Anti-inflammatory and immunomodulatory effects of Critonia aromatisans leaves: Downregulation of pro-inflammatory cytokines.

Critonia aromatisans (Asteraceae), commonly known as "Chiople", is a cultivated species that is used in Mayan traditional medicine to treat inflammation, joint pain and rheumatism. To evaluate the in vivo and in vitro anti-inflammatory and immunomodulatory properties of aqueous and organic extracts prepared from Critonia aromatisans leaves. Methanol, ethyl acetate, methylene chloride, hexanic, and aqueous extracts were obtained from the leaves of C. aromatisans. The anti-inflammatory properties of the extracts were tested in vivo to evaluate their ability to reduce the inflammatory response in the carrageenan-induced hind paw edema model in NIH mice. In addition, to explore the immunomodulatory effects of C. aromatisans, in vitro testing was performed to determine whether C. aromatisans leaf extracts are capable of decreasing macrophage production of nitric oxide (NO), tumour necrosis factor alpha (TNF-α), and cytokines IL-1β, IL-6, and cyclooxygenase 2 (COX-2) without affecting macrophage viability. Single orally administered doses (100mg/kg or 200mg/kg) of a hexanic extract of C. aromatisans leaves significantly reduced carrageenan-induced paw edema in mice (P<0.001) by 76% and 84%, respectively. The effect of the extract in this model was generally comparable to those of the standard drugs used. In the in vitro determination, the extracts reduced the amount of NO mainly at 500 and 1000μg/mL. Hexanic extract and subfractions C, D, E, and F at 50 and 100μg/mL produced the lowest concentration of mediators in culture supernatants (protein) and at the mRNA/gene level by the significant down-regulation of cytokines. These findings explain some of the anti-inflammatory activity of this species. Purification of fractions C and D allowed the complete identification of cyclocolorenone, stigmasterol and stigmasterol derivatives as some of their main components. A hexanic extract of C. aromatisans displayed anti-inflammatory effects, validating the traditional practice of Mayan communities wherein an ointment with a petrolatum base, a non-polar substance, is used to treat inflammation. Additionally, C. aromatisans showed strong in vivo and in vitro activity, and one of the mechanisms of its anti-inflammatory response was shown to be inhibition of the production of NO and pro-inflammatory cytokines. The results of this study provide a pharmacological basis for the use of C. aromatisans leaves in the treatment of inflammatory disorders. The presence of stigmasterol and cyclocolorenone could be the responsibles of the anti-inflammatory activity of this specie. Further studies should be done on the antioxidant and anti-inflammatory properties of cyclocolorenone. The results of this study provide a pharmacological basis for the use of C. aromatisans leaves in the treatment of inflammatory disorders.

la Torre Fabiola VD ，Ralf K ，Gabriel B ，Victor Ermilo AA ，Martha MG ，Mirbella CF ，Rocio BA ... -  《-》

Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.

Plants from genus Lavandula have been used as anti-inflammatory drugs in Mediterranean traditional medicine. Nowadays, there is a growing interest for complementary medicine, including herbal remedies, to treat inflammatory bowel disease (IBD). To test the anti-inflammatory properties of Lavandula dentata and Lavandula stoechas extracts in two inflammatory experimental models: TNBS model of rat colitis and the carrageenan-induced paw edema in mice, in order to mimic the intestinal conditions and the extra-intestinal manifestations of human IBD, respectively. The extracts were characterized through the qualitative HPLC analysis. Then, they were assayed in vitro and in vivo. In vitro studies were performed in BMDMs and CMT-93 epithelial cells with different concentrations of the extracts (ranging from 0.1 to 100µg/ml). The extracts were tested in vivo in the TNBS model of rat colitis (10 and 25mg/kg) and in the carrageenan-induced paw edema in mice (10, 25 and 100mg/kg). L. dentata and L. stoechas extracts displayed immunomodulatory properties in vitro down-regulating different mediators of inflammation like cytokines and nitric oxide. They also showed anti-inflammatory effects in the TNBS model of colitis as evidenced by reduced myeloperoxidase activity and increased total glutathione content, indicating a decrease of neutrophil infiltration and an improvement of the oxidative state. Besides, both extracts modulated the expression of pro-inflammatory cytokines and chemokines, and ameliorated the altered epithelial barrier function. They also displayed anti-inflammatory effects in the carrageenan-induced paw edema in mice, since a significant reduction of the paw thickness was observed. This was associated with a down-regulation of the expression of different inducible enzymes like MMP-9, iNOS and COX-2 and pro-inflammatory cytokines, all involved in the maintenance of the inflammatory condition. L. dentata and L. stoechas extracts showed intestinal anti-inflammatory effect, confirming their potential use as herbal remedies in gastrointestinal disorders. In addition, their anti-inflammatory effect was also observed in other locations, thus suggesting a possible use for the treatment of the extra-intestinal symptoms of IBD.

Algieri F ，Rodriguez-Nogales A ，Vezza T ，Garrido-Mesa J ，Garrido-Mesa N ，Utrilla MP ，González-Tejero MR ，Casares-Porcel M ，Molero-Mesa J ，Del Mar Contreras M ，Segura-Carretero A ，Pérez-Palacio J ，Diaz C ，Vergara N ，Vicente F ，Rodriguez-Cabezas ME ，Galvez J ... -  《-》

Aqueous extract from Ipomoea asarifolia (Convolvulaceae) leaves and its phenolic compounds have anti-inflammatory activity in murine models of edema, peritonitis and air-pouch inflammation.

Ipomoea asarifolia (Desr.) Roem. and Schult.(Convolvulaceae), popularly known as salsa or salsa-brava, is a plant of which the decoction of leaves is used in folk medicine to treat various inflammatory disorders such of dermatitis, scabies, symptoms of syphilis, skin ulcers and external wounds. However, little is known about possible compounds and mechanisms of action of the plant to support the activities reported by popular use. The study aimed to identify bioactive molecules present in the crude extract of I. asarifolia leaves and investigate the anti-inflammatory potential of this extract in different experimental in vivo models to improve the understanding on that activity. Aqueous extract of I. asarifolia leaves was prepared by decoction (1:10 m/v) and its chromatographic profile was obtained by high performance liquid chromatography coupled with diode array detector (HPLC-DAD) and liquid chromatography diode array detector coupled with mass spectrometry (LC-DAD-MS). The potential anti-inflammatory activity of the extract was assessed using the following in vivo models: xylene-induced ear edema (20, 30 and 40mg/kg), evaluating the degree of edema formation; carrageenan-induced peritonitis (10, 20 and 30mg/kg), evaluating leukocyte migration and cytokine levels (IL-1β, IL-6, IL-12 and TNF-α) at 4h; zymosan-induced air pouch inflammation (20, 30 and 40mg/kg), evaluating the kinetics of leukocyte migration by total and differential counts at 6, 24 and 48h. The same tests were conducted using pure compounds identified in the aqueous extract from I. asarifolia leaves in different doses for each experimental model. The compounds identified in the aqueous extract of I. asarifolia leaves by HPLC-DAD and LC-DAD-MS were rutin, chlorogenic acid and caffeic acid. The extract significantly reduced ear edema induced by xylene (81%, 85% and 86% for doses of 20, 30 and 40mg/kg, respectively, p<0.001), as well as cell migration in experimental models of peritonitis (70%, 78% and 83% for doses of 10, 20 and 30mg/kg, respectively, p<0.001) and air pouch inflammation (58%, 67% and 53% for doses of 20, 30 and 40mg/kg, respectively, p<0.001). In addition, the extract demonstrated the ability to significantly inhibit the production of cytokines IL-1β, IL-6, IL-12 and TNF-α (p<0.001). The secondary metabolites tested (rutin, chlorogenic acid and caffeic acid) also showed the ability to significantly (p<0.001) decrease the parameters analyzed above. This is the first study to identify and confirm these phenolic compounds in I. asarifolia leaves extract and to suggest that these compounds contribute to the anti-inflammatory activity in vivo, as reported by ethnomedicinal use of this plant. Through the different experimental models performed, we can conclude that the results obtained with the aqueous extract from I. asarifolia leaves support its popular use for the treatment of inflammatory disorders.

Furtado AA ，Torres-Rêgo M ，Lima MCJS ，Bitencourt MAO ，Estrela AB ，Souza da Silva N ，da Silva Siqueira EM ，Tomaz JC ，Lopes NP ，Silva-Júnior AA ，Zucolotto SM ，Fernandes-Pedrosa MF ... -  《-》

The dichloromethane fraction from Mahonia bealei (Fort.) Carr. leaves exerts an anti-inflammatory effect both in vitro and in vivo.

Mahonia bealei has a long history of medical use in traditional Chinese medicine for the treatment of inflammatory-associated diseases. Despite numerous phytochemical and pharmacological studies, there is a lack of systematic studies to understand the cellular and molecular mechanisms of the anti-inflammatory activity of this plant. This study aimed to evaluate the anti-inflammatory activity of the dichloromethane fraction from M. bealei leaves (MBL-CH). RAW 264.7 cells were pretreated with different concentrations of MBL-CH for 30min prior to treatment with 1μg/ml of lipopolysaccharide (LPS). The nuclear factor κB (NF-κB) pathway and subsequent production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor (TNF)-α were investigated. Furthermore, the in vivo mouse model of LPS-induced acute lung injury (ALI) was employed to study the anti-inflammatory effects of MBL-CH. Pre-treatment with MBL-CH significantly inhibited the LPS-stimulated secretion of NO, PGE2, and TNF-α into the culture medium, as well as the mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α, which were associated with a reduction in the phosphorylation of IκBα, Akt, and PI3K and inhibition of the transcriptional activity of NF-κB. Furthermore, in vivo experiments revealed that MBL-CH attenuated LPS-stimulated lung inflammation in mice. Taken together, our findings indicate that MBL-CH attenuates LPS-stimulated inflammatory responses in macrophages by blocking NF-κB activation through interference with activation of the PI3K/Akt pathway, providing scientific evidence that the plant can be employed in traditional remedies.

Hu W ，Wu L ，Qiang Q ，Ji L ，Wang X ，Luo H ，Wu H ，Jiang Y ，Wang G ，Shen T ... -  《-》

In vivo and in vitro anti-inflammatory effects of Zao-Jiao-Ci (the spine of Gleditsia sinensis Lam.) aqueous extract and its mechanisms of action.

Zao-Jiao-Ci (ZJC), as the spine of Chinese Honey locust (Gleditsia sinensis Lam.), is traditionally used as Chinese medicine to reduce inflammation. The present study aimed to investigate an anti-inflammatory effect of ZJC aqueous extract both in vitro and in vivo, as well as its underlying mechanisms. Anti-inflammatory effect of ZJC aqueous extract was evaluated by using carrageenan-induced paw edema in rats. In addition, the inhibitory effects of ZJC on nitric oxide production, intracellular reactive oxygen species production, pro-inflammatory mediator expression and prostaglandin E2 (PGE2) production were determined by using LPS-activated RAW 264.7 cells. The anti-oxidant activity of ZJC was assessed using 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid assay. ZJC aqueous extract showed significant suppressive effect on paw edema in rats at 100mg/kg. Moreover, ZJC aqueous extract decreased the expression of cyclooxygenase (COX)-2 and significantly decreased the PGE2, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 production in LPS-activated macrophages in dose-dependent manners. ZJC aqueous extract inhibited the mRNA expression of these inflammatory cytokines as well. Furthermore, ZJC aqueous extract was found as an anti-oxidant and could inhibit ROS production in the LPS-induced cells. These findings show the potential of ZJC aqueous extract as a naturally occurring COX-2 inhibitor to reduce inflammation.

Li KK ，Zhou X ，Wong HL ，Ng CF ，Fu WM ，Leung PC ，Peng G ，Ko CH ... -  《-》