Evaluation Of Anti-inflammatory Activity Research Articles

In-silico Studies, Synthesis, and Evaluation of Anti-inflammatory Activity of Novel Pyrimidine Scaffold

Background: The heterocyclic nucleus pyrimidine is present in several natural and synthetic chemical analogues and has proved its broad medicinal applications. Further, pyrimidine in the form of parent structure or basic skeleton of RNA and DNA is involved in controlling the immune functioning, and in turn, inflammatory reactions. Objective: The objective of the present study is to evaluate some novel pyrimidine analogues for antiinflammatory action. Methods: Molecular docking studies of Indomethacin and selected analogues were carried out with the COX-2 enzyme (PDB: 4ZOL). The synthesis of derivatives of 4-Phenyl-6-(phenylamino)pyrimidine-2-ol derivatives was begun by following Perkin condensation between substituted acetanilides and substituted aromatic aldehydes to yield an intermediate, which in turn produces the required nucleus for treatment with urea. All synthesized compounds were evaluated for in vivo and in vitro anti-inflammatory activity. Results: The docking interaction reflects a good dock score when compared with indomethacin, a potent Anti-inflammatory drug. In the majority of the compounds, pyrimidine was able to form hydrogen bonding while the rest of the part was involved in hydrophobic bonding. All compounds were synthesized in good yield and confirmed by physical and spectral studies. In vitro studies showed that compounds 5a and 5e were better at controlling inflammation than the conventional treatment Antipyrine, while in vivo data showed that compounds 5a, 5c, 5e, and 5h were better at controlling inflammation than the standard drug Antipyrine. Conclusion: The compound with more than one electron releasing group on the aniline moiety of pyrimidine yields a decent result in the synthetic and experimental studies, but the absence of an electron withdrawing group favours stronger anti-inflammatory activity on the target.

Synthesis of 1,3-substituted 1H-indazole derivatives and evaluation of anti-inflammatory activity in Sprague Dawley rats

Indazole is a very significant group of heterocyclics. Aim of the research was thus planned to synthesize novel derivatives of indazole and evaluate their anti-inflammatory activity. Novel compounds of indazole were first synthesized from reaction of 2-chlorobenzonitrile with phenylhydrazine in presence of catalyst potassium t-butoxide (t-BuOK) and the solvent diglyme. Synthesized derivatives of indazole were analyzed by 1H-NMR and MS spectroscopic techniques. All the synthesized derivatives of indazole were evaluated for their anti-inflammatory activity in Sprague Dawley rats by carrageenan-induced rat paw edema method. All the synthesized derivatives of indazole had shown very good activity in both docking and anti-inflammatory activity in rats in comparison to the standard etoricoxib. Compound 1a in a dose of 30 ​mg/kg body weight had shown most significant inhibition of edema as compared to toxic group and the inhibition was comparable to that of the standard drug, etoricoxib in a dose of 10 ​mg/kg body weight. A convenient means for the synthesis of derivatives of indazole was developed which may find applications in heterocyclic synthesis of derivatives of indazole. Compound 1a i.e., 3-(4-carboxyphenyl)amino-1-phenyl-1H-indazole had shown best anti-inflammatory activity amongst all the synthesized compounds.

Phytochemical characterization, anti-diarrhoeal, analgesic, anti-inflammatory activities and toxicity profile of Ananas comosus (L.) Merr (pineapple) leaf in albino rats

Ethnopharmacological relevanceAnanas comosus (pineapple) leaf is used in ethnomedicine to treat diarrhoea, inflammation, pain, bacterial infections and oedema. Aim of the studyThe aim of this study was to investigate the anti-diarrhoeal, anti-inflammatory and analgesic effects as well as the toxicity profile of the aqueous Ananas comosus leaf extract (AACLE) in rats. MethodsMethanol ACLE was subjected to gas chromatography-mass spectrometry (GC-MS) analysis. In the acute toxicity study, a single oral dose of up to 5000 mg/kg AACLE was administered. In the subacute toxicity study (28 days), rats in groups 2–4 received AACLE orally. The anti-diarrhoeal effect was studied using charcoal meal and castor oil-induced diarrhoea. Anti-inflammatory and analgesic tests were measured using egg albumin-induced paw oedema and acetic acid-induced writhing methods, respectively. For the subacute toxicity, anti-diarrhoeal, analgesic, and anti-inflammatory studies, AACLE was administered orally to rats at doses of 200, 400, and 600 mg/kg body weight. ResultsHexadecanoic acid methyl ester, 2-methoxy-4-vinylphenol, n-hexadecanoic acid and n-heptadecanol-1 were identified among other compounds with known pharmacological activities by GC-MS analysis. No deaths, behavioural changes, or signs of toxicity were observed in the acute toxicity study. Treatment with AACLE (28 days) decreased aspartate aminotransferase, alanine transaminase, total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while high-density lipoprotein cholesterol, glutathione, and catalase increased when compared with control (P < 0.05). Treatment with AACLE did not cause significant changes in haematological or renal function parameters. Treatment with AACLE inhibited gastrointestinal motility and castor oil-induced diarrhoea in rats. Treatment with AACLE resulted in a dose-dependent (200–600 mg/kg) significant (P < 0.05) anti-diarrhoeal, analgesic, and anti-inflammatory effect compared to standard drugs. ConclusionOur study revealed that ACLE is not toxic but contains bioactive compounds with anti-diarrhoeal, anti-inflammatory, antimicrobial, and hepatoprotective activity. AACLE has antidiarrhoeal, analgesic and anti-inflammatory activity in rats, which justifies its therapeutic use in traditional medicine.

Evaluation of anti-inflammatory activity of kaurenol: Experimental evaluation and mechanistic insights.

Kaurenol, a diterpene alcohol found in Copaifera langsdorffii Desf. (known as "copaiba"), is historically used in traditional medicine for inflammatory conditions. This study aims to comprehensively assess the potential anti-inflammatory and antinociceptive properties of kaurenol. To this end, the following experiments were conducted to evaluated toxicity: locomotor performance and acute toxicity; nociception: acetic acid-induced writhing and formalin-induced antinociception; and anti-inflammatory activity: carrageenan and dextran-induced paw edema at 10, 20, and 40 mg/kg, and measurement of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in macrophages at 1, 3, and 9 μg/ml. Kaurenol did not show significant locomotor changes, acute toxicity, and central analgesic activity in the first phase of formalin test at dosages tested. Kaurenol showed 53%, 64%, 64%, and 58% of inhibition in the acetic acid-induced writhing, second phase of formalin test, carrageenan and dextran-induced paw edema, respectively. The anti-inflammatory activity was associated with the regulation of NO release and probably with the regulation of mediators, such as serotonin and prostaglandin in vascular permeability, as well as by being associated with the regulation of IL-6 and IL-10. Kaurenol display anti-inflammatory activity but has no analgesic activity.

Evaluation of Anti-Inflammatory and Anti-Tubercular Activity of 4-Methyl-7-Substituted Coumarin Hybrids and Their Structure Activity Relationships.

Four sets of previously synthesized 4-methyl-7-substituted coumarin derivatives were screened for their in vitro anti-inflammatory and anti-tubercular activities. The anti-inflammatory potential of 3a-t, 5a-o, 6a-n, and 7a-f synthesized compounds was evaluated by an anti-denaturation assay using diclofenac sodium as the reference standard. Evaluation of the anti-tuberculous activity of the mentioned compounds was performed by the Resazurin test method against four different TB strains using rifampicin and isoniazid as reference drugs. Based on the anti-inflammatory results, compounds 3o, 5f, 6c, and 7d proved to be the most active compounds in their respective series. Additionally, compounds 3k-n, 5b-d, 6d-f, 6k, 7a, and 7f were found to be the most potent anti-tuberculous agents. In fact, most of the screened compounds exhibited promising activity profiles compared to the respective standard drugs. The structure-activity connections revealed a few intriguing aspects, indicating that the presence of electron-donating and nitrogen-rich fragments boost the anti-inflammatory effects of the examined compounds. However, the presence of electron-withdrawing substituents was required to boost the anti-tubercular activity of the evaluated compounds.

Molecular networking-guided isolation strategy of a new C-glycosyl flavone rotamer from Stellaria alsine and evaluation of anti-inflammatory and antioxidant activities.

Stellaria alsine has traditionally been used as both a famine relief food and an alternative medicine in East Asia. Modern pharmacological studies have revealed that S. alsine has various biological effects such as anticancer, anti-hepatoma, anti-inflammatory, and antioxidative effects. However, the anti-inflammatory properties of chemical constituents derived from this plant have not been studied well. To identify potential therapeutic candidate for treating inflammatory diseases such as inflammatory bowel disease (IBD). The distribution of chemical compounds was investigated by Global Natural Product Social (GNPS)-based molecular networking (MN) analysis using UPLC-Orbitrap tandem mass spectrometry. The anti-inflammatory and antioxidative effects of S. alsine extracts and fractions were evaluated by measuring interleukin (IL)-8 and reactive oxygen species (ROS) productions. The active EA layer of S. alsine showed the highest percentage of major compounds by feature-based molecular networking. The top candidate structures of EA fraction were rapidly annotated as flavone C- or O-glycosides via an advanced analysis tool, Network Annotation Propagation (NAP). With the GNPS molecular networking-guided isolation strategy, a new C-glycosyl flavone rotamer (1) was isolated. The structures of the major (1a) and minor (1b) rotational isomers were determined by extensive NMR analysis and MS/MS fragmentation. Finally, the anti-inflammatory activity of 1 was predicted by molecular docking simulations with IL-8 protein. These results suggested that the compound 1 is a potential therapeutic candidate for inflammatory bowel disease (IBD).

Evaluation of Anticancer and Anti-Inflammatory Activities of Some Synthetic Rearranged Abietanes.

Synthesis of the rearranged abietane diterpenes pygmaeocins C and D, viridoquinone, saprorthoquinone, and 1-deoxyviroxocine has been successfully achieved. The anticancer and anti-inflammatory activities of selected orthoquinonic compounds 5, 7, 13, and 19, as well as pygmaeocin C (17), were evaluated for the first time. The antitumor properties were assessed using three cancer cell lines: HT29 colon cancer cells, Hep G2 hepatocellular carcinoma cells, and B16-F10 murine melanoma cells. Compounds 5 and 13 showed the highest cytotoxicity in HT29 cells (IC50 = 6.69 ± 1.2 µg/mL and IC50 = 2.7 ± 0.8 µg/mL, respectively). Cytometric studies showed that this growth inhibition involved phase S cell cycle arrest and apoptosis induction, possibly through the activation of the intrinsic apoptotic pathway. Morphological apoptotic changes, including nuclear fragmentation and chromatin condensation, were also observed. Furthermore, the anti-inflammatory activity of these compounds was evaluated on the basis of their ability to inhibit nitric oxide production on the lipopolysaccharide activated RAW 264.7 macrophage cell line. Although all compounds showed high anti-inflammatory activity, with percentages between 40 and 100%, the highest anti-inflammatory potential was obtained by pygmaeocin B (5) (IC50NO = 33.0 ± 0.8 ng/mL). Our results suggest that due to their dual roles, this type of compound could represent a new strategy, contributing to the development of novel anticancer agents.

Synthesis and Evaluation of Amide Codrug of Ibuprofen and Amlodipine for Dual Inhibition of Inflammation and Hypertension

The codrugs approach showed as an effective strategy for targeting diseases synergistically, hence improving the quality of life of patients. The main goal is to address comorbid conditions of hypertension and osteoarthritic pain and inflammation in geriatric patients, eliminate the adverse gastrointestinal adverse effects of the drug, reducing dose with significant reduction of polypharmacy and improve patient compliance. The present study aimed to synthesize amide linked codrugs of Ibuprofen (nonsteroidal anti-inflammatory drug) and Amlodipine (Calcium channel Blocker), its biopharmaceutical study and evaluation of anti-inflammatory and antihypertensive activity. Codrug conjugates were synthesized by a one-pot amidation reaction of Amlodipine with Ibuprofen using DCC as coupling agent and DMAP as catalyst. The obtained compound Ibuprofen-Amlodipine amide linked codrug (IBAM) was characterized by determination of melting point, TLC, DSC, FT-IR, NMR, and mass spectroscopy. The solubility, partition coefficient, plasma protein binding and in vitro hydrolysis study in SGF and SIF were studied to determine biopharmaceutical properties.The anti-inflammatory and antihypertensive activity of synthesized compounds were tested in a carrageenan-induced rat paw oedema model and Fructose induced diabetic hypertensive model and it was discovered that the codrugs underwent significant hydrolysis in SIF (pH 7.4) and IBAM showed effective reduction in hypertension, inflammation in comparison to parent drug. Finally, it is concluded that the codrug approach could be successfully used in drug design and development for overcoming undesirable difficulties without losing the desired activities of the parent drugs.

Nanoemulsions (O/W) prepared from essential oil extracted from Melaleuca alternifolia: synthesis, characterization, stability and evaluation of anticancerous, anti-oxidant, anti-inflammatory and antidiabetic activities

Essential oil from Melaleuca alternifolia (also known as Tea tree essential oil, TTO) is used as traditional medicine and used as therapeutic in medicine, food and cosmetic sectors. However, this oil is highly unstable, volatile and prone to oxidation which limits its practical use. The objective of this study was synthesis of tea tree oil based O/W (oil/water) nanoemulsions (tea tree essential oil nanoemulsions, TNE) and evaluation of its biological potential. Physiological characterization was carried out using UV, fluorescent, and FT-IR techniques. Various biological activities such as anticancerous, antidiabetic and anti-inflammatory were also estimated. Pharmacokinetics study on TNE was carried out. Encapsulation efficiency of nanoemulsions was found to be 83%. Nanoemulsions were spherical in shape with globule size 308 nm, zeta potential −9.42 and polydispersity index was 0.31. Nanoemulsions were stable even after 50 days of storage at different temperatures. Anti-oxidant potential of TNE was conducted by various assays and IC50 were: Nitric oxide radical scavenging activity:225.1, DPPH radical scavenging activity:30.66, Iron chelating assay:38.73, and Iron reducing assay:39.36. Notable anticancer activity was observed with the percent cell viability of HeLa cells after treatment with 1, 2 and 5 µl of TNE was 82%, 41% and 24%, respectively. Antidiabetic study revealed that TNE inhibited -amylase in a dose-dependent manner, with 88% inhibition at its higher volume of 250 µl. Drug kinetic study revealed that nanoemulsions exhibited first-order model. Based on this, the possible role of M. alternifolia oil-based nanoemulsions in cosmetic, food, and pharma sectors has been discussed.

Synthesis of Tricyclic Pterolobirin H Analogue: Evaluation of Anticancer and Anti-Inflammatory Activities and Molecular Docking Investigations.

Pterolobirin H (3), a cassane diterpene isolated from the roots of Pterolobium macropterum, exhibits important anti-inflammatory and anticancer properties. However, its relatively complex tetracyclic structure makes it difficult to obtain by chemical synthesis, thus limiting the studies of its biological activities. Therefore, we present here a short route to obtain a rational simplification of pterolobirin H (3) and some intermediates. The anti-inflammatory activity of these compounds was assayed in LPS-stimulated RAW 264.7 macrophages. All compounds showed potent inhibition of NO production, with percentages between 54 to 100% at sub-cytotoxic concentrations. The highest anti-inflammatory effect was shown for compounds 15 and 16. The simplified analog 16 revealed potential NO inhibition properties, being 2.34 higher than that of natural cassane pterolobirin H (3). On the other hand, hydroxyphenol 15 was also demonstrated to be the strongest NO inhibitor in RAW 264.7 macrophages (IC50 NO = 0.62 ± 0.21 μg/mL), with an IC50NO value 28.3 times lower than that of pterolobirin H (3). Moreover, the anticancer potential of these compounds was evaluated in three cancer cell lines: HT29 colon cancer cells, Hep-G2 hepatoma cells, and B16-F10 murine melanoma cells. Intermediate 15 was the most active against all the selected tumor cell lines. Compound 15 revealed the highest cytotoxic effect with the lowest IC50 value (IC50 = 2.45 ± 0.29 μg/mL in HT29 cells) and displayed an important apoptotic effect through an extrinsic pathway, as evidenced in the flow cytometry analysis. Furthermore, the Hoechst staining assay showed that analog 15 triggered morphological changes, including nuclear fragmentation and chromatin condensation, in treated HT29 cells. Finally, the in silico studies demonstrated that cassane analogs exhibit promising binding affinities and docking performance with iNOS and caspase 8, which confirms the obtained experimental results.

Discovery of Highly Selective and Orally Bioavailable PI3Kδ Inhibitors with Anti-Inflammatory Activity for Treatment of Acute Lung Injury.

PI3Kδ is a promising target for the treatment of inflammatory disease; however, the application of PI3Kδ inhibitors in acute respiratory inflammatory diseases is rarely investigated. In this study, through scaffold hopping design, we report a new series of 1H-pyrazolo[3,4-d]pyrimidin-4-amine-tethered 3-methyl-1-aryl-1H-indazoles as highly selective and potent PI3Kδ inhibitors with significant anti-inflammatory activities for treatment of acute lung injury (ALI). There were 29 compounds designed, prepared, and subjected to PI3Kδ inhibitory activity evaluation and anti-inflammatory activity evaluation in macrophages. (S)-29 was identified as a candidate with high PI3Kδ inhibitory activity, isoform selectivity, and high oral bioavailability. The in vivo administration of (S)-29 at 10 mg/kg dosage could significantly ameliorate histopathological changes and attenuate lung inflammation in lung tissues of LPS-challenged mice. Molecular docking demonstrated the success of scaffold hopping design. Overall, (S)-29 is a potent PI3Kδ inhibitor which might be a promising candidate for the treatment of ALI.

Chemical constituents, antibacterial and anti-inflammatory properties of Pyrus calleryana Dcne. essential oil

Pyrus calleryana, commonly known as bean pear, is a medicinal and edible plant, especially its fruit is utilized in traditional Chinese medicine and processed into fruit wine. Essential oils have proven to be potent antibacterial and anti-inflammatory agents. Hence, this study firstly investigated the chemical components, antibacterial and anti-inflammatory properties of P. calleryana fruit essential oil (EO). According to GC-FID/MS analysis, P. calleryana fruit EO was composed mainly of linalool (20.9 %), α-terpineol (14.4 %), E-nerolidol (11.7 %), trans-3-hexenol (9.4 %), n-hexadecanoic acid (7.4 %), geraniol (6.9 %), and trans-2-hexenol (4.8 %). For antibacterial action against Gram-negative bacteria, it revealed a strong antibacterial effect against Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris with minimal inhibitory concentration (MIC) (19.53–312.50 µg/mL) and minimal bactericidal concentration (MBC) (39.06–625.00 µg/mL) values. In the evaluation of anti-inflammatory activity using Gram-negative bacteria lipopolysaccharide (LPS)-induced RAW264.7 macrophages, P. calleryana fruit EO dramatically suppressed pro-inflammatory mediators (NO and PGE2) and cytokines (TNF-α, IL-1β, and IL-6) over-secretion without cytotoxicity. Meanwhile, it decreased LPS-stimulated mRNA expression of pro-inflammatory cytokines and mRNA and protein expression of iNOS and COX-2. Furthermore, it inhibited LPS-induced ROS generation, MAPKs phosphorylation, and NF-κB nuclear translocation. Hence, P. calleryana fruit EO has bifunctional antibacterial and anti-inflammatory activities and may be a promising therapeutics for infectious diseases with great potential for utilization in the fields of functional foods and pharmaceuticals.

Evaluation of anti-inflammatory activity and identification of a monoterpenoidhydroxylactone (-)-loliolide from Tribulus terrestris L.: In-vivo and In-silico Approaches

The present study aimed to determine the anti-inflammatory effects of Tribulusterrestris L (aerial parts) and to identify the anti-inflammatory agents from active extracts and fractions together with in silico prediction of their mechanism of action, pharmacokinetics, and toxicity profile. The anti-inflammatory activity was evaluated for Dichloromethane, methanol, and its fractions (chloroform, ethyl acetate, n-butanol by Carrageenan induced rat paw edema. The phytoconstituents of the anti-inflammatory active fraction (chloroform fraction of methanol extract) was identified using Thermo Scientific TM DFS high-resolution GC-MS. The GC-MS analysis revealed 13 compounds from which (-)-loliolide was the most abundant compound by peak area. It was docked, using Autodock 4.0 onto three Key enzymes involved in the inflammatory cascade (Cyclooxygenase (COX-1 &amp;2) and 5-lipooxygenase (5-LOX)). It displayed binding energies; -6.98 kcal/mole (COX-1) compared to -6.83kcal/mole for standard, -6.64 kcal/mole (COX-2) compared to -6.88 kcal/mole for standard and -5.25 kcal/mole (5-LOX) compared to -6.89 kcal/mole for standard. Toxicity risks, drug likeliness, and pharmacokinetic properties were studied by different online open-source programs. Good binding energy, drug-likeness, and efficient pharmacokinetic parameters of (-)-loliolide suggest it as a good inhibitor, however, further research is needed.

Phytochemical screening and evaluation of antioxidant, anti-inflammatory, antimicrobial, and membrane-stabilizing activities of different fractional extracts of Grewia nervosa (Lour.) Panigrahi

BackgroundGrewia nervosa (Lour.) Panigrahi, a medicinal herb native to the steep forested region of Bangladesh, is utilized as a treatment for a variety of diseases or conditions, including dysmenorrhea, paratyphoid, bone fractures, jaundice, kidney stones, dyspepsia, heat stroke, cold, fever, diarrhea, hepatitis B, ingestion, and anthelmintic medication. This research aims to investigate the phyto-pharmacological qualities of this herb. MethodsThe herb was extracted using absolute ethanol followed by fractionation with n-hexane and chloroform. Following an initial investigation of phytochemicals, antioxidant, anti-inflammatory, antimicrobial, and membrane stabilization activities were assessed using the DPPH, egg albumin model, disc diffusion method, and erythrocyte hemolysis model, respectively. ResultsA preliminary phytochemical report suggests that G. nervosa contains reducing sugars, gums, amides, alkaloids, glycosides, flavonoids, steroids, tannins, flavonoids, and saponins. In a concentration-dependent approach, its fractional extracts displayed promising antioxidant, anti-inflammatory, antimicrobial, and membrane-stabilizing activity. It was seen that all fractions had a statistically significant capacity to prevent RBCs from hemolyzing, which suggests a potent membrane stabilizing function in-vitro. ConclusionTaken together, G. nervosa possesses important secondary metabolites and exhibits in-vitro antioxidant, anti-inflammatory, antimicrobial, and membrane stabilizing capacities. This endorses the conventional usage of G. nervosa, although additional study is needed on this potentially beneficial plant.

Sesquiterpenoids From the Leaves of Datura metel L.

In the course of chemical investigations of Datura metel L., a new sesquiterpenoid, dmetelin J (1) was isolated from the leaves, along with the 4 known compounds apocynol A (2), blumenol B (3), megastigmane (4), and ( + )-dehydrovomifoliol (5). Structure elucidation was performed by spectroscopic techniques, including 1- and 2-dimensional NMR spectroscopy and HRESIMS. Compounds 2, 3, and 5 were isolated from the Solanaceae for the first time. All isolated compounds were subjected to anti-inflammatory activity evaluation.

Evaluation of Antibacterial, Antiinflammatory Activities and GC-MS Profiling of Millingtonia hortensis Linn. Leaf and Stem Bark Extracts

The present study aimed to evaluate the antibacterial and antiinflammatory activity of Millingtonia hortensis Linn. leaf and stem bark extracts and identify the bioactive compounds by GC-MS analysis. This study determined the antibacterial activities using the agar disc diffusion technique. The results revealed the ethanol extract of M. hortensis Linn. stem bark was the highest potential inhibitory against gram-positive bacteria (Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Bacillus cereus). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were performed. The highest inhibitory effect on Enterococcus faecalis, Enterococcus faecium, and Bacillus cereus with MIC and MBC values of 500 mg/ml. This investigation also indicated the M. hortensis Linn. leaf and stem bark extracts had no cytotoxicity against macrophage RAW264.7 cell line and strong antiinflammatory properties. The results of antiinflammatory activity showed that the ethanol extract of M. hortensis Linn. leaf and stem bark extracts were the most effective in inhibiting nitric oxide secretion with IC50 values of 0.25 and 0.41 mg/ml, respectively. GC-MS profiling analyzed the ethanol extract of M. hortensis Linn. stem bark, which had the highest antibacterial and antiinflammatory activity. There were three bioactive substances: 9,12-Octadecadienoic acid, ethyl ester, trans-13-Octadecenoic acid, and oleic acid. The natural functions were antiinflammatory, dermatitigenicity, antioxidants, and antifungal activities. Therefore, the results suggest that the ethanol extract of M. hortensis Linn. stem bark had the highest potential usefulness for treating gram-positive bacteria infection and inflammation-induced ailment. This research will be helpful toward the better acceptability of this extract in therapeutics.

Pharmacognostic profiles, evaluation of analgesic, anti-inflammatory and anticonvulsant activities of Newbouldia laevis (P. Beauv.) Seem. ex Bureau leaf and root extracts in Wistar rats

Ethnopharmacological relevanceNewbouldia laevis is a popular medicinal plant whose leaves and roots are used in Nigeria as ethnomedicinal prescriptions for pain, inflammation, convulsion, and epilepsy. These claims have not been scientifically verified prior to this study. Aim of the studyTo determine pharmacognostic profiles of the leaves and roots and evaluate the analgesic, anti-inflammatory, and anticonvulsant activities of methanol leaf and root extracts in Wistar rats. Material and methodsThe pharmacognostic profiles of the leaves and roots were determined using standard procedures to serve as fingerprints for the plant. The methanol leaf and root extracts of Newbouldia laevis were tested for acute toxicity using the OECD’s up and down method at the maximum dose of 2000 mg/kg (orally) in Wistar rats. Analgesic studies were carried out in acetic acid-induced writhing in rats and tail immersion. The anti-inflammatory activity of the extracts was evaluated using carrageenan-induced rat paw-oedema and formalin-induced inflammation in rats’ mode. The anticonvulsant activity was determined using strychnine-induced, pentylenetetrazol-induced, and maximal electroshock-induced rat convulsion models. For each of these studies, the extracts doses of 100, 200 and 400 mg/kg were administered to the rats following the oral route. ResultsThe pharmacognostic profiles showed that the leaves possessed deep-sunken paracytic stomata (5-8-16 mm2; adaxial, 8-11-24 mm2; abaxial epidermis), vein islets (2-4-10 mm2; adaxial), vein terminations (10-14-18 mm2; adaxial), palisade ratio (8.3-12.5-16.4 mm2; adaxial, 2.5-6.8-12.2 mm2; adaxial), covering unicellular trichome (8–14; adaxial), spheroidal calcium oxalate crystals (3–5 μm), and oval-shaped striated starch grain with no hilum (0.5–4.3 μm). The transverse section of the leaf showed the presence of spongy and palisade parenchyma as well as a closed vascular bundle. The root powder showed the presence of brachy sclereid, fibers without lumen, and lignin. All physicochemical parameters fall within the acceptable limits, phytochemical contents showed mainly glycosides, alkaloids, and steroids while acute oral toxicity (LD50) of the parts for 14 days did not produce any toxicity signs or mortality in the rats. The extracts produced dose-dependent (100–400 mg/kg) analgesic involving opioid receptors, anti-inflammatory, and anticonvulsant activities in the rats which were significant (p ≤ 0.05) when compared to the standard drugs. The leaf extract possessed the most potent analgesic and anti-inflammatory effects in the rats, while the most anticonvulsant effects were observed in rats treated with the leaf extract. Both extracts showed elevated levels of protection against strychnine-induced, pentylenetetrazol-induced, and maximal electroshock-induced seizure in rats. ConclusionOur study revealed some pharmacognostic profiles of Newbouldia laevis leaves and roots that are vital for its identification from closely related species often used for adulteration in traditional medicine. The study further showed that the leaf and root extracts of the plant possessed dose-dependent analgesics, anti-inflammatory and anti-convulsant activities in rats, thus, justifying its use for the treatment of these diseases in Nigerian traditional medicine. There is a need to further study its mechanisms of action towards drug discovery.

Synthesis and anti-inflammatory activity evaluation of NO-releasing furoxan/1,2,4-triazole hybrid derivatives

An efficient synthesis method was developed for furoxan/1,2,4-triazole hybrids 5a–k from methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1 through two-steps reaction including hydrolyzation and esterification. All of the furoxan/1,2,4-triazole hybrid derivatives were characterized by spectroscopy. On the other hand, the influence of newly synthesized multi-substituted 1,2,4-triazoles on the exogenous NO release ability, in vitro and in vivo anti-inflammatory activity, and in silico predictions were experimentally evaluated. Based on the exogenous NO release ability study and SAR studies of in vitro anti-inflammatory activity, all of compounds 5a–k exhibited slightly NO release ability and potential anti-inflammatory activity on LPS-induced RAW264.7 cells (IC50 = 5.74–15.3 μM) compared to Celecoxib (IC50 = 16.5 μM) and Indomethacin (IC50 = 56.8 μM). Furthermore, compounds 5a–k were also subjected to in vitro COX-1/COX-2 inhibition assays. Particularly, compound 5f exhibited extraordinary COX-2 inhibition (IC50 = 0.0455 μM) and selectivity (SI = 209). In addition, compound 5f was also examined in vivo pro-inflammatory cytokine productions and gastric safety and possessed the better inhibition of cytokine and safety compared with Indomethacin at the same concentration. Through the molecular modeling and in silico physicochemical and pharmacokinetic properties prediction, compound 5f was stabilized in COX-2 active binding site and possessed the fundamental strong H-bond interaction with Arg499 to form the significant physicochemical and pharmacological properties as a candidate drug. Following the in vitro, in vivo, and in silico study results, compound 5f demonstrated to be a potential anti-inflammatory agent and had comparable effects with Celecoxib.

Synthesis and biological evaluation of resveratrol amide derivatives as selective COX-2 inhibitors

Selective COX-2 inhibitors have been considered to be reliable alternatives to tNSAIDs, but most of them were withdrawn from the market due to their risk of heart attack and stroke. Therefore, it is urgent to develop a new type of selective COX-2 inhibitor with high efficiency and low toxicity. Inspired by the cardiovascular protection, and anti-inflammatory activity of resveratrol, we synthesized 38 resveratrol amide derivatives and evaluated their COX-1/COX-2 inhibitory activities. Compounds 8a, 6a, 8c and 13c showed important inhibitory activity against COX-2 (IC50 = 0.42–2.54 μM) with definite selectivity (SI = 48–83). Molecular docking study demonstrated that these compounds partially entered the 2°-pocket of the COX-2 active site and interacted with the amino acid residues responsible for the COX-2 selectivity, which was in a similar orientation and binding interactions to rofecoxib. Further anti-inflammatory activity evaluation in vivo of these active compounds revealed that compound 8a showed no gastric ulcer toxicity, and displayed evident anti-inflammatory effect (45.95% inhibition of edema) with three oral doses of 50 mg/kg, which is worthy of further study. Moreover, compounds 6a and 8c also exhibited superior gastric safety profiles compared to the reference drugs celecoxib and indomethacin.

Synthesis and anti-inflammatory activity evaluation of benzoxazolederivatives as new myeloid differentiation protein 2 inhibitors.

Myeloid differentiation protein 2 (MD2), a key TLR4adaptor protein for sensing LPS, plays animportant role ininflammatoryprocessand has been identified as a promising target for the treatment of avarietyof inflammatory diseases. In our study, aseries of benzoxazolone derivatives weresynthesized, characterized and tested for anti-inflammatory activity in vitro. The compounds 3c, 3dand 3gdemonstrated the greatestanti-inflammatory activityagainst IL-6 with IC50values of 10.14±0.08, 5.43±0.51 and 5.09±0.88µM,respectively. Furthermore, the bis-ANS displacement assay revealed that these compounds competitively inhibited the binding between the probe bis-ANS and the MD2 protein. The most active compound 3g, revealed a directly bind withMD2 proteinvia Arg90binding and a dissociation constant value of 1.52×10-6mol·L-1as determined by the biological layer interference (BLI) assay. Ourfinding suggestedthat compounds3gcould bea promising lead compound as MD2 inhibitor for further anti-inflammatory agent development.