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1.
Antioxidants (Basel) ; 10(7)2021 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-34201527

RESUMEN

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), affects 25% of the global population. Despite the prevalence of NAFLD worldwide, effective therapeutics are currently lacking. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX) is a medicinal herb traditionally used for treating digestive tract disorders in countries across Asia. We aimed to examine the pharmacological effects of the ethyl acetate fraction of AX (AXEF) against tunicamycin (TM)-induced ER stress in a NASH mouse model using C57/BL6J male mice. Following TM injections (2 mg/kg), the mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg), or distilled water daily for 5 days, and the outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH as indicated by decreases in lipid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue and/or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching reactive oxidative stress and its final product lipid peroxide in the hepatic tissue, specifically an increase in metallothionein (MT). To confirm the underlying actions of AXEF, we observed that AXEF increases MT1 gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress in a NASH mice model through the improvement of MTs.

2.
J Ethnopharmacol ; 260: 113102, 2020 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-32544420

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Yuk-Mi-Jihwang-Tang (YJT) has been popularly prescribed to treat aging related disorders over than hundreds of years in East Asia countries. AIM OF THE STUDY: To investigate possible modulatory actions of YJT on chronic restraint stress (CRS)-induced neurodegeneration on hippocampus neuronal injuries. MATERIALS AND METHODS: Mice were orally administered with YJT (100, 200, or 400 mg/kg) or ascorbic acid (100 mg/kg) before 4 h of stress for 28 days. Morris water maze task was completed from day 24th to 28th, and stress hormones and biochemical analyzes were measured. RESULTS: Four weeks of the CRS abnormally affected memory impairments by measurement of escape latency and time spent in the target quadrant. Additionally, neurotransmitters were also drastically altered in serum or hippocampus protein levels by CRS. Gene expressions for 5-hydroxytryptamine (5-HT) receptor, 5-HT-transport, and tryptophan hydroxylase were also altered, whereas YJT led to normalize the above alterations. Additionally, YJT also beneficially worked on endogenous redox system as well as inflammatory reactions in the hippocampal neurons. We observed that hippocampal excitotoxicity was induced by CRS which were evidenced by depletion of phosphor-cAMP response element-binding protein, brain-derived neurotrophic factor, nuclear factor erythroid-2-related factor 2, heme oxygenase-1 and abnormally increases of acetylcholine esterase activities in hippocampus protein levels; however, YJT considerably improved the above pathological conditions. CONCLUSIONS: Our findings supported YJT enhance memory function via regulation of hippocampal excitotoxicity-derived memory impairment, stress hormone, and endogenous redox, respectively.


Asunto(s)
Conducta Animal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Hipocampo/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Memoria/efectos de los fármacos , Degeneración Nerviosa , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Nootrópicos/farmacología , Estrés Psicológico/tratamiento farmacológico , Animales , Enfermedad Crónica , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Hipocampo/patología , Mediadores de Inflamación/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Trastornos de la Memoria/psicología , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Neuronas/patología , Oxidación-Reducción , Restricción Física , Estrés Psicológico/metabolismo , Estrés Psicológico/patología , Estrés Psicológico/psicología
3.
Cell Physiol Biochem ; 51(2): 886-896, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30466095

RESUMEN

BACKGROUND/AIMS: Among different molecular candidates, there is growing data to support that long noncoding RNAs (lncRNAs) play a significant role in acute myeloid leukemia (AML). HOXA-AS2 is significantly overexpressed in a variety of tumors and associated with anti-cancer drug resistance, however, little is known regarding the expression and function of HOXA-AS2 in the chemoresistance of AML. In this study, we aimed to determine the role and molecular mechanism of HOXA-AS2 in adriamycin-based chemotherapy resistance in AML cells. METHODS: Quantitative real-time PCR was used to detect HOXA-AS2 expression in the BM samples and ADR cell lines, U/A and T/A cells. Furthermore, the effects of HOXA-AS2 silencing on cell proliferation and apoptosis were assessed in vitro by CCK8 and flow cytometry, and on tumor growth in vivo. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in AML. RESULTS: In this study, we showed that HOXA-AS2 is significantly upregulated in BM samples from AML patients after treatment with adriamycin-based chemotherapy and in U/A and T/A cells. Knockdown of HOXA-AS2 inhibited ADR cell proliferation in vitro and in vivo and promoted apoptosis. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay and anti-Ago2 RIP assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in ADR cells. S100A4 was predicted as a downstream target of miR-520c-3p, which was confirmed by luciferase reporter assay. CONCLUSION: Our results suggest that HOXA-AS2 plays an important role in the resistance of AML cells to adriamycin. Thus, HOXA-AS2 may represent a therapeutic target for overcoming resistance to adriamycin-based chemotherapy in AML.


Asunto(s)
Leucemia Mieloide Aguda/patología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Proteína de Unión al Calcio S100A4/metabolismo , Regiones no Traducidas 3' , Animales , Antagomirs/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Masculino , Ratones , Ratones Desnudos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/uso terapéutico , Proteína de Unión al Calcio S100A4/química , Proteína de Unión al Calcio S100A4/genética
4.
Int J Mol Sci ; 11(6): 2267-80, 2010 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-20640151

RESUMEN

Tanshinone I (Tan-I) is a diterpene quinone extracted from the traditional herbal medicine Salvia miltiorrhiza Bunge. Recently, Tan-I has been reported to have anti-tumor effects. In this study, we investigated the growth inhibition and apoptosis inducing effects of Tan-I on three kinds of monocytic leukemia cells (U937, THP-1 and SHI 1). Cell viability was measured by MTT assay. Cell apoptosis was assessed by flow cytometry (FCM) and AnnexinV/PI staining. Reverse transcriptase polymerase chain reaction (RT-PCR) and PCR-enzyme-linked immunosorbent assay (ELISA) were used to detect human telomerase reverse transcriptase (hTERT) expression and telomerase activity before and after apoptosis. The activity of caspase-3 was determined by Caspase colorimetric assay kit and Western blot analysis. Expression of the anti-apoptotic gene Survivin was assayed by Western blot and Real-time RT-PCR using the ABI PRISM 7500 Sequence Detection System. The results revealed that Tan-I could inhibit the growth of these three kinds of leukemia cells and cause apoptosis in a time- and dose-dependent manner. After treatment by Tan-I for 48 h, Western blotting showed cleavage of the caspase-3 zymogen protein with the appearance of its 17-kD subunit, and a 89-kD cleavage product of poly (ADP-ribose) polymerase (PARP), a known substrate of caspase-3, was also found clearly. The expression of hTERT mRNA as well as activity of telomerase were decreased concurrently in a dose-dependent manner. Moreover, Real-time RT-PCR and Western blot revealed a significant down-regulation of Survivin. We therefore conclude that the induction of apoptosis by Tan-I in monocytic leukemia U937 THP-1 and SHI 1 cells is highly correlated with activation of caspase-3 and decreasing of hTERT mRNA expression and telomerase activity as well as down-regulation of Survivin expression. To our knowledge, this is the first report about the effects of Tan-I on monocytic leukemia cells.


Asunto(s)
Abietanos/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Telomerasa/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Survivin , Células U937
5.
Ann Hematol ; 89(11): 1089-97, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20512574

RESUMEN

Tanshinone I (Tan I), a diterpene quinone extracted from herbal medicine Salvia miltiorrhiza Bunge, has recently been reported to have antitumor effects. As the mechanism of its proapoptotic effects on human myeloid leukemia cells has not been extensively studied, we performed an in-depth evaluation of the effects of Tan I on apoptosis in human K562 and HL-60 cells. The results revealed that Tan I could inhibit the growth of leukemia cells and cause apoptosis in a time- and dose-dependent manner. Apoptosis was observed clearly by flow cytometry and Hoechst 33258 staining, as well as DNA fragmentation analysis. After treatment by Tan I for 48 h, the percentage of disruption of mitochondrial membrane potential (Δψm) was increased in a dose-dependent manner. Western blotting analysis demonstrated the cleavage of caspase-3 zymogen protein and a dose-dependent cleavage of poly-(ADP-ribose) polymerase. Tan I-induced apoptosis was accompanied by a significant decrease in survivin and an increase in Bax. Moreover, Tan I treatment remarkably downregulated the phosphorylation of both P85/PI3K and Akt in a time-dependent manner, and the PI3K/AKT-specific inhibitor (LY294002) mimicked the apoptosis-inducing effects of Tan I. We therefore conclude that the induction of apoptosis by Tan I in these leukemia cells is mainly related to the disruption of Δψm, the upregulation of Bax expression, and the activation of caspase-3. This process is highly correlated with the inactivation of PI3K/Akt/survivin signaling pathways. The results indicate that Tan I may serve as an effective adjunctive reagent in the treatment of leukemia.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Leucemia Mieloide/fisiopatología , Fenantrenos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Abietanos , Fragmentación del ADN/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Activación Enzimática , Células HL-60/efectos de los fármacos , Humanos , Células K562/efectos de los fármacos , Leucemia Mieloide/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Fenantrenos/química
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