Peripheral anti-nociceptive and anti-inflammatory effect of oleanolic acid in a rat model of osteoarthritis

Author(s):  
Israa Salman ◽  
Marc Fakhoury ◽  
Malak Fouani ◽  
Nada Lawand

Background:: Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid with multifarious actions. Chief among them is the anti-inflammatory effect it exerts when taken orally; however, the underpinning mechanisms of such effects have not yet been fully explored. Methods:: In the present study, we evaluated the anti-inflammatory and anti-nociceptive effect of OA by injecting it directly into the knee joint using an animal model of osteoarthritis. Behavioral and electrophysiological studies were conducted to determine whether OA exerts a direct modulatory effect on primary sensory afferents that could lead to a decrease in pain-related behaviors and inflammatory responses. Rats were divided into two main groups: a pre- and a post-treatment group. Knee joint inflammation was induced by injecting a mixture of 3% kaolin and carrageenan (K/C). In the pre-treatment groups, two different doses of OA [5 mg/ml (n=5) and 30 mg/ml (n=4); 0.1 ml per injection] were administered into the synovial cavity of the knee joint before induction of inflammation. In the post-treatment group, rats received only one dose [5 mg/ml (n=5)] of OA after induction of inflammation. Results:: Results indicate that intra-articular injection of OA improves motor coordination and attenuates nociceptive behav-ior and inflammatory reactions. More importantly, we observed a direct depolarizing action of OA on articular sensory fi-bers, a crucial mechanism that activates descending inhibitory pathways and controls incoming nociceptive signals to the spinal cord. Conclusion:: Overall, our findings suggest that OA can be used as preventive and therapeutic approach for the management of osteoarthritis.

Gene ◽  
2018 ◽  
Vol 675 ◽  
pp. 94-101 ◽  
Author(s):  
Lin Dong ◽  
Lei Yin ◽  
Rong Chen ◽  
Yuanbin Zhang ◽  
Shiyao Hua ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2630 ◽  
Author(s):  
Isabel Gálvez ◽  
Leticia Martín-Cordero ◽  
María Dolores Hinchado ◽  
Alberto Álvarez-Barrientos ◽  
Eduardo Ortega

Anomalous immune/inflammatory responses in obesity take place along with alterations in the neuroendocrine responses and dysregulation in the immune/stress feedback mechanisms. Exercise is a potential anti-inflammatory strategy in this context, but the influence of exercise on the β2 adrenergic regulation of the monocyte-mediated inflammatory response in obesity remains completely unknown. The first objective of this study was to analyze the effect of exercise on the inflammatory profile and phenotype of monocytes from obese and lean animals, and the second aim was to determine whether obesity could affect monocytes’ inflammatory response to β2 adrenergic activation in exercised animals. C57BL/6J mice were allocated to different lean or obese groups: sedentary, with acute exercise, or with regular exercise. The inflammatory profile and phenotype of their circulating monocytes were evaluated by flow cytometry in the presence or absence of the selective β2 adrenergic receptor agonist terbutaline. Exercise caused an anti-inflammatory effect in obese individuals and a pro-inflammatory effect in lean individuals. β2 adrenergic receptor stimulation exerted a global pro-inflammatory effect in monocytes from exercised obese animals and an anti-inflammatory effect in monocytes from exercised lean animals. Thus, β2 adrenergic regulation of inflammation in monocytes from exercised animals seems to depend on the inflammatory basal set-point.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Xin ◽  
Qin Yuan ◽  
Chaoqi Liu ◽  
Changcheng Zhang ◽  
Ding Yuan

Abstract It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. Herein, using LPS to establish acute inflammation model of mouse liver and cell line inflammation model, we investigated whether miR-155/GSK-3β regulated NF-κB signaling pathway, and CsIVa exerted anti-inflammatory effects by regulating miR-155/GSK-3β signaling pathway. Our results showed that LPS induced high expression of miR-155 and miR-155 promoted macrophage activation through GSK-3β. In addition, CsIVa inhibited inflammatory responses in LPS-induced mouse liver and RAW264.7 cells. Furthermore, we demonstrated that CsIVa improved the inflammatory response in LPS-induced RAW264.7 cells by inhibiting miR-155, increasing GSK-3β expression, and inhibiting NF-κB signaling pathway. In conclusion, our study reveals that CsIVa suppresses LPS-triggered immune response by miR-155/GSK-3β-NF-κB signaling pathway.


2020 ◽  
Vol 14 (02) ◽  
pp. 294-298
Author(s):  
Maharani Laillyza Apriasari ◽  
Selviana Rizky Pramitha ◽  
Dewi Puspitasari ◽  
Diah Savitri Ernawati

Abstract Objective This study was designed to assess the anti-inflammatory effect of Musa acuminata through the expression of tumor necrosis factor-α (TNF-α) and nuclear factor kappa β (NF-κB) after 3 days of application of Musa acuminata stem extract (MASE) gel on oral mucosal wound. Materials and Methods An experimental study with post-test only control group design was conducted. Twenty male Rattus norvegicus (Wistar) were injured on their left buccal mucosa and treated three times a day with MASE gel of varying concentrations: 0% (as control), MASE 25%, MASE 37.5%, and MASE 50%. On day 3, a biopsy was performed on each mucosal wound for later immunohistochemical analysis for the expressions of TNF-α and NF-κB. Results The highest expression of TNF-α was observed in the control group (13.20 ± 1.79), while the lowest was in the treatment group using 50% MASE (6.40 ± 1.14). Meanwhile the comparison between treatment groups did not highlight any significant difference (p > 0.05). The highest expression of NF-κB was observed in the control group (13.20 ± 1.30), whereas the lowest was in the treatment group using MASE 50% (6.40 ± 1.14). NF-κB was significantly lower in the treatment group using MASE 50% when compared with other treatment groups (p < 0.05). Conclusion Application of MASE on mucosal wound reduces the expression of TNF-α and NF-κB at all concentrations. The anti-inflammatory effect of MASE 50% was the strongest one.


2017 ◽  
Vol 15 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Ala’a Al-Bakheit ◽  
Saeid Abu-Romman ◽  
Ahmad Sharab ◽  
Mohammad Al Shhab

Varthemia iphionoides is a Jordanian medicinal plant with several health-promoting properties, including antibacterial, antioxidant and anticancer activities. However, its anti-inflammatory properties have been poorly investigated up to date. The current study aimed to investigate the anti-inflammatory effect of V. iphionoides by measuring the production of interleukin-6 in response to a pro-inflammatory stimulus (bacterial lipopolysaccharide) in in vitro cell models of human MRC-5 and PC3 cells. We observed a significant reduction in lipopolysaccharide-induced interleukin-6 release in response to V. iphionoides (125 µg/mL) in both non-cancerous fibroblast MRC-5 and prostate cancerous PC3 cells. However, the anti-inflammatory effect of this medicinal plant was stronger when MRC-5 cells were treated with an aqueous extract, while the methanolic extract was more potent in PC3 cells. The effect of V. iphionoides in reducing interleukin-6 production was not due to its cytotoxicity, and future studies are required to elucidate the mechanisms of action by which this medicinal plant modulates inflammatory responses. In conclusion, the results of our study represent the first report of the potential protective effect of water and methanolic extracts of V. iphionoides against pro-inflammatory stimuli in fibroblasts and cancer cells of human origin, and it is critically important to identify the phytochemical compounds responsible for this effect.


2012 ◽  
Vol 47 (3) ◽  
pp. 549-555 ◽  
Author(s):  
Barbara Bednarczyk-Cwynar ◽  
Lucjusz Zaprutko ◽  
Joanna Marciniak ◽  
Grzegorz Lewandowski ◽  
Michal Szulc ◽  
...  

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Beatriz Gutierrez ◽  
Isabel Gallardo ◽  
Lorena Ruiz ◽  
Yolanda Alvarez ◽  
Victoria Cachofeiro ◽  
...  

Abstract Background Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment. Methods Mice with MOG35–55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects. Results We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract. Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS. Conclusion These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.


Sign in / Sign up

Export Citation Format

Share Document