Design and Synthesis In Silico Drug-like Prediction and Pharmacological Evaluation of Cyclopolymethylenic Homologous of LASSBio-1514

Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2a–e), cyclobutyl- (3a–e), and cyclopropylacylhydrazones (4a–e) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration.

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Antinociceptive and Anti-Inflammatory Activities ofTeucrium persicumBoiss. Extract in Mice

Scientifica ◽

10.1155/2015/972827 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Abdolhossein Miri ◽

Javad Sharifi-Rad ◽

Kaveh Tabrizian ◽

Ali Akbar Nasiri

Keyword(s):

Chronic Pain ◽

Neuropathic Pain ◽

Sciatic Nerve ◽

Analgesic Effect ◽

Formalin Test ◽

Hot Plate ◽

Hot Plate Test ◽

Plate Test ◽

Cotton Pellet ◽

Anti Inflammatory

Background.Therapeutic properties ofTeucriumspecies as antioxidant, antibacterial, analgesic, anticancer, diuretic, and tonic compounds have been proved earlier.Materials and Methods. In this study, the antinociceptive and anti-inflammatory effects of the aqueous extract ofTeucrium persicumon chronic pain, sciatic nerve ligation as a model of neuropathic pain, and inflammatory models were investigated by formalin, hot-plate, and cotton pellet-induced granuloma models in mice, respectively.T. persicumaqueous extracts (100, 200, and 400 mg/kg) were orally gavaged for one week. On 8th day, the time spent and the number of lickings were recorded in formalin test. Morphine and Diclofenac were used intraperitoneally as positive controls. In sciatic nerve ligated animals, as a model of neuropathic pain, doses (100, 200, and 400 mg/kg) ofT. persicumextract (TPE) were orally gavaged for 14 consecutive days. The analgesic effect of this extract was examined 14 days after sciatic nerve ligation using the hot-plate test. Controls received saline and Imipramine (40 mg/kg, i.p.) was used a positive control for neuropathic pain model.Results.In the formalin test, a week oral gavage of all TPE doses (100, 200, and 400 mg/kg) caused a significant decrease on the licking response compared to the control negative animals. In the hot-plate test, doses of 200 and 400 mg/kg showed significant analgesic effects in sciatic nerve ligated animals. Oral gavaged of TPE revealed significant analgesic effect on chronic pain in both formalin test and sciatic nerve ligated animals. The TPEs did not have any significant anti-inflammatory effects in cotton pellet-induced granuloma formation in mice.Conclusions.These results suggest that the aqueous extract fromT. persicumBoiss. produced antinociceptive effects. Its exact mechanism of action still remains indistinct.

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Preventative anti-inflammatory effect of pectic galacturonans after oral administration

Planta Medica ◽

10.1055/s-2007-986797 ◽

2007 ◽

Vol 73 (09) ◽

Cited By ~ 1

Author(s):

S Popov ◽

G Popova ◽

V Golovchenko ◽

R Ovodova

Keyword(s):

Oral Administration ◽

Anti Inflammatory ◽

Inflammatory Effect

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Design and Synthesis of Quinazolinone Derivatives as Anti-inflammatory Agents: Pharmacophore Modeling and 3D QSAR Studies

Medicinal Chemistry ◽

10.2174/1573406409666131128142843 ◽

2014 ◽

Vol 10 (7) ◽

pp. 711-723 ◽

Cited By ~ 4

Author(s):

P. Chaitanya ◽

G. Reddy ◽

G. Varun ◽

L.M. Srikanth ◽

V.V.S.R. Prasad ◽

...

Keyword(s):

3D Qsar ◽

Pharmacophore Modeling ◽

Qsar Studies ◽

Design And Synthesis ◽

Anti Inflammatory ◽

Quinazolinone Derivatives

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Red Grape Polyphenol Oral Administration improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200313152648 ◽

2020 ◽

Vol 20 ◽

Author(s):

Thea Magrone ◽

Emilio Jirillo ◽

Manrico Magrone ◽

Matteo Antonio Russo ◽

Paolo Romita ◽

...

Keyword(s):

Contact Dermatitis ◽

Oral Administration ◽

Allergic Contact Dermatitis ◽

Laboratory Data ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Red Grape ◽

Allergic Contact ◽

Drop Outs

Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Method: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded. Result: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

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The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema

Molecules ◽

10.3390/molecules26123701 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3701

Author(s):

Salah E. M. Eltom ◽

Ahmed A. H. Abdellatif ◽

Hamzah Maswadeh ◽

Mohsen S. Al-Omar ◽

Atef A. Abdel-Hafez ◽

...

Keyword(s):

Oral Administration ◽

Standard Procedure ◽

P Value ◽

Skin Thickness ◽

Paw Edema ◽

Reference Drug ◽

Struthio Camelus ◽

Anti Inflammatory ◽

Nano Emulsion ◽

Inflammatory Effect

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

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New ibuprofen derivatives with thiazolidine-4-one scaffold with improved pharmaco-toxicological profile

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00475-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ioana-Mirela Vasincu ◽

Maria Apotrosoaei ◽

Sandra Constantin ◽

Maria Butnaru ◽

Liliana Vereștiuc ◽

...

Keyword(s):

Analgesic Effect ◽

Visceral Pain ◽

Biological Effects ◽

Maximum Effect ◽

Tail Flick ◽

Paw Edema ◽

Cell Viability Assay ◽

Thermal Nociception ◽

Analgesic Effects ◽

Anti Inflammatory

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 μg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

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Pra-C exerts analgesic effect through inhibiting microglial activation in anterior cingulate cortex in complete Freund’s adjuvant-induced mouse model

Molecular Pain ◽

10.1177/1744806921990934 ◽

2021 ◽

Vol 17 ◽

pp. 174480692199093

Author(s):

Dan-jie Su ◽

Long-fei Li ◽

Sai-ying Wang ◽

Qi Yang ◽

Yu-jing Wu ◽

...

Keyword(s):

Chronic Pain ◽

Mouse Model ◽

Anterior Cingulate Cortex ◽

Analgesic Effect ◽

Microglial Activation ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Freund’S Adjuvant ◽

Complete Freund's Adjuvant ◽

Freund's Adjuvant

Chronic pain is highly prevalent worldwide and severely affects daily lives of patients and family members. Praeruptorin C (Pra-C) is a main active ingredient derived from Peucedanum praeruptorum Dunn, traditionally used as antibechic, anti-bronchitis and anti-hypertension drug. Here, we evaluated the effects of Pra-C in a chronic inflammatory pain mouse model induced by complete Freund’s adjuvant (CFA) injection. Pra-C (3 mg/kg) treatment for just 3 days after CFA challenge relieved CFA-induced mechanical allodynia and hindpaw edema in mice. In the anterior cingulate cortex (ACC), Pra-C treatment inhibited microglia activation and reduced levels of proinflammatory cytokines, TNF-α and IL-1β, and suppressed upregulation of glutamate receptors caused by CFA injection. In addition, Pra-C attenuated neuronal hyperexcitability in ACC of CFA-injected mice. In vitro studies confirmed the analgesic effect of Pra-C was due to its inhibitory ability on microglial activation. In conclusion, Pra-C administration had a certain effect on relieving chronic pain by inhibiting microglial activation, attenuating proinflammatory cytokine releasing and regulating excitatory synaptic proteins in the ACC of the CFA-injected mice.

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