The activities of lung stretch and irritant receptors during cough

In unilaterally vagotomized rabbits, changes in single vagal nerve fibers from the lung stretch and irritant receptors were studied during the cough reflex following ammonia vapour administered into the lungs. The discharge rates of slowly adapting pulmonary stretch receptors (SARs) before the onset of cough and at the onset of cough did not change significantly. In contrast, the occurrence of cough after ammonia inhalation was usually preceded by vigorous stimulation of the rapidly adapting pulmonary stretch receptors (RARs). These results suggest that the genesis of cough provoked by ammonia is mainly mediated by afferent input from RARs.     

Barrier protective activities of curcumin and its derivative

Aim and objective  

Curcumin, a poly-phenolic compound, possesses diverse pharmacologic activities. However, the barrier protective functions of curcumin or its derivative have not yet been studied. The objective of this study was to investigate the barrier protective activities of curcumin and its derivative (bisdemethoxycurcumin, BDMC) on lipopolysaccharide (LPS) barrier disruption in human umbilical vein endothelial cells (HUVECs) were investigated.     

Antiprotozoal activities of phospholipid analogues

The antiprotozoal activity of phospholipid analogues, originally developed as anti-cancer drugs, has been determined in the past decade. The most susceptible parasites are Leishmania spp. and Trypanosoma cruzi with activity also shown against Trypanosoma brucei spp., Entamoeba histolytica and Acanthamoeba spp. Miltefosine, an alkylphosphocholine, was registered for the oral treatment of visceral leishmaniasis (VL) in India in March 2002. This review will focus on the biological activities of phospholipid analogues. Biochemical and molecular targets and mechanism(s) of action have been studied extensively in tumor cells but have not been determined in protozoa.     

Anti-inflammatory effect of intraventricularly administered histamine in rats

Intracerebroventricularly (icv) administered histamine (5, 10 and 20 g) produced a dose-related anti-inflammatory effect against carrageenin-induced pedal edema in rats. The effect of histamine was mimicked by the H₁ receptor agonist, 2-methylhistamine, but not by the H₂ receptor agonist, 2-methylhistamine, The anti-inflammatory effect of centrally administered histamine was antagonised by mepyramine, a H₁ receptor antagonist, but not by cimetidine, a H₂ receptor antagonist.The anti-inflammatory effect of icv histamine was inhibited in bilaterally adrenalectomised rats but was unaffected by peripheral chemical sympathectomy induced by 6-hydroxydopamine.     

姜黄素对糖尿病大鼠心肌的保护作用*

 目的： 研究姜黄素对糖尿病大鼠心肌的保护作用及可能机制。方法: 雄性Wistar大鼠75只,随机抽取10只大鼠作为正常对照组,其余65只大鼠给予高糖高脂饮食喂养8周后腹腔注射链脲佐菌素40 mg/kg,给药72 h和7 d空腹血糖≥11.6 mmol/L为糖尿病模型成功大鼠。糖尿病大鼠随机分为糖尿病心肌病组、姜黄素小剂量治疗组和大剂量治疗组。测定心肌谷胱甘肽过氧化物酶（GSH-Px）活性和丙二醛（MDA）含量,酶联免疫吸附试验检测血清心肌钙蛋白I（cTnI）的变化,Western blotting检测蛋白激酶C（PKC）蛋白表达。结果: 姜黄素治疗后可明显改善糖尿病所致的动物体重下降和空腹血糖升高,抑制心肌中MDA的产生并升高GSH-Px活性,减少血清中cTnI的释放,下调心肌组织PKC蛋白表达。结论: 姜黄素对大鼠糖尿病心肌病具有保护作用,其机制可能与抑制氧化应激有关。     

Anti-inflammatory and in-vitro antibacterial activities of Traditional Chinese Medicine Formula Qingdaisan

Background

Qingdaisan (Formulated Indigo powder, QDS) are widely used for treatment of aphtha, sore throat and bleeding gums in China. The aim of the study is to evaluate the anti-inflammatory, antibacterial and dental ulcer therapeutic effects of QDS.

Methods

Dimethylbenzene-induced ear edema test and cotton pellet-induced granuloma test were used to evaluate anti-inflammatory activities of QDS on acute and chronic inflammatory. The healing time and local pathologic changes were used to assess the therapeutic effects of QDS on dental ulcer. The antibacterial activities of each component and the whole formulation of QDS were determined by agar well diffusion assay. High-dose and low-dose QDS were tested in this experiment and Gui Lin Watermelon Frost Powder (GLWFP) was used as positive control.

Results

Oral treatment with QDS significantly accelerated the healing of ulcerative lesions induced by phenol injury. The dental ulcers of high-dose QDS group were all healed within 6 days. It was shorter than those of low-dose QDS group and GLWFP group. Less quantity of inflammatory cells and plenty fibroblasts were observed in pathological section of QDS groups. QDS also exhibited significant anti-inflammatory activity both in acute and chronic animal models. Although some of the components exhibited antibacterial activities, the whole formulation of QDS didn’t show any significant antibacterial activity in vitro.

Conclusion

The study showed that QDS has obviously anti-inflammatory activity for both acute and chronic inflammatory, also has a remarkable effect for healing dental ulcer caused by phenol. QDS didn’t have antibacterial activity to selected strains in vitro.

     

Anti-inflammatory effects of triptolide on IgA nephropathy in rats

Abstract

IgA nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Recently studies show that inflammation may involve in the progression of renal glomerulosclerosis and tubulointerstitial scarring in IgAN. This study was designed to evaluate the renoprotective effect of triptolide on IgAN rat model. IgAN was induced in Sprague–Dawley rats by oral and intravenous immunization with BSA for 12 weeks. Rats were treated with triptolide (200?μg/kg/d intragastrically) from 12 to 28 weeks. At Week 28, the rats was sacrificed, kidneys and blood samples were collected for further analysis. Our data shown that IgAN rat model showed marked deterioration of proteinuria together with higher levels of the urine protein:creatinine ratio compared to the normal control. Animals that underwent intermittent exposure to triptolide treatment exhibited significant improvements in the functional parameters without severe side effects. Rats developing IgAN had profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, while triptolide treatment significantly attenuated it. We also observed that treatment with triptolide significantly decreases serum levels of IL-1β and IL-18, and may exerted anti-inflammatory effects by down-regulating NLRP3 and TLR4 expression. Our study clearly demonstrated that triptolide prevents IgAN progression via an amelioration of inflammasome-mediated proinflammatory cytokine production, thus brought a light of hope for treatment of IgAN.     

山茱萸总苷抗炎免疫抑制作用及其机理的大鼠实验研究

目的 研究山茱萸总苷（COG）对大鼠佐剂性关节炎（AA）的作用及其机理。方法 采用弗氏完全佐剂形成大鼠AA模型，于造模后不同时间分别测定两侧足趾肿胀度，造模24d后，处死动物观察药物对踝关节组织病理的影响，对T淋巴细胞增殖、炎性细胞因子IL-1、TNF-a、IL-6及迟发型超敏反应（DTH）、前列腺素E2（PGE2）的作用。结果 COG对AA大鼠的原发病变和继发病变均有明显的治疗作用（P〈0.01），对造模引起的踝关节组织病理损伤有明显的改善，且明显抑制从大鼠的T淋巴细胞增殖反应和DTH（P〈0.01），抑制IL-1、TNF-a、IL-6等炎性细胞因子及血浆PGE2的产生（P〈0.01或P〈0.05）。结论COG具有较好的免疫抑制抗炎作用，其机理可能是抑制了炎性介质IL-1、IL-6、TNF-a和PGF2的产生。     

Anti-inflammatory activities of human lactoferrin in acute dextran sulphate-induced colitis in mice

In this study, we investigated the anti-inflammatory effects of orally administered human lactoferrin (hLF) and two peptides, based on the bactericidal region of hLF (HLD1 and HLD2), on the course of experimental colitis. Acute colitis was induced in C57Bl/6 mice by giving 5% dextran sulphate (DX) in the drinking water. The mice were killed after 2 or 7 days of DX exposure. The animals were given hLF or the peptides orally twice a day (2 mg/dose/mouse) during the DX exposure. In the control animals, the hLF or the peptides were replaced by bovine serum albumin or water. The appearance of occult blood in the faeces and macroscopic rectal bleeding were significantly delayed and partly reduced in the hLF-treated animals compared with the control animals. The shortening of the colon, a pathological effect of DX exposure, was significantly less pronounced in the hLF-treated group compared with the control group. Also, the interleukin-1beta (IL-1beta) levels in the blood were significantly diminished in this group after 2 days of DX exposure. A significantly lower crypt score was observed in the distal part of the colon in the hLF-treated group compared with the control group. Also, significantly reduced numbers of CD4 cells, F4/80-positive macrophages and tumour necrosis factor-alpha-producing cells were detected by immunohistochemistry in the distal colon of the hLF-treated animals compared with the control animals after 7 days of DX exposure. A reduction was also observed concerning the IL-10-producing cells in the middle colonic submucosa. The HLD1 and HLD2 treatment, which was carried out for 2 days, only gave results almost identical to those of hLF, concerning clinical parameters after the 2 days of DX exposure. An even stronger effect was observed for HLD2, regarding decreased occult blood in the faeces and colon length. Our results show that perorally given hLF mediates anti-inflammatory effects on the DX-induced acute colitis, and further suggest that the bactericidal region of the hLF molecule may be involved in these activities.     

Anti-inflammatory and antioxidant activities of the leaves of Wissadula amplissima var Rostrata

The present study determined the anti-inflammatory activity of Wissadula amplissima var rostrata (Schum. & Thonn.), and calculated the total phenolic content and total antioxidant capacity of the plant in an attempt to justify the traditional uses of the plant in the Ashanti region of Ghana for the management of spider,wasps and bee stings. Powdered dried leaves of Wissadula amplissima were Soxhlet extracted with Petroleum Ether (PWA, yield: 1.46% (w)/(w)); Chloroform (CWA, yield: 1.18% (w)/(w)) and Methanol (MWA, yield: 3.39% (w)/(w)). These fractions were tested for anti-inflammatory activity using carrageenan-induced foot edema in 7 day old chicks. The effect before the induction of inflammation (pre-emptive protocol) paradigm was used for the assessment. Oral administration of PWA, CWA and MWA (30 - 300 mg/kg) dose dependently reduced edema with maximal effects of 68.25±2.03%, 77.83±0.81% and 62.21±2.61% respectively. Similarly the NSAID, Diclofenac (10 - 100 mg/Kg, i.p) and the steroidal anti-inflammatory drug dexamethasone (0.3 - 3 mg/Kg, i.p) used as positive controls, dose-dependently inhibited the edema with maximal effect of 87.96±1.11% and 67.47±3.51% respectively. The potencies exhibited by all three extracts were comparable to that shown by Diclofenac but higher than that of Dexamethasone. Phenols were detected in all three extracts with the highest concentration in the MWA. The extracts also scavenged DPPH with EC(50) values of 0.9784, 0.9096 and 0.2767 for PWA, CWA, MWA respectively. The results of this study give scientific credence to the local use of Wissadula amplissima to modulate inflammation induced by stings of animals.     

姜黄素对慢性低灌注大鼠的行为学功能保护作用

目的：探讨姜黄素在慢性低灌注大鼠的神经功能保护作用。方法：制备慢性脑缺血模型(2-VO)模型,术后分别给予姜黄素(实验组)和磷酸盐缓冲液(PBS,对照组)干预。术后8周后行Morris水迷宫评价大鼠的空间学习记忆功能变化。同时从Nissl染色观察大鼠神经细胞的变化;Western blot检测炎症因子IL-1β、TNF-α的表达。结果：实验组大鼠的空间学习记忆能力均较对照组明显改善,差异有统计学意义(P<0.05);Nissl染色发现实验组大鼠的缺血区神经元细胞与形态相对较为完整,而对照组大鼠神经元形态不完整,仅有散在的尼氏小体;在姜黄素治疗后缺血区脑细胞中IL-1β、TNF-α的含量明显降低(P<0.05)。结论：姜黄素可以显著改善慢性脑缺血大鼠的空间学习记忆能力,可能与其抗炎症反应相关。     

Anti-inflammatory and anti-proliferative effects of CBS3830 in arterialized vein grafts in rats

Objective: To investigated whether CBS3830, a highly selectively inhibitor of p38MAPK, could ameliorate inflammation and intimal hyperplasia in arterialized vein grafts (AVGs).

Methods: Sixty male Sprague-Dawley rats underwent a reversed right jugular vein to common carotid artery interposition graft and were randomly treatment with vehicle (control) or single-dose (3?mg/kg, preoperative) or double-dose (3?mg/kg, preoperative and 4?d postoperative) CBS3830. Twenty rats underwent sham operation. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by ELISA. Vein grafts were analyzed by intimal/medial morphometry, proliferating cell nuclear antigen (PCNA) expression, and p38MAPK phosphorylation.

Results: TNF-α, IL-1β, and IL-6 gradually increased then slowly decreased in AVG rats. However, at 4?d and 7?d, TNF-α levels decreased by 37.5% and 29.5% (p?=?0.003, 0.05, respectively) in the single-dose CBS3830 group, and by 37.6% and 32.5%, respectively (both p?=?0.003) in the double-dose group compared with those of control. IL-1β levels significantly reduced at 4?d and 14?d in both dosage groups. IL-6 levels significantly reduced at 7?d in both groups. Intima and medial thickening were significantly reduced in both dosage treated groups at 7, 14, and 28?d (all p?=?0.000) compared to the controls. Further study showed CBS3830 inhibited p38MAPK phosphorylation and decreased PCNA expression.

Conclusions: CBS3830 significantly decreases inflammation and intimal hyperplasia in AVGs.     

Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats

The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats.     

Anti-inflammatory effects of methotrexate on reversed passive Arthus reactions in rats

The anti-inflammatory effects of methotrexate (MTX), an anti-rheumatic drug for treating rheumatoid arthritis, on acute inflammation were studied by using Arthus reactions induced in the pleural cavity and dorsal skin of rats. The effects were compared with those of dexamethasone (DEX), a synthetic analog of adrenocortical steroid, and of ketoprofen (KET), a nonsteroidal anti-inflammatory agent. In reversed passive Arthus (RPA) reactions induced in the pleural cavity by an anti-bovine-albumin serum, DEX significantly suppressed both neutrophil accumulation and plasma exudation at the sites of injection of an antibody, whereas MTX and KET had no effect. In the RPA reaction induced in the dorsal skin by an anti-ovalbumin serum, all three drugs inhibited exudation to the same level. However, DEX and MTX suppressed neutrophil accumulation, whereas KET did not. We found that the oral administration of MTX for 3 days significantly inhibited both neutrophil accumulation and exudation in the RPA reaction in the dorsal skin, suggesting that MTX is an effective anti-inflammatory agent. However, the manifestation of these anti-inflammatory effects might be restricted by differences in the inflammation models in rats.     

Antiviral activities of pyrimidine nucleoside analogues: some structure--activity relationships

Seventeen nucleoside derivatives (derived from arabinosylcytosine, resp. cytidine, 5-fluorouracil and uracil) were tested by agar-diffusion plaque-inhibition test for their antiviral activity with herpes simplex, vaccinia, fowl plague, Newcastle disease and western equine encephalomyelitis viruses. The highest antiviral activity against DNA viruses exhibited arabinosylcytosine, N4-acylarabinosylcytosines, arabinosylthiouracil, cyclocytidine and its 5'-chloroderivative. RNA viruses were inhibited by 5-fluorouridine only, whereas other tested compounds were ineffective or showing marginal activity only. By search for relationship between chemical structure and antiviral activity a tendency was found of higher antiviral activity at lower lipophilicity. This is probably due to better transport of the studied compounds into cell. The chemical structure, however, is the main reason of antiviral activity.     

Evaluation of copper-dependent proteasome-inhibitory and apoptosis-inducing activities of novel pyrrolidine dithiocarbamate analogues

Apoptosis has a central role in the pathogenesis of many human diseases, one of which is cancer. One of the most important strategies to regulate apoptosis is via the ubiquitin-proteasome pathway. It has been shown that inhibition of proteasomal chymotrypsin-like activity is a strong apoptosis-inducing stimulus and that actively proliferating cancer cells are more sensitive to proteasome inhibitors than normal or untransformed cells. Dithioscarbamates are a class of metal-chelating compounds with various applications in medicine. We reported previously that certain members of dithiocarbamates, such as pyrrolidine dithiocarbamate (PDTC), diethyldithiocarbamate and disulfiram, are able to bind with tumor cellular copper, forming an active complex with proteasome-inhibitory, apoptosis-inducing and anti-cancer activities. In the current study, we synthesized eight PDTC analogues with substitutions made to the pyrrolidine ring and studied their structure-activity relationships. We found that substitution of the pyrrolidine ring with piperidine had almost no effect on their proteasome-inhibitory and anti-proliferative potencies in human breast cancer cells. However, after the pyrrolidine ring was substituted with morpholine, the activity of the mixtures slightly decreased but was completely lost when piperazine with the attached ethyl group was used for the substitution. This structure-activity relationship was confirmed by the results generated with the corresponding copper complexes. Our data further support the novel concept of using accumulated copper in human cancer cells as a selective approach for chemotherapy.     

姜黄素预处理及缺血后处理对大鼠肾脏缺血再灌注损伤的保护作用

背景：有研究发现姜黄素预处理、缺血后处理对大鼠肾脏缺血再灌注损伤具有保护作用。 目的：建立大鼠肾脏缺血再灌注损伤模型,观察姜黄素预处理、缺血后处理、姜黄素预处理联合缺血后处理对大鼠肾脏缺血再灌注损伤的保护作用。 方法：60只SD雄性大鼠随机均分为5组,假手术组、肾脏缺血再灌注模型组、姜黄素组、缺血后处理组以及联合处理组。肾脏再灌注24 h后,取下腔静脉血测定肌酐和尿素氮。肾组织测定超氧化物岐化酶活性和丙二醛含量,并行苏木精-伊红染色观察各组肾组织病理学变化。 结果与结论：与假手术组比较,其余各组肌酐、尿素氮均升高(P < 0.05)。与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组的肌酐、尿素氮值在再灌注24 h后均下降(P < 0.05)。与姜黄素组和缺血后处理组比较,联合处理组的肌酐更低(P < 0.05)。与假手术组比较,缺血再灌注模型组超氧化物歧化酶活性明显降低,丙二醛含量明显升高,差异有显著性意义(P < 0.05)。与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组的超氧化物歧化酶活性升高,丙二醛含量降低,差异有显著性意义(P < 0.05)。与姜黄素组和缺血后处理组比较,联合处理组的超氧化物歧化酶活性升高,差异有显著性意义(P < 0.05)。与假手术组比较,缺血再灌注模型组肾小管损伤明显;与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组肾小管损伤减轻明显,与姜黄素组和缺血后处理组比较,联合处理组损伤更轻。说明示姜黄素预处理和缺血后处理联合应用具有协同作用,可以更好的保护大鼠缺血再灌注损伤肾脏。     

Anti-inflammatory and antiulcerogenic activities of leaf extracts and sesquiterpene from Teucrium ramosissimum (Lamiaceae)

Teucrium ramosissimum (Lamiaceae) is a native and endemic medicinal plant from South of Tunisia traditionally used for the treatment of many diseases. The anti-inflammatory and antiulcerogenic activities of sesquiterpene (β-eudesmol), chloroform, and ethyl acetate leaf extracts from T. ramosissimum were assayed. Macrophage phagocytic activity and lymphocyte proliferation in the absence and presence of mitogens (lipopolysaccharide [LPS] or lectin) were investigated. Depending on the concentrations, the extracts affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide (NO) release. For lymphocyte proliferation assay, tested extracts enhance significantly cell proliferation either with or without mitogen stimulation. These results suggest that leaf extracts from T. ramosissimum contain potent components such as flavonoids that may be potentially useful for modulating immune cell functions in physiological and pathological conditions. Antiulcerogenic activity was examined on rat ethanol-induced ulcerogenic model. Compared with control (cimetidine), leaf extracts from T. ramosissimum exert different protective effects against ethanol-induced ulcerogenesis.     

Mitogenic and polyclonal B cell activation activities of synthetic lipid A analogues

The activation of murine B cells and macrophages by synthetic lipid A analogues, solubilized with triethylamine and complexed with bovine serum albumin, were investigated in vitro. The analogues used are nonphosphorylated, C-1 or C-4′ monophos-phorylated and C-1,4′ diphosphorylated derivatives of β-1,6-linked D-glucosamine disaccharide possessing both ester- and amide-bound fatty acid substituents. They were divided into 4 groups, A, B, C and D in terms of the fatty acid substitution. Ester- and amine-bound fatty acids of the analogues are both tetradecanoic acids (C₁₄) in group A, C₁₄ and (R)-3-hydroxytetradecanoic acids (C₁₄-OH) in group B, both C₁₄-OH in group C and C₁₄-OH and (R)-3-tetradecanoyloxytetradecanoic acids in group D. Mitogenic activity was exhibited in spleen cells from C3H/HeN mice by the C-1 monophosphorylated analogues in groups A and B, and by the C-4′ monophosphorylated analogues in groups B, C and D, but not in cells from C3H/HeJ mice. Nonphosphorylated analogues in groups A, B and C, and C-4′ monophosphorylated analogue in group A showed negative mitogenic activity. Only the nonphosphorylated analogue in group D exhibited mitogenic activity in spleen cells from C3H/HeJ mice as well as those from C3H/HeN mice. None of the other analogues exhibited the activity in C3H/HeJ spleen cells. Polyclonal B cell activation activity was exhibited by the C-1 monophosphorylated analogues in groups A and B, and by the C-4′ monophosphorylated analogues in groups C and D. Nonphosphorylated analogues in all groups and C-4′ monophosphorylated analogues in groups A and B showed negative PBA activity. None of the analogues tested could induce any cytostatic macrophages from thioglycollate-elicited peritoneal macrophages.