Effects of ryo-kan-kyomi-sin-ge-nin-to extract on degranulation of and histamine release from rat mast cells.

The effects of Ryo-kan-kyomi-sin-ge-nin-to (RKSG)) extract, a medicinal agent traditionally used in China and Japan for treatment of asthma, on the degranulation of and histamine release from rat mast cells were studied. At a concentration of 5 mg/ml RKSG, degranulation of mast cells stimulated either by antigen (DNP-Ascaris) or compound 48/80 was markedly suppressed. At a concentration of 1-5 mg/ml RKSG, histamine release from mast cells due to application of either antigen or compound 48/80 was inhibited in a dose-dependent fashion. These results suggest that RKSG may be useful for the treatment of type I allergy-related diseases.     

Pycnogenol inhibits the release of histamine from mast cells

Oxygen derived free radicals are now increasingly regarded as a primary force of tissue destruction and also have the ability to release histamine from mast cells. Pycnogenol is an extract of the bark of French maritime pine (Pinus pinaster) containing bioflavonoids with a potent ability to scavenge free radicals. Therefore Pycnogenol was investigated for inhibition of histamine release from rat peritoneal mast cells. In addition, its effects were compared with sodium cromoglycate, a known inhibitor of histamine release from the mast cell. Rat peritoneal mast cells were isolated and purified by differential centrifugation and cells pooled from 3-4 animals were suspended at approximately 10(6) cells/mL buffered salt solution. Histamine release was induced by compound 48/80 or the calcium ionophore A-23187 and estimated from supernatant following extraction and by fluorimetric methods. Pycnogenol produced a concentration dependent inhibition of histamine release induced by the two secretagogues. Its inhibitory effect on mast cell histamine release was favourably comparable to sodium cromoglycate.     

仙蓟化斑胶囊对肥大细胞脱颗粒及组胺释放影响的研究

[目的]研究仙蓟化斑胶囊抗变态反应的作用机制,为后期实验及其临床治疗过敏性紫癜提供依据。[方法]制备致敏的大鼠及抗卵蛋白血清,给予不同浓度药物,采用大鼠被动皮肤过敏反应(PCA)实验,测定大鼠皮肤蓝斑直径,同时采用大鼠颅骨骨膜肥大细胞脱颗粒实验、大鼠肥大细胞释放组胺实验,测定脱颗粒百分率和组胺释放水平。[结果]仙蓟化斑胶囊可使蓝斑直径变小、可降低肥大细胞脱颗粒百分率、降低其组胺释放,并呈明显的剂量依赖关系。[结论]仙蓟化斑胶囊有抗变态反应的作用,明显抑制PCA、肥大细胞脱颗粒及组胺的释放。     

Inhibitory effects of Korean folk medicine `Hi-Chum' on histamine release from mast cells in vivo and in vitro

The effect of aqueous extract of Siegesbeckia glabrescence (Compositae) whole plants (SGWP) on systemic or local anaphylaxis was studied. SGWP inhibited compound 48/80-induced systemic anaphylaxis 100% with a dose of 1000 mg/kg. Oral administration of SGWP (100 mg/kg) showed a marked inhibition rate in local immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis reaction. When SGWP was pretreated at concentration ranging from 0.1 to 1000 mg/kg, the serum histamine levels were reduced in a dose-dependent manner. Moreover, SGWP dose-dependently inhibited the histamine release from peritoneal mast cells by compound 48/80. These results indicate that SGWP possess strong antianaphylactic activity by inhibition of histamine release from mast cells.     

Inhibitory activity of Chrysanthemi sibirici herba extract on RBL-2H3 mast cells and compound 48/80-induced anaphylaxis

The effects of extracts from various oriental medicinal herbs on mast cell-mediated allergic reaction were investigated. Among them, Chrysanthemi sibirici herba ethanol extract exerted the potent inhibitory activity on antigen-induced degranulation in RBL-2H3 mast cells. Chrysanthemi sibirici herba dose-dependently inhibited DNP-BSA or compound 48/80-induced degranulation in RBL-2H3 mast cells, with IC(50) values of approximately 49 microg/ml and 76 microg/ml, respectively. This extract strongly suppressed compound 48/80-induced systemic anaphylaxis by 48.7% at a dose of 300 mg/kg in mice. Chrysanthemi sibirici herba also inhibited the expression of TNF-alpha and the activation of the MAP kinase, ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of activating phosphorylation of ERK1/2. These results lead us to conclude that Chrysanthemi sibirici herba may be used clinically to treat various allergic diseases.     

青藤碱组胺释放作用与抗组胺收缩肠管作用研究

目的:探讨青藤碱的组胺释放作用及其对组胺引起的回肠收缩反应的影响。方法:采用豚鼠腹腔肥大细胞体外孵化试验观察组胺释放作用。采用豚鼠离体回肠实验观察组胺诱导的回肠平滑肌收缩张力的变化及药物作用。结果:青藤碱50、100、150、200、250、300μmol/L和CP48/8010μg/ml可引起豚鼠腹腔肥大细胞释放组胺,青藤碱在50-250μmol/L范围内肥大细胞组胺释放率随药物浓度增加而提高,但增加至300μmol/L时,组胺释放率不再随用药浓度而提高。青藤碱10、50、100、150、300μmol/L对豚鼠正常回肠平滑肌节律性收缩曲线未见明显影响。组胺能引起豚鼠回肠平滑肌张力显著增加,青藤碱50、100、150、300μmol/L对组胺引起的回肠收缩有明显抑制作用。结论:青藤碱对豚鼠腹腔肥大细胞具有明显的组胺释放作用,对组胺引起的豚鼠回肠平滑肌收缩青藤碱有显著抑制作用。     

Preventive effect of Shigyaku-san on progression of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats

The study examined whether Shigyaku-san (Si-Ni-San) extract (TJ-35), a traditional Kampo medicine, prevents acute gastric mucosal lesion progression in rats treated once with compound 48/80 (C48/80). Rats treated with C48/80 (0.75 mg/kg body weight, i.p.) received TJ-35 (0.15, 0.35 or 0.75 g/kg body weight, p.o.) 0.5 h after the treatment at which time gastric mucosal lesions appeared. At 0.5 h after C48/80 treatment, the gastric mucosa of the treated rats had increased myeloperoxidase (an index of neutrophil infiltration) and xanthine oxidase activities and thiobarbituric acid reactive substances (an index of lipid peroxidation) content. At 3 h after C48/80 treatment, the gastric mucosa of the treated rats showed progressive lesions and further increases in myeloperoxidase and xanthine oxidase activities and thiobarbituric acid reactive substances content and decreases in vitamin E, ascorbic acid and adherent mucus contents and Se-glutathione peroxidase activity. Post-administered TJ-35 attenuated all these changes found at 3 h after C48/80 treatment dose-dependently. These results indicate that TJ-35 prevents the progression of C48/80-induced acute gastric mucosal lesions in rats possibly by attenuating enhanced neutrophil infiltration, enhanced lipid peroxidation associated with decreased vitamin E and ascorbic acid contents and Se-glutathione peroxidase activity, and destruction of the defensive barrier in the gastric mucosa.     

Inhibition of release of inflammatory mediators in rat peritoneal mast cells and murine macrophages by a chinese herbal medicine formula (RCM‐102)

RCM‐102 is a Chinese herbal medicine formulation derived from a formula which was shown to be effective in treating seasonal allergic rhinitis (SAR) in a randomized placebo‐controlled trial. The aim of this study was to investigate the in vitro effect of RCM‐102 on the formation of inflammatory mediators, histamine, prostaglandin and nitric oxide, which are known to be involved in the pathophysiology of SAR. The effect of RCM‐102 on histamine release was tested in compound 48/80‐stimulated rat peritoneal mast cells. The effects of RCM‐102 on the release of NO and prostaglandins (PGE₂) and the expression of inducible NO synthase (iNOS) and COX‐2 were studied in lipopolysaccharide (LPS)‐stimulated RAW 264.7 cells. In rat peritoneal mast cells, RCM‐102 significantly reduced the compound 48/80‐induced histamine release. It also significantly reduced NO and PGE₂ production as well as the expression of COX‐2 and iNOS in RAW 264.7 cells. These findings indicate that RCM‐102 inhibits the formation of several allergic/inflammatory mediators and thus may be used for treating related conditions such as SAR. The actions of RCM‐102 are likely to be contributed by the synergistic actions of individual herbal ingredients. Copyright © 2009 John Wiley & Sons, Ltd.     

Effects of Chinese herbal medicine "kanbaku-taiso-to" on transmembrane ionic currents and its local anesthetic action

The Chinese herbal medicine, "Kanbaku-taiso-to" (KT) which is a mixture of Glycyrrhizae Radix, Triticii Semen and Zizyphi Fructus, sometimes shows marked effects on insomnia, infantile convulsions and emotional irritability. To elucidate the mechanism of the sedative effect of KT, effects of KT on the transmembrane ionic currents and local anesthetic action were examined and the following results were obtained. KT showed an inhibition of sodium, calcium and potassium currents in snail neurons. KT showed an inhibitory effect on pentylenetetrazol-induced bursting activity. KT had local anesthetic action on frog nerve fibers. Together with our previous study, these results suggest that KT has an inhibitory effect on hyperexcitability of the neuronal membrane and this is the main cause of the sedative effect of KT.     

Effect of acupuncture at complementary acupionts on mast cells and histamine/bradykinin released by mast cells in the regions of acupionts

Objective

To observe the changes in numbers and degranulation status of local mast cells (MCs) of the complementary acupionts, as well as the concentrations of serum histamine and bradykinin after acupuncture at rat’s complementary acupionts of Yanglingquan (GB 34) and Yinlingquan (SP 10), for exploring the mechanisms of the synergistic effect of complementary acupionts.

Methods

Using random number table method, 40 Wistar rats were randomly divided into a blank control group (group K), an acupuncture at Yanglingquan (GB 34) group (group A), an acupuncture at Yinlingquan (SP 9) group (group B), an acupuncture at Yanglingquan (GB 34) and Yinlingquan (SP 9) group (group AB), and an acupuncture at points near Yanglingquan (GB 34) and Yinlingquan (SP 9) group (group CD), 8 rats in each group. Group A received acupuncture at Yanglingquan (GB 34); group B received acupuncture at Yinlingquan (SP 9); group AB received acupuncture at Yanglingquan (GB 34) and Yinlingquan (SP 9); group CD received acupuncture at the control points [points 3 mm away from Yanglingquan (GB 34) and Yinlingquan (SP 9) respectively]. Acupuncture was performed at bilateral points in each group. Rats in group K were fixed using the same method as rats in the other 4 groups without acupuncture stimulation. Needles of 0.35 mm in diameter and 40 mm in length were used for acupuncture. Needle handle was connected to the G6805-II mode electroacupuncture (EA) device after needling qi was obtained, with sparse-dense wave, frequency of 2 Hz/100 Hz and current of 1 mA to keep the needle handles slightly tremulous while the rats kept quiet. Rats were continuously stimulated by EA for 20 min each time. Experimental interventions were conducted on the 1st, 3rd, 5th and 7th days when the experiment started, for 4 times in total. Specimens from rats in each group were collected 2 h after the 7th day. The levels of histamine and bradykinin in serum were detected by enzyme-linked immunosorbent assay (ELISA). Local tissues of the points were used to prepare cryosections. The changes of MCs were observed after toluidine blue staining.

Results

Compared with group K, the numbers and degranulation rates of MCs in group A, group B, group AB and group CD were significantly increased (all P<0.05). The number and degranulation rate of MCs in group AB were significantly higher than those in group A, group B and group CD (all P<0.05). The order of histamine levels from high to low was: group AB > group B > group A > group CD > group K, and the differences were statistically significant (all P<0.05); the levels of bradykinin in group AB, group A and group B were significantly higher than those in group K and group CD (all P<0.05). There was no significant difference in the bradykinin level between group A and group B, nor between group CD and group K (all P>0.05).

Conclusion

The number and degranulation rate of MCs of the complementary acupionts are significantly increased after acupuncture at complementary acupionts of Yanglingquan (GB 34) and Yinlingquan (SP 9) of rats, and the serum levels of histamine and bradykinin are increased, which may be one of the mechanisms of the synergism produced by the combination of complementary acupionts.

     

Effect of Sophora flavescens Aiton extract on degranulation of mast cells and contact dermatitis induced by dinitrofluorobenzene in mice

Ethnopharmacological relevance

The dried root of Sophora flavescens Aiton (Sophorae radix, SR) has long been used in traditional medicine for the treatment of fever and swelling in eastern countries.

Materials and methods

The present study investigated the anti-allergic and anti-inflammatory effects of SR using 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mouse model and in vitro using RBL-2H3 cells.

Results

In mice, the topical application of 10 mg/mL of SR effectively inhibited enlargement of ear thickness and weight induced by repeated painting with DNFB. Topical application of SR also inhibited hyperplasia, edema, spongiosis and infiltration of mononuclear cells in ear tissue. In addition, production levels of interferon-gamma and tumor necrosis factor-alpha were decreased by SR in vivo. Finally, the release of histamine and β-hexosaminidase, and migration were inhibited by treatment with SR.

Conclusions

These data indicate the potential of SR in treating patients with allergic skin diseases and also suggest that related mechanisms are involved in anti-inflammatory action on the Th 1 skewing reaction and inhibition against recruitment and degranulation of mast cells.     

Extract of Naotaifang,a compound Chinese herbal medicine,protects neuron ferroptosis induced by acute cerebral ischemia in rats

ObjectiveOur previous research showed that Naotaifang (a compound traditional Chinese herbal medicine) extract (NTE) has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia. In this study, we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4 (GPX4) and iron metabolism.MethodsWe established an acute brain injury model of middle cerebral artery occlusion (MCAO) in rats, in which we could observe the accumulation of iron in neurons, as detected by Perl’s staining. Using assay kits, we measured expression levels of ferroptosis biomarkers, such as iron, glutathione (GSH), reactive oxygen species (ROS) and malonaldehyde (MDA); further the expression levels of transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), solute carrier family 7 member 11 (SLC7A11) and GPX4 were determined using immunohistochemical analysis, real-time quantitative polymerase chain reaction and Western blot assays.ResultsWe found that treatment with NTE reduced the expression levels of TFR1 and DMT1, reduced ROS, MDA and iron accumulation and reduced neurobehavioral scores, relative to untreated MCAO rats. Treatment with NTE increased the expression levels of SLC7A11, GPX4 and GSH, and the number of Nissl bodies in the MCAO rats.ConclusionTaken together, our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7A11/GPX4 pathways.     

中药对骨髓间充质干细胞向神经细胞分化影响的研究概况

骨髓间充质干细胞（mesenchymal stem cells，MSCs）具有在体内及体外向神经细胞分化的潜能，为多种神经系统疾病的细胞治疗提供了新的思路。开展中药定向诱导间充质干细胞向神经细胞分化研究，可望为今后临床神经细胞移植提供安全有效的诱导分化剂，也可为中医药在间充质干细胞领域的应用开辟新的途径。     

中药诱导肿瘤细胞分化研究的现状及展望

肿瘤细胞诱导分化治疗是肿瘤治疗研究的新途径。其基本特点在于不是杀伤肿瘤细胞而是诱导肿瘤细胞分化为正常或接近正常细胞。８０年代以来，国际分化治疗会议已举行了５届，肿瘤诱导分化治疗已成为了国际肿瘤研究的一个热点。我国学者在近１０多年来，即已开始进行了中药...     

复方中药对辐射小鼠细胞周期及免疫功能的影响

目的 :研究复方中药对辐射小鼠细胞周期及免疫功能的影响。方法 :应用流式细胞仪 (FCM)检测脾脏细胞周期和免疫参数 (NK,CD+4 ,CD+8)。结果 :该复方中药能使受照小鼠脾细胞 S,G2 + M期的比例升高 ,促进脾细胞增殖 ,并能提高N K细胞活性和 CD+4 百分率及 CD+4 / CD+8比值。结论 :复方中药对辐射损伤细胞具有一定的保护作用     

植物类中药寒热药性与有机成分单一化合物相关性的文献研究

目的:探寻化学成分与中药寒热属性的相关性。方法:利用现有文献提供的信息资料,通过文献检索收集植物药化学成分信息,利用化学信息学对资料进行整理,运用多种数据统计分析与挖掘方法分析化学信息数据,建立Logistic回归方程,对中药寒热属性进行判别。结果:以有机成分单一化合物建立的Logistic回归方程,可以对中药的寒热属性进行判别。结论:植物类中药寒热药性与有机成分有相关性。     

中药添加剂对吸烟大鼠呼吸功能及免疫功能的影响

[目的]评价中药添加剂对大鼠吸烟所致的呼吸功能及免疫功能的改善效果。[方法]吸烟组大鼠在烟气环境中每日暴露1 h,对照组大鼠在烟机无卷烟空吸环境中每日暴露1 h,持续3个月,测定肺功能,脏器系数,腹主动脉取血测定血清中抗氧化、免疫因子指标。[结果]各吸烟组大鼠用力肺活量(FVC)与对照组相比差异无统计学意义,但FEV1/FVC%(一秒率)有所下降,其中3号烟组与0号烟组相比显著升高(P0.05)。2、3号烟组用力中期呼气流速(FEF25%~75%)、最大呼气中段流量(MMF)、最大呼气流量(PEF)各项指标与0号烟组相比明显改善,且与对照组值接近;1、2、3号烟组大鼠肺脏、胸腺脏器系数较0号烟组相比,无统计学差异。1号烟组脾脏系数极显著高于0号烟组(P0.01),3号烟组脾脏系数显著高于0号烟组(P0.05);与0号烟组相比,2、3号烟组超氧化物歧化酶(SOD)显著升高(P0.05),丙二醛(MDA)差异无统计学意义;1、2、3号烟组γ-干扰素(IFN-γ)均高于0号烟组,白介素-1β(IL-1β)均低于0号烟组,但差异无统计学意义。与0号烟组相比,1号烟组能极显著降低IL-6(P0.001),3号烟组能显著降低IL-12(P0.05)。[结论]2、3号添加剂可改善吸烟引起的大鼠肺功能降低,和对吸烟造成的抗氧化能力下降有保护作用。1、3号添加剂均可一定程度上改善因吸烟引起的大鼠免疫力下降,由此得出3号添加剂为卷烟的理想添加剂。     

从单方成药到“分子中药学”和“组合中药学”

对中药现代化的问题进行评述,从中药研究的现代基础理论到方法学所提出的一系列创新的观点和方法进行了系统的阐述。主张从3个方向对中药进行现代化研究。三方面同时进行,不要只顾一方面而忽视其他,不要互相排斥,生药,单方颗粒和组合中药3种产品同时进入市场,一方面直接使用生药,完全保留传统中药的处方,煎药和服用的治疗方法,仅仅加强生药的质量研究和管理。定点栽培中药,制定中药饮片的质量标准;另一方面保留中药的全成分,用现代制药技术将中药制备为单方颗粒,并以此进行复方的配制,做到质量可控,服用方便,以期最大程度保留中药成分组成按化学结构和活性分解为若干群体,使问题简化,然后分别研究这些群体的化学组成和结构,将这些群体分为单味中药的表征性成分和非表征性成分,使其系统化,在查明组合分子的组成和药效以后,以单味中药的主要组合分子群组合成新型澡药,该中药质量可控,疗效确切。符合国家关于一、二类新药的标准,接近现代药物的要求,可以面向国内外的广大市场。