Development Of Novel Anti-inflammatory Agents Research Articles

Anti-inflammatory Activity and Computational Biology Study of Indole/Pyrimidine Hybrids

Abstract: This research paper embarks on an interdisciplinary exploration encompassing synthetic chemistry, pharmacology, and computational biology. The development of novel anti-inflammatory agents is an imperative endeavor within pharmaceutical research. Pyrimidines and thienopyrimidines are class of heterocyclic compounds that have gained prominence for their diverse pharmacological properties, including potential anti-inflammatory effects. When augmented with an indole moiety, these compounds exhibit structural diversity that can profoundly influence their biological activities. The integration of computational biology specifically molecular docking, plays a crucial role in predicting and understanding the binding interactions between these compounds and select protein targets associated with inflammatory pathways. This computational approach expedites the screening of potential drug candidates and elucidates the molecular underpinnings of their anti-inflammatory actions. Pyrimidine and thienopyrimidines tethering indole scaffold were obtained according to our reported methods. Subsequently, in vivo evaluation of anti-inflammatory is indispensable to gauge the anti-inflammatory potential of these compounds and establish structure-activity relationships. The experimental and computational biology studies of the target indole-pyrimidines hybrids revealed that these compounds can serve as anti-inflammatory agents. This paper can potentially open new avenues for therapeutic strategies against inflammation-associated disorders. The synergy of synthetic innovation, pharmacological evaluation, and computational insights offers a holistic approach to advance our understanding of pyrimidines with an indole moiety as potential agents for mitigating inflammation.

The synthetic approach of benzimidazole derivatives as anti-inflammatory agents

Anti-inflammatory drugs are a ubiquitous class of analgesics used by millions of people worldwide. Owing to the widespread and prolonged use of Anti-inflammatory drugs, chronic and acute toxicities have been reported in many human physiological systems. As a result, new anti-inflammatory drugs have been created recently, and several of them are in advanced phases of clinical studies. Chemists have been quite interested in heterocyclic compounds because of how similar they are to various biological precursors. One such heterocycle is benzimidazole and the most recent advancements of anti-inflammatory agents bearing benzimidazole have been emphasized in the current review. The review focuses on the synthetic route and the most promising benzimidazole derivative as an anti-inflammatory agent. The lead compound according to the literature will aid in the design and development of novel anti-inflammatory agents that target a diversity of factors contributing to inflammation.

Natural pentacyclic triterpenoid as allosteric modulators of human 5-lipoxygenase with potential anti-inflammatory activity

This study explored new methods to inhibit human 5-lipoxygenase (5-hLOX) by analyzing natural terpenes that share structural similarities with acetoxyboswellic acid (AKBA). Enzymatic assays were used to evaluate the terpene’s ability to inhibit the enzyme, potentially providing anti-inflammatory benefits. Our research focused on how certain types of triterpenes can inhibit 5-hLOX allosterically via a newly discovered allosteric site identified by enzyme crystallization. To determine whether natural boswellic acid analogs mimicked the allosteric known inhibitor AKBA, we combined 5-hLOX inhibition with in silico modeling. Our research has discovered that certain amino acids, specifically Arg 138, Arg 101, Arg 68, and Gln129, located in the allosteric 5-hLOX pocket, play a critical role in stabilizing glycyrrhetinic isomers. These amino acids form hydrogen bonds and hydrophobic interactions that contribute to the inhibitory potency of boswellic acid derivatives. We have found that α and β glycyrrhetinic acid isomers, carbenoxolone, and to a minor extent, prednisolone, have a potent inhibitory effect against 5-hLOX with IC50 values of 8.64, 3.94, 52.98, and 291.20 µM, respectively. These values are in line with our calculated in silico allosteric site binding energy estimations. In contrast, other steroidal or non-steroidal anti-inflammatory agents exhibited inhibitory potencies larger than 500 μM. However, the specific pharmacodynamic mechanisms are currently unknown. We propose that AKBA analogs may lead to the future development of novel anti-inflammatory agents. Communicated by Ramaswamy H. Sarma

New Monoterpene Glycoside Paeoniflorin Derivatives as NO and IL-1β Inhibitors: Synthesis and Biological Evaluation.

Several monoterpene glycoside compounds were extracted from Paeonia lactiflora Pall. Among them, paeoniflorin, a water-soluble monoterpene glycoside found in the root of Paeonia lactiflora Pall, exhibits excellent antioxidant pharmacological functions. Initially, Sc(CF3SO3)3 was employed as the catalyst for paeoniflorin's dehydration and rearrangement reactions with alcohols. Subsequently, structural modifications were performed on paeoniflorin through a series of responses, including acetylation, deacetylation, and debenzoylation, ultimately yielding 46 monoterpene glycoside derivatives. The potential inhibitory effects on the pro-inflammatory mediators interleukin-1 beta (IL-1β) and nitric oxide (NO) were assessed in vitro. The results revealed that compounds 29 and 31 demonstrated notable inhibition of NO production, while eight derivatives (3, 8, 18, 20, 21, 29, 34, and 40) displayed substantial inhibitory effects on the secretion of IL-1β. Computational research was also undertaken to investigate the binding affinity of the ligands with the target proteins. Interactions between the proteins and substrates were elucidated, and corresponding binding energies were calculated accordingly. The findings of this study could provide valuable insights into the design and development of novel anti-inflammatory agents with enhanced pharmacological properties.

In vitro and in silico studies on novel N-substituted-3,5-diaryl-pyrazoline derivatives as COX-2 inhibitors and anti-inflammatory agents

The presence of a reactive α,β-unsaturated keto group along with substituted aryl ring improves biological profile of pyrazoline nucleus. Considering this fact a study was planned to synthesize novel pyrazoline derivatives incorporated with chalcone backbone and their evaluation as COX-2 inhibitors and anti-inflammatory agents. Bovine serum albumin denaturation assay was used to measure in vitro anti-inflammatory activity. Molecular docking study was performed using Schrödinger-Maestro 9.0 molecular docking software and cyclooxygenase-2 (COX-II) receptor PDB ID: 4-COX. Some of the synthesized compounds showed remarkable anti-inflammatory potential. The compound (E)-3-(4-hydroxyphenyl)-1-(3-(4-hydroxyphenyl)-5-phenyl-4,5-dihydropyrazol-1-yl)prop-2-en-1-one 6d was found to be the most potent anti-inflammatory agents with 69.88% inhibition of protein denaturation. The outcome of docking study also supported results of in vitro anti-inflammatory activity and docking score for compound 6d was found to be –6.70379 which was comparable to the co-crystallized ligand. The results reveal that the synthesized compound can serve as potential lead for the development of novel anti-inflammatory agents.

Interleukin-6 inhibitory effect of natural product naringenin compared to a synthesised monoclonal antibody against life-threatening COVID-19.

Coronavirus Disease 2019 (COVID-19) has become a global pandemic in 2020 with high patient mortality due to acute respiratory distress syndrome which is possibly induced by a Cytokine release syndrome and more specifically through an interleukin-6 (IL-6) booster. Currently, IL-6/IL-6R inhibitors indicated an effective function in reducing the inflammatory markers in severe COVID-19 patients. In this comprehensively narrative review, we searched online academic databases including (Google Scholar, Web of Science, and Pub Med), the relevant literature was extracted from the databases by using search terms of COVID-19, IL-6, and IL6 inhibitor as free-text words and also with the combination with OR/AND to summarise the latest discoveries on the inhibitors of IL-6 and its receptor's especially focussing on the role of natural product, Naringin (NAR) as a flavonoid found in citrus fruits, with considerable anti-inflammatory and antiviral properties in COVID-19 treatments. Our data Therefore in comparison with other synthetic monoclonal antibodies NAR may provide a good qualification for the development of novel anti-inflammatory agents, especially against Covid 19 based on recent studies.

Synthesis and cytotoxic activity of ethyl ferulate derivatives as potent anti-inflammatory agents

While a range of pharmacological agents are currently used to alleviate inflammation, the clinical administration of many of these anti-inflammatory drugs is associated with high rates of adverse side effects that make them poorly suited to long-term use. Therefore, there is a critical need for the development of novel anti-inflammatory agents. Natural compounds and derivatives like ethyl ferulate have risen to prominence as a foundation for many drug discovery efforts owing to their structural diversity and wide-ranging biological activities. In the present study, 24 ethyl ferulate derivatives were synthesized. Their anti-inflammatory activity was evaluated in vitro using RAW264.7 cells and CCK-8, ELISA, and Western blotting assays. These analyses revealed that most of the synthesized compounds exhibited moderate to high anti-inflammatory activities. In particular, c10 and c23 exerted more pronounced activity than ethyl ferulate or dexamethasone with respect to the suppression of tumour necrosis factor-α production by RAW264.7 cells through the targeting of the NF-κB and MAPK signalling pathways, suggesting that these compounds warrant further investigation.

Novel alantolactone derivative AL-04 exhibits potential anti-inflammatory activity via modulation of iNOS, COX-2 and NF-κB

Natural compounds and their synthesized analogues continue to be valuable sources in the discovery and development of novel anti-inflammatory agents. AL-04 is a thiol analogue derived from a natural sesquiterpene alantolactone, that demonstrated potential anti-inflammatory activity in vitro in comparison to its parent compound. However, the anti-inflammatory mechanism of action of AL-04 has not been elucidated. In this context, we investigated the signaling pathway that primarily mediate the anti-inflammatory activity of AL-04 and its effect on principal inflammatory mediators including iNOS, COX-2 and ROS. Furthermore, the anti-inflammatory activity was investigated in vivo in carrageenan induced paw oedema model in addition to the exploration of anti-nociceptive activity and acute toxicity. The results suggested that treatment with AL-04 significantly decreased the LPS-induced upregulation of pro-inflammatory cytokines and mediators in addition to the downregulated transcription of TNF-α and IL-6 in RAW 264.7 cell line. Furthermore, mRNA and the protein expression of COX-2 and iNOS were also significantly attenuated with AL-04 at a concentration of 10 µM. Western blot studies further suggested that AL-04 downregulated LPS-stimulated NF-κB p65 expression. In addition to this the anti-inflammatory activity of AL-04 was demonstrated in carrageenan induced paw oedema model with significant inhibition of oedema in a dose-dependent manner. The anti-inflammatory activity of AL-04 was further demonstrated in balb/c mice by inhibition of leukocyte migration and vascular permeability. Besides, AL-04 also inhibited thermally and chemically induced pain in tail-flick and acetic acid induced writing assays respectively in balb/c mice suggesting the analgesic potential of the compound. Acute toxicity studies further suggested the appreciable safety of AL-04 at high dose of 2000 mg/kg with no indications of toxicity or changes in biochemical and haematological parameters. Overall, the study insinuates the anti-inflammatory potential of AL-04 and paves way for further exploration of the compound as a safer therapeutic anti-inflammatory agent.

Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives.

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC50 of 5.84 µM, as compared to indomethacin (IC50 = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 21/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)Å3. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.

Investigation of indole functionalized pyrazoles and oxadiazoles as anti-inflammatory agents: Synthesis, in-vivo, in-vitro and in-silico analysis

There are several potential side and adverse effects are found to be associated with the anti-inflammatory drugs in clinical practice. The long-term use of these clinical agents highly unsafe. It encouraged the development of novel heterocyclic compounds with potential anti-inflammatory activity and low to no toxicity. In present investigation, a total of 12 indole functionalized pyrazole and oxadiazole derivatives were designed, synthesized and evaluated for the in-vivo anti-inflammatory and analgesic potential. These compounds displayed comparable anti-inflammatory and analgesic potential to the reference drugs. Finally, molecular docking analysis was performed considering different anti-inflammatory targets to determine the mechanistic target of the designed molecules. Detailed analysis suggested that the molecules inhibit COX-2, preferably over other anti-inflammatory targets. The results suggested that two compounds (15c and 15f) were found promising candidates for the development of novel anti-inflammatory agents.

Investigations of adsorption behavior and anti-cancer activity of curcumin on pure and platinum-functionalized B12N12 nanocages

Recently boron nitride (BN) nanoparticles have been considered as good carrier candidates in drug delivery systems. Herein, the loading of curcumin (CUR) in different possible states onto a platinum functionalized B12N12 nanocage was studied to improve their solubility and stability using density functional theory (DFT) and time-dependent density functional theory (TDDFT) models by B3LYP and B3PW91 functionals. It was found that the Pt atom in complex I can be strongly bound to B12N12 surface through the B---Pt---N coordination bond or B-Pt-N covalent bond compared to complexes II and III. We investigate the adsorption of CUR onto Pt-B12N12 in gas and solvent (water) phases. IR spectra and UV absorption were computed and investigated in order to identify the most significant alteration that take place as a consequence of interactions between the CUR and Pt-B12N12 nanocage. The decorated Pt on the B12N12 nanocage improves the adsorption of CUR with larger binding energy for both functionals. The strong binding of CUR with Pt-B12N12 can happen by larger charge transfer from the CUR to the cage, which leads to a substantial increase in dipole moment and energy gap change. The study of molecular docking indicates that CUR through its β-diketo group adsorbed on Pt and B atoms of the Pt-B12N12 nanocage and showed the best binding affinity and inhibition potential of tyrosine regulated kinase 2 (DYRK2) and human epidermal growth factor receptor 2 (HER2) as compared with the pure B12N12 nanocage. The results of molecular docking and in silico analysis of absorption, distribution, metabolism, excretion, and toxicity revealed that the chosen complexes agree with the Lipinski Rule and have appropriate pharmacokinetic features which could be used as templates for the development of novel anti-inflammatory agents with substantial anticancer activity.

Structural Optimization of Caffeoyl Salicylate Scaffold as NO Production Inhibitors.

Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.

Evaluation of anti-inflammatory activity of Jasminum sessiliflorum extracts

Medicinal plants are important resources for the development of novel anti-inflammatory agents. Synthetic anti-inflammatory drugs have several adverse effects. Medicinal plants have numerous that are safer well as better substitutes for the prevention and management of various diseases and disorders. The and ethyl acetate extracts of Jasminum were evaluated for their potential as anti-inflammatory agents in by inducing paw edema in rats using . The anti-inflammatory activity of the reference drug was compared with the extracts of Jasminum . The extracts on screening indicated the presence of such as , , , alkaloids, and . The study established significant anti-inflammatory nature of the Jasminum extracts in a manner which is dose-dependent. The results indicate that both the extracts of Jasminum possess anti-inflammatory activity of significance and can be used in the development for novel anti-inflammatory moieties.

Evaluation of Anti-inflammatory Activity of Crinum scillifolium Extracts in Wistar Rats

Aim of study: Inflammation was associated with many diseases in humans. Crinum species have a considerable medicinal reputation as potent folkloric remedies. The main objective of the study was to evaluate the anti-inflammatory activity of aqueous and hydroethanolic extracts of Crinum scillifolium bulbs in in vivo models. Materials and methods: The anti-inflammatory effect of Crinum scillifolium extracts was also evaluated in carrageenan-induced paw edema models and C-reactive protein (CRP) levels was measured. Two doses 100 and 200 mg/kg body weight for each extract, were tested. The results obtained were compared with those of the standard drug (Diclofenac at 25 mg/kg body weight) and those of the control (normal saline). Results: The results showed a highly significant decrease in the edema size (p < 0.01) and significant decrease in CRP values (p < 0.01) compared to control group when the animals were treated with diclofenac at 25 mg/kg, and 200 mg/kg of aqueous and hydroethanolic extracts. Conclusion: The study suggests that the extracts possess enough potential to reduce inflammation on rat model and directs the importance of further research and development of novel anti-inflammatory agents.

IN VITRO ANTI-INFLAMMATORY ACTIVITY OF THE COMPONENTS OF AMOMUM TSAO-KO IN MURINE MACROPHAGE RAW 264.7 CELLS

Background: Plants still remain the prime source of drugs for the treatment of inflammation and can provide leads for the development of novel anti-inflammatory agents. &#x0D; Material and methods: An in vitro bioassay guide revealed that the 80% ethanol (EtOH) extract of the whole plant, Amomum tsao-ko (Zingiberaceae), displayed anti-inflammatory activity after assessing its effects on murine macrophage RAW 264.7 cells. &#x0D; Result: Phytochemical study of the 80% EtOH extract of Amomum tsao-ko led to the isolation of eight compounds: 4-hydroxy-3-methoxy-benzoic acid (1), meso-hannokinol (2), (+)-hannokinol (3), coumaric acid (4), 4-hydroxy-benzoic acid (5), (+)-epicatechin (6), (-)-catechin (7), and myrciaphenone A (8). The results indicated that two of the isolated components, (+)-epicatechin (6) and (-)-catechin (7), inhibited the production of nitric oxide (NO) significantly in lipopolysaccharide treated RAW 264.7 cells. &#x0D; Conclusion: LPS-induced interleukin tumor necrosis factor-alpha (TNF-), IL-1β and IL-10 production was also decreased in a dose-dependent manner. In addition, western blot analysis revealed that (+)-epicatechin (6) and (-)-catechin (7) reduced the expression of inducible nitric oxide synthase and inhibited nuclear localization of nuclear factor kappa-B (NF-κB).

Investigation of 20S-hydroxyvitamin D3 analogs and their 1\u03b1-OH derivatives as potent vitamin D receptor agonists with anti-inflammatory activities

20S-hydroxyvitamin D3 [20S(OH)D3] is anti-inflammatory and not hypercalcemic, suggesting its potential as a lead compound. In this study, side chain modified 20S(OH)D3 analogs (4, 13, 23 and 33) together with their 1α-OH derivatives were synthesized and their metabolism and biological activities tested. 4, 13 and 23 are good substrates for CYP27B1, enabling enzymatic synthesis of their 1α-OH derivatives 5, 14 and 24. However, 33 could not be hydroxylated by CYP27B1 and acts as an inhibitor. All analogs were poorer substrates for CYP24A1 than calcitriol, indicating improved catabolic stability. While the parent analogs showed minimal VDR stimulating activity, their 1α-OH derivatives were potent VDR agonists. 4, 5, 14 and 24 significantly upregulated the expression of CYP24A1 at the mRNA level, consistent with their VDR activation abilities and indicating that 1α-hydroxylation is required to produce analogs with strong activity. These analogs have anti-inflammatory activities that are influenced by side chain composition and by 1α-hydroxylation. To understand their molecular interactions with the VDR, 20S(OH)D3, 4 and 33 were co-crystalized with the VDR ligand binding domain, which revealed subtle differences to the calcitriol-bound receptor. This study demonstrates the potential of the 20S(OH)D3 scaffold for the development of novel anti-inflammatory agents.

Anti-Inflammatory Phenolic Metabolites from the Edible Fungus Phellinus baumii in LPS-Stimulated RAW264.7 Cells.

The edible fungus Phellinus baumii Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of P. baumii was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The resulting fractions were chemically investigated, leading to isolation of three phenolic compounds (1–3), a sesquiterpene (4), two steroids (5–6), a fatty acid (7), and a cerebroside (8). Spectroscopic analyses including 1D and 2D NMR spectroscopy and LC/MS were used to determine their chemical structures. Compounds 2, 4, 5, 7 and 8 were identified in P. baumii for the first time. Since all compounds were isolated from active fractions with anti-inflammatory activity, their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells were evaluated in vitro. Compounds 1, 2, 3, 5 and 7 inhibited LPS-stimulated NO production, and compounds 1–3 had IC50 values <10 μM. Treatment of LPS-stimulated RAW264.7 cells with compounds 1–3 inhibited phosphorylation of IKKα and IκBα. In addition, treatment of compounds 1–3 reduced LPS-induced increases of nuclear factor-kappa B (NF-κB) p65, iNOS and COX-2 protein expressions. Collectively, compounds 1–3 inhibited NF-κB-dependent inflammation in RAW264.7 cells. Thus, P. baumii is a potential source of natural anti-inflammatory agents, and active compounds 1–3 could be promising lead compounds for the development of novel anti-inflammatory agents.

Involvement of p38 MAPK and ATF-2 signaling pathway in anti-inflammatory effect of a novel compound bis[(5-methyl)2-furyl](4-nitrophenyl)methane on lipopolysaccharide-stimulated macrophages

Activated macrophages produce various pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) and cyclooxygenase (COX)-2-derived prostaglandin E2 (PGE2) during inflammatory response. However, overproduction of NO and PGE2 appears to be involved in pathogenesis of various inflammatory diseases. Therefore, inhibition of NO and PGE2 production might be useful for the treatment of inflammatory-related diseases. In this study, the bis[(5-methyl)2-furyl](4-nitrophenyl)methane or BFNM was evaluated for the anti-inflammatory activity and mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage. BFNM inhibited NO and PGE2 production in a concentration-dependent manner and down-regulated the expression of iNOS and COX-2 at mRNA and protein levels. BFNM suppressed nuclear translocation of NF-κB p65 subunit only very slightly, and failed to decrease NF-κB DNA binding activity. In contrast, the compound significantly reduced phosphorylation of p38 MAPK and ATF-2, a component of AP-1 known to be involved in the transcriptional regulation of iNOS and COX-2, in a dose-dependent manner in LPS-induced cells. Collectively, these results suggest that BFNM has an anti-inflammatory effect in RAW 264.7 macrophages, at least in part, by suppression of NO and PGE2 production. The inhibitory effect of BFNM is mediated mainly via the p38 MAPK/ATF-2 signaling pathway. Thus, BFNM would be a lead compound for the development of novel anti-inflammatory agents.

Bioactivity-guided isolation of anti-inflammatory triterpenoids from the sclerotia of Poria cocos using LPS-stimulated Raw264.7 cells

Poria cocos Wolf (Polyporaceae) has been used as a medicinal fungus to treat various diseases since ancient times. This study aimed to investigate the anti-inflammatory chemical constituents of the sclerotia of P. cocos. Based on bioassay-guided fractionation using lipopolysaccharide (LPS)-stimulated Raw264.7 cells, chemical investigation of the EtOH extract of the sclerotia of P. cocos resulted in the isolation and identification of eight compounds including six triterpenoids, namely poricoic acid A (1), 3-O-acetyl-16α-hydroxydehydrotrametenolic acid (2), polyporenic acid C (3), 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid (4), trametenolic acid (5), and dehydroeburicoic acid (6), as well as (−)-pinoresinol (7) and protocatechualdehyde (8). The structures of the isolated compounds were determined by spectroscopic analysis, including 1H and 13C NMR spectra, and LC/MS analysis. The anti-inflammatory activities of the isolates were evaluated by estimating their effect on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated Raw264.7 as well as on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compounds 1–5 inhibited NO production and iNOS expression in LPS-stimulated Raw264.7 cells. Among them, compound 1 exerted the highest anti-inhibitory activity and reduced PGE2 levels via downregulation of COX-2 protein expression. The findings of this study provide experimental evidence that the sclerotia of P. cocos are a potential source of natural anti-inflammatory agents for use in pharmaceuticals and functional foods. Furthermore, the most active compound 1, seco-lanostane triterpenoid, could be a promising lead compound for the development of novel anti-inflammatory agents.

Anti-inflammatory effect of Algerian date fruit (Phoenix dactylifera)

ABSTRACTFrom ages, dates are consumed by humans for its beneficial health and nutritional values. The aim of this study was to evaluate anti-inflammatory effect of Algerian date fruit (Phoenix dactylifera). A quantity of 50 mg/kg of the P. dactylifera extract was analyzed in vivo using the formalin-induced paw edema test in mice. The inflammation level was detected by the measure of the edema size, also the dosage of C-reactive protein (CRP) and homocysteine levels in the blood. The results showed a highly significant decrease in the edema size and the level of the homocysteine in the blood (P = .000) and significant decrease in CRP values (P < 0.05) in the 50 mg/kg plant extract group compared to Control, Methionine 400 mg/kg and (Plant + Methionine) groups. The study suggests that the extract possesses enough potential to reduce inflammation by in vivo and directs the importance of further research and development of novel anti-inflammatory agents.