San-Huang-Xie-Xin-Tang attenuates inflammatory responses in lipopolysaccharide-exposed rat lungs

In this study, the potential anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on LPS-induced lung injury were investigated and compared to the profile of dexamethasone (DEXA) in a pre-clinical animal model. Post-treatment with SHXT (75 mg/kg), baicalin (1.5 mg/kg) and DEXA (0.5 mg/kg), significantly inhibited LPS-induced hypotension, lung edema and acute survival rates. Western blotting analysis results indicated that all of them significantly inhibited LPS-induced iNOS, TGF-beta, p38MAPK, and ICAM-1 expressions in the lung tissues. Results from ELISA analysis showed that SHXT, baicalin and DEXA all decreased plasma levels of IL-1beta, TNF-alpha, and MCP-1 caused by LPS. Based on these findings, SHXT and baicalin decreased plasma concentrations of IL-1beta, TNF-alpha, MCP-1, and expressions of TGF-beta, ICAM-1, phosphorylated p38 MAPK, and iNOS, which were associated with lung injury and lethality. These evidences indicated that SHXT and baicalin showed strong anti-inflammatory activity, similar to that observed for DEXA, and therefore implicated that herbal SHXT might be therapeutically useful for the treatment of endotoxic lung injury.     

Effects of three purgative decoctions on inflammatory mediators

In traditional Chinese medicine (TCM), there are three Cheng-Chi-Tang decoctions (CCTDs) including: Ta-Cheng-Chi-Tang (TCCT), Xiao-Chen-Chi-Tang (XCCT) and Tiao-Wei-Chen-Chi-Tang (TWCCT), which are the frequently used purgative remedies to treat "internal heat"-induced symptoms like a bloated and painful abdomen, hard stools and fever, etc. Constituents in each formulation are Rheum palmatum L. (Polygonaceae), Magnolia officinalis Rehd. et Wils. (Magnoliaceae), Citrus aurantium L. (Rutaceae), Mirabilitum (mirabilite, crystals of sodium sulfate, Na2SO4) for TCCT; Rheum palmatum, Magnolia officinalis, Citrus aurantium for XCCT; and Rheum palmatum, Mirabilitum, Glycyrrhiza uralensis Fisch. (Leguminosae) for TWCCT. However, the underlying mechanisms for purging internal pathological heat are far from fully clarified, and few scientific investigations have been carried out to delineate the relationships between the anti-inflammatory effects and laxative potencies of these formulations. In this study, the anti-inflammatory effects of the three CCTDs on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E (PGE2) production in RAW 264.7 cells, carrageenan-induced paw edema in mice and the laxative effect in mice were explored. The results showed that TCCT inhibited LPS-induced NO and PGE2 production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells more effectively than did XCCT or TWCCT. Moreover, paw edema of carrageenan-treated mice was significantly attenuated in mice pretreated with 1 g/kg TCCT. TCCT also showed the strongest purgative activity among the three formulations. These findings indicate that TCCT has anti-inflammatory effects in addition to its traditionally known purgative activities. It may have potential to treat inflammatory disease conditions.     

多索茶碱对慢性阻塞性肺疾病炎性递质的影响

目的观察并比较多索茶碱与氨茶碱治疗慢性阻塞性肺疾病的临床疗效及安全性。方法将126例慢性阻塞性肺疾病患者随机分为A组64例和B组62例。在常规治疗的基础上,A组给予多索茶碱300 mg每天1次,B组给予氨茶碱250 mg每天1次,观察2组慢性阻塞性肺炎患者肺部哮鸣音、喘息症状、血气分析主要指标以及炎性递质的变化情况。结果 A组临床总有效率显著高于B组(P<0.05)。与B组比较,A组治疗后血气分析主要指标改善更好,炎性递质水平下降更明显(P均<0.05)。结论多索茶碱治疗慢性阻塞性肺炎较氨茶碱安全、有效;可作为慢性阻塞性肺炎治疗方案的首选。     

姜黄素对大鼠急性肺栓塞炎性介质的影响

目的观察姜黄素对急性肺栓塞大鼠炎性介质的影响,并探讨其作用机制。方法 32只SD大鼠随机分为正常对照组、模型组及姜黄素低、高剂量组,每组8只。制备急性自体血栓肺栓塞模型。进行血气分析;检测肺系数、湿/干质量;放射免疫法检测血液中内皮素-1（ET-1）、血栓素-2（TXB2）含量;逆转录聚合酶链式反应法（RT-PCR）检测肺组织白细胞介素-1（IL-1）、白细胞介素-6（IL-6）及肿瘤坏死因子-α（TNF-α）mRNA的表达。结果与模型组比较,姜黄素能显著升高p（O2）、p（CO2）水平（P〈0.05）,降低肺系数、湿/干质量、ET-1、TXB2含量（P〈0.05）,降低细胞IL-1、IL-6及TNF-αmRNA表达（P〈0.05）。结论姜黄素能抑制IL-1、IL-6及TNF-αmRNA的表达,降低ET-1、TXB2含量,对急性肺栓塞大鼠有保护作用。     

血必净注射液对急性冠脉综合征炎症递质和预后的影响

目的探讨血必净注射液对急性冠脉综合征患者炎症递质以及预后的影响。方法将2005年4月—2009年2月收入我院心内科90例患者随机分为治疗组46例和对照组44例,对照组按照常规治疗,治疗组在对照组的基础上加用血必净注射液50 mL,每日2次,治疗7 d。采用ELISA法检测IL-6、IL-10、CRP。记录患者28 d主要心血管事件发生率。结果疗程结束时治疗组IL-6、CRP明显低于对照组(P<0.05,P<0.01),IL-10高于对照组(P<0.05);治疗组心绞痛恶化率(4%)、心肌梗死发生率(2%)较对照组(18%,16%)明显降低(P均<0.05),对照组28 d病死率(14%)高于治疗组(4%),但无显著性差异。结论血必净注射液能改善急性冠脉综合征预后,其机制可能为通过调控炎症反应实现。     

轮泻停药膏敷脐对小鼠肠推进及腹泻炎性介质的影响

目的:初步探讨轮泻停药膏敷脐对小鼠肠推进以及对番泻叶所致小鼠腹泻后炎性介质的变化的影响,为临床研究治疗轮状病毒腹泻提供有效依据。方法:将所有实验小鼠随机分为3部分,每部分4组,即空白组、模型组、思密达组及轮泻停药膏组。模型组和空白组给予等量生理盐水,思密达组按(0.06g/mL)0.02mL/g,2次/d灌服,轮泻停药膏组贴敷轮泻停药膏,1剂/d;除空白组,其他组小鼠注射甲硫酸新斯的明,观测小鼠小肠酚红的推进率;观察各组对小鼠给予番泻叶后大便次数增加的变化;检测番泻叶所致小鼠严重腹泻后血清中IL-1β和TNF-α的水平变化。结果:轮泻停药膏组与思密达组比较,小肠的推进距离及推进率差异均有显著性(P<0.05),小鼠大便次数也具有显著性差异(P<0.05);两组的血清IL-1β和TNF-α差异也具有统计学意义(P<0.05)。结论:轮泻停药膏能缓解腹泻程度,保护肠黏膜免受炎性介质的损害,具有潜在的治疗轮状病毒腹泻的疗效。     

Young Yum pill inhibits inflammatory mediators and nuclear factor-kappa B signaling in lipopolysaccharide-stimulated RAW 264.7 macrophages

OBJECTIVE: To investigate the effect of Young Yum pill(YYP) on inflammatory mediators in cultured RAW 264.7 cells and elucidate the nuclear factorkappa B(NF-κB)-related mechanism behind the action.METHODS: YYP was extracted with 95% ethanol Lipopolysaccharide(LPS)-stimulated RAW 264.7 macrophages were used to evaluate the effect of YYP on inflammatory mediators.Production of nitric oxide(NO) and prostaglandin E2(PGE2) were measured by Griess test and enzyme-linked immunosorbent assay, respectively.The levels of genes and proteins involved in the generation of inflammatory mediators were examined using real-time polymerase chain reaction and Western blotting, respectively.RESULTS: YYP dose-dependently suppressed LPSinduced production of NO, PGE2 and tumor necrosis factor-α(TNF-α), and elevation of mRNA and protein levels of inducible NO synthase and cyclooxygenase-2 in RAW 264.7 macrophages.These observations were associated with decreased NF-κB p65 phosphorylation and nuclear localization, enhanced Akt(protein kinase B) phosphorylation, as well as reduced inhibitor of κB(IκB) α degradation and IκB kinase α/β phosphorylation.CONCLUSION: The present study demonstrated an inhibitory effect of YYP on the NF-κB-regulated inflammatory mediators NO, PGE2 and TNF-α in LPSstimulated RAW 264.7 macrophages, providing a pharmacological basis for the use of YYP in treating inflammatory disorders.     

Canna indica L. attenuates high-glucose- and lipopolysaccharide-induced inflammatory mediators in monocyte/macrophage

Ethnopharmacological relevance

Canna indica L. (CI) has been widely used as a folklore medicine in tropical and subtropical areas with beneficial effects in numerous diseases, including infection, rheumatism, hepatitis, and it has also been identified as an antioxidant.

Materials and methods

The present study aimed to investigate the effect of Canna indica CI ethanolic extract (CIE) on productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin-1β (IL-1β) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. In addition, the effects of CIE in high glucose (HG)-induced U937 monocytes on mRNA expressions of IL-8 and monocyte chemoattractant protein-1 (MCP-1), and regulation of mitogen-activated protein kinase (MAPK) pathways were also identified.

Results

CIE was found to inhibit the production of inflammatory mediators including NO, IL-1β, and PGE₂ from LPS-induced RAW 264.7 macrophages. The increases in HG-induced mRNA expressions of IL-8 and MCP-1 were also significantly inhibited by CIE. Stimulation of HG in U937 monocytes resulted in activation of p38 MAPK, ERK1/2, and JNK. However, CIE treatment significantly decreased phosphorylation of p38 MAPK, ERK1/2, and JNK.

Conclusion

The present study demonstrated that CIE suppressed the LPS-induced inflammatory mediator production and also inhibited HG-induced inflammatory mediator expression by the regulation of MAPK pathway.     

急腹症SIRS治疗中加用中药对细胞因子及其它炎症介质的影响

目的 :探讨急腹症SIRS治疗中加用中药对细胞因子及其它介质的影响。方法 :前瞻性研究 ,将 4 3例急腹症SIRS患者按病种及APACHE -II评分分层随机分为综合安慰组及综合中药组 (包括综合大清组和综合承气组 )。动态观察血IL - 6、TNFα、内毒素、LPO。结果 :综合中药组和综合大清组第 3天IL - 6显著降低 ,前者TNFα亦降低 (P <0 .0 5 ) ,各中药组第 3、7天内毒素及LPO均降低 (P <0 .0 5 )。各中药组时段 (第 1～ 3、4～ 7、8～ 14天 )累计便次日均数增多 (P <0 .0 1) ,其于第 1～ 3天与第 3天内毒素、IL - 6、LPO呈负相关 (r =- 0 .4 76 ,P =0 .0 0 4 ;r =- 0 .5 12 ,P =0 .0 4 3;r =- 0 .6 4 3,P =0 .0 0 )。结论 :在西医综合治疗基础上 ,大承气颗粒或并用清胆灵能降低SIRS阶段血IL - 6、TNFα、内毒素和脂质过氧化物 ,阻止全身炎症反应升级扩大。     

Potential ex vivo immunomodulatory effects of San-Huang-Xie-Xin-Tang and its component herbs on mice and humans

Aim of the study

San-Huang-Xie-Xin-Tang (SHXXT), an important Chinese medicine formula, contains Rhei Rhizoma (RR), Scutellariae Radix (SR) and Coptidis Rhizoma (CR). RR and SR are abundant in anthraquinone and flavonoid polyphenols. Pharmacokinetic study of SHXXT indicated that glucuronides were the predominant forms of polyphenols in rats.

Materials and methods

As an extension of pharmacokinetic study, the serum metabolites of SHXXT, RR, SR and CR were prepared from rats and quantitated, then the immunomodulation effects were examined by culturing these serum metabolites with murine and human immune cells.

Results

The results indicated that the inhibitions on nitric oxide (NO) and cytokine production from mitogen-activated peritoneal macrophages by the serum metabolites of SHXXT, RR, SR and CR were through reducing the protein expression of inducible NO synthase (iNOS) and the IC₅₀ were 0.8%, 1.5%, 3.0% and 0.8% of their blood concentrations, respectively. In addition, the serum metabolites of SHXXT, RR, SR and CR significantly decreased the ratios of interferon-gamma (IFN-γ) to interleukin (IL)-4 in mitogen-stimulated mice spleen cells and human peripheral blood mononuclear cells (PBMCs). Moreover, the serum metabolites of SHXXT and SR significantly arrested the mitogen-stimulated mice spleen cells at G2/M stage.

Conclusions

In conclusion, the serum metabolites of SHXXT and the component herbs exerted promising modulation activities on the immune functions and the cell cycle distribution of mice and human immune cells. We suggest that SHXXT is a promising remedy for immunomodulation through Th1/Th2 regulation.     

黄芪甲苷对异丙肾上腺素诱导大鼠主动脉氧化应激和炎症的影响

目的:研究黄芪甲苷(Astragaloside IV,As IV)对异丙肾上腺素(Isoprenaline,ISO)诱导的大鼠主动脉内皮细胞损伤的影响并从氧化应激和抗炎症方面探讨其可能的机制。方法:以异丙肾上腺素15mg/kg腹腔注射7天制备大鼠主动脉内皮损伤模型。60只SD大鼠随机分为6组,在异丙肾上腺素造模前一天给予不同剂量的黄芪甲苷(25、50、100mg/kg)和普萘洛尔40mg/kg或羧甲基纤维素钠(1%)灌胃,第二天同时腹腔注射15mg/kg异丙肾上腺素连续7天。通过循环内皮细胞计数确定内皮细胞损伤程度;通过二氢乙锭(hydroethidine)荧光染色的方法原位定性超氧阴离子;Western-blot测定cu/zn SOD、NF-k B p65、Ik B-α蛋白表达;RT-PCR测定IL-1β,TNF-αmRNA的表达。结果:异丙肾上腺素作用后,外周血液中循环内皮细胞比空白增多了253.59%;血管中超氧阴离子增加了115.12%;cu/zn SOD表达下降了22.80%;p65表达升高了34.40%,IkB-α蛋白表达降低了33.30%;同时主动脉血管组织中炎症因子IL-1β、TNF-α的mRNA表达量分别上升了162.41%、108.20%。与异丙肾上腺素组相比,黄芪甲苷不同剂量组均有所改善,且在黄芪甲苷(50mg/kg)效果最明显,表现为外周血循环内皮细胞数目减少了49.34%,血管组织中超氧因子减少了42.42%,p65蛋白表达降低了16.47%,cu/zn SOD、IkB-α的蛋白表达分别升高了18.37%、29.10%,主动脉血管组织中IL-1β、TNF-α的mRNA表达分别降低了35.02%、43.25%。结论:黄芪甲苷能改善异丙肾上腺素诱导的大鼠主动脉血管内皮细胞的损伤,其机制可能是从抗氧化和抗炎症方面来保护血管内皮细胞,进而改善血管舒缩功能。     

Phellinus linteus inhibits inflammatory mediators by suppressing redox-based NF-kappaB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophage

The mushroom Phellinus linteus has been known to exhibit potent biological activity. In contrast to the immuno-potentiating properties of Phellinus linteus, the anti-inflammatory properties of Phellinus linteus have rarely been investigated. Recently, ethanol extract and n-BuOH fractions from Phellinus linteus were deemed most effective in anti-inflammatory activity in RAW 264.7 macrophages. The regulatory mechanisms of Phellinus linteus butanol fractions (PLBF) on the pharmacological and biochemical actions of macrophages involved in inflammation have not been clearly defined yet. In the present study, we tested the role of PLBF on anti-inflammation patterns in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. To investigate the mechanism by which PLBF inhibits NO and PGE2 production as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, we examined the activation of IkappaB and MAPKs in LPS-activated macrophages. PLBF clearly inhibited nuclear translocation of NF-kappaB p65 subunits, which correlated with PLBF's inhibitory effects on IkappaBalpha phosphorylation and degradation. PLBF also suppressed the activation of mitogen-activated protein (MAP) kinases including p38 and stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Furthermore, macrophages stimulated with LPS generated ROS via activation of membrane-bound NADPH oxidase, and ROS played an important role in the activation of nuclear factor-kappaB (NF-kappaB) and MAPKs. We demonstrated that PLBF directly blocked intracellular accumulation of reactive oxygen species in RAW 264.7 cells stimulated with LPS much as the NADPH oxidase inhibitors, diphenylene iodonium, and antioxidant pyrrolidine dithiocarbamate did. The suppression of NADPH oxidase also inhibited NO production and iNOS protein expression. Cumulatively, these results suggest that PLBF inhibits the production of NO and PGE2 through the down-regulation of iNOS and COX-2 gene expression via ROS-based NF-kappaB and MAPKs activation. Thus, PLBF may provide a potential therapeutic approach for inflammation-associated disorders.     

Regulatory effects of stage-treatment with established Chinese herbal formulas on inflammatory mediators in pediatric asthma

OBJECTIVE： To explore the regulatory effects of es- tablished Chinese herbal formulas on inflammatory mediators released during asthma attacks, and to elucidate the molecular mechanism of Traditional Chinese Medicine in the treatment of asthma. METHODS： Seventy-five asthmatic children were randomly divided into a Chinese medication group （45 cases） and a Western medication control group （30 cases）. Patients in the Chinese medication group were treated with a series of established Chi- nese herbal formulas, whereas the Western medica- tion control group received a leukotriene receptor antagonist and a bronchial relaxant. Real-time PCR was used to determine the mRNA expression levels of interleukin （IL）-4, cysteinyl leukotriene receptor 1 （CysLTR1）, and interferon （IFN）-γ in peripheralblood mononuclear cells before and after treat- ment. Enzyme-linked immunosorbent assay was used to measure the peripheral blood levels of IL-4, leukotriene （LTE）-4, and INF-γ before and after treat- ment. RESULTS： After treatment, the mRNA expression levels of 11-4 and CysLTR1 were down-regulated （P〈 0.01） and the mRNA expression levels of IFN-γ were up-regulated （P〈0.05） in the Chinese medication and Western medication groups; no significant dif- ference was found between the two groups. In the Chinese medication group, IL-4 blood level was de- creased and it was significantly different from that in the Western medication group （P〈0.05）; there was also a significant increase in IFN-γ blood levels after treatment with Chinese medica- tion （P〈0.05）. There were no significant differenc- es in LTE-4 blood levels between the two groups before and after treatment （P〉0.05）. CONCLUSION： Chinese medication has a regulato- ry effect on leukotriene receptor gene expression and the imbalance of Th1/Th2 immune cells dur- ing asthma attacks in pediatric patients.     

Regulatory effects of stage-treatment with established Chinese herbal formulas on inflammatory mediators in pediatric asthma

Objective

To explore the regulatory effects of established Chinese herbal formulas on inflammatory mediators released during asthma attacks, and to elucidate the molecular mechanism of Traditional Chinese Medicine in the treatment of asthma.

Methods

Seventy-five asthmatic children were randomly divided into a Chinese medication group (45 cases) and a Western medication control group (30 cases). Patients in the Chinese medication group were treated with a series of established Chinese herbal formulas, whereas the Western medication control group received a leukotriene receptor antagonist and a bronchial relaxant. Real-time PCR was used to determine the mRNA expression levels of interleukin (IL)-4, cysteinyl leukotriene receptor 1 (CysLTR1), and interferon (IFN)-γ in peripheral blood mononuclear cells before and after treatment. Enzyme-linked immunosorbent assay was used to measure the peripheral blood levels of IL-4, leukotriene (LTE)-4, and INF-γ before and after treatment.

Results

After treatment, the mRNA expression levels of IL-4 and CysLTR1 were down-regulated (P< 0.01) and the mRNA expression levels of IFN-γ were up-regulated (P<0.05) in the Chinese medication and Western medication groups; no significant difference was found between the two groups. In the Chinese medication group, IL-4 blood level was decreased and it was significantly different from that in the Western medication group (P<0.05); there was also a significant increase in IFN-γ blood levels after treatment with Chinese medication (P<0.05). There were no significant differences in LTE-4 blood levels between the two groups before and after treatment (P>0.05).

Conclusion

Chinese medication has a regulatory effect on leukotriene receptor gene expression and the imbalance of Th1/Th2 immune cells during asthma attacks in pediatric patients.     

血必净对急性重症胰腺炎患者炎性介质的影响

目的 观察血必净注射液对急性重症胰腺炎患者炎性介质的影响.方法 将80例急性重症胰腺炎患者按病例尾号随机分为两组各40例,对照组在禁食、补液、抑酸、抗感染等治疗基础上,持续静脉泵入生长抑素6 mg,乌司他丁20万U,连续治疗7 d.治疗组在对照组治疗基础上静脉滴注血必净注射液,50 ml/次,2次/d,连用7 d.观察...     

灯盏乙素对LPS诱导的RAW264.7细胞炎症介质分泌的影响

[目的]研究灯盏乙素对脂多糖(LPS)诱导的RAW264.7细胞炎症的影响,初步探讨其抗炎作用机制。[方法]用噻唑蓝(MTT)法检测灯盏乙素对RAW264.7细胞活力的影响;用Griess法检测灯盏乙素对LPS诱导的RAW264.7细胞中一氧化氮(NO)生成的影响;用荧光素酶报告质粒法检测灯盏乙素对LPS诱导的核转录因子(NF-κB)转录活性的影响;用实时定量聚合酶链反应(PCR)法检测灯盏乙素对LPS诱导的RAW264.7细胞中NF-κB靶基因肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)m RNA表达的影响。[结果]0.01~10μmol/L的灯盏乙素处理24 h后对RAW264.7活力无显著影响;1、10μmol/L的灯盏乙素可以显著抑制LPS诱导的NO的生成及NF-κB转录活性;灯盏乙素可以不同程度的抑制LPS诱导的RAW264.7细胞NF-κB靶基因TNF-α、IL-1β、IL-6m RNA的上调作用。[结论]灯盏乙素可能通过抑制NF-κB的活化及炎症因子的表达发挥一定的抗炎作用。     

Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses inflammatory mediators release from mast cells

Background

PentaHerbs formula (PHF) containing Cortex Moutan, root bark of Paeonia suffruticosa Andr. (Ranunculaceae), Cortex Phellodendri, bark of Phellodendron chinensis Schneid. (Rutaceae), Flos Lonicerae, flower of Lonicera japonica Thunb. (Capri-foliaceae), Herba Menthae, aerial part of Mentha haplocalyx Briq. (Labiatae) and Rhizoma Atractylodis, rhizome of Atractylodes lancea (Thunb.) DC. (Compositae) at the ratio of 2:2:2:1:2 was useful in the management of eczema.

Aim of the study

Since the mechanism of action of PHF is not known, we aimed to investigate the actions of PHF on mast cell activation.

Materials and methods

Effects of aqueous extracts of PHF and individual component herb on mediator release from rat peritoneal mast cells (RPMCs) and cytokine production from HMC-1 were investigated.

Results

PHF, Cortex Moutan and Herba Menthae significantly attenuated histamine release and prostaglandin D₂ synthesis from RPMC activated by anti-IgE and compound 48/80 (p < 0.05). While Flos Lonicerae and Rhizoma Atractylodis suppressed only mediator release from compound 48/80 activated RPMC, Cortex Phellodendri potentiated only anti-IgE induced mediator release (p < 0.05). However, with the exception of Cortex Moutan, PHF and the other four component herbs failed to affect cytokine production in HMC-1.

Conclusions

Although individual herbs demonstrated different modulating effects on mast cells, inhibition of inflammatory mediator release from mast cells would contribute to the therapeutic efficacy of PHF.