RESUMO
Alzheimer's disease (AD) has pathological hallmarks including amyloid beta (Aß) plaque formation. Currently approved single-target drugs cannot effectively ameliorate AD. Medicinal herbs and their derived ingredients (MHDIs) have multitarget and multichannel properties, engendering exceptional AD treatment outcomes. This review delineates how in in vivo models MHDIs suppress Aß deposition by downregulating ß- and γ-secretase activities; inhibit oxidative stress by enhancing the antioxidant activities and reducing lipid peroxidation; prevent tau hyperphosphorylation by upregulating protein phosphatase 2A expression and downregulating glycogen synthase kinase-3ß expression; reduce inflammatory mediators partly by upregulating brain-derived neurotrophic factor/extracellular signal-regulated protein kinase 1/2-mediated signaling and downregulating p38 mitogen-activated protein kinase (p38 MAPK)/c-Jun N-terminal kinase (JNK)-mediated signaling; attenuate synaptic dysfunction by increasing presynaptic protein, postsynaptic protein, and acetylcholine levels and preventing acetylcholinesterase activity; and protect against neuronal apoptosis mainly by upregulating Akt/cyclic AMP response element-binding protein/B-cell lymphoma 2 (Bcl-2)-mediated anti-apoptotic signaling and downregulating p38 MAPK/JNK/Bcl-2-associated x protein (Bax)/caspase-3-, Bax/apoptosis-inducing factor-, C/EBP homologous protein/glucose-regulated protein 78-, and autophagy-mediated apoptotic signaling. Therefore, MHDIs listed in this review protect against Aß-induced cognitive decline by inhibiting Aß accumulation, oxidative stress, tau hyperphosphorylation, inflammation, synaptic damage, and neuronal apoptosis in the cortex and hippocampus during the early and late AD phases.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Plantas Medicinais , Acetilcolina , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Antioxidantes/uso terapêutico , Fator de Indução de Apoptose/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Glucose/efeitos adversos , Quinases da Glicogênio Sintase , Humanos , Mediadores da Inflamação/uso terapêutico , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Plantas Medicinais/metabolismo , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Apoptosis in the penumbra region is the major cell death mechanism occurring during ischemia-reperfusion injury's early phase. Here, we evaluated how the Alpinia oxyphylla Miq (AOM) affects mitochondria-related apoptosis 3 days after transient middle cerebral artery occlusion (MCAo) and examined the mechanisms underlying the regulation of MAPK-mediated mitochondria-related apoptotic signaling in the peri-infarct cortex in rats. The rats were administered the AOM extract intraperitoneally at doses of 0.2[Formula: see text]g/kg (AOM-0.2[Formula: see text]g), 0.4[Formula: see text]g/kg (AOM-0.4[Formula: see text]g), or 0.8[Formula: see text]g/kg (AOM-0.8[Formula: see text]g) at MCAo initiation. The AOM-0.4[Formula: see text]g and AOM-0.8[Formula: see text]g significantly ameliorated apoptotic cell death and considerably downregulated cytochrome c (cyto c) and cleaved caspase-3 immunoreactivity 3 days after reperfusion. Simultaneously, they significantly downregulated cytosolic p-JNK/JNK, cathepsin B/actin, cyto c/actin, Smac/DIABLO/actin, cleaved caspase-3/actin, and AIF/actin and mitochondrial p53/HSP60 and Bax/HSP60 fractions but upregulated cytosolic p-p38 MAPK/p38 MAPK, p-p90RSK/actin, p-Bad/Bad, p-CREB/actin, and XIAP/actin and cytosolic and mitochondrial Bcl-2/Bax and Bcl-xL/Bax fractions in the peri-infarct cortex. Pretreatment with SB203580 - a p38 MAPK inhibitor - completely abrogated the effects of AOM-0.8[Formula: see text]g on the aforementioned protein expression, whereas treatment with SP600125 - a JNK inhibitor - exerted protective effects similar to those of AOM-0.8[Formula: see text]g. Treatment with 0.4 or 0.8[Formula: see text]g/kg AOM has neuroprotective effects against mitochondria-related apoptosis by suppressing cyto c, Smac/DIABLO, and AIF release from the mitochondria to cytosol. The anti-mitochondria related apoptotic effects of the AOM extract are attributable to the interactions between upregulated p38 MAPK/p90RSK-mediated p-Bad and CREB signaling and downregulated JNK/cathepsin B-mediated Bax and p53 signaling in the peri-infarct cortex 3 days after transient MCAo.
Assuntos
Alpinia , Isquemia Encefálica , Fármacos Neuroprotetores , Ratos , Animais , Fármacos Neuroprotetores/farmacologia , Caspase 3/metabolismo , Catepsina B/metabolismo , Catepsina B/farmacologia , Catepsina B/uso terapêutico , Proteína X Associada a bcl-2/metabolismo , Actinas/metabolismo , Proteína Supressora de Tumor p53 , Apoptose , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Reperfusão , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , InfartoRESUMO
BACKGROUND: Whether acupuncture therapy contributes to preserving residual renal function (RRF) remains largely unknown. This case series demonstrated the potential beneficial effects of acupuncture for preserving RRF in five patients with end-stage renal disease undergoing hemodialysis (HD) treatment. PARTICIPANTS: HD patients received eight sessions of weekly 30 min interdialytic acupuncture (Inter-A) at ten selected acupoints, namely Yintang (GV29), Yingxiang (LI20), Shuijin (Tung's Acupuncture), Lianquan (CV23), Shangqu (KI17), Tianshu (ST25), Siman (KI14), Hegu (LI4), Zusanli (ST36) and Sanyingjao (SP6). Residual urine volume (rUV) and residual glomerular filtration rate (rGFR) were recorded once every two weeks Outcomes: Changes in rUV and rGFR were calculated using 24 h urine collection data to assess RRF. Variations in hemoglobin, urea Kt/V and serum albumin levels were measured monthly to evaluate HD adequacy. RESULTS: After eight Inter-A sessions, the mean[standard deviation] rUV and rGFR increased from 612[184] ml/day and 1.48[0.94] ml/min/1.73 m2 at baseline to the peak of 803[289] ml/day and 2.04[1.17] ml/min/1.73 m2 at 2- and 4-week follow-up, respectively. The mean percentage difference increased by 31% in the rUV and 37% in the rGFR. Routine measurements of HD adequacy also showed improvements. CONCLUSIONS: Acupuncture might be an optional add-on treatment for HD population with poor control of water; however, further well-designed controlled trials are warranted.
Assuntos
Terapia por Acupuntura , Falência Renal Crônica , Humanos , Falência Renal Crônica/terapia , Taxa de Filtração Glomerular , Diálise Renal , Rim/fisiologiaRESUMO
BACKGROUND: Intradialytic hypotension (IDH) is a common complication during hemodialysis (HD) and is positively associated with either poor quality of life or mortality. The present case report described the effect of intradialytic acupuncture (IA) in decreasing the occurrence of IDH. METHODS: A 70-year-old female with diabetic nephropathy had been receiving regular dialysis twice weekly since end-stage renal disease was diagnosed. She had several episodes of intradialytic systolic blood pressure (iSBP) drop accompanied with severe complications within one month. In the 10 dialysis sessions prior to IA intervention, the case patient experienced two episodes of nadir iSBP < 90 mmHg, seven episodes of iSBP drop ≥ 20 mmHg, among which two episodes occurred with symptoms; and three episodes of iSBP drop required nursing intervention. INTERVENTIONS: Dialysis sessions proceeded as usual with the patient receiving five sessions of 30-min IA as an add-on therapy starting from the second hour of dialysis. RESULTS: In the 10 sessions with IA administered alternately, she experienced one episode of nadir iSBP < 90 mmHg and three episodes of iSBP drop ≥ 20 mmHg, among which two episodes occurred with symptoms. Occurrence of IDH reduced and no IDH necessitating nursing intervention occurred during IA-HD sessions. CONCLUSIONS: The administration of IA showed potential effect in decreasing the occurrence of IDH.
Assuntos
Terapia por Acupuntura , Hipotensão , Falência Renal Crônica , Terapia por Acupuntura/efeitos adversos , Idoso , Pressão Sanguínea , Feminino , Humanos , Hipotensão/epidemiologia , Hipotensão/etiologia , Hipotensão/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Qualidade de Vida , Diálise Renal/efeitos adversosRESUMO
BACKGROUND: Post-ischemic inflammation is a crucial component in stroke pathology in the early phase of cerebral ischemia-reperfusion (I/R) injury. Inflammation caused by microglia, astrocytes, and necrotic cells, produces pro-inflammatory mediators and exacerbates cerebral I/R injury. This study evaluated the effects of the Alpinia oxyphylla Miq [Yi Zhi Ren (YZR)] extract on cerebral infarction at 1 day after 90 min of transient middle cerebral artery occlusion (MCAo) and investigated the molecular mechanisms underlying the regulation of c-Jun N-terminal kinase (JNK)-mediated inflammatory cascades in the penumbral cortex. Rats were intraperitoneally injected with the YZR extract at the doses of 0.2 g/kg (YZR-0.2 g), 0.4 g/kg (YZR-0.4 g), or 0.8 g/kg (YZR-0.8 g) at MCAo onset. RESULTS: YZR-0.4 g and YZR-0.8 g treatments markedly reduced cerebral infarction, attenuated neurological deficits, and significantly downregulated the expression of phospho-apoptosis signal-regulating kinase 1 (p-ASK1)/ASK1, tumor necrosis factor receptor-associated factor 3 (TRAF3), TRAF3-interacting JNK-activating modulator (T3JAM), ionized calcium-binding adapter molecule 1 (Iba1), p-JNK/JNK, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), nuclear factor-kappa B (NF-κB), and interleukin-6 in the penumbral cortex at 1 day after reperfusion. SP600125 (SP), a selective JNK inhibitor, had the same effects. Furthermore, Iba1- and GFAP-positive cells were colocalized with TLR4, and colocalization of GFAP-positive cells was found with NF-κB in the nuclei. CONCLUSION: YZR-0.4 g and YZR-0.8 g treatments exerted beneficial effects on cerebral ischemic injury by downregulating JNK-mediated signaling in the peri-infarct cortex. Moreover, the anti-infarction effects of YZR extract treatments were partially attributed to the downregulation of JNK-mediated TLR4/T3JAM- and ASK1-related inflammatory signaling pathways in the penumbral cortex at 1 day after reperfusion.
RESUMO
Chinese herbal remedies have long been used for enhancing immunity and treating asthma. However, the evidence-based efficacy remains to be supported. This study aimed to explore the potential bio-signatures in allergic asthma and the effect of You-Gui-Wan (YGW), a traditional Chinese herbal prescription, on dust mite-induced mouse allergic asthma. Extract of Dermatophagoides pteronyssinus (Der p), a dust mite, was intratracheally administered to induce allergic asthma in mice. Serum metabolomic and 16S rRNA-based microbiome profiling were used to analyze untargeted metabolites with levels significantly changed and gut microbiota composition, respectively. Results indicated that 10 metabolites (acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine), mainly associated with branched-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism were markedly elevated after Der p treatment. YGW administration reversed the levels for 7 of the 10 identified metabolites, chiefly affecting BCAA metabolism. On 16S DNA sequencing, disordered Der p-induced gut microbiota was significantly alleviated by YGW. Multiple correlation analysis showed a good correlation between gut microbiota composition and levels of selected metabolites. Our study showed YGW administration effectively alleviated BCAA metabolic disorder and improved gut dysbiosis. This study provides support for YGW administration with benefits for allergic asthma.
Assuntos
Asma , Dermatophagoides pteronyssinus , Medicamentos de Ervas Chinesas/farmacologia , Disbiose , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças Metabólicas , Animais , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/metabolismo , Asma/microbiologia , Disbiose/tratamento farmacológico , Disbiose/metabolismo , Disbiose/microbiologia , Masculino , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , Doenças Metabólicas/microbiologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (Oliv.) Diels (ASD), commonly known as Dang Gui, is a popular Chinese herb that has long been used to treat ischemic stroke. However, the effects of ASD in chronic cerebral ischemia and its underlying mechanisms still remain unclear. AIM OF THE STUDY: This study aimed to determine the effects of the ASD extract on hippocampal neuronal survival at 28 d after transient global cerebral ischemia (GCI) and to investigate the precise mechanisms underlying the p38 mitogen-activated protein kinase (MAPK)-related signaling pathway's involvement in hippocampal neurogenesis. MATERIALS AND METHODS: Rats underwent 25 min of four-vessel occlusion. The ASD extract was intragastrically administered at doses of 0.25 g/kg (ASD-0.25 g), 0.5 g/kg (ASD-0.5 g), 1 g/kg (ASD-1 g), 1 g/kg after dimethyl sulfoxide administration (D + ASD-1 g), or 1 g/kg after SB203580 (a p38 MAPK inhibitor) administration (SB + ASD-1 g) at 1, 3, 7, 10, 14, 17, 21, and 24 d after transient GCI. RESULTS: ASD-0.5 g, ASD-1 g, and D + ASD-1 g treatments had the following effects: upregulation of bromodeoxyuridine (BrdU) and Ki67 expression, and BrdU/neuronal nuclei (NeuN) and Ki67/nestin co-expression in the hippocampal dentate gyrus (DG); upregulation of microtubule-associated protein 2/NeuN co-expression, and NeuN and glial fibrillary acidic protein (GFAP) expression, and downregulation of tumor necrosis factor-α/GFAP co-expression in the hippocampal CA1 region; upregulation of phospho-p38 MAPK (p-p38 MAPK), phospho-cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor A (VEGF-A) expression in the hippocampus. SB + ASD-1 g treatment abrogated the effects of ASD-1 g on the expression of these proteins. CONCLUSIONS: ASD-0.5 g and ASD-1 g treatments promotes neuronal survival by enhancing hippocampal neurogenesis. The effects of the ASD extract on astrocyte-associated hippocampal neurogenesis and dendritic growth are caused by the activation of p38 MAPK-mediated CREB/BDNF, GDNF, and VEGF-A signaling pathways in the hippocampus at 28 d after transient GCI.
Assuntos
Angelica sinensis/química , Isquemia Encefálica , Hipocampo/citologia , Neurogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Imidazóis/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Extratos Vegetais/química , Piridinas/farmacologia , RatosRESUMO
BACKGROUND: This study aimed to evaluate the effects of the Acorus tatarinowii Schott [Shi Chang Pu (SCP)] extract administered at the start of 2 h of middle cerebral artery occlusion (MCAo), followed by 3 d of reperfusion, and to determine mechanisms involved in anti-edema effects in the penumbra of the cerebral cortex. METHOD: Rats were intraperitoneally administered the SCP extract at a dose of 0.25 g/kg (SCP-0.25 g), 0.5 g/kg (SCP-0.5 g), or 1 g/kg (SCP-1 g) at the start of MCAo. RESULT: SCP-0.5 g and SCP-1 g treatments effectively reduced the cerebral infarct size, ameliorated cerebral edema, reduced blood-brain barrier permeability, and restored neurological function. SCP-0.5 g and SCP-1 g treatments markedly downregulated the levels of glial fibrillary acidic protein, Na+-K+-2Cl- cotransporter type 1 (NKCC1), aquaporin 4 (AQP4), phospho-c-Jun N-terminal kinase (p-JNK)/JNK, inducible nitric oxide synthase (iNOS), 3-nitrotyrosine, intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor-A (VEGF-A), and zonula occluden-1 (ZO-1) and upregulated ZO-3 expression in the penumbra of the cerebral cortex 3 d after reperfusion. CONCLUSIONS: SCP-0.5 g and SCP-1 g treatments exert neuroprotective effects against cerebral infarction and cerebral edema partially by mitigating astrocytic swelling and blood-brain barrier disruption. Moreover, the anti-cerebral edema effects of SCP extract treatments are possibly associated with the downregulation of astrocytic NKCC1/AQP4 and JNK/iNOS-mediated ICAM-1/MMP-9 signaling in the penumbra of the cerebral cortex 3 d after reperfusion.
Assuntos
Aquaporina 4/metabolismo , Edema Encefálico/tratamento farmacológico , MAP Quinase Quinase 4/metabolismo , Óxido Nítrico Sintase/metabolismo , Extratos Vegetais/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Acorus , Animais , Masculino , Medicina Tradicional Chinesa/métodos , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Some patients with cancer use adjunctive Chinese medicine, which might improve the quality of life. This study aims to investigate the effects and relative factors of adjunctive Chinese medicine on survival of hepatocellular carcinoma patients at different stages. The study population was 23 581 newly diagnosed hepatocellular carcinoma patients and received surgery from 2004 to 2010 in Taiwan. After propensity score matching with a ratio of 1:10, this study included 1339 hepatocellular carcinoma patients who used adjunctive Chinese medicine and 13 390 hepatocellular carcinoma patients who used only Western medicine treatment. All patients were observed until the end of 2012. Kaplan-Meier method and Cox proportional hazards model was applied to find the relative risk of death between these 2 groups. The study results show that the relative risk of death was lower for patients with adjunctive Chinese medicine treatment than patients with only Western medicine treatment (hazard ratio = 0.68; 95% confidence interval = 0.62-0.74). The survival rates of patients with adjunctive Chinese medicine or Western medicine treatment were as follows: 1-year survival rate: 83% versus 72%; 3-year survival rate: 53% versus 44%; and 5-year survival rate: 40% versus 31%. The factors associated with survival of hepatocellular carcinoma patients included treatment, demographic characteristics, cancer stage, health status, physician characteristics, and characteristics of primary medical institution. Moreover, stage I and stage II hepatocellular carcinoma patients had better survival outcome than stage III patients by using adjunctive Chinese medicine therapy. The effect of adjunctive Chinese medicine was better on early-stage disease.
Assuntos
Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Adulto , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Qualidade de Vida , Estudos Retrospectivos , Taxa de Sobrevida , TaiwanRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (Oliv.) Diels, commonly known as Dang Gui (DG), is one of the most popular traditional Chinese herbal medicines for the treatment of stroke. However, the effects of DG on transient global cerebral ischemia (GCI) and its precise mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate the effects of the DG extract on ischemia-reperfusion (I/R) injury in the hippocampus 7 d after transient GCI and to identify the potential mitogen-activated protein kinase (MAPK)-related signaling pathway in the hippocampus involved in the effects. MATERIALS AND METHODS: Rats were intragastrically administered DG at doses of 0.25 g/kg (DG-0.25g), 0.5 g/kg (DG-0.5g), or 1 g/kg (DG-1g) 1, 3, and 5 d after GCI. RESULTS: DG-0.5g and DG-1g treatments effectively promoted hippocampal cornu ammonis 1 (CA1) neuronal survival. DG-0.5g and DG-1g treatments markedly increased phospho-p38 MAPK (p-p38 MAPK), phospho-90-kDa ribosomal S6 kinase (p-p90RSK), cytosolic and mitochondrial phospho-Bad (p-Bad), phospho-cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and p-CREB/BDNF expression; decreased 4-hydroxy-2-nonenal, cytochrome c (Cytc), and cleaved caspase-3 expression, and inhibited apoptosis in the hippocampal CA1 region. Pretreatment with a specific inhibitor of p38 MAPK, SB203580, completely blocked the effects of DG-1g on the expression of the aforementioned proteins. CONCLUSIONS: DG-0.5g and DG-1g treatments exerted neuroprotective effects on I/R injury by activating p38 MAPK-mediated p90RSK/p-Bad-induced anti-apoptotic-Cytc/caspase-3-related and p90RSK/CREB/BDNF survival signaling in the hippocampus 7 d after transient GCI.
Assuntos
Angelica sinensis , Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Hipocampo/metabolismo , Masculino , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína de Morte Celular Associada a bcl/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: In Asia, Qi-Wei-Du-Qi-Wan (QWDQW) is a traditional Chinese medicine that has been used to treat chest tightness, cough, shortness of breath, night sweats, frequent urination and asthma. QWDQW is recorded in Yi Zong Yi Ren Pian (Medical Physician's Compilation), which was written by Yang Cheng Liu during the Qing Dynasty. AIM OF THE STUDY: The traditional Chinese medicine QWDQW is composed of 7 ingredients and has been used in the treatment of asthma in Asia for hundreds of years. However, the mechanism through which QWDQW affects the immune system in the treatment of asthma is not known. Therefore, this study aimed to investigate whether QWDQW alleviates asthmatic symptoms in mice with chronic asthma induced by repeated stimulation with Dermatophagoides pteronyssinus (Der p) and to explore the underlying immune modulatory mechanism. MATERIALS AND METHODS: BALB/c mice were stimulated intratracheally (i.t.) with Der p (40 µl, 2.5 µg/µl) once weekly for 6 weeks. Thirty minutes prior to Der p stimulation, the mice were treated with QWDQW (0.5 g/kg and 0.17 g/kg) orally. Three days after the last stimulation, the mice were sacrificed, and infiltration of inflammatory cells, lung histological characteristics, gene expression of lung and serum total IgE were assessed. In other experiments, RBL-2H3 cells were stimulated with DNP-IgE/DNP-BSA and then treated with QWDQW, quercetin, ß-carotene, luteolin or a mixture of the three chemicals (Mix13) for 30 min, and the effects of the drugs on RBL-2H3 cell degranulation after DNP stimulation were determined. RESULTS: QWDQW significantly reduced Der p-induced airway hyperreactivity (AHR) and decreased total serum IgE and Der p-specific IgE levels. Histopathological examination showed that QWDQW reduced inflammatory cell infiltration and sputum secretion from goblet cells in the lungs. Gene expression analysis indicated that QWDQW reduced overproduction of IL-12ãIFN-γãIL-13ãIL-4ãRNATESãEotaxin and MCP-1in lung. Additionally, QWDQW and Mix13 suppressed DNP induced RBL-2H3 degranulation, and the effect was maximal when quercetin, ß-carotene and luteolin were administered together. CONCLUSION: These results indicate that QWDQW plays a role in suppressing excessive airway reaction and in specific immune modulation in a mouse model of chronic asthma and that QWDQW suppresses mast cell degranulation at defined doses of quercetin, ß-carotene and luteolin.
Assuntos
Asma/tratamento farmacológico , Degranulação Celular/efeitos dos fármacos , Pulmão/imunologia , Animais , Asma/microbiologia , Células Cultivadas , Dermatophagoides pteronyssinus , Dinitrofenóis/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Expressão Gênica/efeitos dos fármacos , Imunoglobulina E/biossíntese , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Pulmão/efeitos dos fármacos , Luteolina/farmacologia , Masculino , Camundongos , Fitoterapia/métodos , Quercetina/farmacologia , Soroalbumina Bovina/imunologia , Escarro/metabolismo , beta Caroteno/farmacologiaRESUMO
Erianin is the major bibenzyl compound found in Dendrobium chrysotoxum Lindl. The current study was designed to investigate the protective effects of erianin on high glucose-induced injury in cultured renal tubular epithelial cells (NRK-52E cells) and determine the possible mechanisms for its effects. NRK-52E cells were pretreated with erianin (5, 10, 25 or 50â¯nmol/L) for 1â¯h followed by further exposure to high glucose (30â¯mmol/L, HG) for 48â¯h. Erianin concentration dependently enhanced cell viability followed by HG treatment in NRK-52E cells. HG induced reactive oxygen species (ROS) generation, malondialdehyde production, and glutathione deficiency were recovered in NRK-52E cells pretreated with erianin. HG triggered cell apoptosis via the loss of mitochondrial membrane potential, depletion of adenosine triphosphate, upregulation of caspases 9 and 3, enhancement of cytochrome c release, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by erianin. HG also induced activation of p53, JNK, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in NRK-52E cells, which were blocked by erianin. The results suggest that treatment NRK-52E cells with erianin halts HG-induced renal dysfunction through the suppression of the ROS/MAPK/NF-κB signaling pathways. Our findings provide novel therapeutic targets for diabetic nephropathy.
Assuntos
Bibenzilas/farmacologia , Células Epiteliais/efeitos dos fármacos , Glucose/efeitos adversos , Túbulos Renais/citologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Glucose/metabolismo , Túbulos Renais/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Fenol , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
This study assessed the anti-apoptotic effects of the administration of ferulic acid (FrA) in rats 30 min before middle cerebral artery occlusion (MCAo) followed by 3 d of ischemia and the involvement of 70 kDa heat shock protein (HSP70)-mediated signaling in the penumbral cortex. Our results demonstrated that FrA pretreatment at doses of 80 mg/kg (FrA-80 mg) and 100 mg/kg (FrA-100 mg) effectively ameliorated neurological functions and reduced the numbers of cytochrome c-, cleaved caspase-3-, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in the penumbral cortex 3 d after ischemia. Moreover, FrA-80 mg and FrA-100 mg pretreatment markedly upregulated cytosolic HSP70, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) A/B-II and autophagy-related protein 5 (Atg5) expression; cytosolic and mitochondrial X-linked inhibitor of apoptosis (XIAP) expression and the Bcl-2/Bax ratio. FrA pretreatment downregulated cytosolic cytochrome c, apoptosis-inducing factor (AIF), procathepsin B, and cathepsin B expression and mitochondrial and cytosolic second mitochondria-derived activator of caspase/direct inhibitor of apoptosis protein-binding protein with a low isoelectric point (Smac/DIABLO) expression in the penumbral cortex. Pretreatment with VER155008, a HSP70 family inhibitor, significantly inhibited the effects of FrA-100 mg on the expression of the aforementioned proteins expression in the penumbral cortex. FrA-80 mg and FrA-100 mg pretreatment exerts neuroprotective effects against caspase-dependent and -independent apoptosis through activating HSP70/Bcl-2- and HSP70/autophagy-induced signaling pathways. Furthermore, the HSP70/Bcl-2- and HSP70/autophagy-induced anti-apoptotic effects of FrA pretreatment can be attributed to the regulation of Bax/cytochrome c/Smac/DIABLO/XIAP/ caspase-3- (or Bax/AIF-) and Beclin-1/LC3A/B-II/Atg5-mediated signaling, respectively, in the penumbral cortex 3 d after permanent MCAo.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Isquemia Encefálica/genética , Isquemia Encefálica/prevenção & controle , Ácidos Cumáricos/administração & dosagem , Ácidos Cumáricos/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Fitoterapia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Angelica sinensis/química , Animais , Autofagia/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Córtex Cerebral/metabolismo , Ácidos Cumáricos/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
The aim of the present study was to determine the effects of ferulic acid (FerA) administered immediately following the onset of permanent middle cerebral artery occlusion (MCAo) and then 7 days of ischemia, and also to explore the involvement of protein kinase B (Akt)induced signaling in the penumbral cortex. Immediately following the onset of MCAo, FerA was intravenously administered to rats at a dose of 60 mg/kg (FerA60 mg), 80 mg/kg (FerA80 mg), or 100 mg/kg (FerA100 mg). FerA80 mg and FerA100 mg effectively ameliorated cerebral infarction and neurological deficits 7 days following permanent cerebral ischemia. FerA80 mg and FerA100 mg significantly upregulated the expression of phosphoAkt (pAkt), phosphomammalian target of rapamycin (pmTOR), and eukaryotic initiation factor 4E (eIF4E)binding protein 1 (4EBP1), and the phospho4EBP1 (p4EBP1)/4EBP1 and mitochondrial Bcl2/Bax ratios, and markedly downregulated the levels of cytochrome c, cleaved caspase3, and terminal deoxynucleotidyl transferasemediated dUTPbiotin nickend labelingimmunoreactive cells in the penumbral cortex at 7 days postischemia. LY294002, a selective inhibitor of phosphoinositide 3kinase/Akt signaling, was administered 30 min prior to ischemia, which abrogated the upregulating effects of FerA100 mg on the expression of pAkt, pmTOR, 4EBP1, p4EBP1 and eIF4E, the mitochondrial Bcl2/Bax ratio and the ameliorating effect of FerA100 mg on cerebral infarction. FerA administered at doses of 80 and 100 mg/kg exerted beneficial effects against cerebral ischemia by activating Aktinduced signaling. The effects of FerA at doses of 80 and 100 mg/kg on mitochondrial Bcell lymphoma-2 (Bcl2)associated X proteinrelated apoptosis were attributed to the activation of Akt/mTOR/4EBP1/Bcl2 antiapoptotic signaling, and eventually contributed to suppression of the cytochrome c/caspase3 activation pathway in the penumbral cortex 7 days following permanent cerebral ischemia.
Assuntos
Apoptose/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Ácidos Cumáricos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Isquemia Encefálica/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Regulação para Baixo/efeitos dos fármacos , Masculino , Fosfatidilinositol 3-Quinase/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Gigantol is a bibenzyl compound derived from several medicinal orchids. This biologically active compound has shown promising therapeutic potential against diabetic cataracts, but whether this compound exerts beneficial effects on the other diabetic microvascular complications remains unclear. This study was carried out to examine effects of gigantol on high glucose-induced renal cell injury in cultured mouse kidney mesangial cells (MES-13). MES-13 cells were pretreated with gigantol (1, 5, 10 or 20 µmol/L) for 1 h followed by further exposure to high (33.3 mmol/L) glucose for 48 h. Gigantol concentration dependently enhanced cell viability followed by high glucose treatment in MES-13 cells. High glucose induced reactive oxygen species (ROS) generation, malondialdehyde production and glutathione deficiency were recoved in MES-13 cells pretreated with gigantol. High glucose triggered cell apoptosis via the the loss of mitochondrial membrane potential, depletion of adenosine triphosphate, upregulation of caspases 9 and 3, enhancement of cytochrome c release, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by gigantol. High glucose also induced activation of JNK, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in MES-13 cells, which were blocked by gigantol. The results suggest that treatment MES-13 cells with gigantol halts high glucose-induced renal dysfunction through the suppression of the ROS/MAPK/NF-κB signaling pathways. Our data are of value to the understanding the mechanism for gigantol, and would benefit the study of drug development or food supplement for diabetes and nephropathy.
Assuntos
Bibenzilas/farmacologia , Guaiacol/análogos & derivados , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Glucose/metabolismo , Glucose/farmacologia , Guaiacol/farmacologia , Peroxidação de Lipídeos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: In Asia, Jin Gui Shen Qi Wan (JGSQW) has been used for hundreds of years to treat asthma. AIM OF THE STUDY: The traditional Chinese medicine JGSQW is composed of Rehmannia glutinosa, Dioscorea opposita, Cornus officinalis, Poria cocos, Paeonia suffruticosa, Alisma orientalis, Aconitum carmichaelii and Cinnamomum cassia. However, the immunological mechanism underlying the effect of JGSQW treatment on asthma remains unclear. This study examined whether JGSQW has the potential to reduce asthma symptoms in mice with chronic asthma induced by recurrent Dermatophagoides pteronyssinus (Der p) stimulation, as well as its immunoregulatory mechanisms. MATERIALS AND METHODS: The airways of BALB/c mice were stimulated with Der p (i.t.) once per week (50⯵L, 1â¯mg/mL) for 6 consecutive weeks, and the mice were fed JGSQW (1â¯g/kg) 30â¯min prior to the Der p stimulation. Three days after the last stimulation, the mice were sacrificed to evaluate the airway remodelling, infiltration of inflammatory cells, lung histological features, and total IgE in the blood. Additionally, after A549 cells were treated with JGSQW, loganin, or paeoniflorin for 30â¯min, 10â¯ng/mL IL-1ß was added to stimulate the A549 cells to evaluate the effect of the medicine on the ICAM-1 gene expression after IL-1ß stimulation. RESULTS: JGSQW significantly reduced the Der p-induced infiltration of inflammatory cells into airways and decreased the total IgE and Der p-specific IgG1 in serum. Collagen assays and histopathological examinations showed that JGSQW reduced lung airway remodelling. Additionally, an electrophoretic mobility shift assay and immunohistochemical staining verified that JGSQW inhibited the NF-kB expression in airway epithelial cell nuclei. JGSQW, loganin, and paeoniflorin inhibited the ICAM-1 gene expression caused by the IL-1ß stimulation of A549 cells, and loganin and paeoniflorin had the maximum inhibitory effect when mixed according to the combination of doses in JGSQW. CONCLUSION: These results indicated that in the chronic asthma mouse model, JGSQW inhibits the infiltration of inflammatory cells into the airways and airway remodelling and exhibits specific immunoregulatory effects. JGSQW with certain doses of loganin and paeoniflorin inhibited ICAM-1 gene expression in epithelial cells.
Assuntos
Antialérgicos/uso terapêutico , Asma/tratamento farmacológico , Células A549 , Remodelação das Vias Aéreas/efeitos dos fármacos , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/imunologia , Asma/patologia , Asma/fisiopatologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Molécula 1 de Adesão Intercelular/genética , Masculino , Medicina Tradicional Chinesa , Camundongos Endogâmicos BALB C , FitoterapiaRESUMO
Antrodia camphorata mycelium is used in traditional Chinese medicine in Taiwan. The wild-type mycelium is rare and expensive, so a solid-state-cultured mycelium of A. camphorata (SCMAC) has been developed. Previous studies have found SCMAC to have anti-inflammatory effects. However, the immunomodulatory effects of SCMAC and of its active phytosterol compounds EK100 and 9A on asthma remain unknown. In this study, BALB/c mice were repeatedly exposed to Dermatogoides pteronyssinus (Der p) at 1-week intervals and were orally administered crude SCMAC extract before the Der p challenge. The mice were sacrificed 72â¯h after the last challenge to examine the airway remodeling, inflammation, and expression profiles of cytokines and various genes. Then, 30-µg/mL Der p-stimulated MH-S cells with 9A or EK100 were collected for real-time PCR analysis, and the effects of 9A and EK100 on macrophages were evaluated. The crude extract reduced Der p-induced airway hyperresponsiveness, total serum immunoglobulin E levels, and recruitment of inflammatory cells to the bronchoalveolar lavage fluid through cytokine downregulation and Th1/Th2/Th17 response modulation. Additionally, 9A and EK100 inhibited IL-1ß and IL-6 expression in alveolar macrophages. These results indicate that the pharmacologically active compounds in a crude SCMAC extract exert synergistic effects on multiple targets to relieve asthma symptoms.
Assuntos
Corticosteroides/farmacologia , Antrodia/química , Proteínas Fúngicas/farmacologia , Macrófagos/efeitos dos fármacos , Hipersensibilidade Respiratória/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Asma/tratamento farmacológico , Modelos Animais de Doenças , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Micélio/química , Reação em Cadeia da Polimerase em Tempo Real , Organismos Livres de Patógenos EspecíficosRESUMO
This study evaluated the effects of Angelica sinensis extract [Dang Gui (DG)] administered before 60[Formula: see text]min of middle cerebral artery occlusion followed by 3[Formula: see text]d of reperfusion and investigated the involvement of mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor (HIF)-1[Formula: see text] signaling in the cortical ischemic penumbra. DG was intraperitoneally administered at a dose of 0.25[Formula: see text]g/kg (DG-0.25g), 0.5[Formula: see text]g/kg (DG-0.5g), or 1[Formula: see text]g/kg (DG-1g) 30[Formula: see text]min before the onset of cerebral ischemia. Our study results revealed that DG-0.5g and DG-1g pretreatment effectively attenuated cerebral infarct and improved neurological deficits. DG-0.5g and DG-1g pretreatment significantly downregulated glial fibrillary acidic protein (GFAP), cytochrome c, and cleaved caspase-3 expression and upregulated phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK, phospho-cAMP response element-binding protein (p-CREB)/CREB, cytosolic and mitochondrial phospho-Bad (p-Bad)/Bad ratios, and HIF-1[Formula: see text], vascular endothelial growth factor-A (VEGF-A), phospho-90 kDa ribosomal S6 kinase (p-p90RSK), and von Willebrand factor (vWF) expression in the cortical ischemic penumbra. Pretreatment with SB203580, a p38 MAPK inhibitor, dramatically abrogated the upregulating effects of DG-1g on p-p38 MAPK/p38 MAPK, p-CREB/CREB, and p-Bad/Bad ratios and HIF-1[Formula: see text], VEGF-A, and vWF expression and the downregulating effects of DG-1g on GFAP, cytochrome c, cleaved caspase-3, and cerebral infarction. DG-0.5g and DG-1g pretreatment provided neuroprotective effects against astrocyte-mediated cerebral infarction by activating angiogenic and anti-apoptotic signaling. Moreover, the angiogenic and anti-apoptotic effects of DG pretreatment can be attributed to the activation of p38 MAPK/HIF-1[Formula: see text]/VEGF-A/vWF signaling and p38 MAPK/HIF-1[Formula: see text]/VEGF-A/p-Bad-related regulation of cytochrome c/caspase-3 signaling, respectively, in the cortical ischemic penumbra 3[Formula: see text]d after reperfusion.
Assuntos
Angelica sinensis/química , Indutores da Angiogênese , Apoptose/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Fator 1 Induzível por Hipóxia/metabolismo , Fitoterapia , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Isquemia Encefálica/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Fator 1 Induzível por Hipóxia/fisiologia , Infusões Parenterais , Masculino , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologiaRESUMO
BACKGROUND: Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. METHODS: A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). Patients were treated with Indigo naturalis ointment (n = 16) or matched placebo (n = 8) twice daily for 8 weeks, with 1 week of follow-up. RESULTS: At week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in Indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, which included the up-regulation of the interleukin (IL)-17 pathway as a key component; Indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway. Using an in vitro keratinocyte assay, an IL-17-inhibitory effect was observed for tryptanthrin, a component of Indigo naturalis. CONCLUSIONS: This study demonstrated the clinical efficacy of Indigo naturalis in moderate psoriasis, and exemplified a novel experimental medicine approach to understand TCM targeting mechanisms. TRIAL REGISTRATION: NCT01901705 .
Assuntos
Indigofera/química , Interleucina-17/imunologia , Extratos Vegetais/administração & dosagem , Psoríase/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Interleucina-17/genética , Masculino , Pessoa de Meia-Idade , Psoríase/genética , Psoríase/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The aging process, including physical dysfunction and age-related memory impairment (AMI), are considered to be correlated with cumulative oxidative damages and insulin/IGF-1 signaling pathway. PURPOSE: The present study was to elucidate the in vivo effects on delaying aging and ameliorating AMI and underlying molecular mechanisms of Cistanche tubulosa (CT), a herb used in traditional Chinese medicine to improve sexual function and treat kidney dysfunction. METHODS: The flies, treated and untreated with CT, were observed for lifespan, resistance to oxidative stress with H2O2 or paraquat, starvation assay, cognitive behaviors with T-maze, and transcript levels of target genes with quantitative RT-PCR. RESULTS: Administering CT extended the mean and maximum lifespan and increased resistance to oxidative stress in flies. CT supplementation also enhanced memory formation in young flies and suppressed AMI upon aging. Several genes and signaling pathways, including the mechanistic target of rapamycin (mTOR) and Notch networks, have been identified as causing these pharmacological effects and alterations in the gene expression of glutamate receptors. CONCLUSION: Our results indicate that CT supplementation may contribute to slowing aging phenotypes and alleviating cognitive behavioral decline in flies, indicating potential applicability for enhancing human health and reducing susceptibility to age-related disorders.