RESUMEN
BACKGROUND: Sinomenine (SIN) is the main pharmacologically active component of Sinomenii Caulis and protects against rheumatoid arthritis (RA). In recent years, many studies have been conducted to elucidate the pharmacological mechanisms of SIN in the treatment of RA. However, the molecular mechanism of SIN in RA has not been fully elucidated. PURPOSE: To summarize the pharmacological effects and molecular mechanisms of SIN in RA and clarify the most valuable regulatory mechanisms of SIN to provide clues and a basis for basic research and clinical applications. METHODS: We systematically searched SciFinder, Web of Science, PubMed, China National Knowledge Internet (CNKI), the Wanfang Databases, and the Chinese Scientific Journal Database (VIP). We organized our work based on the PRISMA statement and selected studies for review based on predefined selection criteria. OUTCOME: After screening, we identified 201 relevant studies, including 88 clinical trials and 113 in vivo and in vitro studies on molecular mechanisms. Among these studies, we selected key results for reporting and analysis. CONCLUSIONS: We found that most of the known pharmacological mechanisms of SIN are indirect effects on certain signaling pathways or proteins. SIN was manifested to reduce the release of inflammatory cytokines such as Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1ß, thereby reducing the inflammatory response, and apparently blocking the destruction of bone and cartilage. The regulatory effects on inflammation and bone destruction make SIN a promising drug to treat RA. More notably, we believe that the modulation of α7nAChR and the regulation of methylation levels at specific GCG sites in the mPGES-1 promoter by SIN, and its mechanism of directly targeting GBP5, certainly enriches the possibilities and the underlying rationale for SIN in the treatment of inflammatory immune-related diseases.
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Artritis Reumatoide , Morfinanos , Humanos , Artritis Reumatoide/tratamiento farmacológico , Antiinflamatorios/farmacología , Morfinanos/farmacología , Morfinanos/uso terapéutico , Transducción de SeñalRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a common systemic autoimmune disease with high morbidity and disability rate. Currently, there is no effective allopathic treatment for RA, and most of the drugs provoke many adverse effects. Simiao Yong'an decoction (SMYAD) is a traditional Chinese prescription for the treatment of sore and gangrene caused by hot poison. With the development of pharmacology and clinical research, SMYAD has remarkable anti-inflammatory properties and has been used for RA treatments for years. AIM OF THE STUDY: This study aimed to investigate the anti-arthritic effect of SMYAD and further explore the immunopharmacological mechanisms. MATERIALS AND METHODS: Arthritis was induced in DBA/1 mice by two-time immunizations. Collagen-induced rheumatoid arthritis (CIA) mice were divided into 4 groups: control, model, methotrexate (MTX), and SMYAD group (n = 6). The administration groups were given MTX (0.5 mg/kg/3 d) and SMYAD (4.5 g/kg/d) by gavage from day 14. The arthritis index (AI) score was evaluated every 3 days after the second immunization. Hematoxylin and eosin (H&E) staining, Safranin-O fast green staining, Trap staining, and Micro-CT were used to measure the histopathology injuries and bone destruction of joints. Granulocyte changes in the spleen, bone marrow, and period blood were analyzed by flow cytometry. The expression of inflammatory cytokines and chemokines in joints were detected by qRT-PCR. SMYAD-containing serum was obtained from SD rats gavaged with SMYAD. Neutrophils were isolated from peripheral blood and bone marrow for the in vitro experiments of transwell cell assay, apoptosis assay, reactive oxygen species (ROS) generation and neutrophil extracellular traps (NETs) formation. RESULTS: SMYAD significantly relieved arthritis severity in CIA mice. The AI score was significantly decreased in the SMYAD group compared with the model group. Additionally, SMYAD alleviated inflammatory infiltration, cartilage damage, osteoclast formation, and bone damage in the ankle joints. In the flow cytometry assay, SMYAD significantly reduced granulocytes number in the spleen and bone marrow, while increased in peripheral blood. Furthermore, compared with the CIA group, SMYAD suppressed the mRNA levels of inflammatory factors including TNF-α, IL-1ß, IL-6 and chemokines CXCL1, CXCL2, and IL-8 in the inflamed joints. In the in vitro studies, 20% SMYAD-containing serum effectively inhibited the migration of neutrophils, promoted neutrophils apoptosis, reduced ROS production and NETs formation. CONCLUSION: Collectively, our results demonstrated that SMYAD effectively restrained arthritis in CIA mice by modulating neutrophil activities.
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Artritis Experimental , Artritis Reumatoide , Ratones , Ratas , Animales , Artritis Experimental/patología , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno , Ratas Sprague-Dawley , Ratones Endogámicos DBA , Artritis Reumatoide/tratamiento farmacológico , Citocinas/metabolismo , MetotrexatoRESUMEN
Inflammation is closely linked to the abnormal phospholipid metabolism chain of cyclooxygenase-2/microsomal prostaglandin E2 synthase-1/prostaglandin E2 (COX-2/mPGES-1/PGE2). In clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) as upstream COX-2 enzyme activity inhibitors are widely used to block COX-2 cascade to relieve inflammatory response. However, NSAIDs could also cause cardiovascular and gastrointestinal side effects due to its inhibition on other prostaglandins generation. To avoid this, targeting downstream mPGES-1 instead of upstream COX is preferable to selectively block overexpressed PGE2 in inflammatory diseases. Some mPGES-1 inhibitor candidates including synthetic compounds, natural products and existing anti-inflammatory drugs have been proved to be effective in in vitro experiments. After 20 years of in-depth research on mPGES-1 and its inhibitors, ISC 27864 have completed phase II clinical trial. In this review, we intend to summarize mPGES-1 inhibitors focused on their inhibitory specificity with perspectives for future drug development.
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Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Prostaglandina-E Sintasas/antagonistas & inhibidores , Prostaglandina-E Sintasas/metabolismo , Animales , HumanosRESUMEN
Olives are a rich source of compounds with antioxidant and anti-inflammatory activities. This study was designed to investigate whether a standardized olive cake extract was able to alleviate oxidative stress, inflammation and intestinal villus damage in a model of lipopolysaccharide (LPS)-challenged piglets. Thirty weaned piglets (6.9 ± 0.9 kg) were assigned to five groups using a randomized complete block design. Piglets were fed a basal diet before intraperitoneal (i.p.) injection of physiological saline (C); fed a basal diet alone (CL) or fed a basal diet plus an olive cake extract (OL), antibiotics (AL), or olive cake extract plus antibiotics (OAL) before i.p. injection of LPS. The feeding period lasted for 2 weeks. Piglets were euthanized 4 h after the LPS injection. Systemic oxidative and inflammatory status and intestinal morphology were evaluated. LPS challenge significantly lowered the serum levels of GSH-Px, SOD and ALB and increased the serum concentration of MDA, NO, LDH, ALT, AST, TNF-α, IL-6, DAO and D-xylose (P < 0.05), as extracted from the comparison of piglets in the C and CL groups. Intestinal morphology was altered in the duodenum and ileum, displaying that the CL group had significantly lower villus height (VH), higher crypt depth (CD) and lower VH/CD compared with the control group (P < 0.05). Moreover, feed supplementation was able to partially mitigate the negative effects of LPS challenge in all groups (OL, AL, and OAL), as evidenced by the significantly increased serum levels of GSH-Px, SOD, ALB and IL-10 and decreased concentration of MDA, NO, LDH, ALT, AST, TNF-α, IL-6, DAO and D-xylose, compared with the CL group (P < 0.05). Alterations in intestinal morphology were also prevented and the OL, AL, and OAL groups had significantly lower CD and higher VH/CD compared with the CL group (P < 0.05), both in the ileum and duodenum. Furthermore, the positive effect in the relative abundance of intestinal Lactobacillus and Clostridium at the genus level was also observed for the OL group compared to the CL group. In summary, dietary supplementation with an olive cake extract stabilized the physiological condition of piglets subjected to an acute LPS challenge by reducing oxidative stress and the inflammatory status, improving intestinal morphology and increasing the abundance of beneficial intestinal bacteria. This trial was registered at Zhejiang University (http://www.lac.zju.edu.cn) as No. ZJU20170529.
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Microbioma Gastrointestinal/efectos de los fármacos , Íleon/metabolismo , Inflamación/tratamiento farmacológico , Aceite de Oliva/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Alimentación Animal , Animales , Antioxidantes/farmacología , Dieta/métodos , Duodeno/metabolismo , Íleon/microbiología , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/metabolismo , Lipopolisacáridos/efectos adversos , PorcinosRESUMEN
A large number of macrophages in inflamed sites not only amplify the severity of inflammatory responses but also contribute to the deleterious progression of many chronic inflammatory diseases, autoimmune diseases and cancers. Macrophage migration is a prerequisite for their entry into inflammatory sites and their participation of macrophages in the pathologic processes. Inhibition of macrophage migration is therefore a potential anti-inflammatory mechanism. Moreover, alleviation of inflammation also prevents the macrophages infiltration. Sinomenine (SIN) is an alkaloid derived from the Chinese medicinal plant Sinomenium acutum. It has multiple pharmacological effects, including anti-inflammation, immunosuppression, and anti-arthritis. However, its anti-inflammatory molecular mechanisms and effect on macrophage migration are not fully understood. The purpose of this research was to investigate the pharmacological effects and the molecular mechanism of SIN on macrophage migration in vivo and in vitro as well as to elucidate its anti-inflammatory mechanisms associated with macrophage migration. Our results showed that SIN reduced the number of RAW264.7 cells migrating into inflammatory paws and blocked lipopolysaccharide (LPS)-induced RAW264.7 cells and bone marrow-derived macrophages (BMDMs) migration in vitro. Furthermore, SIN attenuated the 3D mesenchymal migration of BMDMs. The absence of macrophage migration after circulatory and periphery macrophages depletion led to a reduction in the severity of inflammatory response. In macrophages depleted (macrophages-/-) mice, as inflammatory severity decreased, RAW264.7 cells migration was suppressed. A non-obvious effect of SIN on the inflammatory response was found in macrophages-/- mice, while the inhibitory effect of SIN on RAW264.7 cells migration was still observed. Furthermore, the migration of RAW264.7 cells pre-treated with SIN was suppressed in normal mice. Finally, Src/focal adhesion kinase (FAK)/P130Cas axis activation, which supports macrophages mesenchymal migration, and iNOS expression, NO production, integrin αV and in integrin ß3 expressions, which promote Src/FAK/P130Cas activation, were down-regulated by SIN. However, SIN had no obvious effect on the expression of the monocyte chemoattractant protein-1 (MCP-1), which is an important chemokine for macrophage migration. These results indicated that SIN significantly inhibited macrophage mesenchymal migration by down-regulating on Src/FAK/P130Cas axis activation. There was a mutual regulatory correlation between the inflammatory response and macrophage migration, and the effects of SIN on macrophage migration were involved in its anti-inflammatory activity.
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Antiinflamatorios/farmacología , Movimiento Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Macrófagos/efectos de los fármacos , Morfinanos/farmacología , Animales , Antiinflamatorios/química , Proteína Sustrato Asociada a CrK/metabolismo , Quinasa 1 de Adhesión Focal/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Ratones , Morfinanos/química , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Sinomenium/química , Familia-src Quinasas/metabolismoRESUMEN
The side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in the cardiovascular system mainly result from its inhibitory effect on cyclooxygenase-2 (COX-2). Since NSAIDs are one of the most commonly used anti-inflammatory drugs in the clinic, it is necessary to identify new anti-inflammatory drugs that are safer than NSAIDs. Nardosinanone N (NAN), a compound isolated from the roots and rhizomes of Nardostachys chinensis, was evaluated for its anti-inflammatory effects using the lipopolysaccharide (LPS)-stimulated RAW264.7 cell line and rat peritoneal macrophage models. First, we found that NAN down regulated the levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS) and prostaglandin E2 (PGE2), but not cyclooxygenase-2 (COX-2). Additionally, NAN reduced the M1 macrophage phenotype and increased the M2 macrophage phenotype. Furthermore, mechanistic studies showed that NAN activated the nuclear factor-erythroid 2 -related factor 2 (Nrf2) signaling pathway, which, in turn, increased the expression of antioxidant protein heme oxygenase-1 (HO-1) to achieve its anti-inflammatory effect. Finally, Nrf2 siRNA and the HO-1 inhibitor significantly attenuated the anti-inflammatory effect of NAN. More interestingly, we found that NAN did not affect COX-2 expression and activity but reduced the PGE2 concentration by selective inhibition of microsomal prostaglandin E synthase-1 (mPGES-1). In conclusion, NAN may be a new anti-inflammatory drug that has fewer side effects than NSAIDs and can be a new potential Nrf2 activator and mPGES-1 inhibitor.
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Compuestos Epoxi/farmacología , Lipopolisacáridos/farmacología , Activación de Macrófagos/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Nardostachys/química , Preparaciones de Plantas/farmacología , Prostaglandina-E Sintasas/metabolismo , Terpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Células Cultivadas , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Compuestos Epoxi/química , Expresión Génica/efectos de los fármacos , Macrófagos/clasificación , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Microsomas/efectos de los fármacos , Microsomas/enzimología , Estructura Molecular , Factor 2 Relacionado con NF-E2/genética , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Preparaciones de Plantas/química , Prostaglandina-E Sintasas/genética , Células RAW 264.7 , Ratas , Transducción de Señal/efectos de los fármacos , Terpenos/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Nardochinoid B (NAB) is a new compound isolated from Nardostachys chinensis. Although our previous study reported that the NAB suppressed the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW264.7 cells, the specific mechanisms of anti-inflammatory action of NAB remains unknown. Thus, we examined the effects of NAB against LPS-induced inflammation. In this study, we found that NAB suppressed the LPS-induced inflammatory responses by restraining the expression of inducible nitric oxide synthase (iNOS) proteins and mRNA instead of cyclooxygenase-2 (COX-2) protein and mRNA in RAW264.7 cells, implying that NAB may have lower side effects compared with nonsteroidal anti-inflammatory drugs (NSAIDs). Besides, NAB upregulated the protein and mRNA expressions of heme oxygenase (HO)-1 when it exerted its anti-inflammatory effects. Also, NAB restrained the production of NO by increasing HO-1 expression in LPS-stimulated RAW264.7 cells. Thus, it is considered that the anti-inflammatory effect of NAB is associated with an induction of antioxidant protein HO-1, and thus NAB may be a potential HO-1 inducer for treating inflammatory diseases. Moreover, our study found that the inhibitory effect of NAB on NO is similar to that of the positive drug dexamethasone, suggesting that NAB has great potential for developing new drugs in treating inflammatory diseases.
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Hemo-Oxigenasa 1/metabolismo , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ciclooxigenasa 2/metabolismo , Citocinas/biosíntesis , Mediadores de Inflamación , Magnoliopsida/química , Ratones , Modelos Biológicos , Estructura Molecular , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Células RAW 264.7RESUMEN
When dairy cows are exposed to high-temperature environment, their antioxidant capacity and productive performance decrease, leading to economic losses. Emerging evidence has shown that selenium (Se) can effectively alleviate heat stress in dairy cows; however, the cellular mechanism underlying this protection is not clear. The purpose of this study was to investigate and compare the protective effects of inorganic Se (sodium selenite, SS) and organic Se (selenite methionine, SM) in MAC-T (mammary alveolar cells-large T antigen, a bovine mammary epithelial cell (BMEC) line) cells during heat stress. MAC-T cells were treated in 4 ways unless otherwise described: (i) cells in the heat treatment (HT) group were cultured at 42.5°C for 1 h and then recovered in 37°C for another 12 h; (ii) the SM group was pretreated with organic Se for 2 h, cultured at 42.5°C for 1 h, and then recovered in 37°C for 12 h; (iii) the SS group was treated similarly to the SM group except that the cells were pretreated with inorganic Se instead of organic Se; and (iv) the control group was continuously cultured in 37°C and received no Se treatment. The results showed that heat shock at 42.5°C for 1 h triggered heat shock response, sabotaged the redox balance, and reduced cell viability in MAC-T cells; and pretreatment of cells with SM or SS effectively alleviated the negative effects of heat shock on the cells. However, the cells were much more sensitive to SS treatment but more tolerant to SM. In addition, two forms of Se appeared to affect the expression of different genes, including nuclear factor erythroid 2-related factor 2 (Nrf2) and inducible nitric oxide synthase (iNOS) in the SM group and thioredoxin reductase 1 (TXNRD1) in the SS group in Nrf2-ARE (antioxidant response element) antioxidant pathway and inflammation response. In summary, results showed the mechanistic differences in the protective effects of organic and inorganic Se on heat stress in BMECs.
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Antioxidantes/farmacología , Células Epiteliales/metabolismo , Respuesta al Choque Térmico/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Selenio/farmacología , Selenito de Sodio/farmacología , Animales , Bovinos , Línea Celular , Células Epiteliales/patología , Femenino , Glándulas Mamarias Animales/patología , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Tiorredoxina Reductasa 1/metabolismoRESUMEN
BACKGROUND: Qingjie Fuzheng granules (QFGs) are part of a traditional Chinese medicine formula, which has been widely used and found to be clinically effective with few side effects in various cancer treatments, including colorectal cancer (CRC). However, the precise mechanisms and molecular signaling pathways involved in the activity of QFGs' anticancer effect have not been reported in the literature. In this study, we hypothesized that QFGs can inhibit the growth of colorectal cancer cells, and that its mechanism is closely related to one or more intracellular signal transduction pathways. AIM: To better evaluate the mechanism underlying the anti-cancer effect of QFGs on the CRC cell lines HCT-116 and HCT-8. METHOD: First, we measured cell viability and cytotoxicity by performing MTT and lactate dehydrogenase (LDH) assays. We evaluated the role of QFGs in cell proliferation and apoptosis by assessing colony formation and analyzing Hoechst 33258 staining. Second, cell cycle and apoptosis rates were measured by fluorescence activated cell sorting, and the expression levels of survivin, cyclin D1, CDK4, p21, Bax, Bcl-2, Fas, FasL, and cleaved-caspase-3/-8/-9 were measured by performing western blots and caspase activity assays. Furthermore, inhibitors of caspase-3/-8/-9 were used to elucidate the specific apoptosis pathway induced by QFGs in cancer cells. Finally, activation of the PI3K/AKT and ERK signaling pathways was examined using the western blot assay to investigate the possible mechanism. RESULTS: MTT and LDH assays revealed that after 0.5-2.0 mg/mL of QFGs treatment, cell viability was reduced by (6.90% ± 1.03%)-(59.70% ± 1.51%) (HCT-116; P < 0.05) and (5.56% ± 4.52%)-(49.44% ± 2.47%) (HCT-8; P < 0.05), and cytotoxicity was increased from 0.52 ± 0.023 to 0.77 ± 0.002 (HCT-116; P < 0.01) and from 0.56 ± 0.054 to 0.81 ± 0.044 (HCT-8; P < 0.01) compared with the non-QFGs treatment groups. Additionally, colony formation and Hoechst 33258 staining assays showed that QFGs inhibited proliferation and induced apoptosis in CRC cells. QFGs also increased the expression levels of Bax, Fas and FasL, decreased the level of Bcl-2, and stimulated the activation of caspase-3/-8/-9, which were revealed by western blot and caspase activity assays. In contrast, when adding the three caspase inhibitors, the suppression effect of QFGs on cell viability and apoptosis were markedly inhibited. Moreover, QFGs suppressed the phosphorylation levels of PI3K, AKT and ERK. CONCLUSION: These results demonstrated that QFGs can inhibit CRC cell proliferation and induce apoptosis by suppressing the PI3K/AKT and ERK signaling pathways.
RESUMEN
Pectin is a non-fiber carbohydrate (NFC) that exists in forages, but it is not clear how pectin exerts its effect on populations of either known microbial species or uncultured ruminal bacteria. PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR analysis were used in the present study to investigate the effects of pectin on microbial communities in an in vitro rumen fermentation system. The fermentations were conducted using forage (corn stover or alfalfa), an NFC source (pectin or corn starch), or their combination as the substrates. Addition of pectin increased acetate (P < 0.05), whereas inclusion of starch increased butyrate production (P < 0.05). The pectate lyase activity was higher with alfalfa than with corn straw, or with pectin than with corn starch (P < 0.05), while the amylase activity was higher in corn starch-included treatments than the others (P < 0.05). The cluster analysis of the bacterial 16S rRNA gene showed that the DGGE banding patterns differed significantly between the treatments and led to the identification of three groups that were highly associated with the NFC sources. The specific bands associated with pectin-rich treatments were identified to be dominated by members of the Treponema genus. The growth of the Treponema genus was remarkably supported by the inclusion of pectin, highlighting their specific ability to degrade pectin. The results from the present study expand our knowledge of the microbial populations associated with pectin digestion, which may not only facilitate future research on utilization of pectin in feeds, but also improve our understanding of pectin digestion with respect to the rumen micro-ecosystem.
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Bacterias/aislamiento & purificación , Microbiota , Pectinas/metabolismo , Rumen/microbiología , Treponema/aislamiento & purificación , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Fermentación , Técnicas In Vitro , Filogenia , Rumen/metabolismo , Treponema/clasificación , Treponema/genética , Treponema/metabolismoRESUMEN
Treponema saccharophilum is a pectinolytic bacterium isolated from the bovine rumen. The abundance of this bacterium has not been well determined, reflecting the lack of a reliable and accurate detection method. To develop a rapid method for monitoring T. saccharophilum, we performed pyrosequencing of genomic DNA isolated from rumen microbiota to explore the 16S rRNA gene sequences of T. saccharophilum candidates. Species-specific primers were designed based on fifteen sequences of partial 16S rRNA genes generated through pyrosequencing with 97% or higher similarity with T. saccharophilum DSM2985 along with sequence from type strain. The relative abundance of T. saccharophilum was quantified in both in vitro and in vivo rumen systems with varied pectin-containing forages using real-time PCR. There was a clear association of T. saccharophilum with alfalfa hay, which contains more pectin than Chinese wild rye hay or corn stover. The relative abundance of T. saccharophilum was as high as 0.58% in vivo, comparable with the population density of other common rumen bacteria. It is recognized that T. saccharophilum plays an important role in pectin digestion in the rumen.
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Pectinas/metabolismo , Rumen/microbiología , Treponema/aislamiento & purificación , Alimentación Animal , Animales , Bovinos/microbiología , Cartilla de ADN/genética , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Femenino , Lolium/química , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Treponema/genética , Zea mays/químicaRESUMEN
An 888-bp full-length ascorbate peroxidase (APX) complementary DNA (cDNA) gene was cloned from Anthurium andraeanum, and designated as AnAPX. It contains a 110-bp 5'-noncoding region, a 28-bp 3'-noncoding region, and a 750-bp open reading frame (ORF). This protein is hydrophilic with an aliphatic index of 81.64 and its structure consisting of α-helixes, ß-turns, and random coils. The AnAPX protein showed 93%, 87%, 87%, 87%, and 86% similarities to the APX homologs from Zantedeschia aethiopica, Vitis pseudoreticulata, Gossypium hirsutum, Elaeis guineensis, and Zea mays, respectively. AnAPX gene transcript was measured non-significantly in roots, stems, leaves, spathes, and spadices by real-time polymerase chain reaction (RT-PCR) analysis. Interestingly, this gene expression was remarkably up-regulated in response to a cold stress under 6 °C, implying that AnAPX might play an important role in A. andraeanum tolerance to cold stress. To confirm this function we overexpressed AnAPX in tobacco plants by transformation with an AnAPX expression construct driven by CaMV 35S promoter. The transformed tobacco seedlings under 4 °C showed less electrolyte leakage (EL) and malondialdehyde (MDA) content than the control. The content of MDA was correlated with chilling tolerance in these transgenic plants. These results show that AnAPX can prevent the chilling challenged plant from cell membrane damage and ultimately enhance the plant cold tolerance.
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Araceae/fisiología , Ascorbato Peroxidasas/química , Ascorbato Peroxidasas/genética , Clonación Molecular/métodos , Respuesta al Choque Térmico/genética , Nicotiana/enzimología , Plantas Modificadas Genéticamente/fisiología , Secuencia de Aminoácidos , Activación Enzimática , Estabilidad de Enzimas , Datos de Secuencia Molecular , Proteínas Recombinantes/metabolismoRESUMEN
OBJECTIVE: To explore the intervention effect of the auricular stimulator in the cavum concha for diabetes. METHODS: Forty-five cases were treated with auricular simulator in the cavum concha for 30 min, once daily for consecutive 3 months. The changes of the fasting plasma glucose (FBG), blood glucose load after 2-hour 75 g oral glucose tolerance test (P2 BG)and glycosylated hemoglobin (HbA1c) were compared before and after treatment. RESULTS: The level of the HbA1c was obviously decreased (P < 0.05, P < 0.01), and there were also statistically significant differences in FBG and P2 BG after the treatment (P < 0.05, P < 0.01). CONCLUSION: With the auricular stimulator, the stimulation in the cavum concha is benefit for the improvement of HbA1c of the diabetes.
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Acupuntura Auricular , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Glucosa/metabolismo , Adulto , Anciano , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Reducing methane emission from ruminant animals has implications not only for global environmental protection but also for efficient animal production. Tea saponins (TS) extracted from seeds, leaves or roots of tea plant are pentacyclic triterpenes. They have a lasting antiprotozoal effect, but little effect on the methanogen population in sheep. There was no significant correlation between the protozoa counts and methanogens. The TS decreased methanogen activity. It seems that TS influenced the activity of the methanogens indirectly via the depressed ciliate protozoal population. The TS addition decreased fungal population in the medium containing rumen liquor in in vitro fermentation, but no such effect was observed in the rumen liquor of sheep fed TS. Tea saponins had a minor effect on the pattern of rumen fermentation and hence on nutrient digestion. When added at 3 g/day in diets, TS could improve daily weight gain and feed efficiency in goats. No positive associative effect existed between TS and disodium fumarate or soybean oil on methane suppression. Inclusion of TS in diets may be an effective way for improving feed efficiency in ruminants.
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Camellia sinensis/metabolismo , Bovinos/fisiología , Contenido Digestivo/microbiología , Cabras/fisiología , Rumen/metabolismo , Rumen/microbiología , Saponinas/farmacología , Ovinos/fisiología , Crianza de Animales Domésticos , Animales , Archaea/efectos de los fármacos , Archaea/fisiología , Bacterias/efectos de los fármacos , Fenómenos Fisiológicos Bacterianos , Camellia sinensis/química , Bovinos/crecimiento & desarrollo , Bovinos/microbiología , Eucariontes/efectos de los fármacos , Eucariontes/fisiología , Fermentación , Contenido Digestivo/efectos de los fármacos , Cabras/crecimiento & desarrollo , Cabras/microbiología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Rumen/efectos de los fármacos , Saponinas/química , Ovinos/crecimiento & desarrollo , Ovinos/microbiologíaRESUMEN
A new diterpene glycoside, tomentoside I (1), along with eleven known compounds, including the four coumarins, 4,5-dimethoxyl-7-methylcoumarin (2), 4,7-dimethoxyl-5-methylcoumarin (3), isofraxidin (4) and fraxidin (5) as well as the seven triterpenoids, oleanolic acid (6), oleanolic acid 3-O-α-L-arabinopyranoside (7), oleanolic acid 3-O-ß-D-galactopyranosyl-(1â3)-ß-D-glucopyranoside (8), hederagenin 3-O-α-L-arabinopyranoside (9), betulinic acid (10), 18-hydroxyursolic acid (11) and 2α,3ß,23-trihydroxyurs-12-en-28-oic acid (12) were isolated from the ethanolic extract of the root of Anemone tomentosa and their chemical structures were elucidated by spectroscopic methods. The antimicrobial activities of compounds 1-12 were measured using the agar disc-diffusion method. Also, their antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) were evaluated.
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Anemone/metabolismo , Medicamentos Herbarios Chinos/farmacología , Raíces de Plantas/química , Anemone/química , Cumarinas/síntesis química , Cumarinas/química , Cumarinas/farmacología , Medicamentos Herbarios Chinos/química , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Glicósidos/síntesis química , Glicósidos/química , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Pruebas de Sensibilidad Microbiana , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Triterpenos Pentacíclicos , Fitosteroles/síntesis química , Fitosteroles/química , Fitosteroles/farmacología , Fitoterapia , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Esteroles/química , Esteroles/aislamiento & purificación , Esteroles/farmacología , Relación Estructura-Actividad , Triterpenos/síntesis química , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Ácido BetulínicoRESUMEN
This study was conducted to assess the effects of dietary corn oil and vitamin E supplementation on fatty acid (FA) profiles and abundances of acetyl-CoA carboxylase (ACC) and Delta(9) stearoyl-CoA desaturase (SCD) mRNA of Hu sheep. Animals were allocated to three dietary treatments: basal and supplemented with 3% corn oil (CNO), or CNO plus 500 mg/kg vitamin E (COE). The experiment lasted for 10 weeks. No differences were observed in growth performance and carcass qualities among the three treatments (P > 0.05). Feeding CNO and COE diets increased polyunsaturated FAs including cis 9 trans 11 conjugated linoleic acid, and decreased saturated FA in longissimus muscle (P < 0.05). The mRNA abundances of ACC and SCD as detected by real-time PCR were reduced (P < 0.05) in liver and subcutaneous fat by supplementary oil, while the SCD mRNA level in longissimus muscle was also reduced (P < 0.05). Inclusion of vitamin E did not have further effects on mRNA abundances of these two enzymes. It is suggested that dietary corn oil supplementation may reduce FA biosynthesis and influence FA profiles in Hu sheep through decreased expression of both ACC and SCD genes.
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Acetil-CoA Carboxilasa/genética , Aceite de Maíz/administración & dosificación , Ácidos Grasos/biosíntesis , Expresión Génica/efectos de los fármacos , Ovinos/genética , Estearoil-CoA Desaturasa/genética , Vitamina E/administración & dosificación , Animales , Suplementos Dietéticos , Masculino , Músculo Esquelético/metabolismo , ARN Mensajero/metabolismo , Ovinos/metabolismoRESUMEN
OBJECTIVE: To investigate the effect of Lianggesan on the expression of signal transducer and activator of transcription 1 (STAT1) in rats with lipopolysaccharide (LPS)-induced acute lung injury and explore the possible mechanisms of the therapeutic effects. METHODS: Endotoxemia was induced in Wistar rats by intravenous injection of LPS (5 mg/kg). The rats were randomly divided into 6 groups, namely the control group, acute lung injury group (LPS group), 3 Lianggesan groups treated at different doses, and LPS+DEX treatment group. Each group, except for the control group, was further divided into 5 subgroups and examined at 1, 2, 4, 8 and 16 h after LPS injection. Western blotting was used to detect the protein expression of STAT1 and p-STAT1 in the lung tissue. RESULTS: In LPS group, the expression of STAT1 began to increase at 1 h following LPS injection, reaching the peak level at 4 h; the peak expression of p-STAT1 occurred at 2 h after LPS administration (P<0.01). Compared with LPS group, the 3 Lianggesan groups and DEX group showed significantly decreased expressions of STAT1 and p-STAT1 at 2, 4 and 8 h after LPS injection (P<0.05 or 0.01). CONCLUSION: Abnormal expression of STAT1 occurs in the lung tissue in the event of ALI. Lianggesan can relieve LPS-induced acute lung injury in rats by decreasing the expression of STAT1 and p-STAT1.
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Lesión Pulmonar Aguda/metabolismo , Medicamentos Herbarios Chinos/farmacología , Pulmón/metabolismo , Factor de Transcripción STAT1/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Lipopolisacáridos , Distribución Aleatoria , Ratas , Ratas Wistar , Factor de Transcripción STAT1/genéticaRESUMEN
Phorbol esters are the main toxins in Jatropha curcas seed and oil. The aim of this study was to assess the acute toxicity of phorbol esters given by intragastric administration and to determine the LD50 for Swiss Hauschka mice. The LD50 and 95% confidence limits for male mice were 27.34 mg/kg body mass and 24.90-29.89 mg/kg body mass; and the LD5 and LD95 were 18.87 and 39.62 mg/kg body mass, respectively. The regression equations between the probits of mortalities (Y) and the log of doses (D) was Y=-9.67+10.21 log (D). Histopathological studies on the organs from the dead mice showed: (1) no significant abnormal changes in the organs at the lowest dose (21.26 mg/kg body mass) studied, (2) prominent lesions mainly found in lung and kidney, with diffused haemorrhages in lung, and glomerular sclerosis and atrophy in kidney at doses > or = 32.40 mg/kg body mass, and (3) multiple abruption of cardiac muscle fibres and anachromasis of cortical neurons at the highest dose of 36.00 mg/kg body mass. The results obtained would aid in developing safety measures for the Jatropha based biofuel industry and in exploiting the pharmaceutical and agricultural applications of phorbol esters.
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Jatropha/química , Ésteres del Forbol/toxicidad , Administración Oral , Alimentación Animal , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/patología , Corazón/efectos de los fármacos , Hemorragia/inducido químicamente , Hemorragia/patología , Dosificación Letal Mediana , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/patología , Masculino , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Extractos Vegetales/toxicidad , Organismos Libres de Patógenos EspecíficosRESUMEN
OBJECTIVE: To observe the therapeutic effect of suspended moxibustion at Baihui (GV 20) for insomnia. METHODS: 75 cases were divided randomly into two groups, with 40 cases in the treatment group treated by suspended moxibustion over Baihui (GV 20) and 35 cases in the control group treated by oral administration of Estazolam. RESULTS: The difference in therapeutic effect between the two groups was not statistically significant (P > 0.1). CONCLUSION: It was concluded that suspended moxibustion at Baihui (GV 20) is as effective as Estazolam for insomnia.
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Moxibustión/métodos , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effects of breviscapine on the functions of spatial learning and memory of focal cerebral ischemia rats. METHODS: Rots withl the left middle cerebral artery occluded were made by an intraluminal filament. Then breviscapine (20 mg/kg,40 mg/kg) in experimental group and 10% glucose in control group were administered intraperitoneally once a day for 2 weeks, and the Morris water maze tasks were carried out for 5 days. RESULTS: Compared with sham-operation group,the animals of ischemia-control group exhibited seriously impaired spatial learning and memory in both place navigation test and spatial probe test. In the place navigation test, the mean value of escape latency in breviscapine group was significantly shorter than that in ischemia control group (P < 0.01 for lower-dose and P < 0.05 for higher-dose breviscapine group, respectively). In the spatial probe test,compared with sham-operation (P < 0.01) and breviscapine group (P < 0.01), the rats of ischemia-control group spent more time in the no-former platform quadrant, and showed reduced frequency of crossing former platform site significantly. The numbers of neurons with Nissl staining and choline acetyltransferase (ChAT) immunopositive neurons in ipssilateral cortex in the breviscapine group were significantly more than those in the ischemia-control group (P < 0.01). In hippocampus, the numbers of neurons with Nissl staining and ChAT immunopositive neurons in the stratum pyramidale of CA area were similar among the groups. CONCLUSION: These results indicate that breviscapine can improve the functions of spatial learning and memory of focal cerebral ischemia rats and the protection against the loss of ChAT immunopositive neuron in new cortex may be involved in its mechanisms.