status during stepwise gastrocarcinogenesis needs to be further clarified. MATERIALS AND METHODS: By the use of frozen tissue microarrays constructed with the tissue spots cored from defined histological regions in tissue blocks, the pattern of caspase-3 expression in noncancerous, premalignant (atrophic gastritis and intestinal metaplasia) tissue and cancer spots were analyzed under the same experimental conditions by the methods of immunohistochemistry and mRNA-in situ hybridization. RESULTS: Caspase-3 was expressed in all 34 of the noncancerous mucosa (100%), in 16 of the 17 premalignant tissues (94.1%) and in 15 of the 48 gastric cancers (31.3%). The incidences of caspase-3 detection were significantly different (p<0.01) between noncancerous mucosa and intestinal as well as diffuse gastric cancers. CONCLUSION: Down-regulated caspase-3 is closely correlated with gastric cancer formation and would be a potential indicator of tumor formation and progression. Helicobacter pylori (H. pylori; Hp) infection is but not the only one element responsible to the enhanced caspase-3 expression in gastric epithelia.
Asunto(s)
Caspasas/metabolismo , Gastritis/enzimología , Gastritis/patología , Lesiones Precancerosas/enzimología , Lesiones Precancerosas/patología , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/patología , Estómago/enzimología , Estómago/patología , Apoptosis , Caspasa 3 , Mucosa Gástrica/enzimología , Mucosa Gástrica/patología , Humanos , Inmunohistoquímica , Hibridación in Situ , Mucosa Intestinal/enzimología , Mucosa Intestinal/patología , Metaplasia , ARN/aislamiento & purificación , Análisis de Matrices TisularesRESUMEN
Interaction of nuclear beta-catenin and TCF4 is the end point of canonical Wnt signaling, which is believed to trigger the transcription of multiple cancer-associated genes, including CD44. So far, the combined status of beta-catenin and TCF4 and its relevance for lymph node metastasis and CD44 expression have not been well studied in gastric cancers (GCs). To address these issues, we examined 31 GCs, 17 premalignant tissues, 10 noncancerous gastric mucosae, 17 regional lymph node metastases, and 4 human GC cell lines (MGC803, MGC823, AGS, and HGC-27) using immunohistochemical and immunofluorescence staining, reverse transcriptase polymerase chain reaction, and Western blot analysis. Frequent TCF4 up-regulation and nuclear translocation of beta-catenin were found in both primary and metastatic tumors. Standard CD44 was detected in all gastric tissue samples. The frequency of variant CD44 expression increased in parallel with stepwise gastrocarcinogenesis and tumor spread, but the rates of detection did not match that of nuclear beta-catenin and TCF4, especially in the premalignant and noncancerous samples. The data from the 4 cell lines were in accordance with the in vivo findings in terms of beta-catenin nuclear translocation, TCF4 activation, and CD44 expression. Our results suggest an established Wnt signaling pathway in most GCs, a close correlation of beta-catenin/TCF4-mediated signaling with tumor dissemination, and the unlikelihood of a direct effect of activated Wnt signaling on CD44 expression. The influence of beta-catenin-TCF4 interaction on alternative CD44 splicing was not established. These 3 alterations may be regarded as unfavorable features of GC.
Asunto(s)
Adenocarcinoma/secundario , Núcleo Celular/metabolismo , Receptores de Hialuranos/metabolismo , Ganglios Linfáticos/patología , Neoplasias Gástricas/patología , Factores de Transcripción TCF/biosíntesis , beta Catenina/biosíntesis , Transporte Activo de Núcleo Celular , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Western Blotting , Línea Celular Tumoral , Núcleo Celular/patología , Enfermedad Crónica , Gastritis/genética , Gastritis/metabolismo , Gastritis/patología , Perfilación de la Expresión Génica , Humanos , Receptores de Hialuranos/genética , Ganglios Linfáticos/metabolismo , Metástasis Linfática , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Factores de Transcripción TCF/genética , Análisis de Matrices Tisulares , Proteína 2 Similar al Factor de Transcripción 7 , beta Catenina/genéticaRESUMEN
The potential correlation of E-cadherin reduction and Wnt2 up-regulation in determining the intracellular distribution of beta-catenin in gastric cancers was investigated by the methods of frozen tissue array-based immunohistochemistry, Western blot and RT-PCR analysis. It was revealed that membranous E-cadherin was reduced frequently in the two major subtypes of gastric cancer (intestinal gastric cancer, i-GC and diffuse gastric cancer, d-GC) and closely correlated with the risk of lymphoid node metastasis (P < 0.05). The reduction of membranous E-cadherin was paralleled with cytosolic and nuclear accumulation of beta-catenin and the increased Wnt2 expression. These results indicate that the reduced E-cadherin is a common genetic phenotype of GCs and plays beneficial roles in tumor metastasis. Altered beta-catenin distribution may result from the imbalance of E-cadherin production and Wnt expression, which confers on gastric cancer cells more aggressive behaviors.
Asunto(s)
Cadherinas/metabolismo , Proteínas del Citoesqueleto/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Transactivadores/metabolismo , Cadherinas/análisis , Cadherinas/genética , Línea Celular Tumoral , Membrana Celular/química , Núcleo Celular/química , Proteínas del Citoesqueleto/análisis , Citosol/química , Humanos , Péptidos y Proteínas de Señalización Intercelular/análisis , Péptidos y Proteínas de Señalización Intercelular/genética , Metástasis Linfática , Mutación , Neoplasias Gástricas/genética , Análisis de Matrices Tisulares , Transactivadores/análisis , Proteínas Wnt , Proteína wnt2 , beta CateninaRESUMEN
Wnt/beta-catenin signalling pathway is integrally associated with human tumour development and progression. Aberrant beta-catenin intracellular distribution has been found in gastric cancer, but the pattern of Wnt expression in stepwise gastrocarcinogenesis and its potential influence in beta-catenin distribution are still lesser known. By the methods of frozen tissue array-based immunohistochemistry, Western blot analysis and RT-PCR, a paralleled study was conducted to check Wnt2 expression and beta-catenin intracellular distribution in two major subtypes of gastric cancers (intestinal gastric cancer, i-GC and diffuse gastric cancer, d-GC) and their premalignant (intestinal metaplasia, IM and chronic gastritis, CG) and noncancerous counterparts. According to the results obtained and the clinical data collected, correlation of Wnt2 expression with beta-catenin translocalisation and their links with tumour dissemination were elucidated. The results demonstrated (1) that Wnt2 expression and cytoplasmic/nuclear beta-catenin accumulations appeared in most gastric cancers irrespective to their morphological phenotypes, (2) that over-expressed Wnt and nuclear translocalisation of beta-catenin were found in 68 and 58% of i-GCs and in 47 and 47% of d-GCs in a closely related pattern (P<0.01) and (3) that co-existence of Wnt2 up-regulation/beta-catenin nuclear translocalisation were positively associated with lymph node metastasis (P<0.05) as well as T-stage. These data indicate that Wnt/beta-catenin signalling pathway is activated in most of gastric cancers, which may play pivotal roles either in gastric cancer formation or in tumour invasion and dissemination.
Asunto(s)
Proteínas del Citoesqueleto/biosíntesis , Proteínas del Citoesqueleto/farmacocinética , Perfilación de la Expresión Génica , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas/farmacocinética , Neoplasias Gástricas/genética , Neoplasias Gástricas/fisiopatología , Transactivadores/biosíntesis , Transactivadores/farmacocinética , Western Blotting , Núcleo Celular/química , Transformación Celular Neoplásica , China , Citoplasma , Humanos , Inmunohistoquímica , Invasividad Neoplásica , Metástasis de la Neoplasia , Lesiones Precancerosas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Regulación hacia Arriba , Proteína wnt2 , beta CateninaRESUMEN
Altered distribution of beta-catenin has been found in many human malignancies including gastric cancer, but its reason(s) and biological implications have not yet been fully clarified. By the methods of frozen tissue array-based immunohistochemistry, RT-PCR and PCR-SSCP followed by DNA sequencing, the patterns of beta-catenin distribution in the subtypes of gastric cancers and their premalignant and non-cancerous counterparts were examined and the potential correlation of beta-catenin alteration with invasion was elucidated. Membranous beta-catenin was detected constantly in non-cancerous mucosa but became reduced or absent in cancer tissues. The cytoplasmic and nuclear accumulation of beta-catenin could be observed in premalignant (atrophic gastritis and intestinal metaplasia) and cancer tissues, particularly in those infiltrated into deep muscular region. beta-catenin mutation was not detected in all of tissue samples with and without translocalized beta-catenin. These results indicate that beta-catenin translocalization is a common phenomenon in gastric cancers as well as their related lesions. The loss of membranous and the gain of cytoplasmic and nuclear beta-catenin in gastric cancers checked in this study are not due to the mutational event. beta-catenin molecules translocalized in the nuclei are closely correlated with tumor invasion.
Asunto(s)
Núcleo Celular/metabolismo , Proteínas del Citoesqueleto/metabolismo , Gastritis Atrófica/metabolismo , Invasividad Neoplásica/patología , Lesiones Precancerosas/metabolismo , Neoplasias Gástricas/metabolismo , Transactivadores/metabolismo , Membrana Celular/metabolismo , Membrana Celular/patología , Núcleo Celular/patología , Citoplasma/metabolismo , Proteínas del Citoesqueleto/genética , Progresión de la Enfermedad , Humanos , Neoplasias Intestinales/metabolismo , Neoplasias Intestinales/patología , Metaplasia/metabolismo , Metaplasia/patología , Mutación/genética , Polimorfismo Conformacional Retorcido-Simple , Lesiones Precancerosas/patología , Transporte de Proteínas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Transactivadores/genética , Resultado del Tratamiento , beta CateninaRESUMEN
It has been reported recently that the immunosuppressant FK506 produced neurotrophic and neuroprotective effects on dopaminergic neurons in vitro and in vivo. We investigated whether tripchlorolide, an immunosuppressive extract of Chinese herb Tripterygium wilfordii Hook F, could exert similar neurotrophic and neuroprotective effects similar to those of FK506. It was found that tripchlorolide promoted axonal elongation and protected dopaminergic neurons from a neurotoxic lesion induced by 1-methyl-4-phenylpyridinium ion (MPP+) at concentrations of as low as 10(-12) to 10(-8) M. In situ hybridization study revealed that tripchlorolide stimulated brain-derived neurotrophic factor (BDNF) mRNA expression. In vivo administration of tripchlorolide (1 microg/kg, ip) for 28 days effectively attenuated the rotational behavior challenged by D-amphetamine in the model rats by transection of the medial forebrain bundle. In addition, tripchlorolide treatment (0.5 or 1 microg/kg/day for 28 days) increased the survival of dopaminergic neurons in substantia nigra pars compacta by 50 and 67%, respectively. Moreover, tripchlorolide markedly prevented the decrease in amount of dopamine in the striatum of model rats. Taken together, our data provide the first evidence that tripchlorolide acts as a neuroprotective molecule that rescues MPP+ or axotomy-induced degeneration of dopaminergic neurons, which may imply its therapeutic potential for Parkinson's disease. The underlying mechanism may be relevant to its neurotrophic effect and its efficacy in stimulating the expression of BDNF.
Asunto(s)
Diterpenos/farmacología , Medicamentos Herbarios Chinos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fenantrenos , Tripterygium , 1-Metil-4-fenilpiridinio/antagonistas & inhibidores , 1-Metil-4-fenilpiridinio/toxicidad , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Axotomía , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , División Celular/efectos de los fármacos , Células Cultivadas , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Ácido Homovanílico/metabolismo , Inmunohistoquímica , Inmunosupresores/farmacología , Haz Prosencefálico Medial/efectos de los fármacos , Haz Prosencefálico Medial/fisiología , Neuritas/efectos de los fármacos , Neuronas/citología , Neuronas/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Tripterygium/químicaRESUMEN
AIM: To study whether the immunosuppressant tripchlorolide (T4) exerts neuroprotective effect on dopaminergic neurons. METHODS: A rat model of Parkinson's disease (PD) was set up by transection of the medial forebrain bundle (MFB) with a wire knife. The rotational behavior, HPLC-ECD, tyrosine hydroxylase (TH) immunocytochemistry, ELISA methods were used to evaluate the influence on the dopaminergic neurons following T4 treatment. RESULTS: T4 treatment was shown to effectively attenuate the rotational behavior challenged by amphetamine (2.5 mg.kg-1, i.p.) in the PD rats. T4 markedly prevented the decrease of dopamine content in the striatum and the loss of dopaminergic neurons in the substantia nigra pars compacta. T4 was found to suppress the abnormal increase of TNF-alpha and IL-2 level in brain tissues of PD rats after MFB transection. CONCLUSION: The evidence that the immunosuppressive Chinese herb extract T4 possesses neuroprotective activities on the dopaminergic neurons in PD rats was presented. The underlying mechanism of T4 may be relevant to its immunosuppressive activity.