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1.
PeerJ ; 10: e13636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915752

RESUMO

Aims: To investigate the quality of care and prescription patterns of patients with diabetic kidney disease (DKD) receiving primary care at local clinics in Taiwan. Methods: A retrospective chart review was conducted in 43 primary care clinics in Taiwan. The patients' baseline characteristics, laboratory tests, presence of complications and antidiabetic agents prescribed were analyzed. Results: 7,200 patients with type 2 diabetes mellitus were enrolled. Percentage of HbA1c, blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) goals reached were 52.5% in HbA1c < 7%, 40.9% in BP < 130/80 mmHg and 79.7% in LDL-C < 2.59 mmol/L. 18.3% achieved all three ABC goals. However, patients with DKD had a lower rate of ABC goal attainment and higher rate of complications. Among DKD patients with eGFR ≥ 30 ml/min/1.73 m2 and on monotherapy, metformin was most frequently prescribed. As for dual therapy, the most common combinations were metformin with sulfonylurea and metformin with DPP-4 inhibitors. Conclusions: Diabetes patients in Taiwan receiving primary diabetes care at local clinics had generally satisfactory management performance. However, more aggressive HbA1c, BP, and LDL-C management among DKD patients should be emphasized. Contrary to current recommendations, SGLT-2 inhibitors and GLP-1 receptor agonists as frontline therapy were under-prescribed.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Metformina , Humanos , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Hemoglobinas Glicadas , LDL-Colesterol , Estudos de Coortes , Estudos Retrospectivos , Metformina/uso terapêutico
2.
J Tissue Viability ; 26(3): 202-207, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28454680

RESUMO

Zerumbone is a monocyclic sesquiterpene compound. Based on report, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The study was undertaken to evaluate the therapeutic effects of topical zerumbone on excision wounds in rats. A 1% (w/w) simple ointment containing zerumbone was applied topically (100 mg ointment per rat) once a day on full-thickness excision wounds created on rats. The wound tissue was removed and used for estimation of antioxidant activity and to observe histopathological changes. Immunohistochemical staining was performed to study the expression pattern of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1 and collagen IV. Zerumbone exhibited antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans and Candida tropicali. Zerumbone ointment has potent wound healing capacity as evident from the wound contraction on 15th post wounding day. The histopathological examinations of healed wound sections showed greater tissue regeneration, more fibroblasts and angiogenesis in zerumbone ointment-treated group. VEGF, TGF-ß1 and collagen IV expression were also correlative with the healing pattern observed. Zerumbone possesses potent antioxidant activity by increasing superoxide dismutase, catalase, glutathione and decreased lipid peroxidation. The synergistic effects of both antimicrobial and antioxidant activities in zerumbone are deduced to have accelerated the wound repair. The results demonstrate that zerumbone possessed strong wound healing potential and can be exploited to accelerate excision wound healing.


Assuntos
Sesquiterpenos/farmacologia , Cicatrização/fisiologia , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colágeno/análise , Colágeno/sangue , MAP Quinase Quinase Quinases/análise , MAP Quinase Quinase Quinases/sangue , Masculino , Pomadas/administração & dosagem , Pomadas/uso terapêutico , Ratos , Ratos Wistar/sangue , Sesquiterpenos/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/sangue
3.
Molecules ; 21(12)2016 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-27973425

RESUMO

Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects.


Assuntos
Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Microvasos/efeitos dos fármacos , Vasos Retinianos/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Fator de Transcrição RelA/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Permeabilidade Capilar/efeitos dos fármacos , Fenofibrato/análogos & derivados , Fenofibrato/uso terapêutico , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Masculino , Microvasos/lesões , Ratos , Ratos Wistar , Retina/efeitos dos fármacos , Vasos Retinianos/lesões , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Fator de Transcrição RelA/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Nutrients ; 8(9)2016 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-27649243

RESUMO

Plantaginis semen, the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd. (Plantaginaceae), has been traditionally used to treat blurred vision in Asia. The aim of this work was to investigate the effect of plantaginis semen ethanol extract (PSEE) on the amelioration of diabetic retinopathy (DR) in streptozotocin (STZ)-diabetic rats. PSEE has abundant polyphenols with strong antioxidant activity. PSEE (100, 200 or 300 mg/kg) was oral administrated to the diabetic rats once daily consecutively for 8 weeks. Oral administration of PSEE resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and retinal vascular permeability and leukostasis in diabetic rats. In addition, PSEE administration increased the activities of superoxidase dismutase (SOD) and catalase (CAT), and glutathione peroxidase (GSH) level in diabetic retinae. PSEE treatment inhibited the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) and the phosphorylation of Akt without altering the Akt protein expression in diabetic retinae. PSEE not only down-regulated the gene expression of hypoxia-inducible factor-1α (TNF-α) and interleukin-1ß (IL-1ß), but also reduced ICAM-1 and VCAM-1 expression in diabetic retinae. Moreover, PSEE reduced the nuclear factor-κB (NF-κB) activation and corrected imbalance between histone deacetylases (HDAC) and histone acetyltransferases (HAT) activities in diabetic retinae. In conclusion, phenolic antioxidants extract from plantaginis semen has potential benefits in the prevention and/or progression of DR.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Extratos Vegetais/farmacologia , Plantago/química , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Glutationa Peroxidase/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Hiperglicemia/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Polifenóis/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Retina/efeitos dos fármacos , Retina/metabolismo , Vasos Retinianos/efeitos dos fármacos , Vasos Retinianos/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Nutrients ; 8(8)2016 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-27463726

RESUMO

Diabetic retinopathy (DR), the most ordinary and specific microvascular complication of diabetes, is a disease of the retina. Zerumbone (ZER) is a monocyclic sesquiterpene compound, and based on reports, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The aim of the current study is to evaluate the protective effect of zerumbone against DR in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were treated with ZER (40 mg/kg) once a day orally for 8 weeks. ZER administration significantly (p < 0.05) lowered the levels of plasma glucose (32.5% ± 5.7% lower) and glycosylated hemoglobin (29.2% ± 3.4% lower) in STZ-diabetic rats. Retinal histopathological observations indicated that disarrangement and reduction in thickness of retinal layers were reversed in ZER-treated diabetic rats. ZER downregulated both the elevated levels of advanced glycosylated end products (AGEs) and the higher levels of the receptors for AGEs (RAGE) in retinas of diabetic rats. What's more, ZER significantly (p < 0.05) ameliorated diabetes-induced upregulation of tumor necrosis factor-α, interleukin (IL)-1 and IL-6. ZER also attenuated overexpression of vascular endothelial growth factor and intercellular adhesion molecule-1, and suppressed activation of nuclear factor (NF)-κB and apoptosis in the retinas of STZ-diabetic rats. Our results suggest ZER possesses retinal protective effects, which might be associated with the blockade of the AGEs/RAGE/NF-κB pathway and its anti-inflammatory activity.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Retinopatia Diabética/prevenção & controle , Suplementos Nutricionais , Hipoglicemiantes/uso terapêutico , Rizoma/química , Sesquiterpenos/uso terapêutico , Zingiberaceae/química , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores/sangue , Biomarcadores/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/imunologia , Hemoglobinas Glicadas/análise , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/sangue , Hiperglicemia/prevenção & controle , Molécula 1 de Adesão Intercelular/química , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Distribuição Aleatória , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/agonistas , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Retina/imunologia , Retina/metabolismo , Retina/patologia , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fatores de Crescimento do Endotélio Vascular/metabolismo
6.
Vascul Pharmacol ; 76: 18-27, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26319672

RESUMO

Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the ethanol extract from Zingiber zerumbet (L.) Smith rhizome (EEZZR) has been indicated to ameliorate hyperglycemia in diabetes, its protective effect on DR remains unclear. The aim of this study was to determine the effects of EEZZR on DR in streptozotocin (STZ) diabetic rats. Diabetic rats were treated orally with EEZZR (200, 300 mg/kg per day) or calcium dobesilate (CD; 500 mg/kg per day) for 12 weeks. EEZZR displayed similar characteristics to CD in reducing blood-retinal barrier permeability in diabetic rats. Retinal histopathological observation showed that retinal vessels were decreased in EEZZR-treated diabetic rats. EEZZR decreased the increased retinal expression of vascular endothelial growth factor (VEGF) and upregulate the expressions of renal pigment epithelium-derived factor (PEDF) in diabetic rats. Retinal mRNA expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6, monocyte chemotactic proteins-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in EEZZR-treated diabetic rats. Moreover, EEZZR could attenuate phosphorylation of nuclear factor Kappa B (NF-κB) p65 and extracellular signal-regulated kinase (ERK)1/2 as well as inhibit the nuclear translocation of pNF-κB p65 induced by diabetes. In conclusion, restoring the balance between stimulators and inhibitors of angiogenesis may be associated with the protective effect of EEZZR on DR. In addition, EEZZR can ameliorate retinal inflammation via transrepression of NF-κB and inhibition of ERK1/2 signaling pathway.


Assuntos
Etanol/química , Extratos Vegetais/farmacologia , Retina/efeitos dos fármacos , Vasos Retinianos/efeitos dos fármacos , Rizoma/química , Zingiberaceae/química , Animais , Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas do Olho/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo , Fatores de Crescimento Neural/metabolismo , Ratos , Ratos Wistar , Retina/metabolismo , Vasos Retinianos/metabolismo , Serpinas/metabolismo , Estreptozocina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Nutrients ; 7(10): 8670-84, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26506376

RESUMO

Nonalcoholic steatohepatitis (NASH) is characterized as fat accumulation in the hepatic tissue associated with various degrees of inflammation and progressive fibrosis. The potent anti-inflammatory and ethnopharmacological properties of Lonicera japonica Thunb. (Caprifoliaceae) make it an excellent source of novel medicinal targets for the treatment of NASH. The aim of the study was to investigate the effects of L. japonica ethanol extract (LJEE) on NASH in mice. C57BL/6J mice were fed with methionine-choline-deficient diet (MCDD) for eight weeks to promote the development of NASH. After development of the model, the mice were administered LJEE once daily via oral gavage at doses of 100, 200, or 300 mg/kg for another four weeks. Simultaneous treatments with LJEE (300 mg/kg/day) resulted in pronounced improvements in liver steatosis, ballooning degeneration, and inflammation. LJEE prevented MCDD-induced plasma level increases in aspartate aminotransferase and alanine aminotransferase. LJEE significantly reduced hepatic malondialdehyde level and ameliorated hepatic inflammation and fibrosis in MCDD-fed mice, which were associated with down-regulation of cytochrome P450 2E1 suppression of multiple proinflammatory and profibrotic genes. LJEE can prevent hepatic steatosis by reducing hepatic peroxisome acyl-CoA:diacylglycerol acyltransferase 2 expression, as well as by inducing proliferator-activated receptor α expression. In addition, the LJEE treatments caused significant reduction in the phosphorylated form of Jun N-terminal kinase along with an increase in the phosphorylated level of extra cellular signal-regulated kinase 1/2. Our study demonstrated the protective role of LJEE in ameliorating nutritional steatohepatitis.


Assuntos
Fígado/efeitos dos fármacos , Lonicera , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Deficiência de Colina/complicações , Dieta/efeitos adversos , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Masculino , Metionina/administração & dosagem , Metionina/deficiência , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Extratos Vegetais/farmacologia , Transdução de Sinais
8.
Nutrients ; 7(9): 7821-41, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26389948

RESUMO

The present study investigates the amelioration of diabetic retinopathy (DR) by Zingiber zerumbet rhizome ethanol extracts (ZZRext) in streptozotocin-induced diabetic rats (STZ-diabetic rats). ZZRext contains high phenolic and flavonoid contents. STZ-diabetic rats were treated orally with ZZRext (200, 300 mg/kg per day) for three months. Blood-retinal barrier (BRB) breakdown and increased vascular permeability were found in diabetic rats, with downregulation of occludin, and claudin-5. ZZRext treatment effectively preserved the expression of occludin, and claudin-5, leading to less BRB breakdown and less vascular permeability. Retinal histopathological observation showed that the disarrangement and reduction in thickness of retinal layers were reversed in ZZRext-treated diabetic rats. Retinal gene expression of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, vascular endothelial growth factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in ZZRext-treated diabetic rats. Moreover, ZZRext treatment not only inhibited the nuclear factor κB (NF-κB) activation, but also downregulated the protein expression of p38 mitogen-activated protein kinase (MAPK) in diabetic retina. In conclusion, the results suggest that the retinal protective effects of ZZRext occur through improved retinal structural change and inhibiting retinal inflammation. The antiretinopathy property of ZZRext might be related to the downregulation of p38 MAPK and NF-κB signal transduction induced by diabetes.


Assuntos
Anti-Inflamatórios/farmacologia , Barreira Hematorretiniana/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Zingiberaceae , Animais , Anti-Inflamatórios/isolamento & purificação , Barreira Hematorretiniana/metabolismo , Barreira Hematorretiniana/patologia , Claudina-5/metabolismo , Citoproteção , Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/etiologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Relação Dose-Resposta a Droga , Mediadores da Inflamação/metabolismo , Masculino , Ocludina/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Polifenóis/isolamento & purificação , Ratos Wistar , Rizoma , Transdução de Sinais/efeitos dos fármacos , Zingiberaceae/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Phytomedicine ; 22(4): 452-61, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25925967

RESUMO

The aim of the study was to investigate the effects of [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) in experimental models of non-alcoholic steatohepatitis. HepG2 cells were exposed to 500 µmol/l oleic acid (OA) for 24 h and preincubated for an additional 24 h with [6]-gingerol (25, 50 or 100 µmol/l). [6]-Gingerol (100 µmol/l) inhibited OA-induced triglyceride and inflammatory marker accumulation in HepG2 cells. After being fed a high-fat diet (HFD) for 2 weeks, male golden hamsters were dosed orally with [6]-gingerol (25, 50 or 100 mg/kg/day) once daily for 8 weeks while maintained on HFD. [6]-Gingerol (100 mg/kg/day) alleviated liver steatosis, inflammation, and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. The expression of inflammatory cytokine genes and nuclear transcription factor-κB (NF-κB) were increased in the HFD group; these effects were attenuated by [6]-gingerol. The hepatic mRNA expression of lipogenic genes such as liver X receptor-α, sterol regulating element binding protein-1c and its target genes including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase 1, and acyl-CoA:diacylglycerol acyltransferase 2 in HFD-fed hamsters was also blocked by [6]-gingerol. [6]-Gingerol may attenuate HFD-induced steatohepatitis by downregulating NF-κB-mediated inflammatory responses and reducing hepatic lipogenic gene expression.


Assuntos
Catecóis/farmacologia , Álcoois Graxos/farmacologia , Inflamação/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Colesterol/metabolismo , Cricetinae , Citocinas/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Triglicerídeos/metabolismo
10.
Nutrients ; 7(2): 999-1020, 2015 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-25658238

RESUMO

Non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), appears to be increasingly common worldwide. The aim of the study was to investigate the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone), a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of NASH. In HepG2 cells, 6-gingerol (100 µmol/L) treatment inhibited free fatty acids mixture (0.33 mmol/L palmitate and 0.66 mmol/L oleate)-induced triglyceride and inflammatory marker accumulations. Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet to induce steatohepatitis. After four weeks of MCD diet feeding, the mice were dosed orally with 6-gingerol (25, 50 or 100 mg/kg/day) once daily for another four weeks. 6-Gingerol (100 mg/kg/day) attenuated liver steatosis and necro-inflammation in MCD diet-fed mice. The expressions of inflammatory cytokine genes, including those for monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and nuclear transcription factor (NF-κB), which were increased in the livers of MCD diet-fed mice, were attenuated by 6-gingerol. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with induction of peroxisome proliferator-activated receptor α. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to lipid metabolism and inflammation.


Assuntos
Catecóis/farmacologia , Álcoois Graxos/farmacologia , Inflamação/dietoterapia , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Extratos Vegetais/farmacologia , Animais , Catecóis/administração & dosagem , Quimiocina CCL2/genética , Deficiência de Colina , Modelos Animais de Doenças , Álcoois Graxos/administração & dosagem , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/genética , Inflamação/induzido quimicamente , Interleucina-6/genética , Metabolismo dos Lipídeos/genética , Masculino , Metionina/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/administração & dosagem , Fator de Necrose Tumoral alfa/genética
11.
Biomed Res Int ; 2014: 652680, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25136608

RESUMO

The aim of the study was to investigate the protective effects of ruscogenin, a major steroid sapogenin in Ophiopogon japonicus, on experimental models of nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 µmol/l palmitic acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h. Ruscogenin (10.0 µmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis. Gene expression of inflammatory cytokines, chemoattractive mediator, nuclear transcription factor-(NF-) κB, and α-smooth muscle actin were increased in the HFD group, which were attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-κB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins in ß-oxidation pathway.


Assuntos
Inflamação/tratamento farmacológico , Lipogênese/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Espirostanos/administração & dosagem , Animais , Cricetinae , Dieta Hiperlipídica , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Inflamação/genética , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/genética , Masculino , Mesocricetus , Redes e Vias Metabólicas/efeitos dos fármacos , NF-kappa B/biossíntese , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Mensageiro/biossíntese , Fator de Necrose Tumoral alfa/biossíntese
12.
BMC Complement Altern Med ; 14: 156, 2014 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-24886259

RESUMO

BACKGROUND: The polysaccharides from Liriopes Radix (PSLR) has been indicated to ameliorate insulin signaling transduction and glucose metabolism. We aimed to investigate whether PSLR exerts an ameliorative effect on renal damage in diabetes induced by streptozotocin. METHODS: Diabetes was induced with STZ (60 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats in the treatment group were orally dosed with PSLR (200 and 300 mg/kg/day for 8 weeks. The normal rats were chosen as nondiabetic control group. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses. RESULTS: Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight. All of these abnormalities were significantly reversed by PSLR. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with PSLR. The less protein expressions of renal nephrin and podocin in diabetic rats were increased following treatment with PSLR. PSLR reduced the accumulation of ED-1-expressing macrophages in renal tissue of diabetic rats. PSLR almost completely abolished T cells infiltration and attenuated the expression of proinflammatory cytokines. PSLR treatments not only reduced the degradation of inhibitory kappa B kinase, but also downregulated the protein expression of nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) in diabetic kidney. CONCLUSIONS: The results suggest that the renal protective effects of PSLR occur through improved glycemic control and renal structural changes, which are involved in the inhibition of NF-κB and p-38 MAPK mediated inflammation.


Assuntos
Nefropatias Diabéticas/prevenção & controle , Liliaceae/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Inflamação/metabolismo , Insulina/metabolismo , Rim/efeitos dos fármacos , Masculino , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Ratos , Ratos Wistar , Transdução de Sinais , Estreptozocina
13.
Food Chem Toxicol ; 69: 132-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24709573

RESUMO

We investigated the effects of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on high-fat diet (HFD)-induced hyperlipidemic hamsters. After being fed HFD for 2 weeks, Syrian golden hamsters were dosed orally with zerumbone (25, 50, and 100 mg/kg) once daily for 8 weeks. Decreased plasma levels of TC, TG and LDL-C, as well as the concentrations of hepatic lipids, with a simultaneous increase in fecal lipids were found. The ratios of LDL-C/HDL-C and TC/HDL-C were elevated by zerumbone. Zerumbone exhibited the ability to decreased hepatic mRNA levels of fatty acid synthase, malic enzyme, sterol-regulatory element binding protein and 3-hydroxy-3-methyl-glutaryl-CoA reductase reductase. The hepatic mRNA expression of peroxisome proliferator-activated receptor α, together with its target gene carnitine palmitoyl transferase and acyl-CoA oxidase were also upregulated by zerumbone. Zerumbone is effective to improve dyslipidemia by modulating the genes expression involving in the lipolytic and lipogenic pathways of lipids metabolism.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Sesquiterpenos/farmacologia , Zingiberaceae/química , Animais , Peso Corporal/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/genética , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Fezes , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/induzido quimicamente , Lipase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Lipólise/efeitos dos fármacos , Lipólise/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Mesocricetus , Sesquiterpenos/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
14.
BMC Complement Altern Med ; 14: 110, 2014 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-24666993

RESUMO

BACKGROUND: Ruscogenin is a major steroid sapogenin in the traditional Chinese herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have demonstrated that ruscogenin is involved in down-regulation of intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) activation in anti-inflammatory pathways. We hypothesized that ruscogenin protects against diabetic nephropathy (DN) by inhibiting NF-κB-mediated inflammatory pathway. To test this hypothesis, the present study was to examine the effects of ruscogenin in rats with streptozotocin (STZ)-induced DN. METHODS: Diabetes was induced with STZ (60 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats in the treatment group were orally dosed with 0.3, 1.0 or 3.0 mg/kg ruscogenin for 8 weeks. The normal rats were chosen as nondiabetic control group. The rats were sacrificed 10 weeks after induction of diabetes. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses. RESULTS: Ruscogenin administration did not lower the levels of plasma glucose and glycosylated hemoglobin in STZ-diabetic rats. Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight, that were reversed by ruscogenin. Ruscogenin treatment was found to markedly improve histological architecture in the diabetic kidney. Renal NF-κB activity, as wells as protein expression and infiltration of macrophages were increased in diabetic kidneys, accompanied by an increase in protein content of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in kidney tissues. All of the above abnormalities were reversed by ruscogenin treatment, which also decreased the expression of transforming growth factor-ß1 and fibronectin in the diabetic kidneys. CONCLUSIONS: Our data demonstrated that ruscogenin suppressed the inflammation and ameliorated the structural and functional abnormalities of the diabetic kidney in rats might be associated with inhibition of NF-κB mediated inflammatory genes expression.


Assuntos
Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Rim/efeitos dos fármacos , Ophiopogon/química , Fitoterapia , Espirostanos/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Quimiocina CCL2/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Regulação para Baixo , Fibronectinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Rim/metabolismo , Masculino , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Transdução de Sinais , Espirostanos/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismo
15.
Planta Med ; 80(2-3): 121-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24431014

RESUMO

The anti-inflammatory potential of Lonicera japonica makes it an excellent source of novel medicinal targets to reduce inflammation in diabetic nephropathy. We aimed to investigate whether the ethanol extract of the flowering aerial parts of L. japonica exerts an ameliorative effect on diabetic renal inflammation using streptozotocin-induced diabetic rats. Diabetic rats were treated orally with the ethanol extract of the flowering aerial parts of L. japonica (100 and 200 mg/kg/day) for 8 weeks. The rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen, and proteinuria, along with a marked elevation in the ratio of kidney weight to body weight; all of these abnormalities were significantly reversed by the ethanol extract of the flowering aerial parts of L. japonica. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with the ethanol extract of the flowering aerial parts of L. japonica. It reduced the accumulation of ED-1-expressing macrophages in renal tissue of diabetic rats, almost completely abolished T cell infiltration and attenuated the expression of proinflammatory cytokines. The ethanol extract of the flowering aerial parts of L. japonica downregulated the protein expression of p38 mitogen-activated protein kinase in the kidney of diabetic rats. The results suggest that it has the property to inhibit the activity of p-38 MAPK-mediated inflammatory response to halt the progression of diabetic nephropathy.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Lonicera/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Rim/efeitos dos fármacos , Rim/patologia , Extratos Vegetais/uso terapêutico , Ratos
16.
Phytother Res ; 28(2): 187-92, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23519881

RESUMO

We investigated the effects of 6-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) on the inhibition of rosiglitazone (RGZ)-induced adipogenesis in 3T3-L1 cells. The morphological changes were photographed based on staining lipid accumulation by Oil-Red O in RGZ (1 µmol/l)-treated 3T3-L1 cells without or with various concentrations of 6-gingerol on differentiation day 8. Quantitation of triglycerides content was performed in cells on day 8 after differentiation induction. Differentiated cells were lysed to detect mRNA and protein levels of adipocyte-specific transcription factors by real-time reverse transcription-polymerase chain reaction and Western blot analysis, respectively. 6-gingerol (50 µmol/l) effectively suppressed oil droplet accumulation and reduced the sizes of the droplets in RGZ-induced adipocyte differentiation in 3T3-L1 cells. The triglyceride accumulation induced by RGZ in differentiated 3T3-L1 cells was also reduced by 6-gingerol (50 µmol/l). Treatment of differentiated 3T3-L1 cells with 6-gingerol (50 µmol/l) antagonized RGZ-induced gene expression of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein α. Additionally, the increased levels of mRNA and protein in adipocyte-specific fatty acid binding protein 4 and fatty acid synthase induced by RGZ in 3T3-L1 cells were decreased upon treatment with 6-gingerol. Our data suggests that 6-gingerol may be beneficial in obesity, by reducing adipogenesis partly through the down-regulating PPARγ activity.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Catecóis/farmacologia , Álcoois Graxos/farmacologia , Tiazolidinedionas/efeitos adversos , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Camundongos , Obesidade , PPAR gama/antagonistas & inibidores , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rosiglitazona , Triglicerídeos/metabolismo
17.
Food Chem Toxicol ; 65: 33-42, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24342243

RESUMO

The beneficial effects of the ethanol extract of Zingiber zerumbet rhizome (EEZZR) for use in the treatment of non-alcoholic fatty liver disease (NAFLD) were investigated. Syrian golden hamsters were fed a high-fat diet to induce NAFLD. EEZZR (100, 200, or 300mg/kg) were orally administered by gavage once daily for 8weeks. The higher plasma levels of total cholesterol, triglycerides, free fatty acids, and hepatic lipids, as well as the degree of insulin resistance were lowered by EEZZR. Histological evaluation of liver specimens demonstrated that the hepatic steatosis of EEZZR-treated groups was improved. EEZZR decreased hepatic mRNA levels of sterol regulatory element-binding protein-1c and its lipogenic target genes. The hepatic mRNA expression of peroxisome proliferator-activated receptor α, together with its target genes responsible for ß-oxidation of fatty acids were also upregulated by EEZZR. In conclusion, these findings suggest that EEZZR has the promising potential to ameliorate NAFLD.


Assuntos
Dieta Hiperlipídica , Fígado Gorduroso/prevenção & controle , Extratos Vegetais/farmacologia , Zingiberaceae/química , Animais , Sequência de Bases , Cricetinae , Citocinas/sangue , Primers do DNA , Etanol/química , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mesocricetus , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais/uso terapêutico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-24223615

RESUMO

We investigated the effects of zerumbone, a natural cyclic sesquiterpene, on hepatic lipid metabolism in Syrian golden hamsters fed on high-fat diet (HFD). After being fed HFD for 2 weeks, hamsters were dosed orally with zerumbone (75, 150, and 300 mg kg(-1)) once daily for 8 weeks. After treatment with zerumbone, the plasma levels of total cholesterol (TC) and triglycerides (TGs) and the contents of TC and TG in hepatic tissue as well as homeostasis model assessment of insulin resistance were lowered, especially in the zerumbone-treated group (300 mg kg(-1)). Moreover, the histological evaluation of liver specimens demonstrated that the steatosis and inflammation in liver of zerumbone-treated groups were improved. Zerumbone exhibited the ability to decrease hepatic mRNA levels of sterol regulatory element-binding protein-1c and its lipogenic target genes, such as fatty acid synthase, acetyl-CoA carboxylase 1, and stearoyl-CoA desaturase 1. The hepatic mRNA expression of peroxisome proliferator-activated receptor α , together with its target genes including carnitine palmitoyl transferase-1, acyl-CoA oxidase, and acyl-CoA oxidase 1, was also upregulated by zerumbone. In conclusion, zerumbone improves insulin sensitivity, decreases lipogenesis, and increases lipid oxidation in the liver of HFD-fed hamsters, implying a potential application in the treatment of nonalcoholic fatty liver disease.

19.
Artigo em Inglês | MEDLINE | ID: mdl-24027593

RESUMO

The tuberous root of Liriope spicata var. prolifera (TRLS; Liliaceae family) is valued for the ability to promote glucose homeostasis, and it may therefore be utilized as an adjuvant therapy in the control of diabetic complications. The aim of the present study was to examine the effects of an aqueous ethanol extract from TRLS (TRLS-ext) (100 or 200 mg kg(-1) per day for eight weeks) on rats with streptozotocin-induced diabetic nephropathy (DN). Renal dysfunction in diabetic rats was ameliorated by TRLS-ext as evidenced by reduced creatinine clearance, as well as increased blood urea nitrogen and proteinuria. Treatment with TRLS-ext was found to markedly improve histological architecture in the diabetic kidney. Hyperglycemia induced degradation of inhibitory kappa B and reduced nuclear factor kappa B activation, leading to increased infiltration of macrophages and increased levels of proinflammatory cytokines, including interleukin-1 and tumor necrosis factor- α . All of the above abnormalities were reversed by TRLS-ext treatment, which also decreased the expression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and fibronectin in the diabetic kidneys. These findings provide a perspective on the renoprotective effects of TRLS-ext in DN.

20.
Planta Med ; 79(8): 616-21, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23568627

RESUMO

This study was undertaken to evaluate the therapeutic effects of topical chlorogenic acid on excision wounds in Wistar rats. A 1 % (w/w) chlorogenic acid or silver sulfadiazine ointment was applied topically once a day for 15 days on full-thickness excision wounds created on rats. The 1 % (w/w) chlorogenic acid ointment had potent wound healing capacity as evident from the wound contraction on the 15th post-surgery day, which was similar to that produced by 1 % (w/w) silver sulfadiazine ointment. Increased rates of epithelialization were observed in the treated rats. It also improved cellular proliferation, increased tumor necrosis factor-α levels during the inflammatory phase (12 h, 24 h, 48 h, and 72 h post-wounding) of wound healing, upregulated transforming growth factor-ß1 and elevated collagen IV synthesis in the chlorogenic acid-treated group. The results also indicated that chlorogenic acid possesses potent antioxidant activity by increasing superoxide dismutase, catalase, and glutathione, and decreasing lipid peroxidation. In conclusion, these results demonstrate that topical application of chlorogenic acid can accelerate the process of excision wound healing by its ability to increase collagen synthesis through upregulation of key players such as tumor necrosis factor-α and transforming growth factor-ß1 in different phases of wound healing as well as by its antioxidant potential.


Assuntos
Antioxidantes/farmacologia , Ácido Clorogênico/farmacologia , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Proliferação de Células , Colágeno Tipo IV/biossíntese , Masculino , Pomadas , Ratos , Ratos Wistar , Sulfadiazina de Prata/administração & dosagem , Fator de Crescimento Transformador beta1/biossíntese , Fator de Necrose Tumoral alfa/metabolismo
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