scholarly journals Mechanisms Underlying the Antinociceptive, Antiedematogenic, and Anti-Inflammatory Activity of the Main Flavonoid fromKalanchoe pinnata

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Raquel Teixeira Ferreira ◽  
Marcela Araújo Soares Coutinho ◽  
David do Carmo Malvar ◽  
Elson Alves Costa ◽  
Iziara Ferreira Florentino ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Inflammatory Diseases ◽  
Subcutaneous Administration ◽  
Mechanisms Of Action ◽  
Selectivity Index ◽  
Kalanchoe Pinnata ◽  
Flavonoid Quercetin ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Kalanchoe pinnata(KP) is popularly used for treating inflammatory diseases. This study investigated the antinociceptive, antiedematogenic, and anti-inflammatory potential of the subcutaneous administration of KP flower aqueous extract (KPFE), its ethyl acetate (EtOAcF) and butanol (BuOHF) fractions, and the main KP flavonoid [quercetin 3-O-α-L-arabinopyranosyl (1→2)α-L-rhamnopyranoside] (KPFV) in mice, as well as its possible mechanisms of action. KPFE (30–300 mg/kg) and KPFV (1–10 mg/kg) inhibited the acetic acid-induced writhing (ID50= 164.8 and 9.4 mg/kg, resp.). KPFE (300 mg/kg), EtOAcF (12 mg/kg), BuOHF (15 mg/kg), or KPFV (0.3–3.0 mg/kg) reduced leukocyte migration on carrageenan-induced pleurisy (ID50= 2.0 mg/kg for KPFV). KPFE (3–30 mg/kg) and KPFV (0.3–3.0 mg/kg) reduced the croton oil-induced ear edema (ID50= 4.3 and 0.76 mg/kg, resp.). KPFE and KPFV reduced the TNF-αconcentration in the pleural exudates on carrageenan-induced pleurisy test. Moreover, KPFV inhibited COX-1 (IC50= 22.1 μg/mL) and COX-2 (IC50> 50 μg/mL). The selectivity index (COX-1IC50/COX-2IC50) was <0.44. These results indicate that KPFE and KPFV produced antinociceptive, antiedematogenic, and anti-inflammatory activities through COX inhibition and TNF-αreduction, revealing that the main flavonoid in KP flowers and leaves plays an important role in the ethnomedicinal use of the plant.

scholarly journals Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract fromFumaria capreolata

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Noureddine Bribi ◽  
Francesca Algieri ◽  
Alba Rodriguez-Nogales ◽  
Jose Garrido-Mesa ◽  
Teresa Vezza ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Inflammatory Diseases ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Proinflammatory Mediators ◽  
Total Alkaloids ◽  
Aerial Parts ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Fumaria Capreolata

Fumaria capreolatais used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts ofFumaria capreolata(AFC) on LPS-induced production of proinflammatory mediators (IL-6, IL-1β, iNOS, TNF-α, COX-2, and MIP-2) in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO) and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1β, iNOS, TNF-α, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis.

scholarly journals Mycophenolate suppresses inflammation by inhibiting prostaglandin synthases: a study of molecular and experimental drug repurposing

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11360
Author(s):  
Fahad Al-Hizab ◽  
Mahmoud Kandeel
Keyword(s):  
Root Mean Square ◽  
Inflammatory Diseases ◽  
Drug Repurposing ◽  
Inflammatory Cells ◽  
Acid Synthesis ◽  
Mean Square ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Mycophenolate mofetil is an established anti-proliferative and immune-suppressive agent that minimizes the proliferation of inflammatory cells by interfering with nucleic acid synthesis. Herein, we report our discovery of the prostaglandin inhibiting properties of MMF, which offers new applications for the drug in the treatment of inflammatory diseases. The estimated values of IC50MMFCOX-1, IC50MMFCOX-2, and IC50MMF5-LOX were 5.53, 0.19, and 4.47 µM, respectively. In contrast, mycophenolic acid (MPA) showed slightly stronger inhibition: IC50MPACOX-1, IC50MPACOX-2, and IC50MPA5-LOX were 4.62, 0.14, and 4.49 µM, respectively. These results indicate that MMF and MPA are, respectively, 28.6 and 33 times more selective for cyclooxygenase-2 than for cyclooxygenase-1, which implies that MMF would have less impact on the gastric mucosa than most nonselective, nonsteroidal anti-inflammatory drugs. Furthermore, MMF provided dose-dependent relief of acute inflammation in the carrageenan-induced rat paw edema test, with results comparable to those of celecoxib and indomethacin. Molecular dynamics simulations indicated that the MMF bond with COX-2 was stable, as evidenced by a low root-mean-square deviation of atomic positions, complementary per-residue root-mean-square fluctuation, and 0–4 hydrogen bonds during the 50-ns simulation time. Therefore, MMF provides immune-suppressing, cyclooxygenase-inhibiting, and inflammation-relieving properties. Our results indicate that MMF can be 1) repositioned for inflammation treatment without the need for further expensive clinical trials, 2) used for local acute inflammations, and 3) used as a sparing agent for other steroid and non-steroid anti-inflammatory medications, especially in topical applications.

New substituted pyrazole derivatives targeting COXs as potential safe anti-inflammatory agents

2019 ◽  
Vol 11 (15) ◽  
pp. 1871-1882
Author(s):  
Khaled RA Abdellatif ◽  
Mohammed T El-Saadi ◽  
Shaimaa G Elzayat ◽  
Noha H Amin
Keyword(s):  
Selectivity Index ◽  
Ulcer Index ◽  
Time Intervals ◽  
Cellular Inflammatory Response ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Substituted Pyrazoles ◽  
Edema Inhibition ◽  
Cox 1

Aim: Everyday studies prove the increasing need for newer and safer agents to control cellular inflammatory response, an underlying cause for the pathophysiology of many other clinical cases. Results: Two newly designed sets of schiff 5a-h and chlacone 6a-f substituted pyrazoles were synthesized and evaluated for their in vivo/vitro anti-inflammatory activities. Most potent representatives were chosen for investigation of ulcerogenic and molecular docking properties. Conclusion: The synthesized compounds showed considerable edema inhibition percentage range if compared with celecoxib (13–93% and 58–93%, respectively) at different time intervals. Compound 6e showed the best screening results if compared with celecoxib (inhibition % = 93.62 and 93.51% at 5 h, COX-1/COX-2 selectivity index SI = 215.44 and 308.16 and ulcer index = 7.25 and 8, respectively).

scholarly journals Premedication with meloxicam exacerbates intracranial haemorrhage in an immature swine model of non-impact inertial head injury

2012 ◽  
Vol 46 (2) ◽  
pp. 164-166 ◽  
Author(s):  
S H Friess ◽  
M Y Naim ◽  
T J Kilbaugh ◽  
J Ralston ◽  
S S Margulies
Keyword(s):  
Platelet Inhibition ◽  
Mechanisms Of Action ◽  
Swine Model ◽  
Inhibition Of Platelet Aggregation ◽  
Subarachnoid Bleeding ◽  
Research Protocols ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Head Rotations ◽  
Cox 1

Meloxicam is a cyclo-oxygenase-2 (COX-2) preferential non-steroidal anti-inflammatory drug with very effective analgesic and anti-inflammatory effects in swine. Previous reports in piglets have demonstrated that meloxicam also inhibits COX-1 and reduces production of thromboxane significantly. We use preinjury analgesia in our immature swine (3–5-day-old piglets) model of brain injury using rapid head rotations without impact. In 23 consecutive subjects we found that premedication with meloxicam ( n = 6) produced a significantly higher mortality rate (5/6 or 83%) than buprenorphine ( n = 17, 1/17 or 6%, P < 0.02). On gross neuropathological examination of the meloxicam-treated swine, we observed massive subdural and subarachnoid bleeding which were not present in buprenorphine-premedicated animals. To our knowledge there are no previous reports in swine of increased bleeding or platelet inhibition associated with meloxicam administration and further research is needed to define mechanisms of action in piglets. We caution the use of meloxicam in swine when inhibition of platelet aggregation might adversely affect refinement of experimental research protocols, such as in stroke, trauma and cardiac arrest models.

scholarly journals Assessment of the impact of PTGS1, PTGS2 and CYP2C9 polymorphisms on pain, effectiveness and safety of NSAID therapies

2020 ◽  
Vol 74 ◽  
pp. 504-516
Author(s):  
Miriam Dawidowicz ◽  
Agnieszka Kula ◽  
Paweł Świętochowski ◽  
Zofia Ostrowska
Keyword(s):  
Enzymatic Activity ◽  
Inflammatory Diseases ◽  
Aspirin Resistance ◽  
Nucleotide Polymorphisms ◽  
Cyclooxygenase 1 ◽  
Genes Encoding ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Impact ◽  
Cox 1

Cyclooxygenase 1 and 2 (COX-1, COX-2) are enzymes that catalyze the first reaction in the arachidonic acid pathway. COXs are the therapeutic target for non-steroidal anti-inflammatory drugs. Inhibition of COX enzymatic activity has an analgesic, anti-inflammatory and sometimes antiplatelet effect. Single-nucleotide polymorphisms (SNPs) within genes encoding COX-1 and COX-2 (PTGS1, PTGS2) influence the risk of pain and their intensity in some diseases. They also affect the effectiveness of NSAID therapy in rheumatoid diseases. Moreover, the relationship between certain polymorphisms of PTGS2 and a higher risk of migraine and the development of aspirin resistance in the prophylaxis of cardiovascular diseases was demonstrated. The isoform of cytochrome P450, CYP2C9 has a significant influence on the efficacy and safety of NSAID use. It is responsible for the metabolism and speed of removal of these drugs. The occurrence of some of its polymorphic forms is associated with a decrease in CYP2C9 enzymatic activity, leading to changes in the pharmacokinetics and pharmacodynamics of NSAIDs. The prolonged half-life and decrease in clearance of these drugs lead to serious side effects such as hepatotoxicity, nephrotoxicity, anaphylactic reactions, cardiovascular or gastrointestinal incidents. Studies on polymorphisms of cyclooxygenases and CYP2C9 may improve the safety and efficacy of NSAIDs therapy by adjusting the dose to individual polymorphic variants, as well as expanding knowledge about the pathomechanism of inflammatory diseases.

scholarly journals Analgesic and Anti-Inflammatory Activities of Methanol Extract ofCissus repensin Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ching-Wen Chang ◽  
Wen-Te Chang ◽  
Jung-Chun Liao ◽  
Yung-Jia Chiu ◽  
Ming-Tsuen Hsieh ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Formalin Test ◽  
Methanol Extract ◽  
Inflammatory Diseases ◽  
Paw Edema ◽  
Tissue Destruction ◽  
Inflammatory Mechanism ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The aim of this study was to investigate possible analgesic and anti-inflammatory mechanisms of theCRMeOH. Analgesic effect was evaluated in two models including acetic acid-induced writhing response and formalin-induced paw licking. The anti-inflammatory effect was evaluated byλ-carrageenan-induced mouse paw edema and histopathologic analyses. The results showed thatCRMeOH(500 mg/kg) decreased writhing response in the acetic acid assay and licking time in the formalin test.CRMeOH(100 and 500 mg/kg) significantly decreased edema paw volume at 4th to 5th hours afterλ-carrageenan had been injected. Histopathologically,CRMeOHabated the level of tissue destruction and swelling of the edema paws. These results were indicated that anti-inflammatory mechanism ofCRMeOHmay be due to declined levels of NO and MDA in the edema paw through increasing the activities of SOD, GPx, and GRd in the liver. Additionally,CRMeOHalso decreased IL-1β, IL-6, NFκB, TNF-α, COX-2, and iNOS levels. The contents of two active ingredients, ursolic acid and lupeol, were quantitatively determined. This paper demonstrated possible mechanisms for the analgesic and anti-inflammatory effects ofCRMeOHand provided evidence for the classical treatment ofCissus repensin inflammatory diseases.

Synthesis and Biological Evaluation of Benzodioxol Derivatives as Cyclooxygenase Inhibitors

2020 ◽  
Vol 17 (9) ◽  
pp. 1117-1125
Author(s):  
Nidal Jaradat ◽  
Mohammed Hawash ◽  
Murad Abualhasan
Keyword(s):  
Acetic Acid ◽  
Biological Evaluation ◽  
Cyclooxygenase Inhibitors ◽  
Moderate Activity ◽  
Selectivity Ratio ◽  
Preliminary Screening ◽  
Screening Study ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutics; they are competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the conversion of arachidonic acid to inflammatory prostaglandins. Objective: In this study, new benzodioxol derivatives with different core cycles and functional groups (i.e., aryl acetate, aryl acetic acid and diazepine) were designed, synthesized, identified and evaluated for their analgesic and anti-inflammatory activity, as a preliminary screening study to identify the most potent and more selective groups. Methods: The synthesized compounds were identified using FTIR, HRMS, 1H-NMR and 13C-NMR, and evaluated for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay kit. Results: Six compounds were synthesized as a preliminary screening study to identify which was the most potent and more selective group towards COX-2 versus COX-1, compared to ketoprofen as non-selective NSAIDs. The compounds have three different groups: aryl acetate, aryl acetic acid and diazepine. The results showed that the most potent compound against the COX- 1 enzyme was 4b (which has diazepine and 2-chlorophenyl) with IC50 = 0.363 μM, and the selectivity ratio of 4b was found to be better than ketoprofen. In contrast, compound 4a (which has diazepine and 3-chlorophenyl) was the most selective with a COX-1/COX-2 ratio value of 0.85 in comparison with a ketoprofen ratio value of 0.20. Conclusion: In general, the synthesized library has moderate activity against both enzymes (i.e., COX-1 and COX-2). Moreover, all six compounds have better COX-2 inhibition selectivity compared to the commercial drug ketoprofen.

scholarly journals Analgesic and Anti-Inflammatory Activities of Quercetin-3-methoxy-4′-glucosyl-7-glucoside Isolated from Indian Medicinal Plant Melothria heterophylla

Medicines ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 59 ◽  
Author(s):  
Arijit Mondal ◽  
Tapan Kumar Maity ◽  
Anupam Bishayee
Keyword(s):  
Acetic Acid ◽  
Analgesic Activity ◽  
Tail Flick ◽  
Test Compound ◽  
Active Components ◽  
Hot Plate ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: Melothria heterophylla (family: Cucurbitaceae), commonly known as kudari, is used in the Indian traditional medicine to treat various inflammation-associated diseases, such as asthma, arthritis and pain. However, the anti-inflammatory active components of this plant have not been identified yet. The aim of this study was to investigate the potential analgesic and anti-inflammatory activities of a compound, quercetin-3-methoxy-4′-glucosyl-7-glucoside, isolated from M. heterophylla. Methods: The anti-inflammatory activity was determined using carrageenan- and dextran-induced rat paw edema as well as cotton pellet-induced granuloma in rats, whereas the analgesic activity was analyzed using acetic acid-induced writhing, hot plate and tail flick response in mice. The test compound was orally administered at a dose of 5, 10 or 15 mg/kg. The cyclooxygenase-1 (COX-1)- and COX-2-inhibitory capacity of the test compound was studied by enzyme immunosorbent assay. Results: Quercetin-3-methoxy-4′-glucosyl-7-glucoglucoside at 15 mg/kg exhibited a maximum inhibition of carrageenan-induced inflammation (50.3%, p < 0.05), dextran (52.8%, p < 0.05), and cotton pellets (41.4%, p < 0.05) compared to control animals. At the same dose, it showed a 73.1% inhibition (p < 0.05) of the pain threshold in acetic acid-induced writhing model. It also exhibited a considerable analgesic activity by prolonging the reaction time of the animals based on hot plate as well as tail flick response. The test compound was found to inhibit COX-1 (IC50 2.76 µg/mL) and more efficiently, COX-2 (IC50 1.99 µg/mL). Conclusions: Quercetin-3-methoxy-4′-glucosyl-7-glucoside possessed substantial analgesic and anti-inflammatory activities possibly due to inhibition of prostaglandin production, supporting the ethnomedicinal application of M. heterophylla to treat various inflammatory disorders.

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Hee-Soo Han ◽  
Eungyeong Jang ◽  
Ji-Sun Shin ◽  
Kyung-Soo Inn ◽  
Jang-Hoon Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Molecular Data ◽  
Mrna Levels ◽  
Protein Levels ◽  
Stat3 Phosphorylation ◽  
Stat Signaling ◽  
Cox 2 ◽  
Anti Inflammatory

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

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