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1.
Food Sci Nutr ; 12(1): 116-130, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268910

RESUMO

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.

2.
Heliyon ; 9(5): e15406, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37144207

RESUMO

Alzheimer's disease (AD) is one of the neurodegenerative disorders, the hallmarks of which include deposits of extracellular beta-amyloid (Aß) as well as intracellular tau neurofibrillary tangles (NFTs) tangles. With disease progression, neuronal apoptosis combined with cerebral atrophy occurs, leading to cognitive impairment and long-term memory loss. Recently, Chlorella species have been identified as a functional food and are being explored for the prevention of various diseases widely studied to prevent or treat many neurodegenerative diseases. Hence, we for the first time investigated the neuroprotective effects of Chlorella pyrenoidosa short-chain peptides (CPPs) i.e. <1 kDa, 1-3 kDa, 3-10 kDa, and >10 kDa on the in vitro and in vivo neuronal injury models. Our in vitro results showed that CPP with a molecular weight of 1-3 kDa and 3-10 kDa could elevate the survival rate of Aß1-42 or l-Glutamic acid-injured N2A cells. These treatments also inhibited Aß and tau NFTs in N2A cells and prevented progressive neuronal cellular damage by suppressing inflammatory cytokines such as PGE2, iNOS, IL-6, TNF-α, COX-2, IL-1ß, TGF-ß1, and NF-κB. Further, our in vivo Aß1-42-induced AD mice model demonstrated that 1-3 kDa or 3-10 kDa CPP could improve spatial cognition and learning memory. We also observed a decreased cell loss ratio in CA1-CA3 hippocampal regions. Taken together, our findings imply that CPPs may exert their anti-AD impact through anti-inflammatory, and anti-amyloid activities via reducing APP and tau NFT.

3.
Int J Mol Sci ; 24(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36901874

RESUMO

Diabetes nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) globally. Medication options to stop or slow the progression of chronic renal disease (CKD) are limited, and patients with DN remain at a high risk of developing renal failure. Inonotus obliquus extracts (IOEs) of Chaga mushroom have been shown to have anti-glycemic, anti-hyperlipidemia, antioxidant, and anti-inflammatory effects against diabetes. In this study, we examined the potential renal protective role of an ethyl acetate layer after water-ethyl acetate separation from Inonotus obliquus ethanol crude extract (EtCE-EA) from Chaga mushrooms in diabetic nephropathy mice after preparation with 1/3 NT + STZ. Our data showed that treatment with EtCE-EA can effectively regulate blood glucose, albumin-creatinine ratio, serum creatinine, and blood urea nitrogen (BUN) levels, and it can improve the renal damage in 1/3 NT + STZ-induced CRF mice with an increase in concentration (100, 300, and 500 mg/kg). In the immunohistochemical staining test, EtCE-EA can effectively reduce the expression of TGF-ß and α-SMA after induction according to the increase in the concentration (100 mg/kg, 300 mg/kg), thereby slowing down the degree of kidney damage. Our findings demonstrate that EtCE-EA could provide renal protection in diabetes nephropathy, possibly due to the decreased expression of transforming growth factor-ß1 and α-smooth muscle actin.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Camundongos , Animais , Nefropatias Diabéticas/metabolismo , Estreptozocina/farmacologia , Rim/metabolismo , Nefrectomia/efeitos adversos , Diabetes Mellitus/metabolismo
4.
Cartilage ; 13(4): 157-170, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36250247

RESUMO

OBJECTIVE: Osteoarthritis (OA) progression has been shown to increase the expression of inflammatory cytokines in joints, leading to the destruction of cartilage matrix. Interleukin (IL)-1ß is a potent inflammatory cytokine associated with osteoarthritic synovial fluid. The protective effects of polysaccharides from Enteromorpha prolifera against acute hepatic injury was reported. DESIGN: In this study, we examined the effects of Enteromorpha polysaccharide extracts (EPEs) in the treatment of OA. The effects of the EPEs were assessed using an IL-1ß-stimulated SW1353 and SW982 cells. The expression levels of specific mRNA and proteins were evaluated using semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and western immunoblotting. An OA animal study involving C57BL/6J mice was also conducted to assess the effects on tactile sensitivity and anterior cruciate ligament transection (ACLT). RESULTS: Acidic polysaccharide extract (APE) was shown to significantly reduce cytokine and chemokine mRNA levels in IL-1ß-stimulated SW1353 and SW982 cells and attenuate the expression of proinflammatory cytokines and p38/AP-1 in SW1353 cells. APE was also shown to minimize the effect of osteolytic lesions in the knee joints of ACLT-induced osteoarthritic mice. CONCLUSIONS: APE is a potent inhibitor of joint degeneration associated with OA.


Assuntos
Condrócitos , Osteoartrite , Camundongos , Animais , Condrócitos/metabolismo , Camundongos Endogâmicos C57BL , Osteoartrite/metabolismo , Anti-Inflamatórios/metabolismo , Citocinas/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Polissacarídeos/uso terapêutico , RNA Mensageiro/metabolismo , Modelos Teóricos
5.
Toxicology ; 456: 152750, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-33737140

RESUMO

Paraquat, an herbicide used extensively worldwide, can cause severe toxicity in humans and animals, leading to irreversible, lethal lung fibrosis. The potential of CO-releasing molecules (CORMs), substances that release CO (Carbon monoxide) within animal tissues, for treating paraquat-induced ROS generation and inflammation is investigated here. Our results show that the fast CO releaser CORM-3 (4-20 µM) acts as a potential scavenger of free radicals and decreases fibrosis progression by inhibiting paraquat-induced overexpression of connective tissue growth factor and angiotensin II in MRC-5 cells. The slow CO releaser CORM-A1 (5 mg/kg) clearly decreased expression of the lung profibrogenic cytokines COX-2, TNF-α, and α-SMA and serum hydroxyproline, resulting in a lower mortality rate in paraquat-treated mice. Mice treated with higher-dose CORM-A1 (10 mg/kg) had relatively intact lung lobes and fewer fibrotic patches by gross observation, with less collagen deposition, mesangial matrix accumulation, and pulmonary fibrosis resulting from the mitigation of TGF-ß overexpression. In conclusion, our data demonstrate for the first time that CORM-A1 alleviated the development of the fibrotic process and improved survival rate in mice exposed to PQ, would be an attractive therapeutic approach to attenuate the progression of pulmonary fibrosis following PQ exposure.


Assuntos
Boranos/uso terapêutico , Monóxido de Carbono , Carbonatos/uso terapêutico , Herbicidas/toxicidade , Doenças Pulmonares Intersticiais/induzido quimicamente , Paraquat/toxicidade , Fibrose Pulmonar/induzido quimicamente , Animais , Boranos/farmacologia , Monóxido de Carbono/metabolismo , Carbonatos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Distribuição Aleatória
6.
J Orthop Surg Res ; 13(1): 259, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30340603

RESUMO

BACKGROUND: Osteoarthritis (OA) is a slow progressing, degenerative disorder of the synovial joints. Guilu Erxian Glue (GEG) is a multi-component Chinese herbal remedy with long-lasting favorable effects on several conditions, including articular pain and muscle strength in elderly men with knee osteoarthritis. The present study aimed to identify the effects of Guilu Erxian Paste (GE-P) and Liquid (GE-L) extracted from Guilu Erxian Glue in anterior cruciate ligament transection (ACLT)-induced osteoarthritis mice, and to compare the effectiveness of different preparations on knee cartilage degeneration during the progression of osteoarthritis. METHODS: Male C57BL/6J mice underwent anterior cruciate ligament transection to induce mechanically destabilized osteoarthritis in the right knee. 4 weeks later, the mice were orally treated with PBS, celecoxib (10 mg/kg/day), Guilu Erxian Paste (100 or 300 mg/kg/day), and Guilu Erxian Liquid (100 or 300 mg/kg/day) for 28 consecutive days. Von Frey and open-field tests (OFT) were used to evaluate pain behaviors (mechanical hypersensitivity and locomotor performance). Narrowing of the joint space and osteophyte formation were examined radiographically. Inflammatory cytokine (IL-1ß, IL-6, and TNF-α) levels in the articular cartilage were determined by quantitative real-time PCR. Histopathological examinations were conducted to evaluate the severity and extent of the cartilage lesions. RESULTS: Guilu Erxian Paste and Guilu Erxian Liquid (300 mg/kg/day) were significantly more effective (p < 0.01) than celecoxib (10 mg/kg/day) in decreasing secondary allodynia when compared to the saline-treated group (#p < 0.05). Open-field tests revealed no significant motor dysfunction between the Guilu Erxian Paste- and Guilu Erxian Liquid-treated mice compared to the saline-treated mice. Radiographic findings also confirmed that the administration of Guilu Erxian Paste and Guilu Erxian Liquid (100 and 300 mg/kg/day) significantly and dose-dependently reduced osteolytic lesions and bone spur formation in the anterior cruciate ligament transection-induced osteoarthritis mice when compared to the saline-treated group. Notably, Guilu Erxian Liquid (100 mg/kg/day) treatment significantly reduced the mRNA levels of IL-1ß, IL-6, and TNF-α as well as relative the protein expression of IL-1ß and TNF-α to the effect of celecoxib. Guilu Erxian Paste and Guilu Erxian Liquid (300 mg/kg/day) markedly attenuated cartilage destruction, surface unevenness, proteoglycan loss, chondrocyte degeneration, and cartilage erosion in the superficial layers (##p < 0.01 and ###p < 0.001 respectively). CONCLUSIONS: As expected, our findings suggest that the anti-inflammatory effects of Guilu Erxian Liquid (GE-L), following marked decrease on both IL-1ß and TNF-α during the early course of post-traumatic osteoarthrosis (OA), may be of potential value in the treatment of osteoarthritis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite/tratamento farmacológico , Animais , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Citocinas/biossíntese , Citocinas/genética , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Osteólise/diagnóstico por imagem , Osteólise/tratamento farmacológico , Radiografia
8.
Int J Mol Sci ; 17(9)2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27649140

RESUMO

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM). Inonotus obliquus (IO) is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs) have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ)-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP), from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD) plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10-100 kDa, LIOP (300 mg/kg) had progressively increased their sensitivity to glucose (less insulin tolerance), reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR) compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-ß on renal cortex in mice. Consistently, three days of LIOP (100 µg/mL) incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1), while the levels of NF-κB and TGF-ß expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF-κB/TGF-ß1 signaling pathway in diabetic nephropathy mice.


Assuntos
Agaricales/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Polissacarídeos Fúngicos/administração & dosagem , Estreptozocina/efeitos adversos , Animais , Sobrevivência Celular , Células Cultivadas , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Carpóforos/metabolismo , Polissacarídeos Fúngicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/sangue , Células Mesangiais/citologia , Células Mesangiais/efeitos dos fármacos , Camundongos , Peso Molecular , Fator de Crescimento Transformador beta/metabolismo , Triglicerídeos/metabolismo
9.
J Diabetes Res ; 2015: 723190, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26258146

RESUMO

Diabetes mellitus (DM) is currently ranked among leading causes of death worldwide in which type 2 DM is reaching an epidemic proportion. Hypoglycemic medications for type 2 DM have either proven inadequate or posed adverse effects; therefore, the Chinese herbal products are under investigation as an alternative treatment. In this study, a novel combination of fruiting body and mycelia powder of herbal Cordyceps militaris number 1 (CmNo1) was administered to evaluate their potential hypoglycemic effects in high-fat diet- (HFD-) induced type 2 DM in C57BL/6J mice. Body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and blood biochemistry indexes were measured. Results indicated that CmNo1 lowered the blood glucose level by increasing insulin sensitivity, while no change in body weight was observed. Increased protein expression of IRS-1, pIRS-1, AKT, pAKT, and GLUT-4 in skeletal muscle and adipose tissue was found indicating restoration of insulin signaling. Additionally, PPAR-γ expression in adipose tissue restored the triglyceride and cholesterol levels. Finally, our results suggest that CmNo1 possesses strong hypoglycemic, anticholesterolemic, and antihypertriglyceridemic actions and is more economical alternate for DM treatment.


Assuntos
Glicemia/efeitos dos fármacos , Cordyceps , Diabetes Mellitus Tipo 2/metabolismo , Carpóforos , Hipoglicemiantes/farmacologia , Micélio , Preparações de Plantas/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Western Blotting , Colesterol/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/efeitos dos fármacos , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , PPAR gama/efeitos dos fármacos , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Triglicerídeos/metabolismo
10.
Biomed Res Int ; 2015: 159015, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26114099

RESUMO

Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.


Assuntos
Ansiedade/fisiopatologia , Arsênio/toxicidade , Transtorno Depressivo/fisiopatologia , Estresse Psicológico , Animais , Ansiedade/induzido quimicamente , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/induzido quimicamente , Transtorno Depressivo/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Receptor trkB/metabolismo , Natação
11.
Food Chem Toxicol ; 69: 347-56, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24751968

RESUMO

Momordica charantia Linn. (Cucurbitaceae), also called bitter melon, has traditionally been used as a natural anti-diabetic agent for anti-hyperglycemic activity in several animal models and clinical trials. We investigated the differences in the anti-diabetic properties and mechanism of action of Taiwanese M. charantia (MC) between type 1 diabetic (T1D) and type 2 diabetic (T2D) mice. To clarify the beneficial effects of MC, we measured non-fasting glucose, oral glucose tolerance, and plasma insulin levels in KK/HIJ mice with high-fat diet-induced diabetes (200 mg/kg/day of charantin-rich extract of MC [CEMC]) and in ICR mice with STZ-induced diabetes. After 8 weeks, all the mice were exsanguinated, and the expression of the insulin-signaling-associated proteins in their tissue was evaluated, in coordination with the protective effects of CEMC against pancreatic ß-cell toxicity (in vitro). Eight weeks of data indicated that CEMC caused a significant decline in non-fasting blood glucose, plasma glucose intolerance, and insulin resistance in the KK/HIJ mice, but not in the ICR mice. Furthermore, CEMC decreased plasma insulin and promoted the sensitivity of insulin by increasing the expression of GLUT4 in the skeletal muscle and of IRS-1 in the liver of KK/HIJ mice; however, CEMC extract had no effect on the insulin sensitivity of ICR mice. In vitro study showed that CEMC prevented pancreatic ß cells from high-glucose-induced cytotoxicity after 24 h of incubation, but the protective effect was not detectable after 72 h. Collectively, the hypoglycemic effects of CEMC suggest that it has potential for increasing insulin sensitivity in patients with T2D rather than for protecting patients with T1D against ß-cell dysfunction.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Momordica charantia/química , Extratos Vegetais/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/química , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Camundongos Endogâmicos ICR , Camundongos Endogâmicos , Extratos Vegetais/química
12.
Chin Med ; 7(1): 24, 2012 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-23134744

RESUMO

BACKGROUND: Xiao-Yao-San (XYS) is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES) to extract the major active components of XYS and enhance their psycho-pharmacological effects. METHODS: The neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM) test and the antidepressant effects were evaluated by the forced swimming test (FST) and tail suspension test (TST). Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting. RESULTS: XYS/RTSES (300 µg/mL) diminished reserpine-induced glial cell death more effectively than either XYS (300 µg/mL) or fluoxetine (30 µM) at 24 h (P = 0.0481 and P = 0.054, respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; P = 0.0177) and shuttle activity (P = 0.00149) on the EPM test, and reduced the immobility time by 90% on the TST (P = 0.00000538) and FST (P = 0.0000053839). XYS/RTSES also improved the regulation of blood glucose (P = 0.0305) and increased the insulin sensitivity (P = 0.0093). The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions. CONCLUSION: The RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.

13.
Artigo em Inglês | MEDLINE | ID: mdl-22474523

RESUMO

Diabetes mellitus is the most common chronic disease in the world, and a wide range of drugs, including Chinese herbs, have been evaluated for the treatment of associated metabolic disorders. This study investigated the potential hypoglycemic and renoprotective effects of an extract from the solid-state fermented mycelium of Cordyceps sinensis (CS). We employed the KK/HIJ diabetic mouse model, in which the mice were provided with a high-fat diet for 8 weeks to induce hyperglycemia, followed by the administration of CS or rosiglitazone for 4 consecutive weeks. Several parameters were evaluated, including changes in body weight, plasma lipid profiles, oral glucose tolerance tests, insulin tolerance tests, and plasma insulin concentrations. Our results show that the CS extract significantly elevated HDL/LDL ratios at 4 weeks and decreased body weight gain at 8 weeks. Interestingly, CS treatment did not lead to obvious improvements in hyperglycemia or resistance to insulin, while in vitro MTT assays indicated that CS protects pancreatic beta cells against the toxic effects of STZ. CS also enhanced renal NKA activity and reduced the accumulation of mesangial matrix and collagen deposition. In conclusion, CS extract can potentially preserve ß-cell function and offer renoprotection, which may afford a promising therapy for DM.

14.
Invest New Drugs ; 30(1): 164-75, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20890633

RESUMO

Designed from a high throughput screened hit compound, novel 2-amino-1-thiazolyl imidazoles were synthesized and demonstrated cytotoxicity against human cancer cells. 1-(4-Phenylthiazol-2-yl)-4-(thiophen-2-yl)-1H-imidazol-2-amine (compound 2), a 2-amino-1-thiazolyl imidazole, inhibited tubulin polymerization, interacted with the colchicine-binding sites of tubulins, and caused cell cycle arrest at the G(2)/M phase in human gastric cancer cells. Disruption of the microtubule structure in cancer cells by compound 2 was also observed. Compound 2 concentration-dependently inhibited the proliferation of cancer cells in histocultured human gastric and colorectal tumors. Given orally, compound 2 prolonged the lifespans of leukemia mice intraperitoneally inoculated with the murine P388 leukemic cells. We report 2-amino-1-thiazolyl imidazoles as a novel class of orally active microtubule-destabilizing anticancer agents.


Assuntos
Antineoplásicos/administração & dosagem , Imidazóis/administração & dosagem , Neoplasias Experimentais/tratamento farmacológico , Tiazóis/administração & dosagem , Moduladores de Tubulina/administração & dosagem , Administração Oral , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Ligação Competitiva , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colchicina/metabolismo , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Imidazóis/síntese química , Imidazóis/metabolismo , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos DBA , Camundongos Nus , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Estrutura Molecular , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/metabolismo , Fatores de Tempo , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/metabolismo
15.
Chin J Physiol ; 55(5): 331-6, 2012 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-23282207

RESUMO

Gold particles have been used in complementary medicine for decades, and many beneficial effects have been reported. Our present study sought to evaluate the therapeutic effects of nanogold in carbon tetrachloride (CCl4)-injured liver of rats. Male SD rats were subjected to liver injury induction by CCl4, then the rats were fed with zero to high dose (0, 1, 5 or 10 ppm) of nanogold water every day for 4 weeks. Biochemical analyses on liver functions were then performed to evaluate the therapeutic effects of nanogold. Our results revealed that gold nanoparticles lowered serum aspartate aminotransaminase (AST) and alanine aminotransferase and exerted serum total protein-recovering effects, which might be partially associated with the elevation of anti-inflammatory cytokine IL-10 level. In addition, serum triglyceride level fell after continuous ingestion of nanogold. Finally, the experimental animals recovered body weight after 4 weeks of nanogold ingestion. This is the first report indicating inflammation alleviating effects of nanogold on hepatic injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Terapias Complementares/métodos , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Relação Dose-Resposta a Droga , Interleucina-10/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/citologia , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue
16.
Toxicol Appl Pharmacol ; 256(2): 146-53, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21851829

RESUMO

Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor ß (LXRß) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRß activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRß and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element.


Assuntos
Arsenicais/efeitos adversos , Aterosclerose/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Proteína C-Reativa/análise , Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol/análise , Proteínas de Choque Térmico HSP70/sangue , Lipoproteínas HDL/sangue , Fígado/química , Receptores X do Fígado , Masculino , Receptores Nucleares Órfãos/análise , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Triglicerídeos/sangue , Poluentes Químicos da Água/toxicidade , Abastecimento de Água
17.
Biosci Biotechnol Biochem ; 75(4): 624-32, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21512226

RESUMO

It has been reported that medicinal mushrooms might induce different types of immune responses. Anthodia camphorata (A. camphorata) has attracted much attention for its therapeutic effects in treating hepatoma. We tested this anti-tumor effects using immunomodulation of macrophages and extracts of A. camphorata. We evaluated the anti-proliferation effects of various extracts of A. camphorata from fruiting bodies (AC-FB), mycelium of solid-state cultures (AC-SS), liquid-state cultures (AC-LS) and polyaccharide extracts from liquid-state cultures (AC-PS), and extracts of A. camphorata stimulated RAW 264.7 macrophage cell-conditioned mediums (MC-CMs). We measured cell proliferation and, did migration assays by cell cycle analysis and by observing apoptosis-related proteins (AKT, PARP-1, and NF-κB) and the mRNA expression of cytokines (TNF-α and IL-1ß) of macrophages in human hepatoma cell lines. Our results revealed that two of the extracts (AC-FB and AC-SS) had better anti-proliferation effects, implying an immunomodulatory role the macrophages might play. This outcome is consistent with findings that AC-FB and AC-SS increase mRNA expression of TNF-α and the corresponding expression of apoptosis-related proteins on activation of MC-CMs, while A. camphorata polysaccharides induce macrophage-derived anti-tumor activities in human hepatoma cells via IL-1ß and Akt activation. These results indicate that anti-tumor effects exerted by modulation of macrophage activation of A. camphorate may be influenced by the other constituents which (contained little or no polysaccharide) of A. camphorata.


Assuntos
Antrodia/química , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Técnicas de Cultura , Carpóforos/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunomodulação/efeitos dos fármacos , Interleucina-1beta/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Macrófagos/imunologia , Extratos Vegetais/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética
18.
Invest New Drugs ; 29(2): 195-206, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19960226

RESUMO

In our previous study, a series of novel cyclic cyanoguanidine compounds, eg. 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4- pyrimidinone derivatives have been successfully synthesized and showed remarkable cytotoxicity in several cancer cell lines. In this present study, it is our aim to screen more potential candidates among the cyclic pyridyl cyanoguanidine compounds (BPR-DC-1, 2, 3) by in vitro and in vivo studies for the therapy of lung cancer, alternatively. Our results showed that BPR-DC-2 significantly inhibited proliferation of tumor cells with an IC50 of 3.60 ± 1.27 and 14.81 ± 4.23 µM in human lung carcinoma cells, H69 and A549, respectively by the MTT assay at 48 hr; BPR-DC-2 also obviously suppressed the tumor proliferation and MDR-1 gene expression, even induced cell apoptosis in the ex vivo histocultured lung tumor. We further demonstrated that, in the nude mouse model of metastatic lung cancer, BPR-DC-2 could diminish the tumor mass, retard the progression of metastasis, and prolong the survival time. In addition, it was found that BPR-DC-2 exerted its anti-tumor effects through the inhibition of MDR-1 gene expression and down-regulation of tumor anti-apoptosis signals (activated p-AKT and over-expression of PARP-1) by western blotting analysis. In conclusion, in this present study we have demonstrated that BPR-DC-2, derived from a series of novel synthetic cyclic cyanoguanidine compounds, has proved its potential as an anti-tumor drug candidate in treating lung cancer.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Regulação para Baixo , Guanidinas/uso terapêutico , Neoplasias Pulmonares/enzimologia , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Bromodesoxiuridina/metabolismo , Antígeno Carcinoembrionário/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Guanidinas/química , Guanidinas/farmacologia , Humanos , Marcação In Situ das Extremidades Cortadas , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Análise de Sobrevida
19.
Cancer Sci ; 102(1): 182-91, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21040217

RESUMO

BPR0C261 is a synthetic small molecule compound cytotoxic against human cancer cells and active prolonging the lifespan of leukemia mice. In the present study, we further investigated the mechanisms of its anticancer action and found that BPR0C261 inhibited microtubule polymerization through interacting with the colchicine binding sites on tubulins, disrupted microtubule arrangement and caused cell cycle arrest at G(2)/M phase in cancer cells. BPR0C261 also inhibited the clonogenic growths of cancer cells and showed cytotoxicity against human cervical cancer cells of multidrug-resistant phenotype. In addition, BPR0C261 concentration-dependently inhibited the proliferation and migration of HUVECs and disrupted the endothelial capillary-like tube formations in HUVEC and rat aorta ring cultures. Given orally, BPR0C261 inhibited angiogenesis in s.c. implanted Matrigel plugs in mice. Notably, its IC(50) values against the endothelial cell growths were approximately 10-fold lower than those against the cancer cells. It was found orally absorbable in mice and showed a good oral bioavailability (43%) in dogs. BPR0C261 permeated through the human intestinal Caco-2 cell monolayer, suggesting oral availability in humans. Orally absorbed BPR0C261 distributed readily into the s.c. xenografted tumors in nude mice in which the tumor tissue levels of BPR0C261 were found oral dose-dependent. BPR0C261 showed in vivo activities against human colorectal, gastric, and nasopharyngeal tumors in nude mice. Most interestingly, the combination of BPR0C261 plus cisplatin synergistically prolonged the lifespans of mice inoculated with murine leukemia cells. Thus, BPR0C261 is a novel orally active tubulin-binding antitumor agent with antimitotic, apoptosis-inducing, and vasculature disrupting activities.


Assuntos
Inibidores da Angiogênese/farmacologia , Antimitóticos/farmacologia , Antineoplásicos/farmacologia , Indóis/farmacologia , Tiazóis/farmacologia , Administração Oral , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cães , Humanos , Leucemia Experimental/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos , Microtúbulos/química , Microtúbulos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
20.
J Med Chem ; 53(6): 2409-17, 2010 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-20170097

RESUMO

2-Amino-1-arylidenaminoimidazoles, a novel class of orally (po) active microtubule-destabilizing anticancer agents, were synthesized. The compounds were designed from a hit compound identified in a drug discovery platform by using cancer cell-based high throughput screening assay. Selective synthesized compounds exerted cell cytotoxicity against human cancer cells. The underlying mechanisms for the anticancer activity were demonstrated as interacting with the tubulins and inhibiting microtubule assembly, leading to proliferation inhibition and apoptosis induction in the human tumor cells. Furthermore, two compounds showed in vivo anticancer activities in both po and intravenously (iv) administered routes and prolonged the life spans of murine leukemic P388 cells-inoculated mice. These new po active antimitotic anticancer agents are to be further examined in preclinical studies and developed for clinical uses.


Assuntos
Antineoplásicos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Neoplasias/tratamento farmacológico , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Imidazóis/química , Concentração Inibidora 50 , Leucemia P388/tratamento farmacológico , Leucemia P388/patologia , Camundongos , Camundongos Endogâmicos DBA , Camundongos Nus , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Modelos Químicos , Estrutura Molecular , Neoplasias/patologia , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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