scholarly journals Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Hsum Yap ◽  
Yang Mooi Lim
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Diseases ◽  
Experimental Models ◽  
Arachidonic Acid Metabolism ◽  
Protective Effects ◽  
Pentacyclic Triterpene ◽  
Maslinic Acid ◽  
Anti Inflammatory

Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs) are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX) enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS). The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in variousin vivoandin vitroexperimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB)/COX-2 expression, upstream protein kinase signaling, and phospholipase A2enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli.

scholarly journals The impact of indole-3-lactic acid on immature intestinal innate immunity and development: a transcriptomic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wuyang Huang ◽  
Ky Young Cho ◽  
Di Meng ◽  
W. Allan Walker
Keyword(s):  
Lactic Acid ◽  
Mechanistic Model ◽  
Transcriptomic Analysis ◽  
Dependent Manner ◽  
Protective Effects ◽  
Very Preterm Infants ◽  
Anti Inflammatory ◽  
The Impact

AbstractAn excessive intestinal inflammatory response may have a role in the pathogenesis of necrotizing enterocolitis (NEC) in very preterm infants. Indole-3-lactic acid (ILA) of breastmilk tryptophan was identified as the anti-inflammatory metabolite involved in probiotic conditioned media from Bifidobacteria longum subsp infantis. This study aimed to explore the molecular endocytic pathways involved in the protective ILA effect against inflammation. H4 cells, Caco-2 cells, C57BL/6 pup and adult mice were used to compare the anti-inflammatory mechanisms between immature and mature enterocytes in vitro and in vivo. The results show that ILA has pleiotropic protective effects on immature enterocytes including anti-inflammatory, anti-viral, and developmental regulatory potentials in a region-dependent and an age-dependent manner. Quantitative transcriptomic analysis revealed a new mechanistic model in which STAT1 pathways play an important role in IL-1β-induced inflammation and ILA has a regulatory effect on STAT1 pathways. These studies were validated by real-time RT-qPCR and STAT1 inhibitor experiments. Different protective reactions of ILA between immature and mature enterocytes indicated that ILA’s effects are developmentally regulated. These findings may be helpful in preventing NEC for premature infants.

Advances in Anti-inflammatory Activity, Mechanism and Therapeutic Application of Ursolic Acid

2021 ◽  
Vol 21 ◽  
Author(s):  
Mingzhu Luan ◽  
Huiyun Wang ◽  
Jiazhen Wang ◽  
Xiaofan Zhang ◽  
Fenglan Zhao ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Inflammatory Activity ◽  
Inflammatory Factors ◽  
Inflammatory Stimuli ◽  
Bowel Diseases ◽  
Anti Inflammatory

: In vivo and in vitro studies reveal that ursolic acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli, and has favorable anti-inflammatory effects. The anti-inflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of signal pathway, down-regulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.

scholarly journals In Vitro Anti-Inflammatory and In Vivo Antiarthritic Activities of Aqueous and Ethanolic Extracts of Dissotis thollonii Cogn. (Melastomataceae) in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Stephanie Flore Djuichou Nguemnang ◽  
Eric Gonzal Tsafack ◽  
Marius Mbiantcha ◽  
Ateufack Gilbert ◽  
Albert Donatien Atsamo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Denaturation ◽  
Inflammatory Diseases ◽  
Ros Production ◽  
Zymosan A ◽  
Ethanolic Extracts ◽  
Anti Inflammatory ◽  
Promising Source

Dissotis thollonii Cogn. (Melastomataceae) is a tropical plant widely used in traditional Cameroonian medicine to relieve and treat many pathologies. It is widespread in the western region where it is used to treat typhoid fever, gastrointestinal disorders, and inflammatory diseases. The purpose of this study is to scientifically demonstrate the anti-inflammatory and antiarthritic properties of the aqueous and ethanolic extracts of the leaves of Dissotis thollonii. The anti-inflammatory properties were evaluated in vitro by inhibition tests for cyclooxygenase, 5-lipoxygenase, protein denaturation, extracellular ROS production, and cell proliferation; while antiarthritic properties were evaluated in vivo in rats using the zymosan A-induced monoarthritis test and the CFA-induced polyarthritis model. This study shows that aqueous and ethanolic extracts at a concentration of 1000 μg/ml inhibit the activity of cyclooxygenase (47.07% and 63.36%) and 5-lipoxygenase (66.79% and 77.7%) and protein denaturation (42.51% and 44.44%). Similarly, both extracts inhibited extracellular ROS production (IC50 = 5.74 μg/ml and 2.96 μg/ml for polymorphonuclear leukocytes, 7.47 μg/ml and 3.28 μg ml for peritoneal macrophages of mouse) and cell proliferation (IC50 = 16.89 μg/ml and 3.29 μg/ml). At a dose of 500 mg/kg, aqueous and ethanolic extracts significantly reduce edema induced by zymosan A (69.30% and 81.80%) and CFA (71.85% and 79.03%). At the same dose, both extracts decreased sensitivity to mechanical hyperalgesia with 69.00% and 70.35% inhibition, respectively. Systemic and histological analyzes show that both extracts maintain the studied parameters very close to normal and greatly restored the normal architecture of the joint in animals. Dissotis thollonii would therefore be a very promising source for the treatment of inflammatory diseases.

scholarly journals Betulinic Acid-Azaprostanoid Hybrids: Synthesis and Pharmacological Evaluation as Anti-inflammatory Agents

2020 ◽  
Vol 19 (3) ◽  
pp. 254-267
Author(s):  
Tatyana S. Khlebnicova ◽  
Yuri A. Piven ◽  
Fedor A. Lakhvich ◽  
Iryna V. Sorokina ◽  
Tatiana S. Frolova ◽  
...  
Keyword(s):  
Cell Lines ◽  
Betulinic Acid ◽  
Inflammatory Diseases ◽  
Toxic Agent ◽  
Analgesic Effects ◽  
Low Toxic ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Background: Prevention and treatment of chronic inflammatory diseases require effective and low-toxic medicines. Molecular hybridization is an effective strategy to enhance the biological activity of new compounds. Triterpenoid scaffolds are in the focus of attention owing to their anti-inflammatory, antiviral, antiproliferative, and immunomodulatory activities. Heteroprostanoids have different pleiotropic effects in acute and chronic inflammatory processes. Objective: The study aimed to develop structurally new and low toxic anti-inflammatory agents via hybridization of betulinic acid with azaprostanoic acids. Methods: A series of betulinic acid-azaprostanoid hybrids was synthesized. The synthetic pathway included the transformation of betulin via Jones' oxidation into betulonic acid, reductive amination of the latter and coupling obtained by 3β-amino-3-deoxybetulinic acid with the 7- or 13-azaprostanoic acids and their homo analogues. The hybrids 1-9 were investigated in vivo on histamine-, formalin- and concanavalin A-induced mouse paw edema models and two models of pain - the acetic acid-induced abdominal writhing and the hotplate test. The hybrids were in vitro evaluated for cytotoxic activity on cancer (MCF7, U- 87 MG) and non-cancer humane cell lines. Results: In the immunogenic inflammation model, the substances showed a pronounced anti-inflammatory effect, which was comparable to that of indomethacin. In the models of the exudative inflammation, none of the compounds displayed a statistically significant effect. The hybrids produced weak or moderate analgesic effects. All the agents revealed low cytotoxicity on human immortalized fibroblasts and cancer cell lines compared with 3β- amino-3-deoxybetulinic acid and doxorubicin. Conclusion: The results indicate that the principal anti-inflammatory effect of hybrids is substantially provided with the triterpenoid scaffold and in some cases with the azaprostanoid scaffold, but the latter makes a significant contribution to reducing the toxicity of hybrids. Hybrid 1 is of interest as a potent low toxic agent against immune-mediated inflammation.

scholarly journals Engineered anti-inflammatory peptides inspired by mapping an evasin–chemokine interaction

2020 ◽  
Vol 295 (32) ◽  
pp. 10926-10939 ◽  
Author(s):  
Benoit Darlot ◽  
James R. O. Eaton ◽  
Lucia Geis-Asteggiante ◽  
Gopala K. Yakala ◽  
Kalimuthu Karuppanan ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Titration Calorimetry ◽  
Protein Activity ◽  
Binding Interface ◽  
Chemokine Ligand ◽  
Therapeutic Development ◽  
Hydrogen Deuterium ◽  
Anti Inflammatory

Chemokines mediate leukocyte migration and homeostasis and are key targets in inflammatory diseases including atherosclerosis, cytokine storm, and chronic autoimmune disease. Chemokine redundancy and ensuing network robustness has frustrated therapeutic development. Salivary evasins from ticks bind multiple chemokines to overcome redundancy and are effective in several preclinical disease models. Their clinical development has not progressed because of concerns regarding potential immunogenicity, parenteral delivery, and cost. Peptides mimicking protein activity can overcome the perceived limitations of therapeutic proteins. Here we show that peptides possessing multiple chemokine-binding and anti-inflammatory activities can be developed from the chemokine-binding site of an evasin. We used hydrogen–deuterium exchange MS to map the binding interface of the evasin P672 that physically interacts with C–C motif chemokine ligand (CCL) 8 and synthesized a 16-mer peptide (BK1.1) based on this interface region in evasin P672. Fluorescent polarization and native MS approaches showed that BK1.1 binds CCL8, CCL7, and CCL18 and disrupts CCL8 homodimerization. We show that a BK1.1 derivative, BK1.3, has substantially improved ability to disrupt P672 binding to CCL8, CCL2, and CCL3 in an AlphaScreen assay. Using isothermal titration calorimetry, we show that BK1.3 directly binds CCL8. BK1.3 also has substantially improved ability to inhibit CCL8, CCL7, CCL2, and CCL3 chemotactic function in vitro. We show that local as well as systemic administration of BK1.3 potently blocks inflammation in vivo. Identification and characterization of the chemokine-binding interface of evasins could thus inspire the development of novel anti-inflammatory peptides that therapeutically target the chemokine network in inflammatory diseases.

scholarly journals A REVIEW ON IN VIVO AND IN VITRO EXPERIMENTAL MODELS TO INVESTIGATE THE ANTI-INFLAMMATORY ACTIVITY OF HERBAL EXTRACTS

2018 ◽  
Vol 11 (11) ◽  
pp. 29
Author(s):  
Inayat Kabir ◽  
Imtiyaz Ansari
Keyword(s):  
Reference Model ◽  
Experimental Models ◽  
Inflammatory Activity ◽  
Herbal Extracts ◽  
Double Positive ◽  
Arthritis Models ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The article emphasizes the anti-inflammatory effects of herbal extracts on different experimental models that are repeatedly used to test the in vivo anti-inflammatory activity of herbal components. Edema, granuloma and arthritis models are used to test the anti-inflammatory activity of plant extracts whereas formalin or acetic acid-induced writhing test and hot plate methods are the most repeatedly used to evaluate anti-nociceptive potentials of the herbal extracts. Although adjuvant-induced and collagen-induced arthritis models are also quite efficient, they have been used seldom to evaluate anti-inflammatory tendencies of the herbs. Here, we suggest a double positive reference model using both steroid and nonsteroidal anti-inflammatory drugs at the same time, instead of using only one of them either.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aloe Vera ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Raw264.7 Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

scholarly journals Extract from Bougainvillea xbuttiana (Variety Orange) Inhibits Production of LPS-Induced Inflammatory Mediators in Macrophages and Exerts a Protective Effect In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Rodolfo Abarca-Vargas ◽  
Vera L. Petricevich
Keyword(s):  
Inflammatory Mediators ◽  
Ethanolic Extract ◽  
Peritoneal Macrophages ◽  
Experimental Models ◽  
Nitric Oxide Release ◽  
Lps Challenge ◽  
Secretion Of Mediators ◽  
Anti Inflammatory

Background. Different pharmacological properties, such as antioxidant, antiproliferative, and anti-inflammatory properties, have been described among natural products. We previously described that the Bougainvillea xbuttiana (Variety Orange) ethanolic extract (BxbO) has an anti-inflammatory effect; however, this action is not fully understood. In this study, the action of the BxbO extract on the secretion of inflammatory mediators in two experimental models, in vitro and in vivo, after LPS challenge was evaluated. Methods. Peritoneal macrophages were obtained from female BALB/c mice and LPS-challenged with or without the BxbO extract. For the evaluation of mediators, the supernatants at 0, 12, 24, 36, and 48 hours were collected. For in vivo estimation, groups of female BALB/c mice were first intraperitoneously injected with different amounts of LPS and later administered the oral BxbO extract (v.o.) for 144 hours. To understand the mechanism of action, sera obtained from mice were collected at 0, 2, 4, 8, 12, and 24 hours after LPS challenge (with or without BxbO) for the detection of mediators. Results. The results showed that, in both peritoneal macrophages and sera of mice treated with the BxbO extract 1 hour before or together with LPS challenge, proinflammatory cytokines and nitric oxide release were unquestionably repressed. In contrast, in both systems studied here, the IL-10 levels were elevated to 5 to 9 times. At lethal doses of LPS, the BxbO extract treatment was found to protect animals from death. Conclusions. The results revealed that the inhibitory, protective, and benign effects of the BxbO extract were due to its capacity to balance the secretion of mediators.

Platelet inhibition by aspirin is diminished in patients during carotid surgery: a form of transient aspirin resistance?

2004 ◽  
Vol 92 (07) ◽  
pp. 89-96 ◽  
Author(s):  
David Payne ◽  
Chris Jones ◽  
Paul Hayes ◽  
Sally Webster ◽  
A. Naylor ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Platelet Inhibition ◽  
Aspirin Resistance ◽  
Arachidonic Acid Metabolism ◽  
Significant Rise ◽  
Control Group

SummaryThe majority of patients who suffer peri-operative thromboembolic complication while undergoing vascular procedures do so despite taking aspirin. This study examined the antiplatelet effect of aspirin during surgery in patients undergoing carotid endarterectomy (CEA). Fifty patients undergoing CEA were standardised to 150 mg aspirin daily for ≥2 weeks. Platelet aggregation in response to arachidonic acid (AA) was measured in platelet rich plasma prepared from blood taken prior to, during, and at the end of surgery. Spontaneous platelet aggregation was also studied, as was the role of physiological agonists (ADP, collagen, thrombin, and epinephrine) in mediating the in vivo and in vitro responses to AA. Eighteen patients undergoing leg angioplasty, also on 150 mg aspirin, without general anaesthesia, served as a control group. In the CEA patients aggregation induced by AA (5 mM) increased significantly from 7.6 ± 5.5% pre-surgery to 50.8 ± 29.5% at the end of surgery (p <0.0001). Aggregation to AA was even greater in samples taken mid-surgery from a sub-set of patients (73.8 ± 7.2%; p = 0.0001), but fell to 45.9 ± 7.4% by the end of surgery. The increased aggregation in response to AA was not due to intra-operative release of physiological platelet agonists since addition of agents that block/neutralise the effects of ADP (apyrase; 4 µg/ml), thrombin (hirudin; 10 units/ml), or epinephrine (yohimbine; 10 µM/l) to the samples taken at the end of surgery did not block the increased aggregation.The patients undergoing angioplasty also showed a significant rise in the response to AA (5 mM), from 5.6 ± 5.5% pre-angioplasty to 32.4 ± 24.9% at the end of the procedure (p <0.0001), which fell significantly to 11.0 ± 8.1% 4 hours later. The antiplatelet activity of aspirin, mediated by blockade of platelet arachidonic acid metabolism, diminished significantly during surgery, but was partially restored by the end of the procedure without additional aspirin treatment.This rapidly inducible and transient effect may explain why some patients undergoing cardiovascular surgery remain at risk of peri-operative stroke and myocardial infarction.

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