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1.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1113-1121, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621918

RESUMO

This study systematically collected, analyzed, and evaluated randomized controlled trial(RCT) in the treatment of diabetic foot ulcer(DFU). The aim as provide references for future studies and to enhance the application of clinical evidence. The RCT of DFU treated with Chinese Patent Medicine was obtained and analyzed using the AI-Clinical Evidence Database of Chinese Patent Medicine(AICED-CPM). The analysis was supplemented with data from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science. A total of 275 RCTs meeting the requirements were retrieved, with only 7 of them having a sample size of 200 or more. These trials involved 66 different Chinese patent medicine including 25 oral medications, 24 Chinese herbal injections, and 17 external drugs. Among the 33 different intervention/control designs identified, the most common design was Chinese patent medicine + conventional treatment vs conventional treatment(86 cases, 31.27%). Out of the 275 articles included in the literature, 50 did not provide information on the specific course of treatment(18.18%). A total of 10 counting indicators(with a frequency of 426) and 36 measuring indicators(with a frequency of 962) were utilized. The methodological quality of the RCT for the treatment of DFU with Chinese patent medicine was found to be low, with deficiencies in blind methods, other bias factors, study registration, and sample size estimation. There were noticeable shortcomings in the reporting of allocation hiding and implementation bias(blind method application). More studies should prioritize trial registration, program design, and strict quality control during implementation to provide valuable data for clinical practice and serve as a reference for future investigations.


Assuntos
Diabetes Mellitus , Pé Diabético , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5863-5870, 2023 Nov.
Artigo em Zh | MEDLINE | ID: mdl-38114182

RESUMO

This study aims to investigate the effects of baicalein(BAI) on lipopolysaccharide(LPS)-induced human microglial clone 3(HMC3) cells, with a focus on suppressing inflammatory responses and elucidating the potential mechanism underlying the therapeutic effects of BAI on ischemic stroke via modulating the cAMP-PKA-NF-κB/CREB pathway. The findings have significant implications for the application of traditional Chinese medicine in treating cerebral ischemic diseases. First, the safe dosage of BAI was screened, and then an inflammation model was established with HMC3 cells by induction with LPS for 24 h. The cells were assigned into a control group, a model group, and high-, medium-, and low-dose(5, 2.5, and 1.25 µmol·L~(-1), respectively) BAI groups. The levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in cell extracts, as well as the levels of interleukin-1ß(IL-1ß), IL-6, tumor necrosis factor-α(TNF-α), and cyclic adenosine monophosphate(cAMP) in the cell supernatant, were measured. Western blot was performed to determine the expression of protein kinase A(PKA), phosphorylated cAMP-response element binding protein(p-CREB), and nuclear factor-kappa B p65(NF-κB p65). Hoechst 33342/PI staining was employed to assess cell apoptosis. High and low doses of BAI were used for treatment in the research on the mechanism. The results revealed that BAI at the concentrations of 10 µmol·L~(-1) and below had no impact on normally cultured HMC3 cells. LPS induction at 200 ng·mL~(-1) for 24 h reduced the SOD activity and increased the MDA content in HMC3 cells. However, 5, 2.5, and 1.25 µmol·L~(-1) BAI significantly increased the SOD activity and 5 µmol·L~(-1) BAI significantly decreased the MDA content. In addition, BAI ameliorated the M1 polarization of HMC3 cells induced by LPS, as indicated by cellular morphology. The results of ELISA demonstrated that BAI significantly lowered the levels of TNF-α, IL-1ß, IL-6, and cAMP in the cell supernatant. Western blot revealed that BAI up-regulated the protein levels of PKA and p-CREB while down-regulating the expression of NF-κB p65. Hoechst 33342/PI staining results indicated that BAI mitigated the apoptosis of HMC3 cells. Overall, the results indicated that BAI had protective effects on the HMC3 cells induced by LPS, and could inhi-bit inflammatory response and improve cell apoptosis, which might be related to the regulation of the cAMP-PKA-NF-κB/CREB pathway.


Assuntos
Microglia , NF-kappa B , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Superóxido Dismutase/metabolismo
3.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5284-5291, 2022 Oct.
Artigo em Zh | MEDLINE | ID: mdl-36472035

RESUMO

This study aims to observe the therapeutic effect of salidroside on cerebral ischemia-reperfusion(I/R) model rats, and to specifically explore the protection of salidroside on endothelial cell barrier after I/R and the mechanism. In the experiment, SD rats were randomized into sham group, model group, and high-, medium-, and low-dose(10, 5, and 2.5 mg·kg~(-1)) salidroside groups. The suture method was used to induce I/R in rats. The infarct area, neurobehavioral evaluation, and brain water content were used to evaluate the efficacy of salidroside. As for the experiment on the mechanism, high-dose and low-dose salidroside groups were designed. The pathological morphology was observed based on hematoxylin and eosin(HE) staining, and ultrastructure of vascular endothelial cells based on transmission electron microscopy. The content of nitric oxide(NO) in serum, four indexes of blood coagulation, and the content of von Willebrand factor(vWF) in plasma were measured. Western blot(WB) and immunofluorescence(IF) were employed to determine the expression of tight junction proteins(ZO-1, occluding, and claudin-1) and matrix metalloproteinase 9(MMP-9) in the cortex. The results showed that the model group had obvious neurological deficit, obvious infarct in the right brain tissue, and significant increase in water content in brain tissue compared with the sham group. Compared with the model group, high-dose and low-dose salidroside groups showed decrease in neurobehavioral score, and the high-, medium-, and low-dose salidroside groups demonstrated obviously small infarct area and significant decrease in water content in brain tissue. The results of HE staining and transmission electron microscopy showed that rats had necrosis of neurons, damage of original physiological structure of endothelial cells, and disintegration of the tight junction between endothelial cells after I/R compared with the sham group. Compared with the model group, the high-dose and low-dose salidroside groups showed alleviation of neuron injury and intact physiological structure of endothelial cells. The model group had significantly lower serum level of NO, significantly higher plasma levels of vWF and fibrinogen(FIB), and significantly shorter thrombin time(TT) and prothrombin time(PT) than the sham group. Compared with model group, the high-dose and low-dose salidroside groups increased the serum content of NO in serum, decreased the plasma levels of FIB and vWF, and significantly prolonged TT and PT. WB and IF results showed that the model group had significantly lower levels of ZO-1, occluding, and claudin-1 among endothelial cells and significantly higher level of MMP-9 than the sham group. Compared with the model group, high-dose and low-dose salidroside significantly increased the levels of ZO-1, occluding, and claudin-1 in the cortex. The above experimental results show that salidroside has clear therapeutic effect on I/R rats and protects the brain. To be specific, it alleviates the damage of endothelial cells by increasing NO synthesis in endothelial cells, inhibiting coagulation reaction and MMP-9 expression, up-regulating the expression of ZO-1, occludin, and claudin-1, thereby protecting the brain.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Ratos , Metaloproteinase 9 da Matriz/metabolismo , Células Endoteliais/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Barreira Hematoencefálica , Claudina-1/metabolismo , Claudina-1/farmacologia , Claudina-1/uso terapêutico , Fator de von Willebrand/metabolismo , Fator de von Willebrand/farmacologia , Fator de von Willebrand/uso terapêutico , Ratos Sprague-Dawley , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral , Reperfusão , Água/metabolismo
4.
Zhongguo Zhong Yao Za Zhi ; 47(4): 1031-1038, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35285204

RESUMO

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.


Assuntos
Edema Encefálico , Isquemia Encefálica , Animais , Aquaporina 4/genética , Astrócitos , Edema Encefálico/tratamento farmacológico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Flavonoides , Infarto da Artéria Cerebral Média/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Reperfusão , Canais de Cátion TRPV/uso terapêutico
5.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5226-5232, 2021 Oct.
Artigo em Zh | MEDLINE | ID: mdl-34738423

RESUMO

Buyang Huanwu Decoction, a representative prescription in traditional Chinese medicine(TCM) for tonifying Qi and activating blood, has been proved to be effective in preventing and treating acute cerebral infarction(ACI). It consists of Astragali Radix, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Pheretima, Chuanxiong Rhizoma, Carthami Flos, and Persicae Semen, possessing multiple active ingredients. The neurovascular unit is a functionally and structurally interdependent multicellular complex composed of neurons-glial cells-blood vessels. It plays an important role in the pathological changes of cerebral ischemia and the permeability variation of the blood-brain barrier. In recent years, Buyang Huanwu Decoction has been found to protect the integrity of neurovascular units and improve the permeability of the blood-brain barrier, thereby alleviating stroke and other diseases caused by cerebral ischemia. This paper collated and summarized the protective effects of Buyang Huanwu Decoction on neurovascular units.


Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , Isquemia Encefálica/tratamento farmacológico , Infarto Cerebral , Humanos , Medicina Tradicional Chinesa
6.
Zhongguo Zhong Yao Za Zhi ; 43(4): 786-793, 2018 Feb.
Artigo em Zh | MEDLINE | ID: mdl-29600656

RESUMO

This study aimed to observe the general state and changes in pathophysiological indexes of multiple cerebral infarction rat model with Qi-deficienty and Blood-stasis syndrome. Rats were randomly divided into 4 groups(with 30 in each group): the normal group, the sham group, the model group and the Yiqi Huoxue recipe group. Rats in the model group and Yiqi Huoxue group were provided with interruptable sleep deprivation for 7 days before the multiple cerebral infarction operation, and followed by another 4 weeks of sleep deprivation; rats in the Yiqi Huoxue group were intragastrically administrated with drug at a dose of 26 g·kg⁻¹, once a day for 4 weeks. The general state was observed, and the pathophysiological indexes were measured at 48 h, 2 weeks and 4 weeks after administration. The results showed that rats in the normal group and the sham group represented a good general state and behaviors, with a normal morphological structure of brain tissues; rats in the model group featured yellow fur, depression, accidie, loose stools and movement disorder, with obvious brain histomorphological damage, which became aggravated with the increase of modeling time; rats in the Yiqi Huoxue group showed release in the general state and above indexes. Compared with the sham group at three time points, rats in the model group showed decrease in body weight, exhaustive swimming time and RGB value of tongue surface image, and increase in whole blood viscosity of the shear rate under 5, 60 and 150 S⁻¹, reduction in cerebral cortex Na⁺-K⁺-ATPase, Ca²âº-ATPase activity and contents of 5-HT, rise in TXB2 levels and decline in 6-keto-PGF1a in serum(P<0.05, P<0.01). Compared with the model group, rats in the Yiqi Huoxue group showed alleviations in the above indexes at 2 w and 4 w(P<0.05, P<0.01). The results showed that the characterization and pathophysiological indexes in the multiple cerebral infarction rat model with Qi-deficiency and blood-stasis syndrome were deteriorated; Yiqi Huoxue recipe could significantly alliviate the abnormal conditions, which suggested of the model was stable and reliable and the pathophysiologic evolutionary mechanism might be related to energy metabolism dysfunction, vasoactive substance abnormality and changes in neurotransmitters.


Assuntos
Infarto Cerebral/fisiopatologia , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético , Animais , ATPases Transportadoras de Cálcio/metabolismo , Medicina Tradicional Chinesa , Qi , Ratos , ATPase Trocadora de Sódio-Potássio/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 42(11): 2168-2174, 2017 Jun.
Artigo em Zh | MEDLINE | ID: mdl-28822164

RESUMO

To further study the brain behavior and the pharmacokinetics of baicalin in intercellular fluid of brain, and study the recovery rate and stability of brain and blood microdialysis probe of baicalin in vitro and in vivo. The concentration of baicalin in brain and blood microdialysates was determined by LC-MS/MS and the probe recovery for baicalin was calculated. The effects of different flow rates (0.50, 1.0, 1.5, 2.0,3.0 µL•min⁻¹) on recovery in vitro were determined by incremental method and decrement method. The effects of different drug concentrations (50.00, 200.0, 500.0, 1 000 µg•L⁻¹) and using times (0, 1, 2) on recovery in vitro were determined by incremental method. The probe recovery stability and effect of flow rate on recovery in vivo were determined by decrement method, and its results were compared with those in in vitro trial. The in vitro recovery of brain and blood probe of baicalin was decreased with the increase of flow rate under the same concentration; and at the same flow rate, different concentrations of baicalin had little influence on the recovery. The probe which had been used for 2 times showed no obvious change in probe recovery by syringe with 2% heparin sodium and ultrapure water successively. In vitro recovery rates obtained by incremental method and decrement method were approximately equal under the same condition, and the in vivo recovery determined by decrement method was similar with the in vitro results and they were showed a good stability within 10 h. The results showed that decrement method can be used for pharmacokinetic study of baicalin, and can be used to study probe recovery in vivo at the same time.


Assuntos
Flavonoides/isolamento & purificação , Microdiálise , Animais , Química Encefálica , Cromatografia Líquida , Flavonoides/sangue , Espectrometria de Massas em Tandem
8.
Bull Environ Contam Toxicol ; 97(6): 763-769, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27670860

RESUMO

Estrogenic activities of river water from four representative cross-sections of the Yellow River (Zhengzhou section) and their effects on reproduction and development of fish were assessed. MVLN assay showed estradiol equivalents of river water from Yiluohe, Xinmanghe, Qinhe and Huayuankou cross-sections were 1.09 ± 0.11, 0.72 ± 0.01, 1.19 ± 0.19 and 0.80 ± 0.04 ng/L, respectively. Significant vitellogenin (VTG) inductions were observed in adult male Japanese madaka (Oryzias latipes) after 30 days of exposure to river water from Yiluohe and Qinhe cross-sections (p < 0.05). Hepatic-somatic index was significantly elevated in fish exposed to water from Qinhe cross-section (p < 0.05). A significant delay in time to hatching was observed in embryos treated by water from Xinmanghe cross-section (p < 0.05). Significant lower survivals were observed in fish treated by water from Yiluohe and Xinmanghe cross-sections after a full life cycle exposure (p < 0.05). Exposure of water from Yiluohe and Qinhe cross-sections induced significantly elevated VTG levels in the first sexually mature male fish (p < 0.05). Both the in vitro and in vivo bioassay demonstrate endocrine disrupting chemicals exist in the Yellow River (Zhengzhou section) and fish in Yiluohe and Qinhe cross-sections can be at a risk of reproductive and developmental impairment.


Assuntos
Disruptores Endócrinos/análise , Oryzias/metabolismo , Poluentes Químicos da Água/análise , Animais , Bioensaio , Estradiol/análise , Estágios do Ciclo de Vida , Fígado/efeitos dos fármacos , Masculino , Reprodução/efeitos dos fármacos , Rios , Vitelogeninas/efeitos dos fármacos , Poluentes Químicos da Água/farmacologia
9.
Org Biomol Chem ; 13(17): 4925-30, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25812133

RESUMO

The first example of palladium-catalyzed Suzuki-Miyaura coupling between benzyl sulfonates and arylboronic acids was reported in this paper. In the presence of a well-defined, air-stable and easily available NHC-Pd(II)-Im complex, all reactions worked well to give the desired products in good to almost quantitative yields under the optimal conditions. Electron-rich, -neutral, -poor and sterically-hindered substituents on both substrates are tolerated in such transformation, providing a convenient, efficient and alternative method for the synthesis of diarylmethanes.

10.
Zhongguo Zhong Yao Za Zhi ; 40(10): 1984-8, 2015 May.
Artigo em Zh | MEDLINE | ID: mdl-26390660

RESUMO

To observe the protective effect and mechanism of Sailuotong capsule in focal cerebral ischemia/reperfusion. The 90 min middle cerebral artery occlusion (MCAO) reperfusion model was established. The expressions of dynamin-related protein 1 ( Drp1) and optic atrophy 1 (Opa1) were tested by Western blot. The transmission electron microscope was used to observe the changes in the mitochondrial ultra-structure. The pathological morphological changes were observed through the HE staining. The immunohistochemical method was used to test Drp1 and Opa1 expressions. Sailuotong capsule (33, 16.5 mg x kg(-1), ig) can inhibit the abnormal mitochondrial fission and fusion in the cortical area on the ischemia side and the mitochondrial fission gene expression and promote the mitochondrial fusion gene Opa1 expression, so as to alleviate the energy metabolism disorder caused by ischemia/reperfusion. Sailuotong capsule can inhibit the abnormal mitochondrial dynamics in peri-ischemic regions and maintain the normal morphology of mitochondria, which may be the mechanism of Sailuotong capsule in promoting the self-recovery function in the ischemic brain region.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/cirurgia , Dinaminas/genética , Dinaminas/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Humanos , Masculino , Mitocôndrias/metabolismo , Ratos
11.
Fish Physiol Biochem ; 40(6): 1927-35, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25154921

RESUMO

Adverse effects of five typical environmental estrogens, namely estrone (E1), 17ß-estradiol (E2), 4-n-octylphenol (4-n-OP), 4-n-nonylphenol (4-n-NP) and bisphenol A (BPA) on adult male goldfish (Carassius auratus) were investigated both individually and in binary mixtures, using serum vitellogenin (VTG) induction and gonadosomatic index (GSI) as the endpoints. Doses of individual and binary mixtures of estrogens were chosen at broad ranges. Five individual estrogens induced common dose-dependent increases of serum VTG in the experimental fish when injection doses of the estrogen series were comparatively low. The levels of VTG induction in fish descended after peaked at a certain dose of the individual estrogen. Significant GSI decreases were observed in fish treated by all dose series of E1 and E2, and comparatively high doses of 4-n-OP, 4-n-NP and BPA when compared with that of solvent control (SC). Effects of binary mixtures of the five typical estrogens on VTG induction in male goldfish were in additive manner at low-effect doses, but divergences occurred at high dose levels, with the predicted effects by additive manner exceeding those were observed. All of GSI of fish treated by the binary mixtures were about or lower than 10(-3)%. Serious atrophy of gonads was observed in all the mixture treatment groups when compared with that of SC. These findings highlight the potential reproductive risk of fish resulted from existing mixtures of hormones in the aquatic environment, and they have important implications for environmental estrogen hazard assessment.


Assuntos
Estrogênios/farmacologia , Carpa Dourada/fisiologia , Animais , Estrogênios/administração & dosagem , Estrogênios/sangue , Carpa Dourada/sangue , Masculino , Vitelogeninas/sangue
12.
Zhongguo Zhong Yao Za Zhi ; 38(13): 2182-6, 2013 Jul.
Artigo em Zh | MEDLINE | ID: mdl-24079250

RESUMO

OBJECTIVE: To observe the protective effect of the Weinaokang (WNK) and its active compound bilobalide on focal cerebral ischemia reperfusion, and their mechanisms. METHOD: The 60-minute middle cerebral artery occlusion (MCAO) was adopted to establish the 24 h-14 d reperfusion model. The expression of Beclin-1 was detected by the Western blotting technique. The transmission electron microscopy was used to observe ultrastructural changes. Neurogenesis was detected by the immunofluorescence staining. RESULT: WNK (20, 10 mg x kg(-1), ig) or its active compound bilobalide (10, 5 mg x kg(-1), ig) could promote the generation of mature neurons (BrdU(+) -MAP-2+) at the ischemic side, and inhibit expression of autophagy-related gene Beclin-1, so as to reduce the neuron injury induced by focal cerebral ischemia reperfusion. CONCLUSION: WNK and its active compound bilobalide can inhibit neuron autophagy and improve neurogenesis in ischemic peripheral area, suggesting that neurogenesis may be the intervention target for WNK to promote self-repairing of ischemic area.


Assuntos
Autofagia/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Ciclopentanos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Furanos/farmacologia , Ginkgolídeos/farmacologia , Neurogênese/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Masculino , Neurônios/ultraestrutura , Ratos , Ratos Sprague-Dawley
13.
Zhongguo Zhong Yao Za Zhi ; 38(4): 585-90, 2013 Feb.
Artigo em Zh | MEDLINE | ID: mdl-23713288

RESUMO

OBJECTIVE: To observe the effect and mechanism of Huatuo Zaizao extractum (HTZZ) on focal ischemia/reperfusion (I/R) blood-brain barrier injury induced by middle cerebral artery occlusion. METHOD: Sixty healthy male adult Sprague-Dawley rats was randomly divided into the sham operation group, the MCAO model group, the Tanakan (20 mg x kg(-1)) group, and high, middle and low-dose HTZZ groups (5, 2.5, 1.25 g x kg(-1)), with 10 in each group and single-dose duodenal administration. Middle cerebral artery occlusion was adopted to establish the rat focal I/R model. After ischemia for 90 min and reperfusion for 24 h, the pathological injury at the ischemia side was observed by HE staining. The blood-brain barrier structure was observed under transmission electron microscope. Expressions of G protein-coupled receptor kinases 2 (GRK2), matrix metalloproteinases 2 (MMP-2) and MMP-9 were detected by western blotting technique. RESULT: After 90 min MCAO/24 h reperfusion, penumbra cerebral cortical micro-vessels showed edema, mitochondrial injury, vacuolation, membrane injury and reduction. Along with the changes, sub-cells of G protein-coupled receptor kinase 2 (GRK2) in cortical penumbra brain tissues transferred from cytoplasm to membrane, with increase in expressions of MMP-2 and MMP-9. HTZZ could effectively recover cerebral micro-vascular endothelial edemaand blood-brain barrier ultrastructure injury induced by I/R, reduce expression of functional (membrane coupling) GRK2, and inhibit expressions of MMP-2 and MMP-9. CONCLUSION: Cell membrane coupling GRK2 may be the effective target of Huatuo Zaizao extractum.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/lesões , Medicamentos de Ervas Chinesas/farmacologia , Infarto da Artéria Cerebral Média/complicações , Traumatismo por Reperfusão/complicações , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Relação Dose-Resposta a Droga , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Microvasos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia
14.
Food Sci Nutr ; 11(10): 6459-6469, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37823169

RESUMO

Obesity is characterized by chronic inflammation, insulin resistance, and gut microbiota dysbiosis. Dioscorea opposita Thunb. is a traditional food and medicine homolog from China. In the present study, polysaccharides isolated from a water extract of Dioscorea opposita Thunb. (DOTPs) were prepared. We showed that DOTPs reduced body weight, accumulation of fat tissues, insulin resistance, and inflammation in high-fat diet (HFD)-fed mice. Further experiments showed that DOTPs could regulate the composition of the gut microbiota in HFD mice. DOTPs supplementation in HFD-fed mice resulted in the reduction of the Firmicutes-to-Bacteroidetes ratio. We further demonstrated that DOTPs supplementation enhanced bacterial levels of Akkermansia and reduced levels of Ruminiclostridium_9. A significant reduction of glycolysis metabolism related to obesity and gut microbiota dysbiosis was also observed upon administration of DOTPs. Our results suggest that DOTPs can produce significant anti-obesity effects, by inhibiting systematic inflammation and ameliorating gut microbiota dysbiosis in diet-induced obese mice.

15.
Yao Xue Xue Bao ; 47(7): 870-7, 2012 Jul.
Artigo em Zh | MEDLINE | ID: mdl-22993850

RESUMO

The rat model of multi-infarct was adopted in this study to elucidate the protective mechanism of Sailuotong capsule (Sailuotong) in recovery period of multiple cerebral infarction. The effects of Sailuotong on levels of Glu, GABA and the expression of NMDA receptor subtypes including NR1, NR2A and NR2B, were detected. The multi-infarct model rats were established by injecting embolizing microsphere via internal carotid artery, and were given Sailuotong treatment (16.5 and 33.0 mg x kg(-1)) for 60 days. The pathological changes in brain ultrastructure were observed by transmission electron microscope. The levels of Glu and GABA in brain tissue were measured with high performance liquid chromatography. The expression of NMDA receptors including NR1, NR2A and NR2B in neurons was evaluated by immunohistochemical staining. Compared with the sham rats, abnormal changes were observed in ultrastructures of neurons, neuroglia cells and synapses of model rat brains. Moreover, significant decrease of Glu and GABA, as well as the elevated expression of NR1, NR2A and NR2B were detected in brain tissues. Sailuotong (16.5 and 33.0 mg x kg(-1)) could improve ultrastructure of cerebral tissue, facilitate synthesis of Glu and GABA, and down-regulate expression of NR1, NR2A and NR2B in neurons. The results demonstrated that Sailuotong could exert neuroprotective effects to some extent in the recovery phase of multiple cerebral infarction by promoting expression of NMDA receptors and synthesis of Glu and GABA.


Assuntos
Infarto Cerebral/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ácido Glutâmico/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptores de N-Metil-D-Aspartato/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Cápsulas , Córtex Cerebral/metabolismo , Infarto Cerebral/patologia , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Ginkgo biloba/química , Hipocampo/metabolismo , Masculino , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Panax/química , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/classificação , Sinapses/metabolismo , Sinapses/patologia
16.
Zhongguo Zhong Yao Za Zhi ; 37(19): 2943-6, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23270238

RESUMO

OBJECTIVE: To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism. METHOD: All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues. RESULT: Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01). CONCLUSION: Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Demência por Múltiplos Infartos/complicações , Medicamentos de Ervas Chinesas/farmacologia , Acetilcolinesterase/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Colina O-Acetiltransferase/metabolismo , Transtornos Cognitivos/metabolismo , Demência por Múltiplos Infartos/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
Appl Microbiol Biotechnol ; 91(3): 731-40, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21556920

RESUMO

Ideal immunogenicity in antigens is a prerequisite to eliciting a sufficiently strong immune and memory response via either DNA or protein vaccines. To improve immunogenicity, efforts have focused on high-level expression of target proteins and on maintaining their natural conformations. In the present work, two trimer motifs (MTQ and MTI) were designed and introduced into a plasmid vector with the tissue plasminogen activator signal peptide (tPA-SP). Next, we examined the efficacy and the efficiency of the two motifs as well as the introduction of tPA-SP and its mutant forms, 22P/A and 22P/G, in facilitating the secretory expression of trimeric proteins in mammalian cells. We found that both trimer motifs could produce the target protein in a trimeric form at a high level. Introduction of tPA-SP 22P/A markedly increased the secretory expression level. The combination of the trimer motif, MTQ, and the signal peptide, 22P/A, may serve as a universal mammalian vector for producing trimeric proteins in vaccine development.


Assuntos
Motivos de Aminoácidos/imunologia , Complexos Multiproteicos , Sinais Direcionadores de Proteínas/genética , Ativador de Plasminogênio Tecidual/genética , Sequência de Aminoácidos , Ensaio de Imunoadsorção Enzimática , Células HEK293 , HIV/genética , HIV/metabolismo , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/metabolismo , Mutação , Estrutura Secundária de Proteína , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Ativador de Plasminogênio Tecidual/imunologia , Vacinas de DNA/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
18.
Front Pharmacol ; 11: 911, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670058

RESUMO

Quinazoline derivatives display multiple pharmacological activities and target various biological receptors. Based on the skeleton of quinazoline core, we designed and synthesized three new quinazoline-phenyl chlormethine conjugates (I-III) bearing a Schiff base (C = N) linker, and investigated their anti-tumor effects on HepG2-xenografted tumor and human cancer cell line HepG2. Among these compounds, compound II showed better inhibitory effect against HepG2 cells. In the present study, TUNEL staining, western blot, molecular docking, and siRNA were used to investigate the inhibitory mechanism of compound II towards hepatoma. Compound II inhibited HepG2-xenografted tumor growth in nude mice. Moreover, Compound II not only up-regulated Bax/Bcl-2 ratio and active-caspase 3 level, but also down-regulated Sirt1 expression and its activity, as well as PGC-1α expression. Furthermore, compound II also significantly suppressed the promotion of HepG2 cell proliferation, as evidenced by MTT assay and lactate dehydrogenase (LDH) release assay. Of note, the cytotoxicity of Compound II on HepG2 cells mainly via regulating Sirt1/caspase 3 signaling pathway, consisting with the results in vivo. Intriguingly, z-DEVD-FMK, a caspase 3 inhibitor, almost abolished the inhibitory effects of compound II. Of note, knockdown of caspase 3 by siRNA significantly reversed the inhibitory effect of compound II on HepG2. Interestingly, compound II directly bonded to Sirt1, indicating that Sirt1 might be a promising therapeutic target of compound II. In summary, our findings reveal that compound II, a new synthetical phenyl chlormethine-quinazoline derivative, contributes to the apoptosis of HepG2 cells both in vivo and in vitro through mediating Sirt1/caspase 3 singling pathway. These findings demonstrate that compound II may be a new potent agent against hepatocellular carcinoma.

19.
Front Pharmacol ; 10: 29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804781

RESUMO

Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 µg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.

20.
Aging (Albany NY) ; 11(15): 5705-5725, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400752

RESUMO

Accumulating evidence reveals the principal role of long noncoding RNAs in the progression of clear cell renal cell carcinoma (ccRCC). However, little is known about the underlying mechanism of ADAM metallopeptidase with thrombospondin type 1 motif, 9 antisense RNA 2 (ADAMTS9-AS2) in ccRCC. Here, bioinformatics analyses verified ADAMTS9-AS2 is a long noncoding RNA and its high expression was associated with better prognosis of ccRCC. ADAMTS9-AS2 was clearly downregulated in ccRCC clinical samples and cell lines. Clinical data showed low-expressed ADAMTS9-AS2 was correlated with worse overall survival in ccRCC patients. Next, miR-27a-3p was identified as an inhibitory target of ADAMTS9-AS2 by dual-luciferase reporter and RNA immunoprecipitation assays. Both overexpressed ADAMTS9-AS2 and underexpressed miR-27a-3p in ccRCC cell lines led to the inhibition of cell proliferation and the reduction of chemoresistance. Additionally, Forkhead Box Protein O1 (FOXO1) was confirmed as the inhibitory target of miR-27a-3p. Induced by ADAMTS9-AS2 overexpression, cell proliferation and chemoresistance exhibited an obvious reduction, FOXO1 expression showed an evident increase, but all were reversed after miR-27a-3p was simultaneously overexpressed. Collectively, these results suggest ADAMTS9-AS2 inhibits the progression and impairs the chemoresistance of ccRCC via miR-27a-3p-mediated regulation of FOXO1 and may serve as a prognostic biomarker and therapeutic target for ccRCC.


Assuntos
Proteína ADAMTS9/antagonistas & inibidores , Proteína ADAMTS9/genética , Carcinoma de Células Renais/genética , Proteína Forkhead Box O1/genética , Neoplasias Renais/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Biologia Computacional , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Proteína Forkhead Box O1/antagonistas & inibidores , Proteína Forkhead Box O1/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , RNA Antissenso/genética , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais
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