Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression

Ethnopharmacological relevance

The YiQiFuMai injection (YQFM) is a traditional Chinese medicine for the treatment of chronic heart failure (CHF). The present study not only evaluated the cardioprotective effect and anti-inflammatory mechanism of the YQFM injection in an experimental model of CHF but also investigated its bioactive constituents in vitro.

Materials and methods

The left anterior descending coronary artery (LAD) in rats was ligated to make an animal model of CHF. From this, electrocardiographic parameters and exterior signs of rat hearts were recorded. Additionally, the histopathology of heart tissues was examined, and parameters of inflammatory stress were measured. Experiments were performed over two months in LAD-ligation rats treated with YQFM or vehicle. Treatment with Captopril was used as a positive control, which has previously been shown to prevent CHF, and rats without LAD-ligation were used as a negative control. Furthermore, we screened and identified potential anti-inflammatory constituents by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) combined with NF-κB activity luciferase reporter assay systems. Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors from YQFM.

Results

The administration of YQFM significantly improved cardiac function and ameliorated the activity level of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) in CHF rats. Eight potential anti-inflammatory ingredients, ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3, were characterized and confirmed. Among these compounds, ginsenoside Ro was revealed as a new NF-κB inhibitor.

Conclusion

The results suggested that NF-κB inactivation and cytokine suppression might be one of the main mechanisms of YQFM that caused ameliorative effects in CHF rats, and the major constituents of ginsenosides were identified playing a key role in the treatment of CHF.     

Sophocarpine administration preserves myocardial function from ischemia-reperfusion in rats via NF-κB inactivation

Ethnopharmacological relevance

Sophora alopecuroides L. (the clinical usefulness of compound Kudouzi injection) has been used mainly for the treatment of fever, inflammation, edema and pain. Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides L. Sophocarpine injection (called the Kangke injection) has been demonstrated to have significant antivirus effects against coxsackievirus B3 and therapeutic effects for viral myocarditis in clinical.

Aim of the study

The present study was to evaluate the protective effect of sophocarpine on the inhibition of NF-kappaB (NF-κB) and effect on inflammatory markers during myocardial ischemia-reperfusion (I/R) injury in rat.

Materials and methods

Myocardial I/R injury was induced by the occlusion of left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. 2 h after reperfusion was established, the hemodynamics and infarct size were examined. Blood samples were collected for biochemical analysis. Expression of NF-κB and mitogen-activated protein kinases (MAPKs) in ischemic myocardial tissue were assayed by western blot.

Results

Administration of sophocarpine significantly improved cardiac function and reduced infarct size in I/R rat heart in vivo. Furthermore, sophocarpine ameliorated the contents of inflammatory mediators (tumor necrosis factor-alpha, TNF-α; interleukin-6, IL-6; IL-10), neutrophil infiltration and myeloperoxidase (MPO) activity. Interestingly, sophocarpine also significantly inhibited translocation of NF-κB, which was associated with attenuated phosphorylations of p38 and c-Jun NH2-terminal protein kinase (JNK).

Conclusions

Inflammatory mediators, infiltration of neutrophil, and MPO were ameliorated via down-regulation of JNK and p38, and inactivation of NF-κB. This might be one of the important mechanisms of sophocarpine that protected myocardial injury from I/R.     

Inhibitory effects of Angelica sinensis ethyl acetate extract and major compounds on NF-κB trans-activation activity and LPS-induced inflammation

Aim of the study

Previous study showed that the ethyl acetate (EtOAc) fraction from Angelica sinensis (Oliv.) Diels (Apiaceae) (AS) inhibited nitric oxide (NO) and prostaglandin E₂ secretions in vitro. This study was to evaluate anti-inflammatory activity of AS EtOAc extract and its major compounds in vivo and in vitro.

Materials and methods

NF-κB luciferase activity and pro-inflammatory cytokine secretions from lipopolysaccharide (LPS) plus interferon (IFN)-γ-stimulated RAW 264.7 cells pre-treated with EtOAc extract or compounds were analyzed. For further in vivo study, BALB/c mice were tube-fed with 1.56 (AS1 group), 6.25 (AS2 group) mg/kg body weight/day in 100 μl soybean oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 100 μl soybean oil/day only. After 1 week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and 1 h later, all of the mice were injected with 15 mg/kg BW LPS. The pro-inflammatory cytokine levels and lifespan of LPS-challenged mice were determined.

Results

The results showed that AS EtOAc extract significantly inhibited NF-κB luciferase activity and TNF-α, IL-6, macrophage inflammatory protein-2 (MIP-2) and NO secretions from LPS/IFN-γ-stimulated RAW 264.7 cells. The AS1 and PDTC groups, but not AS2, had significantly higher survival rate than the control group. This was characterized by the inhibition of the serum TNF-α and IL-12p40 levels after LPS injection (p < 0.05). The major compounds of AS, ferulic acid and Z-ligustilide, also significantly decreased NF-κB luciferase activity, which may contribute to the anti-inflammatory activity of AS.

Conclusions

Low dose of AS EtOAc extract that inhibits the production of inflammatory mediators alleviates acute inflammatory hazards and protect mice from endotoxic shock.     

Fuyuan Decoction inhibits nitric oxide production via inactivation of nuclear factor-κB in SW1353 chondrosarcoma cells

Ethnopharmacological relevance

Fuyuan Decoction (FYD) is an empirical formula of treating Bi Zheng in traditional Chinese medicine (TCM). Despite the fact that the efficiency of FYD on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. This study was to investigate the effects and mechanisms of FYD on nitric oxide (NO) production and nuclear factor (NF)-κB activation in interleukin (IL)-1β-stimulated chondrocytes.

Materials and methods

SW1353 human chondrosarcoma cells were pretreated with various concentrations of FYD-containing serum (FYD-CS), and then were stimulated by IL-1β. Amounts of NO were determined by Griess reaction assay. Inducible NO synthase (iNOS) expression, inhibitor-κBα (IκBα) degradation and nuclear translocation of p65 protein were determined by Western blot assay. DNA binding activity of NF-κB was determined by ELISA assay using Trans AM^™ kit for p65.

Results

10% and 20% (v/v) FYD-CS significantly decreased NO production in a concentration-dependent manner (p<0.05 or p<0.01) as compared to control in IL-1β-induced SW1353 cells. Besides, 10% and 20% FYD-CS also significantly reduced iNOS protein expression by about 60% and 70% (both p<0.01), respectively. Furthermore, 10% and 20% FYD-CS markedly decreased IκBα degradation by about 45% and 26% (p<0.01 or p<0.05), lessened P65 content in the nucleus by about 28% and 60% (both p<0.01), and repressed DNA binding activity of P65 by about 30% and 45% (both p<0.01) in IL-1β-induced SW1353 cells.

Conclusions

These findings suggested that FYD could inhibit NO production and iNOS expression in IL-1β-induced chondrocytes through suppressing NF-κB activation.     

Inhibitory effects of salvianolic acid B on CCl4-induced hepatic fibrosis through regulating NF-κB/IκBα signaling

Ethnopharmacological relevance

Hepatic fibrosis, a precursor of liver cirrhosis, is a consequence of severe liver damage that occurs in many patients with chronic liver diseases. Salvianolic acid B (SA-B) is one of water soluble compounds derived from Salvia miltiorrhiza Bunge (Danshen in Chinese) widely used for chronic liver diseases. In this study we investigated the protective effects of SA-B on CCl₄-induced hepatic fibrosis.

Materials and methods

Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl₄). Rats were divided into four groups, including normal controls (N group), model (M group), low SA-B of 10 mg/kg body weight (L group), or high SA-B of 20 mg/kg body weight (H group). After 6 weeks, macroscopic features of the liver and weight ratio of liver to body were measured. Liver fibrosis of the rats was evaluated by HE and Massion staining. Activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were checked with automated biochemistry analyzer. Serum levels of hyaluronic acid (HA), type IV collagen (IV-C), Laminin (LN) and procollagen III peptide (PIIIP) were detected by radioimmunoassay (RIA). The expression of NF-κB and IκBα was detected by western blotting.

Results

SA-B was shown to reduce CCl₄-induced hepatic fibrosis in rats. The serum levels of ALT, AST, and TBIL were significantly lower in the SA-B treatment groups than in the M group. Compared the M group, the serum levels of HA, LN, IV-C and PIIIP were decreased markedly after treatment with SA-B, especially in the H group. Treatment with SA-B at 10–20 mg/kg (L and N groups, respectively) dose-dependently decreased the expression of NF-κB in the nucleolus and increased the expression levels of NF-κB and IκBα protein in the cytoplasm compared to that of the M group.

Conclusions

This study reveals that SA-B could prevent the progression of liver angiogenesis and alleviate liver fibrosis possibly by regulating the expression of NF-κB and IκBα.     

Lipid-soluble extracts from Salvia miltiorrhiza inhibit production of LPS-induced inflammatory mediators via NF-κB modulation in RAW 264.7 cells and perform antiinflammatory effects in vivo

Salvia miltiorrhiza, a traditional Chinese herbal medicine, is used to treat various inflammatory diseases. In the present study, the antiinflammatory effects of S. miltiorrhiza lipid-soluble extracts (SMLE) were demonstrated in vitro and in vivo, along with its underlying mechanism of action. SMLE significantly inhibited the production of NO, TNF-α, IL-1β and IL-6 in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. SMLE also inhibited the LPS-induced degradation of IκB-α in the cytoplasm and the translocation of p65 to the nucleus in RAW 264.7 cells. In addition, SMLE inhibited the production of intracellular reactive oxygen species (ROS) and the surface expression of CD14 induced by LPS. In animal models, intraperitoneal administration of SMLE increased the survival rate of endotoxemia and sepsis in mice. The topical administration of SMLE significantly inhibited ear edema induced by PMA. It was found that SMLE inhibits the LPS-induced gene and protein expression of iNOS, TNF-α, IL-1β and IL-6 in macrophages by blocking NF-κB activation, and these effects are mediated, at least in part, through the inhibition of intracellular ROS generation and the surface expression of CD14. The results suggest a possible therapeutic application of SMLE in inflammatory diseases and provide scientific evidence in support of the traditional Chinese medical practice of treatment with S. miltiorrhiza.     

Anti-inflammatory effects of Polygala tenuifolia root through inhibition of NF-κB activation in lipopolysaccharide-induced BV2 microglial cells

Ethnopharmacological relevance

The root of Polygala tenuifolia Willd is a well-known traditional Oriental medicine and has been prescribed for treatment of dysfunction in memorial systems and various brain inflammatory diseases. The present study was designed to validate the anti-inflammatory effects of the water extract of Polygala tenuifolia root (WEPT).

Materials and methods

The anti-inflammatory properties of WEPT were studied using lipopolysaccharide (LPS)-stimulated murine BV2 microglia model. As inflammatory parameters, the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were evaluated. We also examined the extract's effect on the activity of nuclear factor-kappaB (NF-κB), and toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (Myd-88) expression.

Results

WEPT suppressed LPS-induced production of NO, PGE₂, and expression of iNOS and COX-2 in a dose-dependent manner, without causing cytotoxicity. It also significantly reduced generation of proinflammatory cytokines, including IL-1β and TNF-α. In addition, WEPT suppressed NF-κB translocation by blockade of IkappaB-α (IκB-α) degradation and inhibited TLR4 and Myd-88 expression in LPS-stimulated BV2 cells.

Conclusions

These results indicate that the inhibitory effects of WEPT on LPS-stimulated inflammatory mediator production in BV2 microglia are associated with suppression of the NF-κB and toll-like receptor signaling pathways. Therefore, Polygala tenuifolia extracts may be useful in treatment of neurodegenerative diseases by inhibition of inflammatory mediator production in activated microglia.     

Protective effects of 4-geranyloxy-2,6-dihydroxybenzophenonel on DSS-induced ulcerative colitis in mice via regulation of cAMP/PKA/CREB and NF-κB signaling pathways

Hypericum sampsonii Hance has traditionally been used to treat enteritis and diarrhea. As one of the main benzophenones isolated from H. sampsonii, 4-geranyloxy-2,6-dihydroxybenzophenonel (4-GDB) has been shown to possess anti-inflammatory effects. However, the therapeutic effect and potential mechanisms of 4-GDB in ulcerative colitis (UC) remain unclear. This study aimed to evaluate the role of 4-GDB in UC using a dextran sulfate sodium-induced colitis mouse model. Intragastric administration of 4-GDB (20 mg/kg/day) for 8 days significantly attenuated colonic injury, reduced the expression of inflammatory mediators, and improved colonic barrier function in mice with colitis. Furthermore, in vivo and in vitro experiments indicated that 4-GDB could activate cAMP/PKA/CREB and inhibit the NF-κB pathway. Collectively, 4-GDB may be a potential agent for treating UC by regulating the cAMP/PKA/CREB and NF-κB pathways.     

Inhibitory effects of β,β-dimethylacrylshikonin on hepatocellular carcinoma in vitro and in vivo

β,β-Dimethylacrylshikonin is one of the most abundant naphthoquinones in the root extracts of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), which have been reported to have antitumor effects. This study evaluated the antiproliferative activity of β,β-dimethylacrylshikonin on human hepatocellular carcinoma (HCC) cells both in vitro and in vivo. In vitro, the MTT assay showed that β,β-dimethylacrylshikonin inhibited the proliferation of SMMC-7721 cells in both dose- and time-dependent manners with its 50% inhibitory concentration (IC(50) ) at 48 h being 15.01 ± 0.76 μg/mL. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and Hoechst staining detected the characteristics of cell apoptosis in β,β-dimethylacrylshikonin-treated cells and the apoptotic rates of treated groups were increased in a dose-dependent manner. Flow cytometric analysis revealed that β,β-dimethylacrylshikonin could block the cell cycle arrest at G2 phase. Furthermore, β,β-dimethylacrylshikonin down-regulated the mRNA and protein expression of Bcl-2 but up-regulated that of Bax. The cleaved caspase-3 protein was also detected in treated cells. The experiment in vivo showed that β,β-dimethylacrylshikonin significantly suppressed the growth of H(22) transplantable hepatoma, and induced the activation of caspase-3 determined by immunohistochemistry. The results indicate that β,β-dimethylacrylshikonin has significant antitumor effects on hepatocellular carcinoma both in vitro and in vivo.     

Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells

As an active compound extracted from the Chinese herb Tripterygium wilfordii, triptolide (TP) was demonstrated to have potent antiinflammatory and immunosuppressive properties in previous studies. Recently, it has been shown that TP prevented the loss of dopaminergic neurons in the substantia nigra of rats in a model of Parkinson's disease, but little is known about the precise neuroprotective mechanism of TP. This study was designed to elucidate whether the neuroprotective effect of TP is partially based on its direct inhibition of inflammatory molecules by investigating the effects of TP on the expression of cyclooxygenase (COX)‐2 and prostaglandin E2 (PGE2) related to the nuclear factor (NF)‐κB pathway in lipopolysaccharide (LPS)‐stimulated PC12 cells. The activation of related upstream molecules such as NF‐κB, P38, extracellular signal‐regulated kinase (ERK)1/2, and beta‐alanyl‐alpha‐ketoglutarate transaminase (AKT), in PC12 cells were investigated by real time polymerase chain reaction (PCR), western blotting and enzyme‐linked immunosorbent assay (ELISA). Our results showed that TP directly inhibited the expression of both mRNA and protein of COX‐2 (p < 0.01), decreased PGE2 production (p < 0.01) in a dose‐dependent manner, down‐regulated NF‐κB activity (p < 0.01), and significantly inhibited the phosphorylation of p38, ERK1/2 (p42/p44) and AKT in PC12 cells after LPS challenge. This suggests that the neuroprotective effects of TP may be partially mediated by direct inhibition of the expression of COX‐2, activation of NF‐κB, and phosphorylation of p38, ERK1/2 (p42/p44) and AKT proteins of neuronal cells. Copyright © 2011 John Wiley & Sons, Ltd.     

Euonymus alatus extract attenuates LPS-induced NF-κB activation via IKKβ inhibition in RAW 264.7 cells

Aim of the study

The present study was performed to investigate the underlying mechanisms of anti-inflammatory effects with the extract of Euonymus alatus (EEA), and specially focused on nuclear factor κB (NF-κB) signaling pathway by targeting the IκB kinase β (IKKβ).

Materials and methods

The effect of EEA for IKKβ activity was analyzed using an immobilized metal affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The effect of EEA on lipopolysaccharide (LPS)-induced NF-κB activation in murine macrophage RAW 264.7 cells with western blotting and immunofluorescent staining was evaluated.

Results

IKKβ studies based on IMAP-TR-FRET showed that EEA possesses a potent IKKβ inhibitory activity with IC₅₀ value of 11.83 μg/ml. EEA (10, 30 μg/ml) also attenuated the LPS-induced IκBα phosphorylation/degradation, NF-κB translocation and subsequent NO synthesis in RAW 264.7 cells.

Conclusions

These results suggest that EEA abrogates LPS-induced NF-κB signaling pathway by targeting the IKKβ in RAW 264.7 cells and these properties may provide a molecular basis for understanding the inhibitory effects of EEA on LPS-mediated inflammation.     

Anti-inflammation of Tripterygium wilfordii Polycoride on Macrophages and Its Regulation to Inflammation via TLR4/NF-κB

Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride(TWP) towards the pro-inflammatory factors(TNF-α and IL-1β) on the inflammatory reaction in macrophages induced by LPS and its regulatory effect and influence on the inflammation via TLR4/NF-k B. Methods The MTT method was adopted to test the effect of drugs, TWP, dexamethasone(DXM) and azathioprine(AZA) on cell growth and to select the appropriate concentration. LPS was used to induce the inflammatory reaction in RAW264.7 cell line of mice. Elisa kit was adopted to test the levels of TNF-α and IL-1β. Western blotting was adopted to test the protein expression of TNF-α and IL-1β. RT-PCR was adopted to test the expression of TLR4 and NF-κB. Results The inhibiting effect of TWP on the release of TNF-α and IL-1β in a dose dependent manner. The inhibitory effect of three different TWP dose groups is weaker than that in DXM group. However, TWP in high dose is better than AZA on TNF-α and is as strong as AZA on IL-1β. The dose dependent manner also exits in the effect on the expression of TLR4 and NF-κB, the effect is not weaker, but even stronger than that of DXM and AZA. Conclusion The research shows that down regulation of TLR4 and NF-k B p65 may be one of the mechanisms about the TWP inhibitory effect on TNF-α and IL-1β.     

Inhibitory effect of St. John׳s Wort oil macerates on TNFα-induced NF-κB activation and their fatty acid composition

Ethnopharmacological relevance

The oil macerates of Hypericum perforatum L. (St. John?s Wort=SJW) have a long history of medicinal use and SJW has been used in traditional medicine both orally and topically for centuries worldwide mainly for wound healing, ulcer and inflammation.

Materials and methods

We analyzed the fatty acid composition of 10 traditionally (home-made) and 13 commercially (ready-made) prepared SJW oil macerates by GC–MS. The acid, peroxide, iodine, saponification values, and the unsaponifiable matters of the samples were determined according to the European Pharmacopoeia. We also explored potential mechanism of wound healing effect of the samples, i.e. TNFα-induced NF-κB activation.

Results

The most home-made oil samples contained oleic acid predominantly and complied with the requirements set for olive oil by European Pharmacopoeia. However, majority of the ready-made samples appeared to have adulteration with some other oils. Moderate NF-κB inhibitory effects have been observed with some of the oil samples.

Conclusion

This study sheds light on the fact that application of the proper traditional method to prepare olive oil macerates from Hypericum perforatum is able to get bioactive constituents in the oil. Besides, inhibition of TNFα-induced NF-κB activation appears to be a potential mechanism for topical wound healing activity of SJW oil macerates.     

Achyranthes japonica exhibits anti-inflammatory effect via NF-κB suppression and HO-1 induction in macrophages

Ethnopharmacological relevance

The roots of Achyranthes japonica Nakai have been used in traditional herbal medicine for the treatment of edema and arthritis in Korea.

Aim of the study

In this study, we investigated the molecular mechanism responsible for anti-inflammatory effects of the aqueous extract of A. japonica roots (AJ) in LPS-stimulated macrophages.

Materials and methods

Nitric oxide (NO) production and as inducible nitric oxide synthase (iNOS) expression were examined in TG-elicited peritoneal macrophages and RAW 264.7 cells. Cell viability was monitored by MTT assay. Protein and mRNA expressions were determined by Western blotting and RT-PCR, respectively. The activity of NF-κB and Nrf2 were examined by EMSA, immunocytochemistry or reporter assay.

Results

AJ inhibited LPS-induced NO secretion as well as iNOS expression, without affecting cell viability. Furthermore, AJ suppressed LPS-induced NF-κB activation, degradation of IκB-α, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38. Further study demonstrated that AJ induced heme oxygenase-1 (HO-1) gene expression via nuclear translocation and transactivation of Nrf2. In addition, the inhibitory effects of AJ on iNOS expression were abrogated by small interfering RNA-mediated knock-down of HO-1.

Conclusions

These results suggest that AJ suppresses LPS-induced NO production and iNOS expression in macrophages through the inhibition of IκB/NF-κB and MAPK as well as the Nrf2-mediated HO-1 induction. These findings provide the scientific rationale for anti-inflammatory therapeutic use of A. japonica roots.     

Traditionally used Veronica officinalis inhibits proinflammatory mediators via the NF-κB signalling pathway in a human lung cell line

Ethnopharmacological relevance

Extracts from Veronica officinalis L. are traditionally used for the treatment of lung diseases; however, the effective compounds and the mode of action are still unknown.

Aim of the study

Here we analyzed the effects of a standardized Veronica extract on genes expression and signalling protein production associated with the development of inflammatory lung diseases.

Material and methods

The degranulation capacity of primary mast cells, as well as gene expression and release of inflammatory mediators from human lung epithelial cells (A549 cells) were analyzed in relation to the synthetic drugs azelastine and dexamethasone. Gene and protein expression of cyclooxygenase-2 were investigated by semi-quantitative RT-PCR and western blotting, respectively. The involvement of phosphorylated mitogen-activated protein kinases and NF-κB signaling in regulation of these molecules were characterized by western blotting and electrophoretic mobility shift assays. Characteristic extract components were identified by LC–MS and verminoside was quantified by HPLC analysis.

Results

We demonstrated that Veronica officinalis has a small influence on the degranulation capacity of mast cells but rather inhibits gene and protein expression of the chemokine eotaxin in A549 lung epithelial cells, which is essential for recruitment of inflammatory-associated cells in lung diseases. Furthermore, release of the inflammatory mediator PGE₂ was diminished through inhibition of COX-2 expression via the NF-κB signaling pathway in TNF-α-activated A549 cells. Phytochemical analysis identified verproside and verminoside as the most abundant iridoid glycosides.

Conclusion

Our results are a contribution to explaining the observed anti-inflammatory effects of Veronica offcinalis extract on a molecular level. However, its clinical potency has at first to be proven in animals and subsequently in clinical trials.     

Influence of ShenFu Injection on Expressions of NF-κB p65 and COX-2 in Aged Myocardial Ischemia Reperfusion Rat Model

目的:探讨参附注射液对心肌缺血再灌注老年大鼠心肌组织NF-κB p65及COX-2的影响.方法:健康Wistar老年大鼠30只,18月龄,随机分为3组,假手术组(S组)、缺血再灌注组(I/R组)、参附注射液组(SF组),每组10只.采用结扎左冠状动脉前降支制备心肌缺血再灌注模型.观察参附注射液对缺血再灌注老年大鼠血清中肌酸激酶同工酶(CK-KB)、天门冬氨基转移酶(AST)、乳酸脱氢酶(LDH)溢出量的影响;运用免疫组化法观察心肌缺血再灌注后心肌组织细胞中NF-κB p65的活性及COX-2的蛋白表达.结果:参附注射液能显著减少I/R老年大鼠血清中CK-KB、AST、LDH的溢出量.与S组比较,I/R组心肌组织NF-κB p65的活性增高,COX-2的蛋白表达明显增加(P＜0.05).SF组中NF-κB p65、COX-2显著下降(P＜0.05).结论:NF-κB p65和COX-2在心肌缺血再灌注中均有高水平表达,提示炎症参与了心肌缺血再灌注,机制可能是NF-κB p65通过对COX-2的转录调控发挥了重要作用;参附注射液可抑制NF-κB p65活性,降低COX-2的蛋白表达水平,减轻I/R心肌炎症反应,对心肌起保护作用.