LIG抗炎,解热活性的研究

本文研究了当归提取物LIG的抗炎,解热活性.研究发现LIG(2.5,5,10 mg/kg)对角叉菜和右旋糖苷诱导的足肿胀的抑制率分别为22.2%,49.4%,76.5%和20.8%,44.2%,75.3%(P＜0.001);对棉球肉芽肿的抑制率为29.2%,44.9%,58.8%(P＜O.001);对小鼠白细胞迁移的抑制率为20.7%,35.6%,48.2%(P＜0.001).此外,LIG可降低啤酒酵母导致的高热(P＜0.001).并且,LIG的抗炎,解热作用均成剂量依赖性.以上结果显示LIG具有非常强的抗炎,解热活性.     

The anti-inflammatory activity of Enicostemma littorale and Mollugo cerviana

The anti-inflammatory activity of E. littorale and M. cerviana was assessed by carrageenan-induced inflammation and cotton pellet granuloma method in rats. E. littorale and M. cerviana exerted 54 and 26% anti-inflammatory activity for a dose of 100 mg/100 g body wt, respectively, in carrageenan-induced acute inflammation. In chronic inflammation of cotton pellet granuloma, E. littorale and M. cerviana exerted 30 and 46% anti-inflammatory activity at the above dosage, respectively. The optimal dose for these drugs was determined in carrageenan inflammation. The effect of the alcoholic extract of these drugs on human erythrocyte membrane stabilization and inhibition of cobra venom phospholipase A2 was studied in vitro and the drugs were found to be effective. Further, these drugs were found to inhibit the levels of lipid peroxides, acid phosphatase, and gamma-glutamyl transpeptidase activity in the exudate of cotton pellet granuloma. The effects were compared with those of standard anti-inflammatory drug, hydrocortisone. A possible mode of action of these drugs is suggested.     

Design,synthesis, and pharmacological evaluation of novel oxadiazole and oxadiazoline analogs as anti-inflammatory agents

Two novel series of oxadiazole and oxadiazoline analogs possessing an indole nucleus were synthesized for their potential anti-inflammatory activity. The structures of the compounds were elucidated by elemental and spectral (IR, ¹H-NMR, ¹³C-NMR, and MS) analysis. Most of the test compounds demonstrated appreciable anti-inflammatory activities. The anti-inflammatory activity of oxadiazoles at doses of 100?mg/kg was shown by their ability to provide 27–66%, 14–32%, and 20-51%. protection against carrageenan-induced rat paw edema, moist cotton pellet-induced, and dry cotton pellet-induced granuloma, respectively. On the other hand, the anti-inflammatory properties of oxadiazolines at doses of 100?mg/kg were reflected by their ability to provide 20-56%, 11–26%, and 25–47% protection against carrageenan-induced rat paw edema, moist cotton pellet-induced, and dry cotton pellet-induced granuloma, respectively. The ulcerogenic potential of the compounds was determined. Structure–activity relationships among synthesized compounds were also established.     

Preparation, partial characterization and bioactivity of water-soluble polysaccharides from boat-fruited sterculia seeds

Crude water-soluble polysaccharides (SP) isolated from boat-fruited sterculia seeds by hot water extraction and ethanol precipitation were fractionated into a neutral polysaccharide (NSP) and an acidic one (ASP) by anion-exchange chromatography. The molecular weight, intrinsic viscosity and radius of gyration of NSP and ASP were determined by high performance size exclusion chromatography (HPSEC). NSP was rich in glucose (85.86%), with small amounts of galactose, arabinose and xylose. Whereas ASP consisted mainly of galacturonic acid (40.13%) along with rhamnose, arabinose, galactose, and small amounts of xylose and glucose, indicating a pectin-like polysaccharide which was confirmed by FT-IR spectra. Bioactivity of NSP and ASP was tested using ear edema induced by dimethylbenzene and cotton pellet-induced granuloma tissue in murine models. The results showed ASP possessed a potent dose-dependent anti-inflammatory activity. The results from the current study provided a scientific basis for the traditional use of this plant as a medical remedy for its anti-inflammation effects.     

Mycobacterial lipomannan induces granuloma macrophage fusion via a TLR2-dependent, ADAM9- and beta1 integrin-mediated pathway

Tuberculous granulomas are the sites of interaction between the host response and the tubercle bacilli within infected individuals. They mainly consist of organized aggregations of lymphocytes and macrophages (Mf). A predominant role of mycobacterial envelope glycolipids in granulomas formation has been recently emphasized, yet the signaling events interfering with granuloma cell differentiation remain elusive. To decipher this molecular machinery, we have recently developed an in vitro human model of mycobacterial granulomas. In this study, we provide evidence that the mycobacterial proinflammatory phosphatidyl-myo-inositol mannosides and lipomannans (LM), as well as the anti-inflammatory lipoarabinomannan induce granuloma formation, yet only the proinflammatory glycolipids induce the fusion of granuloma Mf into multinucleated giant cells (MGC). We also demonstrate that LM induces large MGC resembling those found in vivo within the granulomas of tuberculosis patients, and that this process is mediated by TLR2 and is dependent on the beta(1) integrin/ADAM9 cell fusion machinery. Our results demonstrate for the first time that the Mf differentiation stage specifically occurring within granulomatous structures (i.e., MGC formation) is triggered by mycobacterial envelope glycolipids, which are capable of inducing the cell fusion machinery. This provides the first characterization of the ontogeny of human granuloma MGC, thus resulting in a direct modulation by a particular mycobacterial envelope glycolipid of the differentiation process of granuloma Mf.     

Discovery of a potent,metabolically stabilized resorcylic lactone as an anti-inflammatory lead

With bioactivity-guided phenotype screenings, a potent anti-inflammatory compound f152A1 has been isolated, characterized and identified as the known natural product LL-Z1640-2. Metabolic instability precluded its use for the study on animal disease models. Via total synthesis, a potent, metabolically stabilized analog ER-803064 has been created; addition of the (S)-Me group at C4 onto f152A1 has resulted in a dramatic improvement on its metabolic stability, while preserving the anti-inflammatory activities.     

Annexin A1 regulates intestinal mucosal injury, inflammation, and repair

During mucosal inflammation, a complex array of proinflammatory and protective mechanisms regulates inflammation and severity of injury. Secretion of anti-inflammatory mediators is a mechanism that is critical in controlling inflammatory responses and promoting epithelial restitution and barrier recovery. AnxA1 is a potent anti-inflammatory protein that has been implicated to play a critical immune regulatory role in models of inflammation. Although AnxA1 has been shown to be secreted in intestinal mucosal tissues during inflammation, its potential role in modulating the injury/inflammatory response is not understood. In this study, we demonstrate that AnxA1-deficient animals exhibit increased susceptibility to dextran sulfate sodium (DSS)-induced colitis with greater clinical morbidity and histopathologic mucosal injury. Furthermore, impaired recovery following withdrawal of DSS administration was observed in AnxA1 (-/-) animals compared with wild-type (WT) control mice that was independent of inflammatory cell infiltration. Since AnxA1 exerts its anti-inflammatory properties through stimulation of ALX/FPRL-1, we explored the role of this receptor-ligand interaction in regulating DSS-induced colitis. Interestingly, treatment with an ALX/FPRL-1 agonist, 15-epi-lipoxin A4 reversed the enhanced sensitivity of AnxA1 (-/-) mice to DSS colitis. In contrast, 15-epi-lipoxin A4 did not significantly improve the severity of disease in WT animals. Additionally, differential expression of ALX/FPLR-1 in control and DSS-treated WT and AnxA1-deficient animals suggested a potential role for AnxA1 in regulating ALX/FPRL-1 expression under pathophysiological conditions. Together, these results support a role of endogenous AnxA1 in the protective and reparative properties of the intestinal mucosal epithelium.     

Anti-inflammatory and analgesic activity of Indian Hypericum perforatum L

A standardised 50% aqueous ethanolic extract of the Indian variety of Hypericum perforatum (IHp) was examined for its putative anti-inflammatory and analgesic activity at the doses of 100 and 200 mg/kg, po. The experimental paradigms used were carrageenan induced pedal edema and cotton pellet induced granuloma for anti-inflammatory activity, whereas the tail flick, hot plate and acetic acid induced writhing methods were used to asses analgesic activity. Indomethacin (20 mg/kg, ip) was used as the standard anti-inflammatory drug. Pentazocine (10 mg/kg, ip) and aspirin (25 mg/kg, ip), both clinically used analgesics, were used as standard analgesics for comparison. IHp extract showed significant anti-inflammatory and analgesic activity at both dose levels, in all the paradigms used. Additionally, IHp potentiated the anti-inflammatory activity of indomethacin and analgesic activities of pentazocine and aspirin.     

Design and synthesis of benzo-lipoxin A4 analogs with enhanced stability and potent anti-inflammatory properties

A new class of chemically and metabolically stable lipoxin analogs featuring a replacement of the tetraene unit of native LXA(4) with a substituted benzo-fused ring system have been designed and studied. These molecules were readily synthesized via a convergent synthetic route involving iterative palladium-mediated cross-coupling, and exhibit enhanced chemical stability, as well as resistance to metabolic inactivation via eicosanoid oxido-reductase. These new LX analogs were evaluated in a model of acute inflammation and were shown to exhibit potent anti-inflammatory properties, significantly decreasing neutrophil infiltration in vivo. The most potent among these was compound 9 (o-[9,12]-benzo-15-epi-LXA(4) methyl ester. Taken together, these findings help identify a new class of stable and easily prepared LX analogs that may serve as novel tools and as promising leads for new anti-inflammatory agents with improved therapeutic profile.     

Research update on the association between SFRP5, an anti-inflammatory adipokine,with obesity,type 2 diabetes mellitus and coronary heart disease

Secreted frizzled-related protein 5 (SFRP5), an anti-inflammatory adipokine secreted by adipocytes, has been demonstrated to exert its anti-inflammatory effect via antagonizing the non-canonical wingless-type family member 5A (WNT5A) signalling pathways. The WNT5A protein, as a potent pro-inflammatory signalling molecule, is strongly involved in a variety of inflammatory disorders such as obesity, type 2 diabetes mellitus (T2DM) and atherosclerosis. In this review, we systematically outlined the current understanding on the roles of SFRP5 in the pathogenesis of three inflammatory diseases including obesity, T2DM and coronary heart disease (CHD). Our review might stimulate future research using SFRP5 as a promising novel therapeutic target for the treatment of obesity, T2DM and CHD.     

Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.

An aqeuous extract of Lobaria pulmonaria (L.) Hoffm., from which a tea is prepared and consumed as treatment for various diseases in northeastern Turkey, was tested for its anti-inflammatory and antiulcerogenic effects in rats. The carrageenan-induced paw edema, cotton pellet granuloma and indomethacin-induced gastric damage models were used to determine these effects. The extract exhibited moderate anti-inflammatory and strong antiulcerogenic activities.     

Evaluation of anti-inflammatory activity of Vernonia cinerea Less. extract in rats.

The methanol extract of the whole plant of Vernonia cinerea Less. was evaluated for its anti-inflammatory activity in acute (carrageenin, histamine and serotonin induced rat paw edema) and a chronic model (cotton pouch induced granuloma). The methanol extract (250 and 500 mg/kg(-1) p.o.) exhibited significant activity (p < 0.001) against all phlogistic agents used in a dose dependant manner. In the chronic model (cotton pouch granuloma method) the methanol extract exhibited significant anti-inflammatory activity. All these effects were compared with standard drug phenylbutazone (100 mg/kg(-1) p.o.).     

Naphthalene derivatives: A new series of selective cyclooxygenase-2 inhibitors

A new series of potent and selective cyclooxygenase-2 inhibitors have been prepared. Some of these compounds show good oral anti-inflammatory activity in rats.     

藏药西藏棱子芹抗炎镇痛药效学研究

本文采用二甲苯致小鼠耳廓肿胀法、棉球致小鼠肉芽肿法观察藏药西藏棱子芹的抗炎作用,采用热板法、醋酸扭体法观察藏药西藏棱子芹的镇痛作用。结果表明藏药西藏棱子芹能明显抑制二甲苯所致小鼠耳廓肿胀和棉球所致小鼠肉芽肿;能提高小鼠对热板疼痛的阈值,减少小鼠扭体反应的次数,延长醋酸所致小鼠扭体反应的潜伏时间。藏药西藏棱子芹具有显著的抗炎镇痛作用,值得开发研究。     

Design,synthesis and evaluation of some pyrazolo[3,4-d]pyrimidine derivatives bearing thiazolidinone moiety as anti-inflammatory agents

Two new series of pyrazolo[3,4-d]pyrimidine bearing thiazolidinone moiety were designed and synthesized. The newly synthesized compounds were evaluated for their in vitro (COX-1 and COX-2) inhibitory assay. Compounds that showed promising COX-2 selectivity were further subjected to in vivo anti-inflammatory screening applying formalin induced paw edema (acute model) and cotton-pellet induced granuloma (chronic model) assays using celecoxib and diclofenac sodium as reference drugs. The histopathological and ulcerogenic potential were also determined. In vivo anti-inflammatory data showed that compounds 2, 6, 7d displayed anti-inflammatory activity higher than both references in the formalin induced paw edema model. On the other hand, compounds 2, 3d, 3e, 7b and 7d displayed anti-inflammatory activity greater than or nearly equivalent to diclofenac sodium in the cotton pellet-induced granuloma assay. Moreover, most of the tested compounds revealed good gastrointestinal safety profile. Collectively, compounds 2 and 7d were considered as promising candidates in managing both acute and chronic inflammation with safe gastrointestinal margin.     

Radiation resistance, invasiveness and metastasis are inflammatory events that could be suppressed by lipoxin A4

Radiation induces overexpression and activity of the MET oncogene that, in turn, enhances the production of prostaglandin E(2), a pro-inflammatory molecule. Prostaglandin E(2) promotes tumor cell invasion, prevents apoptosis, enhances their metastasis and causes radioresistance. It is proposed that lipoxin A(4), a potent endogenous anti-inflammatory molecule, opposes the actions of prostaglandin E(2) and thus, could promote radiosensitivity, suppress tumor cell proliferation, invasiveness and suppress metastasis. Thus, methods designed to enhance endogenous lipoxin A(4) formation or its synthetic analogs may be useful in the management of cancer.     

Evaluation of the in vivo anti-inflammatory activity of a flavonoid glycoside from Boldoa purpurascens

The anti-inflammatory effect of 4′,5-dihydroxy-6,7-methylenedioxyflavonol 3-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-xylopyranoside, a constituent of the leaves of Boldoa purpurascens Cav. (Nyctaginaceae), was evaluated for its anti-inflammatory activity in the dextran 1% induced rat paw oedema model (acute inflammation) and the cotton pellet induced granuloma rat model (chronic inflammation). Flavonoid glycoside at doses of 2.5, 5 and 10 mg/kg, indomethacin at a dose of 7 mg/kg and the vehicle were administered orally. The compound showed significant anti-inflammatory activity in the acute phase in a dose dependent manner, most notably at the highest test dose 10 mg/kg. Also in the cotton pellet induced granuloma model, the compound showed a dose-dependent anti-inflammatory activity, with the highest effect at 10 mg/kg. In both assays, the test compound was more active than indomethacin tested at 7 mg/kg.     

Macrolactonolides: A novel class of anti-inflammatory compounds

A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats. The synthesis, in vitro and in vivo anti-inflammatory activity of this novel class of compounds are described.     

Design,synthesis, evaluation,and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents

Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by ¹H NMR, ¹³C NMR, and HRMS. Most of the synthesized compounds showed pronounced anti-inflammatory effects at 100?mg/kg. In particular, compound 11b, which displayed the most potent anti-inflammatory activity of all of the compounds prepared, with 69.76% inhibition after intraperitoneal administration, was more potent than the reference drugs indomethacin and ibuprofen. The cytotoxicity of the compounds was also assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC₅₀ >100?μmol/L). Furthermore, molecular docking studies of the synthesized compounds were performed to rationalize the obtained biological results. Overall, the results indicate that compound 11b could be a therapeutic candidate for the treatment of inflammation.     

'Antiflammins': two nonapeptide fragments of uteroglobin and lipocortin I have no phospholipase A2-inhibitory and anti-inflammatory activity

The 'antiflammin' nonapeptides P1 and P2 [(1988) Nature 335, 726-730] were synthesized and tested for inhibition of phospholipase A2 and release of prostaglandin E2 and leukotriene C4 in stimulated cells in vitro, and in vivo for anti-inflammatory activity in rats with carrageenan-induced paw oedema. Porcine pancreatic phospholipase A2 was not inhibited at concentrations of 0.5-50 microM. Prostaglandin E2 and leukotriene C4 release by mouse macrophages stimulated with zymosan or ATP was not affected up to a concentration of 10 microM, nor was prostaglandin release by interleukin 1 beta-stimulated mesangial cells and angiotensin II-stimulated smooth muscle cells. Both peptides exhibited no anti-inflammatory activity in carrageenan-induced rat paw oedema after topical (250 micrograms/paw) or systemic administration (1 or 4 mg/kg s.c.). These results do not support the claim of potent phospholipase A2-inhibitory and anti-inflammatory activity of the 'antiflammins' P1 and P2.