RESUMO
In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment. The brain was taken and fixed. The positive expression of dopamine receptor D1(DRD1) was detected by TSA, and the changes in neurotransmitters such as dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC) in the brain were detected by enzyme-linked immunosorbent assay(ELISA). The protein and mRNA expression levels of tyrosine hydroxylase(TH) and α-synuclein(α-Syn) in substantia nigra(SN) were detected by RT-PCR and Western blot. The results showed that after the injection of reserpine, the hair color of the model group became yellow and dirty; the arrest behavior was weakened, and the body weight was reduced. The spontaneous movement and exploration behavior were reduced, and the coordination exercise ability was decreased. The number of oral chewing was increased, but the cognitive ability was decreased, and the proportion of DRD1 positive expression area in SN was decreased. The expression of TH protein and mRNA was down-regulated, and that of α-Syn protein and mRNA was up-regulated. After cinnamaldehyde intervention, it had an obvious curative effect on PD model animals. The spontaneous movement behavior, the time of staying in the rod, the time of movement, the distance of movement, and the number of standing times increased, and the number of oral chewing decreased. The proportion of DRD1 positive expression area in SN increased, and the protein and mRNA expression levels of α-Syn were down-regulated. The protein and mRNA expression levels of TH were up-regulated. In addition, the levels of DA, DOPAC, and homovanillic acid(HVA) neurotransmitters in the brain were up-regulated. This study can provide a new experimental basis for clinical treatment and prevention of PD.
Assuntos
Acroleína/análogos & derivados , Doença de Parkinson , Ratos , Masculino , Animais , Doença de Parkinson/etiologia , Doença de Parkinson/genética , Reserpina/efeitos adversos , Reserpina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Ratos Wistar , Substância Negra/metabolismo , RNA Mensageiro/metabolismo , Neurotransmissores/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
BACKGROUND: Intestinal stem cells (ISCs) are the reservoir source of various types of intestinal cells, and the decline of stem cell function in the gut may be a potential factor for aging-related disease. The present study aimed to explore the regulatory mechanisms of Panax ginseng C.A.Meyer (Araliaceae, Panax genus) that could restore gut aging by enhancing intestinal function and regulating ISCs in aging mice based on the Wnt/ß-catenin signaling pathway. METHODS: A total of 60 ICR male mice were randomly divided into control, model, metformin, and ginseng water decoction (GWD) 3.6, 1.8, and 0.9 g/kg groups. The aging model was induced by 1 % D-galactose (s.c. 0.1 mL/10 g) for 28 days. Moreover, GWD was given to aging mice intragastrically (i.g.) once a day for 28 successive days. The learning memory ability, pathological status, and function in the ileum tissue, the activity of digestive enzymes, and short-chain fatty acid (SCFA) content in the colon were evaluated, and the related mechanism was investigated. RESULTS: Ginseng can decrease the escape latency time and increase the swimming speed and the number of crossing platforms in aging mice. Moreover, the pathology of ileum tissue improved, the length of the intestinal villi increased, and the width of the villi and the depth of the crypts decreased. The activities of trypsin, α-amylase, and lipase increased in duodenal content and intestinal mucosa. In the colon, the content of SCFA, such as acetic acid, propionic acid and butyric acid, increased, indicating that ginseng significantly improves intestinal function impairment. The mRNA expressions and protein levels of ß-catenin, C-myc, GSK-3ß, Lgr5, and Olfm4 were upregulated in the ginseng group. CONCLUSIONS: Ginseng improves intestinal function and regulates the function of ISCs in order to protect intestinal health by activating the Wnt/ß-catenin signaling pathway in aging mice.
Assuntos
Panax , Via de Sinalização Wnt , Camundongos , Masculino , Animais , Galactose/farmacologia , Galactose/metabolismo , Panax/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos Endogâmicos ICR , Células-Tronco/metabolismo , Envelhecimento , Mucosa Intestinal/metabolismoRESUMO
Hemp seed, the dried fruit of Cannabis sativa L. (Moraceae), has been extensively documented as a folk source of food due to its nutritional and functional value. This study evaluated the antidepressant effect of hemp seed oil (HSO) during its estrogen-like effect in Perimenopausal depression (PMD) rats induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Female SD rats (SPF, 10 weeks, sham operated group, ovariectomy (OVX) model group, ovariectomy - chronic unpredictable mild stress (OVX-CUMS) group, HSO + OVX-CUMS group, fluoxetine (FLU) + OVX-CUMS group, n=8) were subjected to treatment with HSO (4.32 g/kg) or fluoxetine (10 mg/kg) for 28 days (20 mL/kg by ig). Sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), estrogen receptor α (ERα) and estrogen receptor ß (ERß) expression, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol (CORT), adrenocorticotropic hormone (ACTH), corticotropin releasing hormone (CRH), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels are measured to evaluate the function of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-adrenal (HPA) axis. The results showed that OVX-CUMS significantly decrease sucrose preference rate in SPT, increase immobility time in FST and OFT, and decrease movement distance and stand-up times in OFT. HSO treatment significantly improves depression-like behaviors, upregulates the expression of ERα and ERß, improves HPO axis function by increasing E2 levels and decreasing FSH and LH levels, reverses HPA axis hyperactivation by decreasing CORT, ACTH, and CRH levels, and upregulates NE, 5-HT, and 5HIAA levels in model rats. The findings suggested that HSO could improve depression-like behavior in OVX-CUMS rats by regulating HPO/HPA axis function and neurotransmitter disturbance.
Assuntos
Cannabis , Depressão , Ratos , Feminino , Animais , Depressão/tratamento farmacológico , Depressão/prevenção & controle , Sistema Hipotálamo-Hipofisário/metabolismo , Cannabis/metabolismo , Receptor alfa de Estrogênio/metabolismo , Fluoxetina/metabolismo , Fluoxetina/farmacologia , Serotonina/metabolismo , Serotonina/farmacologia , Receptor beta de Estrogênio/metabolismo , Perimenopausa , Ratos Sprague-Dawley , Sistema Hipófise-Suprarrenal/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Hormônio Foliculoestimulante/metabolismo , Hormônio Foliculoestimulante/farmacologia , Sacarose , Estresse Psicológico/tratamento farmacológico , Modelos Animais de DoençasRESUMO
This paper aims to explore the neuroprotective effect of cinnamaldehyde(CA) in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson's disease(PD) and the mechanism. To be specific, male C57 BL/6 mice(n=72, SPF) were randomized into control group, model group, positive control(madopar 0.1 mg·g~(-1)) group, and low-dose, me-dium-dose, and high-dose CA groups(0.15, 0.30, 0.60 mg·g~(-1)). MPTP(intraperitoneal injection, 0.03 mg·g~(-1), once a day for 5 days) was used to induce subacute PD in mice except for the control group. The administration began from the day of modeling and lasted 19 days. On the 0 th, 12 th, and 19 th day, the open field test, pole test, and rotarod test were carried out. After the tests, the mice were killed and brains were separated. In addition, the organ index was measured. The number of cells in substantia nigra(SN) in the midbrain of MPTP-induced PD model mice was detected based on hematoxylin and eosin(HE) staining. The levels of tyrosine hydroxylase(TH)-and α-synuclein(α-Syn)-positive cells in SN were determined by immunohistochemical staining, and the protein levels of TH and α-Syn in SN by Western blot. The results showed that the MPTP-stimulated mice had abnormal behaviors such as erect hair, arched back, rigidity of the tail, slow movement, and tremor, decreased number of crossings and rearing, increased frequency of urination and defecation, longer time of pole climbing, and shorter time of staying on the rotating rod. In addition, the mice showed obvious damage of neurons in the SN and reduced neuron cells in irregular arrangement with some shrinking. In addition, the average optical density of TH in SN decreased and that of α-Syn increased. All these suggested the successful modeling. CA displayed obvious therapeutic effect on the PD mice, as manifested by the increased number of crossings and rearing, decreased frequency of urination and defecation, shorter time of climbing pole, longer time of staying on the rotating rod, and more neuron cells in the SN with a few pykno-tic cells. Moreover, CA significantly alleviated the decrease of TH and the overexpression of α-Syn in SN. As a result, the MPTP-induced injury of dopaminergic neurons was alleviated. The performance of 0.3 mg·g~(-1) CA was the best. This study is expected to lay a scientific basis for the development of CA products.
Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Masculino , Camundongos , Animais , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Neurônios Dopaminérgicos , Substância Negra/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Context: Panax ginseng C. A. Meyer (Araliaceae) root and leaf have always been considered in the traditional theory as hot and cold properties, respectively.Objective: To clarify the hot and cold properties of ginseng root and leaf from a thermodynamic viewpoint.Materials and methods: Thirty ICR male mice were randomly assigned to control (water), ginseng root group (GRP) and ginseng leaf group (GLP) with a concentration of 0.075 g/mL; the volume was 0.1 mL/10 g (body mass) per day by intragastric administration for 20 days. Ultra-Performance Liquid Chromatography (UPLC) was used to determine quality control through seven ginsenosides contained in ginseng root and leaf. Rest metabolic rate (RMR) and energy expenditure were monitored every 9 days by TSE System. At the 20th day, serum T3 or T4, liver or brown adipose tissue (BAT) mitochondrial respiration were investigated.Results: The quality control of GRP and GLP were within requirements of 2015 China Pharmacopoeia. The RMR (mLO2/h) in GLP (47.95 ± 4.20) was significantly lower than control (52.10 ± 4.79) and GRP (55.35 ± 4.48). Mitochondrial protein concentration and respiration were significantly increased in GRP (BAT, 79.12 ± 2 .08 mg/g, 239.89 ± 10.24 nmol O2/min/g tissue; Liver, 201.02 ± 10.89, 202.44 ± 3.24) and decreased in GLP (BAT, 53.42 ± 3.48, 153.49 ± 5.58; Liver, 138.69 ± 5.69, 104.50 ± 6.25) compared with control.Conclusions: The hot and cold properties of ginseng root and leaf are correlated with thermogenic capacity and mitochondrial function of BAT and liver, which deserve to further research.
Assuntos
Mitocôndrias/efeitos dos fármacos , Panax , Extratos Vegetais/farmacologia , Folhas de Planta , Raízes de Plantas , Termogênese/efeitos dos fármacos , Animais , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Extratos Vegetais/isolamento & purificação , Termogênese/fisiologiaRESUMO
Cassia seed is the dried ripe seed of Cassia obtusifolia L. or Cassia tora L., which is widely used as a food or traditional Chinese medicine. The aim of the present study was to detect the components and metabolites in the culture of human or rat intestinal microflora suspension with the water decoction of cassia seed in vitro, using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry system equipped with a negative ion scan mode. Initially, ellagic acid was identified in the cassia seed decoction. Subsequently, six different metabolites, including urolithin (uro)-A, uro-B, uro-D, uro-M6, uro-M7 and uro-B-glucuronide (glur), were detected after co-culture of the cassia seed decoction with intestinal microflora, but not in the cassia seed decoction alone. Uro-M6, uro-M7, uro-A and uro-B were common metabolites in the culture of human or rat intestinal microflora suspension with the water decoction of cassia seed. However, uro-D was only detected in the culture of rat intestinal microflora suspension with the water decoction of cassia seed, and uro-B-glur was only detected in the culture of human intestinal microflora with the water decoction of cassia seed. The uro and intermediate metabolites were produced by ellagic acid in the cassia seed decoction under the action of the intestinal microflora. The production of metabolites might be related to the abundance and diversity of the intestinal microflora in humans and rats. The present study provided rationale for further pharmacological and clinical studies on the mechanisms of action of cassia seeds.
RESUMO
OBJECTIVE: To compare the therapeutic effect of Compound Recipe Gengniankang ( GNK) with that of hormone replacement treatment (HRT) on climacteric female rats with osteoporosis, and to investigate the roles of estrogen and estrogen receptors in the mechanism of osteoporosis. METHODS: Climacteric female rats with osteoporosis were chosen and divided into three groups (GNK group, HRT group and control group). Apoptosis of ovarian granulose cells was measured by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay. Serum level of estradiol (E(2)), follicle stimulating hormone (FSH), luteinizing hormone (LH) were determined by the method of radioimmunoassay (RIA). Reverse transcriptase polymerase chain reaction (RT-PCT) technology was used to evaluate the expression of estrogen receptor (ER) in bone. Bone mineral density (BMD) was measured by double energy X-ray absorption (DEXA). RESULTS: In the climacteric rats, BMD, serum E(2), ER mRNA expression in bone decreased remarkably, and serum FSH, LH and apoptosis of ovarian granulose cells increased obviously. After treating with GNK, all the indexes were reversed except serum E(2). The increase of E(2) was not significant. CONCLUSION: GNK is effective on climacteric osteoporosis female rats. Its role is performed not by increasing serum E(2) but by enhancing ER in the bone and inhibiting apoptosis of ovarian granulose cells. GNK can deter further exhaustion of ovarian function.
Assuntos
Osso e Ossos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hormônios/sangue , Osteoporose/metabolismo , Receptores de Estrogênio/biossíntese , Fatores Etários , Animais , Apoptose , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Climatério , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Terapia de Reposição Hormonal , Hormônio Luteinizante/sangue , Ovário/efeitos dos fármacos , Ovário/fisiologia , RatosRESUMO
OBJECTIVE: To observe the effect of compound gengniankang (GNK) in regulating the endocrine and immune functions in aged female rats. METHODS: Aged female rats with osteoporosis were selected as the object for observation and healthy young rats were taken for control. Animals were administered by GNK and nilestriol respectively, through gastric perfusion, for 3 months to observe the therapeutic effect of drug treatment on osteoporosis and the regulatory effect on endocrine and immune function. Bone mineral density (BMD) was measured by double energy X-ray absorption technique, serum levels of estradiol (E2), follicule-stimulating hormone (FSH) and luteinizing hormone (LH) were determined by RIA, T-cell subsets and apoptosis in spleen were detected by flow cytometry. RESULTS: In aged rats with osteoporosis, the BMD decreased, serum level of E2 lowered, FSH and LH levels raised, splenic CD4+, CD4+/CD8+ significantly decreased and T-cell apoptosis rate significantly elevated. GNK could increase the BMD, lower the FSH and LH levels, but showed no significant effect on E2 level. It could increase the CD4+ and CD4+/CD8+ ratio to nearby the normal range, and reduce the apoptosis of T-cells. CONCLUSION: GNK has therapeutic effect on osteoporosis in aged rats, and is able to regulate the endocrine and enhance the immune function in organism.