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1.
Sci Rep ; 9(1): 15087, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636354

RESUMO

Inflammation is a complex physiological process that poses a serious threat to people's health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/ß and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31275420

RESUMO

Anemoside B4 (B4) isolated from Radix Pulsatilla has anti-inflammatory activities in the colon and antitumor effects. However, its role in the prevention and treatment of kidney injury has not been reported. Here, we reported the effects of B4 on chronic kidney injury (CKI) and studied its related mechanism based on an adenine-induced kidney injury model in rats. The results showed that serum BUN (blood urea nitrogen), Crea (creatinine), and urinary proteins increased significantly after oral administration of adenine. Meanwhile, the adenine contents in both renal tissue and urine increased markedly compared with those of normal rats. Moreover, IL-1ß, IL-6, TNFα, and NFκB expression was upregulated in the kidney. Simultaneously, the expression of NLRP3 (the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3) in the inflammasome, which consists of Caspase 1, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and IL-18, was significantly upregulated. B4 could significantly decrease BUN and Crea; reduce urinary proteins in rats; suppress the expression of IL-6, IL-1ß, NFκB, NLRP3, Caspase 1, ASC, and IL-18; and increase urinary adenine contents and promote its excretion. In addition, B4 also upregulated the expression of podocin and nephrin, two major podocyte proteins, and reduced the fiber collagen in the renal interstitial, suggesting that B4 could protect the glomerular matrix from adenine injury in addition to its anti-inflammatory effects. The results of this study show new perspective of B4 as a potential drug against adenine-induced renal injury.

3.
Zhongguo Zhong Yao Za Zhi ; 44(5): 996-1003, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989861

RESUMO

In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 µmol·L-1 to more than 430 µmol·L-1. Among them,5 rats showed less than 100 µmol·L-1 serum Crea,20 rats with 100-200 µmol·L-1 serum Crea and 12 rats with more than 430 µmol·L-1. Rats with serum Crea between 300-430 µmol·L-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 µmol·L-1 continued to increase,while the serum Crea in the group of Crea 200-300 µmol·L-1 and the group of Crea 300-370 µmol·L-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 µmol·L-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.


Assuntos
Lesão Renal Aguda/patologia , Traumatismo por Reperfusão , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Rim/patologia , Túbulos Renais/patologia , Ligadura , Masculino , Ratos , Ratos Sprague-Dawley , Artéria Renal
4.
Pharmacol Res ; 142: 102-114, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30794925

RESUMO

Dihydrotanshinone (DHT), one of the major ingredients of Salvia miltiorrhiza Bunge (Danshen), displays many bioactivities. However, the activity and underlying mechanism of DHT in anti-inflammation have not yet been elucidated. In this study, we investigated the anti-inflammatory activity and molecular mechanism of action of DHT both in vitro and in vivo. Our data showed that DHT significantly decreased the release of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, THP-1 cells, and bone marrow-derived macrophages (BMDMs), and altered the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, flow cytometry results indicated that DHT reduced the calcium influx, and generation of reactive oxygen species (ROS), and nitric oxide (NO) generation in LPS-stimulated RAW264.7 cells. Moreover, DHT suppressed the transcription of nuclear factor-κB (NF-κB), the expressions of NF-κB proteins, and nuclear translocation of NF-κB/p65, thereby suggesting that the NF-κB pathway played a role in the anti-inflammatory action of DHT. In addition, DHT attenuated LPS-challenged activator protein-1 (AP-1) activity, resulting from interference of the mitogen-activated protein kinase (MAPK) pathway. The molecular docking simulation of DHT to toll-like receptor 4 (TLR4) suggested that DHT binds to the active sites of TLR4 to block TLR4 dimerization, which was further corroborated by cellular thermal shift assay and co-immunoprecipitation (Co-IP) experiments. Furthermore, the recruitment of myeloid differentiation primary response gene 88 (MyD88) and the expression of transforming growth factor-b (TGF-b)-activated kinase 1 (p-TAK1) were disturbed by the inhibition of TLR4 dimerization. Thus, investigating the molecular mechanism of DHT indicated that TLR4-MyD88-NF-κB/MAPK signaling cascades were involved in the anti-inflammatory activity of DHT in vitro. In in vivo mouse models, DHT significantly ameliorated LPS-challenged acute kidney injury, inhibited dimethylbenzene-induced mouse ear oedema, and rescued LPS-induced sepsis in mice. Taken together, our results indicated that DHT exhibited significant anti-inflammatory activity both in vitro and in vivo, suggesting that DHT may be a potential therapeutic agent for inflammatory diseases.

5.
Chin J Integr Med ; 25(6): 454-461, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28795389

RESUMO

OBJECTIVE: To explore the anti-nociceptive effect of patchouli alcohol (PA), the essential oil isolated from Pogostemon cablin (Blanco) Bent, and determine the mechanism in molecular levels. METHODS: The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to confirm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor (MOR). Cyclooxygenase 2 (COX2) and MOR of mouse brain were expressed for determination of PA's target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. RESULTS: PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution (P<0.01) and allodynia after intra-plantar formalin (P<0.01) in mice. PA also up-regulated COX2 mRNA and protein (P<0.05) with a down-regulation of MOR (P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level (P<0.05) induced by PA may play an important role in its anti-nociceptive effect. PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. CONCLUSIONS: Both COX2 and MOR are involved in the mechanism of PA's anti-nociceptive effect, and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA's effect on MOR.

6.
Mol Brain ; 12(1): 118, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888678

RESUMO

Chronic corticosterone (CORT) stress is an anxiety and depression inducing factor that involves the dysfunction of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), and neuronal plasticity. However, the regulation of proteomic profiles in neurons suffering CORT stress is remaining elusive. Thus, the proteomic profiles of mouse neuronal C17.2 stem cells were comprehensively investigated by TMT (tandem mass tag)-labeling quantitative proteomics. The quantitative proteomics conjugated gene ontology analysis revealed the inhibitory effect of CORT on the expression of mitochondrial oxidative phosphorylation-related proteins, which can be antagonized by berberine (BBR) treatment. In addition, animal studies showed that changes in mitochondria by CORT can affect neuropsychiatric activities and disturb the physiological functions of neurons via disordering mitochondrial oxidative phosphorylation. Thus, the mitochondrial energy metabolism can be considered as one of the major mechanism underlying CORT-mediated depression. Since CORT is important for depression after traumatic stress disorder, our study will shed light on the prevention and treatment of depression as well as posttraumatic stress disorder (PTSD).

7.
Math Biosci Eng ; 14(5-6): 1187-1213, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29161856

RESUMO

This paper is concerned with invasion entire solutions of a monostable time periodic Lotka-Volterra competition-diffusion system. We first give the asymptotic behaviors of time periodic traveling wave solutions at infinity by a dynamical approach coupled with the two-sided Laplace transform. According to these asymptotic behaviors, we then obtain some key estimates which are crucial for the construction of an appropriate pair of sub-super solutions. Finally, using the sub-super solutions method and comparison principle, we establish the existence of invasion entire solutions which behave as two periodic traveling fronts with different speeds propagating from both sides of x-axis. In other words, we formulate a new invasion way of the superior species to the inferior one in a time periodic environment.


Assuntos
Difusão , Modelos Biológicos , Dinâmica Populacional , Comportamento Predatório , Algoritmos , Animais , Ecossistema , Umidade , Modelos Estatísticos , Temperatura Ambiente , Fatores de Tempo
8.
Chin J Nat Med ; 15(10): 732-739, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29103458

RESUMO

Pomegranate leaf (PGL) has a definite role in regulating lipid metabolism. However, pharmacokinetic results show the main active ingredient, ellagic acid, in PGL has lower oral bioavailability, suggesting that the lipid-lowering effect of PGL may act through inhibiting lipid absorption in the small intestine. Our results demonstrated that pomegranate leaf and its main active ingredients (i.e., ellagic acid, gallic acid, pyrogallic acid and tannic acid) were capable of inhibiting pancreatic lipase activity in vitro. In computational molecular docking, the four ingredients had good affinity for pancreatic lipase. Acute lipid overload experiments showed that a large dosage of PGL significantly reduced serum total cholesterol (TG) and triglycerides (TC) levels in addition to inhibiting intestinal lipase activity, which demonstrated that PGL could inhibit lipase activity and reduce the absorption of lipids. We also found that PGL could reverse the reduced tight-junction protein expression due to intestinal lipid overload, promote Occludin and Claudin4 expression in the small intestine, and enhance the intestinal mucosal barrier. In conclusion, we demonstrated that PGL can inhibit lipid absorption and reduce blood TG and TC by targeting pancreatic lipase, promoting tight-junction protein expression and thereby preventing intestinal mucosa damage from an overload of lipids in the intestine.


Assuntos
Inibidores Enzimáticos/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/enzimologia , Intestino Delgado/metabolismo , Lipase/metabolismo , Metabolismo dos Lipídeos , Lythraceae/química , Extratos Vegetais/administração & dosagem , Animais , Inibidores Enzimáticos/química , Humanos , Hiperlipidemias/metabolismo , Absorção Intestinal , Cinética , Lipase/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Folhas de Planta/química , Triglicerídeos/metabolismo
9.
J Int Adv Otol ; 13(1): 32-35, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28555596

RESUMO

OBJECTIVE: This study aimed to observe differences in the efficacy of laser and surgical treatments of middle-ear conductive hearing loss (MECHL). MATERIALS AND METHODS: A total of 276 ears of 267 patients with MECHL were divided into laser (n=172) and surgical (n=104) treatment groups according to the treatment method. Changes in the air-bone gap (ABG) after treatment and at the time of final follow-up were compared. An ABG value <20 dB was defined as effective and an ABG value <10 dB, significantly effective. The long-term treatment effects were also compared at the time of final follow-up. Additionally, postoperative adverse reactions were recorded for both the groups. RESULTS: The mean follow-up period was 76.77±43.62 months (range: 12-168 months). No significant difference in ABG was found between the two groups (21.31±11.64 dB vs. 19.14±9.79 dB, p>0.05). However, the laser treatment group showed slightly better results than the surgical treatment group at the final follow-up, although the difference between the groups was not found to be significant (11.69±9.98 dB vs. 12.62±10.94 dB, p>0.05). There was no difference in the long-term treatment effects between the two groups (effective: 87.21% vs. 88.46%, p>0.05; significantly effective: 55.81% vs. 56.73%, p>0.05). The incidence rates of postoperative adverse reactions were not significantly different. CONCLUSION: The treatment efficacy of laser and surgical treatments for MECHL are similar.


Assuntos
Perda Auditiva Condutiva/cirurgia , Terapia a Laser , Cirurgia do Estribo/métodos , Timpanoplastia , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Terapia a Laser/métodos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Timpanoplastia/métodos
10.
Chin J Nat Med ; 15(3): 178-191, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28411686

RESUMO

Heat stress can stimulate an increase in body temperature, which is correlated with increased expression of heat shock protein 70 (HSP70) and tumor necrosis factor α (TNFα). The exact mechanism underlying the HSP70 and TNFα induction is unclear. Berberine (BBR) can significantly inhibit the temperature rise caused by heat stress, but the mechanism responsible for the BBR effect on HSP70 and TNFα signaling has not been investigated. The aim of the present study was to explore the relationship between the expression of HSP70 and TNFα and the effects of BBR under heat conditions, using in vivo and in vitro models. The expression levels of HSP70 and TNFα were determined using RT-PCR and Western blotting analyses. The results showed that the levels of HSP70 and TNFα were up-regulated under heat conditions (40 °C). HSP70 acted as a chaperone to maintain TNFα homeostasis with rising the temperature, but knockdown of HSP70 could not down-regulate the level of TNFα. Furthermore, TNFα could not influence the expression of HSP70 under normal and heat conditions. BBR targeted both HSP70 and TNFα by suppressing their gene transcription, thereby decreasing body temperature under heat conditions. In conclusion, BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments.


Assuntos
Berberina/farmacologia , Proteínas de Choque Térmico HSP70/genética , Transtornos de Estresse por Calor/tratamento farmacológico , TATA Box/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Animais , Proteínas de Choque Térmico HSP70/metabolismo , Transtornos de Estresse por Calor/genética , Transtornos de Estresse por Calor/metabolismo , Temperatura Alta , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator de Necrose Tumoral alfa/metabolismo
11.
Sci Rep ; 7: 45155, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-28332601

RESUMO

Transient Receptor Potential Melastatin-8 (TRPM8) reportedly plays a fundamental role in a variety of processes including cold sensation, thermoregulation, pain transduction and tumorigenesis. However, the role of TRPM8 in inflammation under cold conditions is not well known. Since cooling allows the convergence of primary injury and injury-induced inflammation, we hypothesized that the mechanism of the protective effects of cooling might be related to TRPM8. We therefore investigated the involvement of TRPM8 activation in the regulation of inflammatory cytokines. The results showed that TRPM8 expression in the mouse hypothalamus was upregulated when the ambient temperature decreased; simultaneously, tumor necrosis factor-alpha (TNFα) was downregulated. The inhibitory effect of TRPM8 on TNFα was mediated by nuclear factor kappa B (NFκB). Specifically, cold stress stimulated the expression of TRPM8, which promoted the interaction of TRPM8 and NFκB, thereby suppressing NFκB nuclear localization. This suppression consequently led to the inhibition of TNFα gene transcription. The present data suggest a possible theoretical foundation for the anti-inflammatory role of TRPM8 activation, providing an experimental basis that could contribute to the advancement of cooling therapy for trauma patients.


Assuntos
Resposta ao Choque Frio/genética , Regulação da Expressão Gênica , Canais de Cátion TRPM/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Animais , Biomarcadores , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Cálcio/metabolismo , Linhagem Celular , Humanos , Masculino , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , Transporte Proteico , RNA Interferente Pequeno/genética , Canal de Cátion TRPA1/metabolismo
12.
World J Gastroenterol ; 23(47): 8321-8333, 2017 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-29307992

RESUMO

AIM: To determine whether fructo-oligosaccharide (FOS) affects visceral sensitivity, inflammation, and production of intestinal short-chain fatty acids (SCFA) in an irritable bowel syndrome (IBS) mouse model. METHODS: Mice were randomly assigned to daily oral gavage of saline solution with or without FOS (8 g/kg body weight) for 14 d. Mice were further assigned to receive either daily one-hour water avoidance stress (WAS) or sham-WAS for the first 10 d. After 2 wk, visceral sensitivity was measured by abdominal withdrawal reflex in response to colorectal distension and mucosal inflammation was evaluated. Gas chromatography, real-time reverse transcription PCR, and immunohistochemistry assays were used to quantify cecal concentrations of SCFA, intestinal cytokine expression, and number of intestinal mast cells per high-power field (HPF), respectively. RESULTS: Mice subjected to WAS exhibited visceral hypersensitivity and low-grade inflammation. Among mice subjected to WAS, FOS increased visceral hypersensitivity and led to higher cecal concentrations of acetic acid (2.49 ± 0.63 mmol/L vs 1.49 ± 0.72 mmol/L, P < 0.05), propionic acid (0.48 ± 0.09 mmol/L vs 0.36 ± 0.05 mmol/L, P < 0.01), butyric acid (0.28 ± 0.09 mmol/L vs 0.19 ± 0.003 mmol/L, P < 0.05), as well as total SCFA (3.62 ± 0.87 mmol/L vs 2.27 ± 0.75 mmol/L, P < 0.01) compared to saline administration. FOS also increased ileal interleukin (IL)-23 mRNA (4.71 ± 4.16 vs 1.00 ± 0.99, P < 0.05) and colonic IL-1ß mRNA (2.15 ± 1.68 vs 0.88 ± 0.53, P < 0.05) expressions as well as increased mean mast cell counts in the ileum (12.3 ± 2.6 per HPF vs 8.3 ± 3.6 per HPF, P < 0.05) and colon (6.3 ± 3.2 per HPF vs 3.4 ± 1.2 per HPF, P < 0.05) compared to saline administration in mice subjected to WAS. No difference in visceral sensitivity, intestinal inflammation, or cecal SCFA levels was detected with or without FOS administration in mice subjected to sham-WAS. CONCLUSION: FOS administration intensifies visceral hypersensitivity and gut inflammation in stress-induced IBS mice, but not in the control mice, and is also associated with increased intestinal SCFA production.


Assuntos
Hipersensibilidade Alimentar/imunologia , Mucosa Intestinal/imunologia , Intestinos/imunologia , Síndrome do Intestino Irritável/imunologia , Oligossacarídeos/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Feminino , Humanos , Mucosa Intestinal/patologia , Intestinos/citologia , Intestinos/patologia , Síndrome do Intestino Irritável/patologia , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Limiar Sensorial , Estresse Psicológico/complicações
13.
Chin J Nat Med ; 14(9): 641-652, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27667509

RESUMO

Angelica dahurica (A. dahurica) is a traditional Chinese medicinal plant being used in clinical practice. The present study demonstrated that A. dahurica could reduce white-fat weight in high-fat-diet hyperlipidemic mice, decrease total cholesterol and triglyceride concentrations in the livers of both high-fat-diet and Triton WR1339 induced hyperlipidemic mice, and enhance the total hepatic lipase activities of them. These findings were further supported by the results derived from the experiments with HepG2 cells in vitro. In addition, the proteins related to lipids metabolism were investigated using LC-MS/MS, indicating that genes of lipid metabolism and lipid transport were regulated by A. dhurica. The results from LC-MS/MS were further conformed by Western blot and real time PCR assays. A. dahurica could down-regulate the expression of catalase (CAT) and sterol carrier protein2 (SCP2) and up-regulate the expression of lipid metabolism related genes-lipase member C (LIPC) and peroxisome proliferator-activated receptor gamma (PPARγ). In the Triton WR1339 mouse liver and HepG2 cells in vitro, A. dahurica was able to increase the expression of LIPC and PPARγ, confirming the results from in vivo experiments. Imperatorin showed the same activity as A. dahurica, suggesting it was one of the major active ingredients of the herb. In conclusion, our work represented a first investigation demonstrating that A. dahurica was able to regulate lipid metabolism and could be developed as a novel approach to fighting against fatty liver and obesity.


Assuntos
Angelica/química , Medicamentos de Ervas Chinesas/administração & dosagem , Fígado Gorduroso/tratamento farmacológico , Obesidade/tratamento farmacológico , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Colesterol/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Obesidade/genética , Obesidade/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Triglicerídeos/metabolismo
14.
Chin J Nat Med ; 14(5): 354-62, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27478098

RESUMO

Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.


Assuntos
Benzopiranos/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Indenos/administração & dosagem , Neurônios/efeitos dos fármacos , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Células Cultivadas , Glucose/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurônios/imunologia , Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
15.
Chin J Nat Med ; 14(6): 441-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27473962

RESUMO

Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.


Assuntos
Benzopiranos/toxicidade , Caesalpinia/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Indenos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Gravidez
16.
World J Gastroenterol ; 22(12): 3486-95, 2016 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-27022230

RESUMO

AIM: To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD). METHODS: Randomized controlled trials (RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English (up to May 2015) were identified by searching PubMed, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio (RR) or a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0. RESULTS: This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12-1.36, P < 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at ≥ 1 year (RR = 1.24; 95%CI: 1.12-1.37, P < 0.0001) but not during short-term follow-up at < 1 year (RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P < 0.00001). CONCLUSION: The decision to eradicate H. pylori in patients with functional dyspepsia requires individual assessment.


Assuntos
Antibacterianos/uso terapêutico , Dispepsia/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Distribuição de Qui-Quadrado , Quimioterapia Combinada , Dispepsia/diagnóstico , Dispepsia/microbiologia , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Indução de Remissão , Fatores de Risco , Resultado do Tratamento
17.
Zhongguo Zhong Yao Za Zhi ; 41(12): 2362-2370, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28901086

RESUMO

A variety of pharmacological effects of berberine (BBR) are constantly being discovered with the deepening of BBR research. What followed is how to rationally use the drug according to these new pharmacological effects. Because of some cardiac toxicity and poor oral absorption, conflicts may arise between improving the bioavailability and controlling the toxicity of BBR. Meanwhile some new therapeutic uses of BBR, such as hypolipidemia, hypoglycemia as well as prevention and treatment of neurodegenerative diseases, need long-termoral administration, thereby may lead to alteration of intestinal flora and potentially affect body's other physiological functions. Based on the stated targets of BBR and related pharmaceutical properties, comprehensive analysis of these issues was conducted in this study. Some suggestions were presented below:the effect of long-term oral administration on body function, especially the intestinal flora, needs to be further investigated; risks shall be considered in changing the composition of the formulation to improve the absorption rate of oral administration; for the medication with higher concentration demand (such as anti-cancer), targeted drug-delivery is worthy to be considered.


Assuntos
Berberina/farmacologia , Administração Oral , Berberina/administração & dosagem , Disponibilidade Biológica , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos
18.
Sci Rep ; 5: 18326, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26671652

RESUMO

Berberine (BBR) is a natural compound with variable pharmacological effects and a broad panel of target genes. We investigated berberine's pharmacological activities from the perspective of its nucleotide-binding ability and discovered that BBR directly regulates gene expression by targeting TATA boxes in transcriptional regulatory regions as well as the poly adenine (poly (A)) tail at the mRNA terminus. BBR inhibits gene transcription by binding the TATA boxes in the transcriptional regulatory region, but it promotes higher levels of expression by targeting the poly (A) tails of mRNAs. The present study demonstrates that TATA boxes and poly (A) tails are the first and second primary targets by which BBR regulates gene expression. The final outcome of gene regulation by BBR depends on the structure of the individual gene. This is the first study to reveal that TATA boxes and poly (A) tails are direct targets for BBR in its regulation of gene expression. Our findings provide a novel explanation for the complex activities of a small molecule compound in a biological system and a novel horizon for small molecule-compound pharmacological studies.


Assuntos
Regiões 3' não Traduzidas , Berberina/farmacocinética , Regulação da Expressão Gênica/efeitos dos fármacos , Poli A , Estabilidade de RNA/efeitos dos fármacos , TATA Box , Transcrição Genética/efeitos dos fármacos , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR
19.
PLoS One ; 10(7): e0134044, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26226164

RESUMO

The purpose of the present study is to confirm the protective effect of berberine (BBR) on gastrointestinal injury caused by acute heavy alcohol exposure, an effect that has not been reported previously. Our research details how BBR protects against gastrointestinal injuries from acute alcohol exposure using both in vivo and in vitro experiments. Acute high alcohol concentrations lead to obvious damage to the gastrointestinal mucosa, resulting in necrosis of the intestinal mucosa. Oral administration of BBR was able to significantly reduce this alcohol-induced damage, inhibit increases of alcohol-induced TNFα and IL-1ß expression in gastrointestinal mucosa as well as their upstream signals TLR2 and TLR4, and regulate cytokines that modulate tight junctions. Alcohol consumption is a popular human social behavior worldwide, and the present study reports a comprehensive mechanism by which BBR protects against gastrointestinal injuries from alcohol stress, providing people with a novel application of BBR.


Assuntos
Alcoolismo/complicações , Berberina/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Interleucina-1beta/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Western Blotting , Células CACO-2/efeitos dos fármacos , Mucosa Gástrica/patologia , Células HEK293/efeitos dos fármacos , Humanos , Interleucina-1beta/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Reação em Cadeia da Polimerase em Tempo Real , Receptor 2 Toll-Like/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos
20.
Zhongguo Zhong Yao Za Zhi ; 39(16): 3142-7, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25509303

RESUMO

Pineapple (Ananas comosus) leaves contain mainly phenolic components with antioxidant and hypolipidemic effects. One of the principle components is p-coumaric acid. In this study, the transport behavior of p-coumaric acid, was observed after the administration of pineapple leaf phenols in vitro. Simultaneously, the effect of the phenols on glucose, total cholesterol and triglycerides transportation and metabolism in HepG2 cells was also observed. The results showed that the phenols had good transport characteristics. 5 min after the administration, p-coumaric acid of the phenols could be detected, and the content of p-coumaric acid reached the peak concentration after 60 min of the administration. p-coumaric acid of phenols have time-and dose-dependent manner. While promoting glucose transporter (GLUT4) and low density lipoprotein receptor (LDLR) expression, the phenols decreased intracellular lipid content. This reduction of intracellular lipid content was highly correlated with the promotion of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) expression, while the reduction of intracellular glucose levels was correlated with glycogen synthesis in the cells.


Assuntos
Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ananas/química , Transporte Biológico/efeitos dos fármacos , Colesterol/metabolismo , Células Hep G2 , Humanos
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