Anti-Inflammatory Effects and Mechanisms of Pudilan Antiphlogistic Oral Liquid
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Abstract:
Pudilan antiphlogistic oral liquid (PDL) is a commercial traditional Chinese medicine widely used in the treatment of a variety of inflammatory diseases. However, the specific mechanisms of PDL's anti-inflammatory effects have not been fully understood. In this research, five classic inflammatory models and a network pharmacology-based strategy were utilized to evaluate its anti-inflammatory efficacy and elucidate its multicomponent and multitarget mode of the anti-inflammatory mechanism. A systems pharmacology approach was carried out via a holistic process of active compound screening, target acquisition, network construction, and further analysis. The potential component-target-associated anti-inflammatory mechanisms of PDL were further verified both in vivo and in vitro. The results showed that PDL exhibited a proven anti-inflammatory effect on multiple types of inflammatory models, including β-hemolytic streptococcus-induced acute pharyngitis, LPS-induced acute lung injury, xylene-induced ear swelling, carrageenan-induced paw edema, and acetic acid-induced capillary permeability-increasing models. Systems pharmacology analysis predicted 45 ingredients of PDL that interact with 185 targets, of which 38 overlapped with the inflammation-related targets. Furthermore, KEGG pathway analysis showed that the predicted targets were mainly involved in hypoxia-inducible factor (HIF)-1, tumor necrosis factor (TNF), nuclear factor kappa-B (NF-κB), and NOD-like receptor (NLR) pathways. Both in vivo and in vitro experiments clarified that PDL has anti-inflammatory potency by inhibiting PI3K and p38 phosphorylation and activating the NLRP3 inflammasome. Our results suggested that PDL has an efficient and extensive anti-inflammatory effect, and its anti-inflammatory mechanisms may involve multiple inflammatory-associated signaling pathways, including HIF-1- and TNF-mediated pathways and NLRP3 inflammasome activation.Keywords:
Anti-inflammatory
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Background: Paracetamol (p-aminophenol) and salicylates are nonsteroidal antiinflammatory drugs that are widely used in the general population. The adverse effects of both drugs continue to be a focus of the pharmaceutical industry in the development of new molecules that will increase treatment safety. In this context, we tested nine compounds derived from paracetamol and salicylates, synthesized in our laboratory, for their safety and ex vivo and in vivo anti-inflammatory activity. Methods: We analyzed the cytotoxicity of the compounds in ex vivo mice neutrophils, and their ability to inhibit the production of pro-inflammatory mediators (nitric oxide and interleukin-6) after stimulating with LPS. Next, in the selected molecules, we evaluated the anti-inflammatory effect on an in vivo inflammatory model of acute lung injury in mice. All nine compounds were also submitted to the cytotoxicity assay, like the original compounds. Results: None of the compounds showed cytotoxicity under the cells used. However, of the initial compounds, only five demonstrated anti-inflammatory effect, inhibiting Nitric Oxide (NO) and interleukin 6 (IL-6) production by neutrophils stimulated with Lipopolysaccharide (LPS). After this initial trial, four modified compounds were able to reduce leukocyte migration and fluid leakage in the bronchoalveolar lavage of mice. However, only the compound 5a1, derived from the esterification of gentisic acid, was able to significantly inhibit the levels of all pro-inflammatory cytokines and increase the levels of antiinflammatory cytokines evaluated. Conclusion: In conclusion, all compounds showed a good safety profile, and many of them had an antiinflammatory effect. However, the compound derived from gentisic acid is highlighted for its significant effects ex vivo and in vivo and in this context, we believe that this compound is a potential candidate for the development of a new anti-inflammatory drug.
Ex vivo
Proinflammatory cytokine
Anti-inflammatory
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In-vivo anti-inflammatory activity of silymarin was tested in different acute inflammation experimental models. In carrageenan-induced paw oedema in rats, silymarin given orally reduced in a dose-dependent manner the food-pad abscesses (ED50 = 62.42 mg kg-1). In xylene-induced ear mouse inflammation, silymarin applied topically was more effective than administered intraperitoneally, with effects comparable with those of indomethacin. Silymarin also produced a dose-dependent inhibition of leukocyte accumulation in inflammatory exudates following intraperitoneal injection of carrageenan in mice; silymarin significantly reduced the number of neutrophils. Silymarin was unable to inhibit phospholipase A2 in an in-vitro assay. Besides its known anti-oxidative properties and its ability to act as a radical scavenger, these results suggest that silymarin exerts an important anti-inflammatory action in-vivo by reducing oedema with the effect markedly influenced by the inhibition of neutrophil migration into the inflamed site.
Carrageenan
ED50
Anti-inflammatory
Intraperitoneal injection
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Anti-inflammatory
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Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.
Anti-inflammatory
Etoricoxib
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Flurbiprofen
Ibuprofen
Anti-inflammatory
Ex vivo
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Anti-inflammatory
Alpha (finance)
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Бұл зерттеужұмысындaКaно моделітурaлы жәнеоғaн қaтыстытолықмәліметберілгенжәнеуниверситетстуденттерінебaғыттaлғaн қолдaнбaлы (кейстік)зерттеужүргізілген.АхметЯссaуи университетініңстуденттеріүшін Кaно моделіқолдaнылғaн, олaрдың жоғaры білімберусaпaсынa қоятынмaңыздытaлaптaры, яғнисaпaлық қaжеттіліктері,олaрдың мaңыздылығытурaлы жәнесaпaлық қaжеттіліктерінеқaтыстыөз университетінқaлaй бaғaлaйтындығытурaлы сұрaқтaр қойылғaн. Осы зерттеудіңмaқсaты АхметЯсaуи университетіндетуризмменеджментіжәнеқaржы бaкaлaвриaт бaғдaрлaмaлaрыныңсaпaсынa қaтыстыстуденттердіңқaжеттіліктерінaнықтaу, студенттердіңқaнaғaттaну, қaнaғaттaнбaу дәрежелерінбелгілеу,білімберусaпaсын aнықтaу мен жетілдіружолдaрын тaлдaу болыптaбылaды. Осы мaқсaтқaжетуүшін, ең aлдыменКaно сaуaлнaмaсы түзіліп,116 студенткеқолдaнылдыжәнебілімберугежәнеоның сaпaсынa қaтыстыстуденттердіңтaлaптaры мен қaжеттіліктерітоптықжұмыстaрaрқылыaнықтaлды. Екіншіден,бұл aнықтaлғaн тaлaптaр мен қaжеттіліктерКaно бaғaлaу кестесіменжіктелді.Осылaйшa, сaпa тaлaптaры төрт сaнaтқa бөлінді:болуытиіс, бір өлшемді,тaртымдыжәнебейтaрaп.Соңындa,қaнaғaттaну мен қaнaғaттaнбaудың мәндеріесептелдіжәнестуденттердіңқaнaғaттaну мен қaнaғaттaнбaу деңгейлерінжоғaрылaту мен төмендетудеосытaлaптaр мен қaжеттіліктердіңрөліaйқын aнықтaлды.Түйінсөздер:сaпa, сaпaлық қaжеттіліктер,білімберусaпaсы, Кaно моделі.
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The nationally-recognized Susquehanna
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musical level.AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA¢AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA Experience choral
singing that will take you to new
heights!
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