Oral and Topical Anti-Inflammatory Activity of Jatropha integerrima Leaves Extract in Relation to Its Metabolite Profile

Jatropha integerrima Jacq., family: Euphorbiaceae, is used in India and subtropical Africa to treat different skin conditions. In this study we evaluated the anti-inflammatory activity of J. integerrima leaves extract (JILE) using rat paw edema model. The extract was administered orally (200 and 400 mg/kg) or applied topically as creams at 2.5, 5, and 10% strength. Four hours post-treatment, maximum reduction of edema volume by 63.09% was observed after oral administration of JILE (400 mg/kg) as compared to indomethacin with 60.43%. The extract anti-inflammatory effect was accompanied by a decrease in NO, prostaglandin PGE2, TNF-a and PKC levels by 19, 29.35, 16.9, and 47.83%, respectively. Additionally, topical applications of JILE showed dose dependent reduction in paw edema and resulted in normalized levels of PGE2, TNF-a, and PKC when used as 10% cream. Signs of inflammations were reduced or absent from paw tissue of animals receiving JILE either orally or topically. Finally, liquid chromatography/mass spectrometry analysis of JILE resulted in the annotation of 133 metabolites including 24 diterpenoids, 19 flavonoids, 10 phenolic acid conjugates, 8 cyclic peptides, 6 phytosterols, 4 sesquiterpenes, and 4 coumarins. Several of the annotated metabolites have known anti-inflammatory activity including vitexin, isovitexin, fraxitin, scopeltin, stigmasterol, and many diterpenoidal derivatives.

Gabapentin Antioxidant Derivatives with Anti-Inflammatory and Neuroprotective Potency

Aims: The aim of this work is to investigate the antioxidant and anti-inflammatory potency of novel gabapentin derivatives, which could be proven useful as neuroprotective agents. Background: Alzheimer’s Disease (AD) is one of the most common neurodegenerative disorders worldwide. Due to its multi-factorial character, no effective treatment has been obtained yet. In this direction, the multi-targeting compounds approach could be useful for the development of novel, more effective drugs against AD. Oxidative stress and inflammation are highly involved in the progression of neurodegeneration, while gabapentin has been investigated for the treatment of behavioral symptoms in AD. Objective: In this work, derivatives of cinnamic acid, trolox and 3,5-di-tertbutyl-4-hydroxybenzoic acid amidated with gabapentin methyl ester, were designed and studied. Compounds with these structural characteristics are expected to act in various biochemical pathways, affecting neurodegenerative processes. Methods: The designed compounds were synthesized with classical amidation methods, purified by flash column chromatography, and identified spectrometrically (1H-NMR and 13C-NMR). Their purity was determined by CHN elemental analysis. They were tested in vitro for their antioxidant and anti-inflammatory properties, and for their inhibitory effect on acetylcholinesterase. Their in vivo anti-inflammatory activity was also tested. Results: Those molecules incorporating an antioxidant moiety possessed inhibitory activity against rat microsomal membrane lipid peroxidation and oxidative protein glycation, as well as radical scavenging activity. Moreover, most of them presented moderate inhibition towards lipoxygenase (up to 51% at 100μΜ) and acetylcholinesterase (AchE) (IC50 up to 274μΜ) activities. Finally, all synthesized compounds presented in vivo anti-inflammatory activity, decreasing carrageenan-induced rat paw edema up to 53% and some of them could inhibit cyclooxygenase significantly. Conclusion: These results indicate that the designed compounds could be proven useful as multi-targeting molecules against AD, since they affect various biochemical pathways associated with neurodegeneration. Thus, more effective drugs can be obtained, and possible adverse effects of drug combination can be limited.

Synthesis and Evaluation of Anti-inflammatory Activity of some Thiazolo[4,5-b]pyridines

The 18 new thiazolo[4,5-b]pyridin-2-one derivatives have been synthesized using alkylation, cyanethylation, hydrolysis, and acylation reactions. The structures of the obtained compounds have been confirmed by 1H NMR spectroscopy, mass spectrometry, and elemental analysis. The study of the in vivo anti-inflammatory activity of the synthesized substances was assessed by using the functional model of carrageenan-induced rat paw edema. The present results of anti-inflammatory activity have shown that the synthesized compounds demonstrated considerable anti-inflammatory effects. Some of them approach or exceed the comparative drug Ibuprofen in terms of activity.

Isolation, Chemical Characterization, Evaluation of Analgesic and Anti-Inflammatory Activities of Triterpenoids from the Tubers of Raphionacme vignei E. A. Bruce (Apocynaceae)

Raphionacme vignei E. A. Bruce (Apocynaceae) is a plant of the traditional African pharmacopoeia, whose parts are used in the treatment of various pathologies. Water-soaked R. vignei tubers are edible. The objective of this study was to isolate triterpenoids from the acetonic extract of R. vignei tubers, evaluate the analgesic and anti-inflammatory activities of each molecule. The isolated compounds, characterized by NMR and mass spectrometry, is composed of six triterpenoids: beta-amyrin dodecanoate 1(DDQ1), lupeol dodecanoate 2(DDQ2), beta-amyrin acetate 3(DDQ3), lupeol acetate 4(DDQ4), luepol 5(DDQ5) and β-sitosterol 6(DDQ6). These molecules (DDQ2, DDQ3, DDQ4, DDQ5, DDQ6) are anti-inflammatory in carrageenan induced rat paw edema, with better anti-inflammatory power for DDQ2 and DDQ4, which would be related to the presence of acetate function and cycle E. DDQ2 and DDQ4 are also analgesic in acetic acid induced contortions and the removal test of rat tail on the heating plate. The analgesic action of DDQ2 and DDQ4, superior to that salicylic acetyl acid, identical to that morphine, suggests a central action of these two molecules. The potent analgesic effect of DDQ2 and DDQ4, could be attributed to the presence of cyclopentane and isoprene substitution in position 19 of the lupane family. DDQ2 and DDQ4 represent a potential for the synthesis of structural analogues with analgesic and/or anti-inflammatory properties.

The cytotoxicity, anti-inflammation, anti-nociceptive and oral ulcer healing properties of coconut shell liquid smoke

Introduction: Coconut shell liquid smoke (CS-LS) from Cocos nucifera L. has been traditionally used by Indonesians as a natural preservative. Besides that, liquid smoke is also used as a medicine to treat various types of wounds. During the storage, liquid smoke resulting from pyrolysis is still questionable in relation to the oxidation process and changes in its properties and potentials. We observed the physical characteristics, components, toxicity, anti-inflammatory, anti-nociceptive properties, and effect in oral ulcer healing of CS-LS. Methods: Acidity was analyzed using a digital pH meter, density test was analyzed using a pycnometer, and the components were determined using gas chromatography-mass spectrometry (GC-MS). Eight concentrations of CS-LS (1%, 2%, 4%, 6%, 8%, 10%, 12%, and 14%) were tested on baby hamster kidney (BHK21) for the extract toxicity, carrageenan-induced rat paw edema for its anti-inflammatory properties, hot-plate test for its anti-nociceptive, and traumatized labial fornix incisive inferior for its oral ulcer healing. Results: The acidity of CS-LS was 2.296 and the density was 1.0102 g/mL. The major components analyzed were phenol (32.75%), 2-methoxy-phenol (17.45%), and furfural (13.09%). The CS-LS 100% and CS-LS 8% were the optimum concentrations for maintaining the BHK21 and increasing the number of fibroblasts in oral ulcer healing. The CS-LS 100% showed potent anti-nociceptive ability compared to other concentrations (P = 0.001), but not for the anti-inflammation properties. Conclusion: CS-LS is a promising natural herb for oral medicine, especially oral ulcer medicine.

Evaluation of in vivo anti-inflammatory activity of Ariflex tablet in comparison with diclofenac and aceclofenac tablet in carrageenan induced rat paw edema model

Background: Osteoarthritis is a major cause of pain and locomotor disability worldwide. Though various pharmacological, mechanical and surgical interventions are used, there is no known cure for OA. The present study was conducted to evaluate anti-inflammatory activity of Ariflex tablet (conceptualized and developed by Ari Healthcare Pvt. Ltd.) in comparison with diclofenac and aceclofenac tablet in carrageenan induced rat paw edema model.Methods: Wistar rats of either sex weighing 150-180 g were taken and divided into 4 groups with 6 animals in each group i.e. group 1 (control group), group 2 (diclofenac tablet), group 3 (aceclofenac tablet) and group 4 (ariflex tablet). The study drugs were orally administered with feeding needle, 30 minutes prior to carrageenan injection. After 30 min 1% w/v of 0.05 ml carrageenan was injected subcutaneously in the rat paw. The paw was marked with ink at the level of lateral malleolus and immersed in mercury up to lateral malleolus mark. The paw volume was measured plethysmographically after injection at 30 minutes, 1 hour, 2 hour, 3 hour, 4 hour and eventually at 5 hour.Results: All the test formulations possess statistically significant (p<0.05) anti-inflammatory activity as compared to control group. The maximum percentage inhibition for Ariflex tablet was 96.97% at the end of 5 hours. When compared to control group, statistically significant reduction of paw edema was observed. The anti-inflammatory activity of Ariflex tablet from 2 hours onwards is comparable to that of diclofenac tablet and aceclofenac tablet.Conclusions: Ariflex tablet possesses significant anti-inflammatory activity.

Inhibition of iNOS by Benzimidazole Derivatives: Synthesis, Docking, and Biological Evaluations

Background: Inducible nitric Oxide Synthase (iNOS) plays a key role in the progression of inflammatory diseases by accelerating the production of NO, which makes it an intriguing target to treat inflammation in complex diseases. Therefore, the search is on to develop molecules as selective iNOS inhibitors. Objective: The present work was aimed to design, synthesize and evaluate benzimidazole-coumarin coupled molecules as anti-iNOS agents through in silico and pharmacological studies. Methods: A critical study of literature reports on iNOS inhibitors led to the selection of a (un)substituted coumarin nucleus, 2-aminobenzimidazole, and a 4-atom linker as important structural components for iNOS inhibition. Two series of compounds (7-16 and 17-26) were designed and synthesized by coupling these components. The compounds were subjected to docking using iNOS (1QW4) and nNOS (1QW6) as targets. All compounds were evaluated for NO and iNOS inhibitory activities in vitro. The selected compound was finally evaluated for anti-inflammatory activity in vivo using the carrageenan-induced rat paw edema model. Results : All compounds showed moderate to good inhibition of NO and iNOS in vitro. Compound 12 was the most potent inhibitor of NO and iNOS. Hence, it was evaluated in vivo for toxicity and anti-inflammatory activity. It was found to be safe in acute toxicity studies, and effective in reducing the rat paw edema significantly. Its anti-inflammatory behaviour was similar to that of aminoguanidine, which is a selective iNOS inhibitor. Conclusion: The newly synthesized benzimidazole-coumarin hybrids may serve as potential leads for the development of novel anti-iNOS agents.

Oral and Topical Anti-Inflammatory and Antipyretic Potentialities of Araucaria bidiwillii Shoot Essential Oil and Its Nanoemulsion in Relation to Chemical Composition

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC–MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), β-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1β and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κβ levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer’s yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.

Anti-inflammatory, analgesic, and acute toxicity evaluation of Litchi chinensis seed extract in albino rat

Litchi chinensis is a edible fruits of soapberry family commonly known as lychee; is traditionally used for the treatment of inflammation, headache, and body pain. The present study investigated the toxicity, anti-inflammatory, and analgesic activity of the ethanolic crude extract of Litchi chinensis to support its traditional use in its folk medicine and to screen the phytochemical constituents. 70% ethanolic extract of seeds of Litchi chinensis (LCSE) was prepared and preliminary phytochemical screening was performed. Acute toxicity of LCSE was carried out based on OECD guidelines 423. In vivo anti-inflammatory and analgesic effect of the extract was evaluated using carrageenan-induced paw edema and hot plate methods in Wistar albino rat's model. Results revealed that LCSE contains phenols, tannins, flavonoids, saponins, steroids, and alkaloids. LD50 values were found to be higher than 5000 mg/kg body weight; no any sign of toxicity, behavior changes, moribund, and mortality were observed in LCSE treated animals. Oral administration of LCSE at the dose of 150, 300, and 600 mg/kg produced a significant (p<0.05) dose-dependent inhibition in carrageenan-induced rat paw edema and hot plate. These results suggest that LCSE is non-toxic, and shows potent anti-inflammatory and analgesic activities over Wistar albino rats. These finding demonstrate that lychee seed extract acts as a good therapeutic candidate for the safe anti-inflammatory agents.