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1.
Toxicon ; 243: 107725, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38642904

RESUMO

Kochiae Fructus (KF) is a traditional Chinese medicine, which has been used to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. In order to fully understand the traditional medicinal value of KF, we evaluated the antioxidant properties and oral safety of its ethanolic extract. Considering flavonoids and phenolics in medicinal plants generally have strong antioxidant activity, we firstly detected the total flavonoids and phenolics contents of KFEE and its fractions. Secondly, we evaluated the antioxidant activities of KFEE and its fractions. Finally, we evaluated the oral safety of KFEE by the acute and 28-day subacute toxicities. The n-butanol fraction (ENBF) possessed the highest phenolics and flavonoids with values of 77.30 ± 3.17 mg gallic acid equivalents/g and 228.81 ± 7.56 mg rutin equivalents/g, respectively. The results of antioxidant tests showed that ENBF possessed potent antioxidant ability. Among them, the high antioxidation capacity observed in ENBF could be attributed to its rich content of flavonoids and phenolics. The results of toxicological studies showed that the LD50 value of KFEE was 6000 mg/kg BW, and the no observed adverse effect level (NOAEL) of KFEE was 600 mg/kg BW. According to the standards of the American Academy of Sciences for the classification of toxic substances, KFEE can be classified as practically non-toxic substance, which provided valuable evidence for the oral safety of KF as a natural aging delay medicine.


Assuntos
Antioxidantes , Extratos Vegetais , Antioxidantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Animais , Fenóis/análise , Flavonoides/análise , Camundongos , Masculino , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Frutas/química , Medicina Tradicional Chinesa , Feminino , Administração Oral , Etanol/química
3.
Int J Biol Macromol ; 261(Pt 2): 129442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232873

RESUMO

In this paper, the effects of extrusion, ultrasound on physicochemical properties of liposomes were studied, and the liposomes were prepared by ethanol injection combined with extrusion-ultrasound. In addition, the quality of PhGs lips, pectin-coated PhGs lips (P-lips) and chitosan-coated PhGs lips (C-lips) was evaluated by the average particle size, encapsulation efficiency (EE) and other indicators, which indicated that the nanoparticles had been successfully prepared. Compared with extrusion or ultrasonic operation alone, the EEs of ethanol injection combined with extrusion-ultrasonic increased by 8 % and 18 % respectively. Subsequently, transmission electron microscopy, Fourier transform infrared spectroscopy and DSC thermal analysis showed that PhGs in PhGs lips may produce hydrogen bonding forces with phospholipids, and pectin and chitosan in P-lips and C-lips were not only coated on the surface of PhGs lips, but also might have some interaction between them. Cell experiments showed that PhGs lips, P-lips and C-lips can effectively improve the bioavailability of PhGs. In addition, the storage stability of P-lips and C-lips was not significantly improved compared to PhGs lips, but their digestive stability was significantly improved, and the final retention rate in simulated intestinal fluid was about 25 % higher than that of PhGs lips.


Assuntos
Quitosana , Lipossomos , Lipossomos/química , Quitosana/química , Pectinas/química , Etanol , Digestão , Tamanho da Partícula
4.
J Ethnopharmacol ; 321: 117405, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952734

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic asthma is a recurring respiratory condition that typically manifests during childhood or adolescence. It is characterized by a dominant type II immune response triggered by the identification and capturing of inhaled allergens by dendritic cells (DCs). Jiangqi Pingxiao Formula (JQPXF), a prescription medicine used for the treatment of pediatric asthma, has been clinically proven to be both safe and effective. However, its mechanism of action in the treatment of asthma has not been fully been fully elucidated. Recent research suggests that several natural compounds have the potential to target dendritic cells (DCs) and alleviate ovalbumin (OVA)-induced asthma, which may also be found within JQPXF. AIM OF THE STUDY: This study aimed to elucidate the effect of JQPXF on OVA-induced asthma model and its molecular mechanism targeting DCs. MATERIALS AND METHODS: The main constituents of JQPXF were analyzed by ultra performance liquid chromatography (UPLC). An asthma model was established by OVA. Hematoxylin-eosin staining and measurement of respiratory function was used to evaluate the treatment effect of JQPXF on asthmatic mice. Cytokine (IL-5, IL-13 and IgE) concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to evaluate inflammatory cell infiltration (T helper 2 cells and DCs) in vivo and DC survival in vivo and vitro. Western blot and immunofluorescence were used to verify the molecular mechanisms. RESULTS: The results suggest that JQPXF can ameliorate pathological conditions and improve lung function in asthmatic mice, as well as the Th2 cells. Treatment with JQPXF significantly reduced the number of DCs and increased the number of Propidium iodide+ (PI) DCs. Furthermore, JQPXF upregulated protein levels of the pro-apoptotic factors Cleaved-caspase-3 and Bax, while downregulating the anti-apoptotic factor Bcl-2. Simultaneously, JQPXF increased autophagy levels by facilitating p62 degradation and promoting translation from LC3B I to LC3B II of DCs in vitro, as well as reducing the integrated optical density (IOD) of p62 within the CD11c-positive area in the lung. 3-Methyladenine (3-MA) was used to block autophagic flux and the apoptotic effect of JQPXF on DCs was abolished in vitro, with the number of DCs decreased by JQPXF being reversed in vivo. We further investigated the upstream key regulator of autophagy, the AMPK/mTOR pathway, and found that JQPXF increased AMPK phosphorylation while decreasing mTOR phosphorylation levels. Additionally, we employed Compound C (CC) as an AMPK inhibitor to inhibit this signaling pathway, and our findings revealed that both autophagic flux and apoptotic levels in DCs were abolished in vitro. CONCLUSIONS: In summary, we have demonstrated that JQPXF could alleviate type II inflammation in an asthmatic model by promoting the apoptosis of DCs through an autophagy-dependent mechanism, achieved by regulating the AMPK/mTOR signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Asma , Humanos , Criança , Camundongos , Animais , Ovalbumina , Proteínas Quinases Ativadas por AMP/metabolismo , Modelos Animais de Doenças , Asma/induzido quimicamente , Asma/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Células Dendríticas , Apoptose , Camundongos Endogâmicos BALB C
5.
J Ethnopharmacol ; 321: 117462, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37981117

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In the ancient book "Shen Nong's Herbal Classic," Panax ginseng CA Mey was believed to have multiple benefits, including calming nerves, improving cognitive function, and promoting longevity. Ginsenosides are the main active ingredients of ginseng. Ginsenoside RK3 (RK3), a rare ginsenoside extracted from ginseng, displays strong pharmacological potential. However, its effect on neurogenesis remains insufficiently investigated. AIM OF THE STUDY: This study aims to investigate whether RK3 improves learning and memory by promoting neurogenesis, and to explore the mechanism of RK3 action. MATERIALS AND METHODS: The therapeutic effect of RK3 on learning and memory was determined by the Morris water maze (MWM) and novel object recognition test (NORT). The pathogenesis and protective effect of RK3 on primary neurons and animal models were detected by immunofluorescence and western blotting. Protein expression of cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway was detected by western blotting. RESULTS: Our results showed that RK3 treatment significantly improved cognitive function in APPswe/PSEN1dE9 (APP/PS1) mice and C57BL/6 (C57) mice. RK3 promotes neurogenesis and synaptogenesis in the mouse hippocampus. In vitro, RK3 prevents Aß-induced injury in primary cultured neurons and promotes the proliferation of PC12 as well as the expression of synapse-associated proteins. Mechanically, the positve role of RK3 on neurogenesis was combined with the activation of CREB/BDNF pathway. Inhibition of CREB/BDNF pathway attenuated the effect of RK3. CONCLUSION: In conclusion, this study demonstrated that RK3 promotes learning and cognition in APP/PS1 and C57 mice by promoting neurogenesis and synaptogenesis through the CREB/BDNF signaling pathway. Therefore, RK3 is expected to be further developed into a potential drug candidate for the treatment of Alzheimer's disease (AD).


Assuntos
Doença de Alzheimer , Ginsenosídeos , Camundongos , Animais , Doença de Alzheimer/patologia , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Ginsenosídeos/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Camundongos Endogâmicos C57BL , Neurogênese , Modelos Animais de Doenças , Hipocampo
6.
Huan Jing Ke Xue ; 44(10): 5788-5799, 2023 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-37827794

RESUMO

Soil microbial carbon (C), nitrogen (N), and phosphorus (P) nutrient requirements and metabolic limitations are closely related to the availability of environmental nutrients. However, it is unclear how manure and chemical fertilization shift nutrient limitations for microbes in terms of the soil enzymatic stoichiometry in an apple orchard. Therefore, based on the long-term experiment located in an apple orchard established in 2008, this study applied the theory and method of soil enzyme stoichiometry to systematically investigate the effects of the combined application of manure and chemical fertilizers on soil C, N, and P turnover-related enzyme activities (ß-1,4-glucosidase, BG; leucine aminopeptidase, NAG; ß-1,4-N-acetylglucosaminidase, LAP; and acid or alkaline phosphatase, PHOS) and their stoichiometric characteristics and analyzed their relationships with environmental factors and microbial carbon use efficiency. The experiment was designed with four treatments, such as, no fertilization input as the control (CK), single application of chemical fertilizer (NPK), combined application of manure and chemical fertilizer (MNPK), and single application of manure (M). The results revealed that:① at different growth stages of fruit trees, the soil microbial biomass C (microC) content of manure fertilizer treatments (MNPK and M) was significantly higher than that of no manure fertilizer treatments (CK and NPK). The content of microbial biomass N (microN) in the NPK, MNPK, and M treatments increased by 89%, 269%, and 213%, respectively, compared with that in CK (P<0.05). ② Compared with those in the fertilization treatments, CK had higher leaf N and P contents (29.8 g·kg-1 and 2.17 g·kg-1) at the germination stage, and the leaf P content at the germination stage alone was significantly negatively correlated with soil available phosphorus (AP) content. ③ Soil enzyme stoichiometry analysis demonstrated that all data points in this study were above the 1:1 line, indicating that microbial communities had a strong phosphorus limitation. The range of vector length and angle was 0.56-0.79 and 59.3°-67.7°, respectively, in the growth period of fruit trees, and the vector angle was >45° in this study, which also reflected the strong phosphorus limitation of microorganisms. ④ RDA and random forest model analysis showed that organic carbon and available nitrogen (AN) were the main physical and chemical factors affecting vector length; AP, AN, and soil water content were the main physical and chemical factors affecting vector angle. Combined with SEM analysis, AN and dissolved organic carbon (DOC) directly affected microC and microN, AP directly affected microP and microN, DOC and AP directly affected vector length, and AP and microN directly affected vector angle. In addition, microbial carbon utilization was positively correlated with vector length and negatively correlated with vector angle. In summary, the combined application of manure and chemical fertilizers regulated microbial carbon and phosphorus metabolism by affecting soil carbon and phosphorus content at different growth stages of fruit trees, thereby affecting microbial carbon utilization. This study provides a scientific basis for manure and chemical fertilizers to improve soil quality and maintain soil health.


Assuntos
Malus , Solo , Solo/química , Fertilizantes/análise , Carbono/análise , Esterco , Microbiologia do Solo , Estações do Ano , Nitrogênio/análise , Fósforo/análise , Agricultura/métodos
7.
Altern Ther Health Med ; 29(8): 699-703, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708537

RESUMO

Objective: The present investigation aims to conduct a comprehensive examination of the infection prevention and control efforts in hospitals of Xinjiang Production and Construction Corps designated for COVID-19 treatment. Methods: By searching the Cochrane Library, PubMed, Embase, Chinese Academic Journal, Full Text Database, Chinese Biomedical Literature Database (CBM), VIP Chinese Scientific, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (CECDB), and using Review Manager 5.2 software, the quality assessment, data extraction, and meta-analysis were carried out for the included literature. Results: Between both the experimental and the control groups, there was a statistically significant difference in the level of public awareness of COVID-19 prevention and control [OR = 1.61, 95% confidence interval (CI) (1.31, 1.99), P < .00001, I2 = 32%, Z = 4]; public concern about COVID-19 prevention and control [OR = 1.56, 95% CI (1.28, 1.90), P < .0001, I2 = 0%, Z = 4.35]; public anxiety on COVID-19 prevention and control [OR = 1.67, 95% CI (1.37, 2.03), P < .00001, I2 = 32%, Z = 5.13]. Conclusion: Chinese prophylaxis and controlling measures for COVID-19 are mainly to protect vulnerable populations, cut off transmission routes, and control the source of infection. Therefore, we must also do our best to prevent and control novel coronavirus pneumonia to protect our health and reduce the burden on our country.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Humanos , COVID-19/prevenção & controle , Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas/uso terapêutico , SARS-CoV-2 , Hospitais
8.
Altern Ther Health Med ; 29(8): 764-769, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708550

RESUMO

Objective: To evaluate the effects of language awakening nursing and thermal insulation nursing on anesthesia in elderly patients undergoing spinal fracture surgery. Methods: Randomized control method was used in this study, 200 elderly patients who underwent spinal fracture surgery under general anesthesia between January and December 2022. Among the patients, 100 cases were selected as the observation group, and the other 100 cases were included in the control group by the random number table method. The control group was treated with thermal insulation nursing, and the observation group was given language arousal nursing (a type of care that helps patients regain consciousness after surgery or anesthesia) combined with thermal insulation nursing (A nursing method for maintaining a patient's body temperature in a medical setting). Results: After the intervention, the observation group showed shorter extubation time, awaking time, eye-opening time, and respiratory recovery time compared to the control group (P < .05). Systolic, diastolic, and MAP decreased in both groups after the intervention, with the observation group showing lower values (P < .05). Heart rate at 5 and 10 minutes after extubation decreased in both groups, with the observation group having a lower heart rate than the control group (P < .05). There were no significant differences in SPO2 between the groups after intervention (P > .05). The observation group reported milder pain and a lower incidence of anesthesia-related adverse reactions (P < .05). These findings suggest that language arousal nursing combined with heat preservation nursing improves anesthesia recovery in elderly patients undergoing spinal fracture surgery, leading to better outcomes and reduced adverse events. Conclusion: Combining language arousal and thermal insulation nursing enhances anesthesia recovery in elderly spinal fracture surgery patients, leading to optimized blood pressure, heart rate, reduced pain, and fewer anesthesia-related adverse events.


Assuntos
Fraturas da Coluna Vertebral , Humanos , Idoso , Saturação de Oxigênio , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Dor , Nível de Alerta
9.
ACS Appl Mater Interfaces ; 15(34): 40267-40279, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37594128

RESUMO

Transdermal cancer therapy faces great challenges in clinical practice due to the low drug transdermal efficiency and the unsatisfactory effect of monotherapy. Herein, we develop a novel bubble pump microneedle system (BPMN-CuS/DOX) by embedding sodium bicarbonate (NaHCO3) into hyaluronic acid microneedles (MNs) loaded with fucoidan-based copper sulfide nanoparticles (Fuc-CuS NPs) and doxorubicin (DOX). BPMN-CuS/DOX can generate CO2 bubbles triggered by an acidic tumor microenvironment for deep and rapid intradermal drug delivery. Fuc-CuS NPs exhibit excellent photothermal effect and Fenton-like catalytic activity, producing more reactive oxygen species (ROS) by photothermal therapy (PTT) and chemodynamic therapy (CDT), which enhances the antitumor efficacy of DOX and reduces the dosage of its chemotherapy (CT). Simultaneously, DOX increases intracellular hydrogen peroxide (H2O2) supplementation and promotes the sustained production of ROS. BPMN-CuS/DOX significantly inhibits melanoma both in vitro and in vivo by the combination of CDT, PTT, and CT. In short, our study significantly enhances the effectiveness of transdermal drug delivery by constructing BPMNs and provides a promising novel strategy for transdermal cancer treatment with multiple therapies.


Assuntos
Melanoma , Melanoma/terapia , Sulfato de Cobre/química , Terapia Fototérmica , Doxorrubicina/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Terapia Combinada , Masculino , Animais , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL
10.
Front Nutr ; 10: 1120254, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37032779

RESUMO

Lycopene (LY) belongs to carotenoids and is abundant in red fruits and vegetables. Several previous studies suggested that LY is beneficial for ameliorating non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are unclear. The present study aimed to clarify the potential mechanisms of LY in preventing NAFLD via exploring the hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota composition in high-fat and high-fructose diet (HFFD)-fed mice. Fifty eight-week-old male C57BL/6J mice were randomly assigned into 5 groups: Normal control group (NC); HFFD group; HFFD with low dose of lycopene group (LLY, 20 mg/kg/d); HFFD with high dose of lycopene group (HLY, 60 mg/kg/d) and HFFD with resveratrol group (RSV, 50 mg/kg/d, positive control). After 8 weeks, feces were collected and the 12 h fasted mice were sacrificed to acquire tissues and blood for parameters measurement. The results showed that the mice in LLY, HLY and RSV groups had significantly lower body weight gain, weight of white adipose tissue, serum levels of high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipopolysaccharide (LPS), alanine aminotransferase (ALT), and hepatic concentrations of triglyceride (TG) and interleukin-6 (IL-6) than that in the HFFD group (p < 0.05). HLY and RSV groups also displayed lower serum levels of TG, total cholesterol (TC) and hepatic levels of tumor necrosis factor-α (TNF-α) than the HFFD group (p < 0.05). Liver protein expressions of NLRP3, Pro-Caspase-1, Caspase-1 and NF-κB were lower in the LLY, HLY and RSV groups than those in the HFFD group (p < 0.05). The feces of LY -treated mice had higher relative levels of SCFAs producing bacteria Allobaculum and lower destructive bacteria, including Firmicutes, Lachnospiraceae_NK4A136_group, Desulfovibrio, and Alistipes over the HFFD group (p < 0.05). RSV group also displayed lower fecal levels of Lachnospiraceae_NK4A136_group, Desulfovibrio, and Alistipes than the HFFD group (p < 0.05). In conclusion, LY might prevent NAFLD by suppressing hepatic NF-κB/NLRP3 inflammasome pathway and attenuating gut microbiota dysbiosis.

11.
Plant Sci ; 330: 111667, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36858208

RESUMO

Male and female gametophyte development processes are essential steps in the life cycles of all land plants. Here, we characterized a gene, FviBAG6-A, screened from the Fragaria viridis (2 n = 2x=14) pollen cDNA library and physically interacted with S-RNase. Ubiquitinated of Sa-RNase might be determined by the interaction of FviBAG6-A in the ubiquitin-proteasome system during fertilization. We found that overexpression of FviBAG6-A in Arabidopsis caused shorter silique length, and decreased silique number. Moreover, overexpression of FviBAG6-A in Fragaria vesca (2 n = 2x=14) led to a greatly reduced seed number, with nearly 80% of the seeds aborted. Analyses of paraffin sections and reactive oxygen species (ROS) content revealed that the majority of severe pollen defects were likely due to the early degradation of the tapetum and middle layer as a result of ROS accumulation and abnormal development of the uninucleate megaspore mother. Moreover, the FviBAG6-A interact with the E3 ligase SIZ1 and contribute to the SUMOylation of FviBAG6-A , which may be induced by the high level of ROS content, further promoting gametophyte abortion in strawberry transgenic lines. This study characterized the FviBAG6-A and reveals its novel function in gametophyte development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fragaria , Proteínas de Arabidopsis/metabolismo , Fragaria/genética , Fragaria/metabolismo , Células Germinativas Vegetais/metabolismo , Diploide , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Pólen/genética , Pólen/metabolismo , Ribonucleases/metabolismo , Ligases/genética , Proteínas Nucleares/metabolismo , Chaperonas Moleculares/genética
12.
Antioxidants (Basel) ; 12(3)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36978912

RESUMO

Tectona grandis is a traditional Dai medicine plant belonging to the Lamiaceae family, which can be used to treat malaria, inflammation, diabetes, liver disease, bronchitis, tumors, cholelithiasis, jaundice, skin disease and as an anti-helminthic. To find more novel therapeutic agents contained in this medicinal plant, the antioxidant, anti-inflammatory and anti-diabetic activities of T. grandis methanolic extract, fractions and compounds were evaluated. In this study, 26 compounds were isolated from the leaves and branches of T. grandis. Their structures were identified based on extensive spectral experiments, including NMR, ESI-MS and comparison with published spectral data. Among them, compounds 1-2, 4-6, 9-14 and 16-22 were reported for the first time for this plant. The antioxidant activity screening results showed that compounds 5, 15 and 23 had potent antioxidant capacities, with SC50 values from 0.32 to 9.92 µmol/L, 0.92 to 1.10 mmol Trolox/L and 1.02 to 1.22 mmol Trolox/L for DPPH, ABTS and FRAP, respectively. In addition, their anti-inflammatory effects were investigated by releasing TNF-α, IL-1ß and IL-6 through the use of mouse monocytic macrophages (RAW 264.7). Compounds 1, 13, 18 and 23 had the effects of reducing the expression of inflammatory factors. Compounds 13 and 18 were reported for the first time for their anti-inflammatory activities. Furthermore, the methanolic extract (ME), petroleum ether extract (PEE) and EtOAc extract (EAE) of T. grandis showed significant glucose uptake activities; compounds 21 and 23 significantly promoted glucose uptake of 3T3-L1 adipocytes at 40 µM. Meanwhile, compounds 4, 5 and 7 showed significant inhibitory activities against α-glucosidase, with IC50 values of 14.16 ± 0.34 µmol/L, 19.29 ± 0.26 µmol/L and 3.04 ± 0.08 µmol/L, respectively. Compounds 4 and 5 were reported for the first time for their α-glucosidase inhibitory activities. Our investigation explored the possible therapeutic material basis of T. grandis to prevent oxidative stress and related diseases, especially inflammation and diabetes.

13.
Phytomedicine ; 112: 154714, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36812746

RESUMO

BACKGROUND: Cognitive deficit is the main clinical feature of Alzheimer's disease (AD), and the massive death of neuronal cells is the leading cause of cognitive deficits. So, there is an urgent clinical need to discover effective drugs to protect brain neurons from damage in order to treat AD. Naturally-derived compounds have always been an important source of new drug discovery because of their diverse pharmacological activities, reliable efficacy and low toxicity. Magnoflorine is a quaternary aporphine alkaloid, which naturally exist in some commonly used herbal medicines, and has good anti-inflammatory and antioxidant effects. However, magnoflorine has not been reported in AD. HYPOTHESIS/PURPOSE: To investigate the therapeutic effect and mechanism of magnoflorine on AD. METHODS: Neuronal damage was detected by flow cytometry, immunofluorescence and western blotting. Oxidative stress was measured by detection of SOD and MDA, as well as JC-1 and reactive oxygen species (ROS) staining. The APP/PS1 mice were given drugs by intraperitoneal injection (I.P.) every day for one month, and then the new object recognition and Morris water maze were used to detect the cognitive ability of the mice. RESULTS: We demonstrated that magnoflorine reduced Aß-induced PC12 cell apoptosis and intracellular ROS generation. Further studies found that magnoflorine significantly improved cognitive deficits and AD-type pathology. Most interestingly, the efficacy of magnoflorine was better than that of the clinical control drug donepezil. Mechanistically, based on RNA-sequencing analysis, we found that magnoflorine significantly inhibited phosphorylated c-Jun N-terminal kinase (JNK) in AD models. This result was further validated using a JNK inhibitor. CONCLUSION: Our results indicate that magnoflorine improves cognitive deficits and pathology of AD through inhibiting of JNK signaling pathway. Thus, magnoflorine may be a potential therapeutic candidate for AD.


Assuntos
Doença de Alzheimer , Aporfinas , Camundongos , Animais , Doença de Alzheimer/metabolismo , Sistema de Sinalização das MAP Quinases , Peptídeos beta-Amiloides/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Aporfinas/farmacologia , Aporfinas/uso terapêutico , Cognição
14.
Biomed Pharmacother ; 158: 114192, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36587558

RESUMO

Alzheimer's disease (AD) has become a major public health problem affecting the elderly population, and there is currently no effective treatment. Although the pathogenesis of AD is unclear, neurotoxicity induced by oxidative stress plays an important role in the progression of AD. Ginseng, the root and rhizome of Panax ginseng C. A. Meyer, is used not only as an herbal medicine but also as a functional food to support bodily functions. Ginsenoside Rk3 (Rk3), the main bioactive component in ginseng, has a strong antioxidant effect and has not been reported in AD. In this study, we showed that Rk3 improved neuronal apoptosis, decreased intracellular reactive oxygen species (ROS) production and restored mitochondrial membrane potential in PC12 and primary neuronal cells. In vivo, we found that Rk3 improved spatial learning and memory deficit in precursor protein (APP)/presenilin 1 (PS1) double transgenic mouse model of AD. Additionally, Rk3 increases glutathione reductase (GSH) and superoxide dismutase (SOD) levels while inhibits malondialdehyde (MDA) production, apoptosis and activation of glial cells in APP/PS1 mice. Mechanistically, we found that the protective effect of Rk3 is in correlation with the activation of AMPK/Nrf2 signaling pathway. In conclusion, the findings of this study provide support for Rk3 as a new strategy for the treatment of AD.


Assuntos
Proteínas Quinases Ativadas por AMP , Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Presenilina-1/genética , Transdução de Sinais
15.
Int J Biol Macromol ; 222(Pt B): 2868-2877, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228816

RESUMO

Acid hydrolysis is a crucial method for modifying granular starch, but it is often conducted at low temperatures (below 55 °C) for an extended period of time to prevent crystallinity loss. The high-temperature acid hydrolysis (HTAH) behavior of heat-moisture treated (HMT) starch at 69 °C was investigated for the first time. The crystalline structure of starch was enhanced by HMT, confirmed by its rheological, thermal, and infrared Fourier transform spectroscopy results. The amorphous structure of HMT starch was preferentially hydrolyzed with high reactivity, related to a fast hydrolysis stage (4.17 × 10-2 min-1). And the crystalline flakes were separated from starch granules, accompanied by strengthened molecular interactions. HMT starch was transformed from 16.98 µm granules to 158 nm thick and 2.57 µm broad flakes with a 6.40 % increase in crystallinity after 40 min of hydrolysis. For native starch, the HTAH destroyed the crystalline structure due to gelatinization, resulting mainly gelatinous aggregates. These evidenced that the hydrolysis of granular starch was successfully performed at a relatively high temperature by introducing heat-moisture pre-treatment. This study could provide a novel perspective on the combination of increasing temperature and pre-treatment for granular starch hydrolysis intensification design, as well as a strategy for efficiently preparing small-sized crystalline starch, which has promising applications in Pickering emulsion and material filler.


Assuntos
Temperatura Alta , Zea mays , Hidrólise , Temperatura , Amido/química , Ácidos
16.
Toxicon ; 219: 106934, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36195155

RESUMO

Kochiae Fructus (KF) was listed as 'top grade' medicinal material by the 'Shennong's Herbal Classic of Materia Medica' and has been used in traditional Chinese medicine to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc. Our research focused on the antioxidant capability of water decoction and fractions from KF based on 2,2-iphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radical scavenging assay, the ferric reducing antioxidant power assay, and inhibitory effects on DNA and protein oxidative damage. The results of total phenolics and flavonoids contents showed that ethyl acetate fraction (EAF) possessed the highest phenolics and flavonoids with values of 112.90 ± 9.58 mg gallic acid equivalents/g and 329.60 ± 20.93 mg rutin equivalents/g, respectively. At the same time, the results of antioxidant capacities showed that EAF possessed best antioxidant abilities. In addition, in this work, we evaluated the oral safety of the water decoction of KF (KFWD) via the 14-day acute and 28-day subacute toxicity tests. The results of in vivo toxicity assessment showed that KFWD did not cause significant changes in the general clinical symptoms, hematology and biochemical parameters, organ weights, or histopathological appearances in mice or rats. In summary, the reason why KF has the traditional effect on delaying aging may be related to the fact that its rich in flavonoids and phenolics. Simultaneously, no toxicity was detected after acute or subacute treatment of KFWD, providing valuable evidence for the traditional safe use of KF.


Assuntos
Antioxidantes , Materia Medica , Camundongos , Ratos , Animais , Antioxidantes/farmacologia , Água , Flavonoides/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ácido Gálico , Rutina , Ácidos Sulfônicos/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 47(13): 3569-3580, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-35850811

RESUMO

The study was designed to determine the influences of Picrorhizae Rhizoma on gut microbiota and metabolites in mice with functional constipation(FC). ICR mice were divided into the blank control group, model group, and the low-, middle-, and high-dose Picrorhizae Rhizoma groups. Mice in the model and low-, middle-, and high-dose Picrorhizae Rhizoma groups were modeled with loperamide hydrochloride. After successful modeling, the ones in the low-, middle-, and high-dose Picrorhizae Rhizoma groups were gavaged with Picrorhizae Rhizoma at the corresponding doses for seven days. The first appearance time of tarry stool, the total fecal volume within 3 h, the fecal moisture content, and the intestinal transit rate were observed in each group. The pathological changes in intestinal mucosa were detected by HE staining. The flora dynamics in colon content were measured by 16 S rDNA sequencing, followed by the examination of fecal metabolomic profiles by gas chromatography-mass spectrometry(GC-MS). The results showed that the first appearance time of tarry stool in the model group was prolonged. The total fecal volume within 3 h, the fecal moisture content, and the intestinal transit rate were significantly reduced. The colon tissue showed inflammatory cell infiltration. Gut microflora and fecal metabolites changed dramatically. Picrorhizae Rhizoma alleviated the constipation symptoms, repaired intestinal mucosa, and partially restored the gut microbiota and metabolite compositions in mice with constipation. As demonstrated by intestinal microbiota sequencing, Picrorhizae Rhizoma remarkably reduced the Firmicutes/Bacteroidetes ratio and the relative abundance of Lactobacillus, but increased the relative abundance of Muribaculaceae, Enterorhabdus, and Eggerthellaceae. According to the linear discriminant analysis effect size(LefSe), the dominant bacterial species in the Picrorhizae Rhizoma groups were Muribaculaceae, Dubosiella, and Akkermansia. A total of 43 differential metabolites were detected in the feces of mice, involving the D-glutamine and D-glutamate metabolism, glutathione metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, purine metabolism, and pyrimidine metabolism. All these have demonstrated that Picrorhizae Rhizoma enhanced gastrointestinal motility, protectd gastrointestinal mucosa, and alleviated constipation symptoms possibly by regulating the intestinal microbial communities and metabolites and affecting the related metabolic pathways.


Assuntos
Microbioma Gastrointestinal , Animais , Constipação Intestinal/tratamento farmacológico , DNA Ribossômico , Fezes/microbiologia , Cromatografia Gasosa-Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR
18.
Molecules ; 27(11)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35684319

RESUMO

Our research focused on the hypoglycemic capability and the possible mechanisms of extract and fractions from Polygoni Avicularis Herba (PAH) based on α-glucosidase, α-amylase inhibition assays, glucose uptake experiment, HPLC-MS analysis, and molecular docking experiment. In addition, DPPH, ABTS, and FRAP assays were used for determining the antioxidant capability. The results of total flavonoids and phenolics contents showed that ethyl acetate fraction (EAF) possessed the highest flavonoids and phenolics with values of 159.7 ± 2.5 mg rutin equivalents/g and 107.6 ± 2.0 mg galic acid equivalents/g, respectively. The results of in vitro hypoglycemic activity showed that all samples had effective α-glucosidase inhibition capacities, and EAF possessed the best inhibitory effect with IC50 value of 1.58 ± 0.24 µg/mL. In addition, n-butanol fraction (NBF) significantly promoted the glucose uptake rate of 3T3-L1 adipocytes. HPLC-MS analysis and molecular docking results proved the interactions between candidates and α-glucosidase. The results of antioxidation capacities showed that EAF possessed the best antioxidation abilities with DPPH, ABTS, and FRAP. In summary, the hypoglycemic activity of PAH might be related to the inhibition of α-glucosidase (EAF > PEF > NBF) and the promotion of glucose uptake in 3T3-L1 adipocytes (NBF). Simultaneously, the antioxidation capacity of PAH might be related to the abundant contents of flavonoids and other phenolics (EAF > PEF > NBF).


Assuntos
Antioxidantes , Hipoglicemiantes , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Glucose , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , alfa-Glucosidases
19.
Zhongguo Zhen Jiu ; 42(5): 541-8, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35543945

RESUMO

OBJECTIVE: To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]). METHODS: Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group. RESULTS: Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (P<0.01). Except for the erythema scores of the dexamethasone group and the surrounding technique group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all decreased in each intervention group as compared with the model group (P<0.01). The infiltration scores and the total scores in the dexamethasone group and the acupoint group were lower than those in the surrounding technique group respectively (P<0.01, P<0.05). In comparison with the blank group, Ki-67 positive cell numbers and the numbers of , and T cells in skin tissue were increased in the mice of the model group (P<0.01). Ki-67 positive cell numbers and the numbers of , and T cells were reduced in each intervention group as compared with the model group (P<0.01), and the numbers of and T cells in the acupoint group were less than the surrounding technique group (P<0.01). Compared with the blank group, the mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all increased in the model group (P<0.01). The mRNA expressions of IL-17, IL-22 and TNF-α and the ratio of p-STAT3 to STAT3 were all decreased in each intervention group as compared with the model group (P<0.01, P<0.05). The mRNA expressions of IL-17, IL-22 and TNF-α in the acupoint group, as well as mRNA expression of IL-17 in the surrounding technique group were all lower than the dexamethasone group (P<0.01), while, the mRNA expression of IL-22 in the acupoint group was lower than the surrounding technique group (P<0.01). CONCLUSION: Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.


Assuntos
Interleucina-17 , Psoríase , Animais , Dexametasona/metabolismo , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Imiquimode/efeitos adversos , Imiquimode/metabolismo , Interleucina-17/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/farmacologia , Pele/metabolismo , Pele/patologia , Fator de Necrose Tumoral alfa/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-35547654

RESUMO

Objective: To analyze the characteristics of pulse graph parameters in patients with polycystic ovary syndrome (PCOS) varied at different body mass index (BMI) levels and to provide pulse diagnosis basis for syndrome differentiation and treatment of PCOS. Methods: Pulse graph parameters of 152 patients with PCOS (26 lean patients, 63 patients with moderate weight, and 63 overweight patients) were measured by a Z-BOX pulse meter, and the pulse graph parameters of patients with PCOS varied at different BMI levels were analyzed. Results: Fine pulse, slippery pulse, and string-like pulse were the most common pulse conditions in patients with PCOS. The common pulse conditions of patients with PCOS varied at different BMI levels. The order of pulse conditions was as follows: lean group: fine pulse > string-like pulse > slippery pulse; moderate group: fine pulse > slippery pulse > string-like pulse; and overweight group: slippery pulse > fine pulse > sunken pulse. Compared to the overweight group, the pulse graph parameters h1, h3, h4, h5, h4/h1, As, and Ad increased in the moderate group (P < 0.05), and the parameters h1, h3, and Ad increased (P < 0.05) and the parameter t1 decreased (P < 0.05) in the lean group. Conclusion: Pulse graph parameters among patients with PCOS varied at different BMI levels, which can probably provide pulse diagnosis basis for syndrome differentiation and treatment of PCOS by traditional Chinese medicine (TCM).

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