Superior Anti-inflammatory Activity Research Articles

Discovery of a New Anti-Inflammatory Agent from Anemoside B4 Derivatives and Its Therapeutic Effect on Colitis by Targeting Pyruvate Carboxylase.

Anemoside B4 (AB4), a triterpenoidal saponin from Pulsatilla chinensis, shows significant anti-inflammatory activity, and may be used for treating inflammatory bowel disease (IBD). Nevertheless, its application is limited due to its high molecular weight and pronounced water solubility. To discover new effective agents for treating IBD, we synthesized 28 AB4 derivatives and evaluated their cytotoxic and anti-inflammatory activities in vitro. Among them, A3-6 exhibited significantly superior anti-inflammatory activity compared to AB4. It showed a significant improvement in the symptoms of DSS-induced colitis in mice, with a notably lower oral effective dose compared to AB4. Furthermore, we discovered that A3-6 bound with pyruvate carboxylase (PC), then inhibited PC activity, reprogramming macrophage function, and alleviated colitis. These findings indicate that A3-6 is a promising therapeutic candidate for colitis, and PC may be a potential new target for treating colitis.

NNO donor Schiff base metal complexes: Enzyme mimicking, DNA binding and biological insights

The present work focuses on the microwave-assisted synthesis, characterization and biological applications of a novel tridentate NNO donor Schiff base ligand derived from the condensation of 4-(Diethylamino)salicylaldehyde and 4,5-Dimethyl-1,2-phenylenediamine, along with its transition metal complexes of Cu(II) and Co(II) in 1:1 and 1:2 ratios each respectively. A theoretical basis for comprehending the electronic framework and characteristics of the complexes has been studied through the use of a computational approach. Further, the distorted octahedral geometry of the Schiff base metal complexes is confirmed by using analytical methods such as elemental analysis, molar conductance, ESI-MS, UV–Vis, FTIR, TGA and NMR spectra, which confirmed that NNO donor site of the ligand is coordinated with the metal ions. The complexes have been screened for their potential application as a catalyst for the catalytic conversion of 3,5-di‑tert‑butyl‑catechol (3,5-DTBC) to 3,5-di‑tert-butylquinone (3,5-DTBQ) and the turnover numbers (Kcat) have been found in the range 36.46–43.05 h−1 in methanol. Absorption spectroscopic technique has been employed to examine the possible modalities of interactions with the synthesized complexes using CT-DNA and the related binding constants exhibited in the range 2.58 × 104 M−1 to 1.98 × 105 M−1 thus depicting appreciable binding affinity. To evaluate the bioactivities, in-vitro assays for anti-oxidant and anti-inflammatory activity have also been implemented. The Cu(II) complex (CuL) has significant anti-oxidant activity and the Co(II) complex (CoL) has superior anti-inflammatory activity compared to all other complexes with IC50 values of 238.78 µM and 140.25 µM respectively. To better understand the molecular-level interactions and identify probable binding energies of inhibitors, molecular docking simulations have been performed.

Insight on novel oxindole conjugates adopting different anti-inflammatory investigations and quantitative evaluation.

Background: A dual COX/5-LOX strategy was adopted to develop new oxindole derivatives with superior anti-inflammatory activity. Methods: Three series of oxindoles - esters 4a-p, 6a-l and imines 7a-o - were synthesized and evaluated for their anti-inflammatory and analgesic activities. Molecular docking and predicted pharmacokinetic parameters were done for the most active compounds. A new LC-MS/MS method was developed and validated for the quantification of 4h in rat plasma. Results: Compounds 4h, 6d, 6f, 6j and 7m revealed % edema inhibition up to 100.00%; also, 4l and 7j showed 100.00% writhing protection. Compound 4h showed dual inhibitory activity with IC50=0.0533 and 0.4195μM for COX-2 and 5-LOX, respectively. Molecular docking rationalized the obtained biological activity. The pharmacokinetic parameters of 4h from rat plasma were obtained.

Design and synthesis of highly selective Janus kinase 3 covalent inhibitors for the treatment of rheumatoid arthritis.

Selective inhibition of Janus kinase 3 (JAK3) is a promising strategy for the treatment of autoimmune diseases. Based on the discovery of a hydrophobic pocket unutilized between the lead compound RB1 and the JAK3 protein, a series of covalent JAK3 inhibitors were prepared by introducing various aromatic fragments to RB1. Among them, J1b (JAK3 IC50 = 7.2 nM, other JAKs IC50 > 1000 nM) stood out because of its low toxicity (MTD > 2 g/kg) and superior anti-inflammatory activity in Institute of Cancer Research mice. Moreover, the acceptable bioavailability (F% = 31.69%) ensured that J1b displayed excellent immune regulation in collagen-induced arthritis mice, whose joints in the high-dose group were almost recovered toa normal state. Given its clear kinase selectivity (Bmx IC50 = 539.9 nM, other Cys909 kinases IC50 > 1000 nM), J1b was nominated as a highly selective JAK3 covalent inhibitor, which could be used to safely treat arthritis and other autoimmune diseases.

Chlorogenic acid ameliorates intestinal inflammation by inhibiting NF-κB and endoplasmic reticulum stress in lipopolysaccharide-challenged broilers

Intestinal inflammation is a primary contributor to poor growth performance during poultry production. Chlorogenic acid (CGA) is a natural phenolic acid that exhibits superior anti-inflammatory activity and improved intestinal health. To investigate the protective effects and molecular mechanisms of CGA during intestinal inflammation in lipopolysaccharide (LPS)-challenged broilers, we randomly divided 288 one-day-old male Cobb broilers into 4 groups: a control group fed a basal diet (CON group), a basal diet + LPS group (LPS group), and 2 basal diet groups fed 500 or 750 mg/kg CGA + LPS (CGA_500 or CGA_750 groups). Broilers were injected with LPS or saline at 15, 17, 19, and 21 d old. Chlorogenic acid supplementation improved the growth performance of LPS-challenged broilers by increasing average daily gain (ADG) and reducing feed/gain (F/G) ratios (P < 0.05). CGA also improved intestinal barrier function in LPS-challenged boilers by enhancing jejunum morphology and integrity, decreasing intestinal permeability, and increasing occludin 3, zonula occludens-1, and mucin 2 expression (P < 0.05). CGA supplementation also improved systemic and jejunum antioxidant capacity by significantly enhancing glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities (P < 0.05), and reducing malonaldehyde (MDA) and protein carbonyl (PCO) levels (P < 0.05). Chlorogenic acid supplementation reduced systemic and jejunum pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, and IL-12) and increased anti-inflammatory cytokines (IL-10) in LPS-challenged broilers (P < 0.05) by inhibiting the toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway (P < 0.05). In addition, the protective effects of CGA toward intestinal inflammation and apoptosis appeared to be correlated with inhibited endoplasmic reticulum (ER) stress (P < 0.05). In summary, CGA supplementation improved intestinal morphology and integrity by inhibiting TLR4/NF-κB and ER stress pathways, which potentially reduced oxidative stress and inflammation, and ultimately improved the growth performance of LPS-challenged broilers.

Quantum mechanical treatment for potential antiphlogistic effects from the leaf extract of Ocimum basilicum citriodorum using gas chromatography-mass spectrometry (GCMS)

Abstract The immune biological response systems and inflammation can be triggered by a number of things such as pathogens, damaged cells and toxic substances. In ethnomedicine, leaves of Lemon basil (Ocimum basilicum citriodorum) have been used for their health benefits. This study examines the anti-inflammatory properties of lemon basil stalks. In a GC/MS study, 24 plant-based bioactive compounds were identified. Comparing the activities in 24 compounds with the largest negative binding energy values helped us determine which compound was most active. It can be seen that only two compounds (Campstool and stigmasterol) with the highest binding energies interact with the 2QVD protein; consequently, the compound with the highest binding energy has superior anti-inflammatory activity. In quantum mechanics, electron energy difference between lowest-unoccupied molecular orbitals (LUMO) and highest-occupied molecular orbitals (HOMO) is described by the quantum-mechanical method, electronegativity (χ), electron affinity (A), global hardness (η), global softness (σ) and ionization potential (I) estimated from the optimized structure. Higher energy molecules are more reactive than other substances reported in this study.

Synthesis and biological evaluation of new nicotinic acid derivatives as potential anti-inflammatory agents with enhanced gastric safety profile

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 ± 0.09. The most active compounds were subjected to evaluation of TNF-α, IL-6, iNOS and COX-2 levels in LPS/INF γ-stimulated RAW 264.7 macrophage cells in comparison to ibuprofen as a reference compound. The five compounds showed comparable inhibition potency of these inflammatory cytokines compared to ibuprofen. Same compounds were further in vivo evaluated for their anti-inflammatory activity via carrageenan induced arthritis in rats. Regarding the ulcerogenic profile, compound 4h showed mild infiltration of gastric mucosa superb to compound 5b displayed severe gastritis. Molecular docking of 4h and 5b in the COX-2 active site was performed to evaluate their preferential COX-2 inhibitory potency. The docking results were in accordance with the biological findings.

Revamped mini-αA-crystallin showed improved skin permeation and therapeutic activity against melittin-induced toxicity

Melittin is honey bee venom's primary and most toxic pharmacologically active component. Melittin causes haemolysis, lymphocyte lysis, long-term pain, localised inflammation followed by rhabdomyolysis, and severe renal failure. Renal failure or cardiovascular complications could lead to the victim's death. Severe honey bee bites are treated with general medication involving antihistaminic, anti-inflammatory, and analgesic drugs, as a specific treatment option is unavailable. An earlier study showed the anti-hemolysis and anti-lymphocyte lysis activity of mini- αA-crystallin (MAC), a peptide derived from human eye lens alpha-crystallin. MAC's use has often been restricted despite its high therapeutic potential due to its poor skin permeability. This study compared the skin permeation, anti-inflammatory and analgesic activities of natural peptide MAC and its modified version (MAC-GRD) formed by attaching cell-penetrating peptide (CPP) and GRD amino residues into MAC. Gel formulations were prepared for MAC and MAC-GRD peptides using carbopol (1% w/w), Tween 80 (1%), and ethanol (10%). An ex-vivo skin permeation study was performed using a vertical-type Franz diffusion apparatus. Preclinical in-vivo experiments were conducted to compare the native and modified peptide formulations against melittin-induced toxicity in Wistar rats. MAC gel, MAC–GRD gel and 1% hydrocortisone cream significantly reduced the melittin-induced writhing (20.16 ± 0.792) response in rats with 15.16 ± 0.47, 11.16 ± 0.477 and 12.66 ± 0.66 wriths, respectively. There was a significant reduction in melittin-induced inflammation when MAC-GRD gel was applied immediately after melittin administration. At 0.5, 1, 3, and 5 h, the MAC-GRD-treated rat paws were 0.9 ± 0.043 mm, 0.750 ± 0.037 mm, 0.167 ± 0.0070 mm, and 0.133 ± 0.031 mm thick. Administration of melittin resulted in reduced GSH (antioxidant) levels (47.33 ± 0.760 μg/mg). However, treatment with MAC-GRD gel (71.167 ± 0.601 μg/mg), MAC gel (65.167 ± 1.138 μg/mg), and 1% hydrocortisone (68.33 ± 0.667 μg/mg) significantly increased the antioxidant enzyme levels. MAC-GRD gel significantly reduced the elevated MDA levels (6.933 ± 0.049 nmol/mg) compared to the melittin group (12.533 ± 0.126 nmol/mg), followed by the 1% hydrocortisone (7.367 ± 0.049 nmol/mg) and MAC gel (7.917 ± 0.048 nmol/mg). MAC-GRD demonstrated more skin permeability and superior anti-inflammatory, analgesic, and antioxidant activities when compared to MAC gel. When compared to standard 1% hydrocortisone cream, MAC-GRD had better anti-inflammatory, analgesic, antioxidant, and comparable action in anti-oxidant restoration against melittin. These findings suggest that the developed MAC-GRD gel formulation could help to treat severe cases of honey bee stings.

Insect Delicacies Among the Mishing and the Tiwa Communities and Their Implications for Diseases and Food Security

The Mishings and the Tiwas, along with various global communities, have traditionally consumed insects for their palatability since ancient times. This study reveals the remarkable nutritional and anti-inflammatory properties of these edible insects, making them viable dietary options. Eupreponotus inflatus was observed to have the highest protein content at 65.81%, Vespa affinis with the highest carbohydrate content at 19.18%, and Anaciaeschna donaldi exhibiting the highest fat content at 27.31%. Apis indica and Gryllotalpa africana demonstrated superior anti-inflammatory activity at 3.48 mg/ ml and 3.45 mg/ ml, respectively. Given that inflammation is implicated in numerous chronic diseases, the observed nutrient profiles and anti-inflammatory characteristics of these edible insects position them as suitable dietary supplements globally. The presented insect species could serve as beneficial additions or alternatives to existing diets. The study underscores the need for broader recognition of the nutritional and anti-inflammatory benefits offered by these edible insects. By aligning with contemporary nutritional needs and global food challenges, integrating these insects into diets could contribute significantly to public health.

Characterization and bioactivity of copaiba essential oil carried in a self-nanoemulsifying drug delivery system

Copaiba essential oil (CEO) is the volatile part of copaiba balsam, which has been topically used for various inflammatory conditions. However, there are some concerns about the CEO safety for oral use. The lipophilic character of CEO also limits its application in the pharmaceutical field. This study prepared a self-nanoemulsifying drug delivery system (SNEDDS) containing CEO and evaluated its toxic effects against a primary culture from pig liver (PLP2) and Green monkey kidney cell line (Vero). The inhibition of oxide nitric production was also evaluated on RAW 264.7 macrophage cell line to access the anti-inflammatory effect. The CEO was extracted by hydrodistillation and β-caryophyllene accounted for 51.8% of the oil. The formulation (FSNEDDS) consisting of CEO, Cremophor and ethyl linoleate was characterized in relation to morphology, stability, rheology, simulated digestion and bioaccessibility in vitro. FSNEDDS displayed Newtonian flow behavior with viscosity depending only on temperature and, in an aqueous medium, it formed small spherical particles (<100 nm size diameter). The FSNEDDS showed higher oxidative stability than the non-formulated CEO. In the simulated digestion, FSNEDDS formed nanoemulsifying droplets in gastric phase and tiny micelles in intestinal phase, and a bioaccessibility of 63%. The FSNEDDS showed a superior anti-inflammatory activity (+11%) than non-formulated CEO and this beneficial concentration was achieved with a non-toxic concentration for none of the cell lines tested. In conclusion, FSNEDDS improves the physicochemical stability, bioaccessibility and bioactivity of CEO, and it could be a phytotherapic option for per oral administration to treat inflammatory diseases.

Study on the extraction process, chemical compositions, and anti-inflammatory activity of total saponins extract from Anemone raddeana Regel

Anemone raddeana Regel. is mainly distributed in the northeast of China, and its rhizomes part is rich in saponins, which is commonly used for treatment of pain, inflammatory and rheumatic illnesses. However, there are few reports on saponins from Anemone raddeana Regel. This research had investigated the extraction process, chemical compositions, and anti-inflammatory activity in vitro of total saponins extract from Anemone raddeana Regel. The extraction process was optimized by the single factor experiment and response surface methodology, and the anti-inflammatory activities were evaluated by determination of the nitric oxide content and cytophagocytic activity in LPS induced RAW 264.7 cells. The optimized extraction parameters for the total saponins extract were as follows: ethanol concentration 50 %, the ratio of liquid to material 43:1 mL/g, ultrasonic extraction time 70 min, and the yield of the total saponin was 1.74 % under these extraction conditions. Forty-three components were preliminarily separated and analyzed from the total saponins fraction by UPLC-QTOF-MS method. In addition, it was found that the total saponins extract could exert the anti-inflammatory effect by reducing the nitric oxide content and inhibiting the phagocytic activity. This study suggested that the total saponins extract from Anemone raddeana Regel. could exhibit the superior anti-inflammatory activity, and be developed as a green and natural anti-inflammatory drug.

Supramolecular nanofiber of indomethacin derivative confers highly cyclooxygenase-2 (COX-2) selectivity and boosts anti-inflammatory efficacy

Herein, we report a facile method for converting carboxylate-containing indomethacin (Idm) into a cyclooxygenase-2 (COX-2) selective inhibitor via the amidation of an unnatural peptide sequence (Nal-Nal-Asp). The resulting indomethacin amides (i.e., Idm-Nal-Nal-Asp) have high selectivity for COX-2, and can self-assemble into a one-component supramolecular hydrogel that acts as a ‘self-delivery’ system for boosting anti-inflammatory efficacy. Self-assembled Idm-Nal-Nal-Asp hydrogel robustly inhibits COX-2 expression in lipopolysaccharide (LPS)-activated Raw 264.7 macrophages while also exhibits superior anti-inflammatory and antioxidant activities via reactive oxygen species (ROS)-related NF-κB and Nrf2/HO-1 pathways. Moreover, a rabbit model of endotoxin-induced uveitis (EIU) reveals that the Idm-Nal-Nal-Asp hydrogel outperforms clinically used 0.1 wt% diclofenac sodium eye drops in terms of in vivo anti-inflammatory efficacy via topical instillation route. As a rational approach to designing and applying COX-2 selective inhibitors, this work presents a simple method for converting non-selective nonsteriodal anti-inflammatory drugs (NSAIDs) into highly selective COX-2 inhibitors that can self-assemble into supramolecular hydrogel for anti-inflammation applications.

Combined acid hydrolysis and fermentation improves bioactivity of citrus flavonoids in vitro and in vivo

Many bioactive plant compounds, known as phytochemicals, have the potential to improve health. Unfortunately, the bioavailability and bioactivity of phytochemicals such as polyphenolic flavonoids are reduced due to conjugation with sugar moieties. Here, we combine acid hydrolysis and tailored fermentation by lactic acid bacteria (Lactiplantibacillus plantarum) to convert the biologically less active flavonoid glycosides hesperidin and naringin into the more active aglycones hesperetin and naringenin. Using a comprehensive approach, we identify the most effective hydrolysis and fermentation conditions to increase the concentration of the aglycones in citrus extracts. The higher cellular transport and bioactivity of the biotransformed citrus extract are also demonstrated in vitro and in vivo. Superior antioxidant, anti-inflammatory and cell migration activities in vitro, as well as intestinal barrier protecting and antioxidant activities in Drosophila melanogaster are identified. In conclusion, the presented biotransformation approach improves the bioactivity of flavonoids, clearly traced back to the increase in aglycone content.

3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach.

In an effort to develop new compounds for managing drug-induced liver injury, we prepared 23 novel hybrids based on 3-acetyl-11-keto-β-boswellic acid (AKBA) using various biocompatible linkers. A bioguided approach was employed to identify the most promising hybrid. Eight compounds exhibited superior anti-inflammatory activity compared to the parent compound. Two of these hybrids (5b and 18) were able to reduce gene expression of TNF-α in LPS-induced inflammation in RAW 264.7 cells, similar to dexamethasone. Subsequently, the hepatoprotective potential of these hybrids was evaluated against acetaminophen (APAP) toxicity in HepG2 cells at doses of 1 and 10 μM. Both hybrids effectively restored cytokine levels, which had been elevated by APAP, to normal levels. Furthermore, they normalized depleted superoxide dismutase and reduced glutathione levels while significantly reducing malondialdehyde (MDA) levels. Network pharmacology analysis suggested that AKBA-based hybrids exert their action by regulating PI3K and EGFR pathways, activating anti-inflammatory mechanisms, and initiating tissue repair and regeneration. Molecular docking studies provided insights into the interaction of the hybrids with PI3K. Additionally, the hybrids demonstrated good stability at different pH levels, following first-order kinetics, with relatively long half-lives, suggesting potential for absorption into circulation without significant degradation.

Degradable carrier-free spray hydrogel based on self-assembly of natural small molecule for prevention of postoperative adhesion.

Postoperative peritoneal adhesion (PPA) is frequent and extremely dangerous complication after surgery. Different tactics have been developed to reduce it. However, creating a postoperative adhesion method that is multifunctional, biodegradable, biocompatible, low-toxic but highly effective, and therapeutically applicable is still a challenge. Herein, we have prepared a degradable spray glycyrrhetinic acid hydrogel (GAG) based on natural glycyrrhetinic acid (GA) by straightforward heating and cooling without the use of any additional chemical cross-linking agents to prevent postoperative adhesion. The resultant hydrogel was demonstrated to possess various superior anti-inflammatory activity, and multiple functions, such as excellent degradability and biocompatibility. Specifically, spraying characteristic and excellent antibacterial activities essentially eliminated secondary infections during the administration of drugs in surgical wounds. In the rat models, the carrier-free spray GAG could not only slow-release GA to inhibit inflammatory response, but also serve as physical anti-adhesion barrier to reduce collagen deposition and fibrosis. The sprayed GAG would shed a new light on the prevention of postoperative adhesion and broaden the application of the hydrogels based on natural products in biomedical fields.

Multifunctional Properties of BMAP-18 and Its Aliphatic Analog against Drug-Resistant Bacteria.

BMAP-18, derived from the N-terminal region of bovine myeloid antimicrobial peptide BMAP-27, demonstrates potent antimicrobial activity without cytotoxicity. This study aimed to compare the antibacterial, antibiofilm, and anti-inflammatory properties of BMAP-18, rich in aromatic phenylalanine residues, with its aliphatic analog, BMAP-18-FL. Both aromatic BMAP-18 and aliphatic BMAP-18-FL exhibited equally potent antimicrobial activities against Gram-positive and Gram-negative bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Mechanistic investigations employing SYTOX green uptake, DNA binding, and FACScan analysis revealed that both peptides acted by inducing membrane permeabilization and subsequent intracellular targeting. Moreover, both BMAP-18 and BMAP-18-FL effectively prevented biofilm formation and eradicated existing biofilms of MRSA and MDRPA. Notably, BMAP-18-FL displayed a superior anti-inflammatory activity compared to BMAP-18, significantly reducing the expression levels of pro-inflammatory cytokines in lipopolysaccharide-stimulated macrophages. This study emphasizes the similarities and differences in the antimicrobial, antibiofilm, and anti-inflammatory properties between aromatic BMAP-18 and aliphatic BMAP-18-FL, providing valuable insights for the development of multifunctional antimicrobial peptides against drug-resistant bacteria.

An additive-free multifunctional β-glucan-peptide hydrogel participates in the whole process of bacterial-infected wound healing

Bacterial infections and excessive inflammation can impede the healing of wounds. Hydrogels have emerged as a promising approach for dressing bacterial-infected injuries. However, some antibacterial hydrogels are complex, costly, and even require assistance with other instruments such as light, making them unsuitable for routine outdoor injuries. Here, we developed an in-situ generating hydrogel via hybridizing oxidized β-D-glucan with antimicrobial peptide C8G2 through the Schiff base reaction. This hydrogel is easily accessible and actively contributes to the whole healing process of bacterial-infected wounds, demonstrating remarkable antibacterial activity and biological compatibility. The pH-sensitive reversible imine bond enables the hydrogel to self-heal and sustainably release the antibacterial peptide, thereby improving its bioavailability and reducing toxicity. Meanwhile, the immunoregulating β-D-glucan inhibits the release of inflammatory factors while promoting the release of anti-inflammatory factors. In methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin wound models, the hybrid hydrogel showed superior antibacterial and anti-inflammatory activity, enhanced the M2 macrophage polarization, expedited wound closure, and regenerated epidermis tissue. These features make this hydrogel an appealing wound dressing for treating multi-drug-resistant bacteria-infected wounds.

Anti-Inflammatory Effects of Essential Oils from the Peels of Citrus Cultivars.

Citrus cultivars have remarkable health benefits, but only the anti-inflammatory activities of the major varieties have been studied. This study investigated the anti-inflammatory effects of various citrus cultivars and their active anti-inflammatory components. The essential oils of 21 citrus peels were extracted via hydrodistillation using a Clevenger-type apparatus, and the chemical compositions of the essential oils were analyzed. D-Limonene was the most abundant constituent. To evaluate the anti-inflammatory effects of the citrus cultivars, the gene expression levels of an inflammatory mediator and proinflammatory cytokines were investigated. Among the 21 essential oils, those extracted from C. japonica and C. maxima exhibited superior anti-inflammatory activities, being able to inhibit the expression of the inflammatory mediators and proinflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The essential oils of C. japonica and C. maxima were distinguished into seven distinct constituents, α-pinene, myrcene, D-limonene, β-ocimene, linalool, linalool oxide, and α-terpineol, compared with other essential oils. The anti-inflammatory activities of the seven single compounds significantly inhibited the levels of inflammation-related factors. In particular, α-terpineol exhibited a superior anti-inflammatory effect. This study showed that the essential oils from C. japonica and C. maxima exhibit high anti-inflammatory activity. In addition, α-terpineol is an active anti-inflammatory compound that contributes to inflammatory responses.

Antioxidant and Anti-inflammatory Activities of the Extract and Solvent Fractions of Hemistepta lyrata Bunge

This study investigated antioxidant and anti-inflammatory in order to confirm the possibility of functional materials that can improve skin diseases using &lt;i&gt;Hemistepta lyrata&lt;/i&gt; Bunge extracts and solvent fractions. As a result of measuring the total polyphenol content, the content was high in EtOAc fraction, and then the BuOH fraction is next. As a result of measuring DPPH free radical scavenging activities, it was confirmed that BuOH fractions had superior antioxidant activity compared to other solvent fractions. In particular, in the case of EtOAc fraction, it was confirmed that the antioxidant ability was excellent even at a low concentration compared to other fractions in ABTS and FRAP assay. Through this, it was confirmed that the higher the total polyphenol content, the higher the antioxidant effect. In addition, as a result of verifying the inflammatory efficacy of the extract and the solvent fraction using the J774 cell line, it was confirmed that the NO level decreased when the extract and the solvent fraction were treated. In particular, it is determined that the ethyl acetate fraction having a high total polyphenol content has superior antioxidant and anti-inflammatory activities and contains more active substances than other fractions. Therefore, in order to conduct additional research, it is determined that research on the compounds contained in the ethyl acetate fraction is necessary.

Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and eudragits L and s in the treatment of ulcerative colitis in rats

The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. 5-ASA matrix pellets with a 70% drug load were prepared by the extrusion-spheronization method. The optimal coating formula which included Eudragit S (ES) + Eudragit L (EL) + Ethylcellulose (EC) was predicted for the targeted drug delivery to the colonic area by a 32 factorial design. The ratio of ES:EL:EC and coating level were considered as independent variables while the responses were the release of less than 10% of the drug within 2 h (Y1), the release of 60–70% within 10 h at pH 6.8 (Y2) and lag time of less than 1 h at pH 7.2 (Y3). Also, 5-ASA layered pellets were prepared by the powder layering of 5-ASA on nonpareils (0.4–0.6 mm) in a fluidized bed coater and then coated with the same optimum coating composition. The coated 5-ASA layered or matrix pellets were tested in a rat model of ulcerative colitis (UC) and compared with the commercial form of 5-ASA pellets (Pentasa®). The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon. The coated 5-ASA pellets were spherical with uniform coating as shown by SEM and met all of our release criteria as predicted. In-vivo studies demonstrated that the optimum 5-ASA layered or matrix pellets had superior anti-inflammatory activities than Pentasa® in terms of colitis activity index (CAI), colon damage score (CDS), colon/body weight ratio and colon’s tissue enzymes of glutathione (GSH) and malondialdehyde (MDA). The optimum coating formulation showed a high potential for colonic delivery of 5-ASA layered or matrix pellets and triggered drug release based on pH and time.