Remarkable Anti-inflammatory Effects Research Articles

Effects of histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors on proliferative, differentiative, and regenerative functions of Toll-like receptor 2 (TLR-2)-stimulated human dental pulp cells (hDPCs).

This in vitro study aimed to modify TLR-2-mediated effects on the paracrine, proliferative, and differentiation potentials of human dental pulp-derived cells using histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors. Cell viability was assessed using the XTT assay. Cells were either treated with 10μg/ml Pam3CSK4 only, or pre-treated with valproic acid (VPA) (3mM), trichostatin A (TSA) (3μM), and MG-149 (3μM) for a total of 4h and 24h. Control groups included unstimulated cells and cells incubated with inhibitors solvents only. Transcript levels for NANOG, OCT3-4, FGF-1 and 2, NGF, VEGF, COL-1A1, TLR-2, hβD-2 and 3, BMP-2, DSPP, and ALP were assessed through qPCR. After 24h, TSA pre-treatment significantly upregulated the defensins and maintained the elevated pro-inflammatory cytokines, but significantly reduced healing and differentiation genes. VPA significantly upregulated the pro-inflammatory cytokine levels, while MG-149 significantly downregulated them. Pluripotency genes were not significantly affected by any regimen. At the attempted concentrations, TSA upregulated the defensins gene expression levels, and MG-149 exerted a remarkable anti-inflammatory effect; therefore, they could favorably impact the immunological profile of hDPCs. Targeting hDPC nuclear function could be a promising option in the scope of the biological management of inflammatory pulp diseases.

Polyscias scutellaria: An emerging source of natural antioxidants and anti-inflammatory compounds for health

Polyscias scutellaria (PS), an increasingly recognized botanical marvel, has emerged as a remarkable reservoir of natural antioxidants and anti-inflammatory compounds, holding immense potential for enhancing health and promoting overall well-being. In this comprehensive investigation, we meticulously examined the multifaceted properties of PS through various parameters, including DPPH scavenging activity, total phenol, and total flavonoid content in its ethanol extract (EEPS), ethyl acetate extract (EAPS), and n-hexane extract (nhPS). Additionally, we conducted in-depth assessments of cellular responses to EEPS and EAPS, encompassing cell viability, nitric oxide (NO) production, and the modulation of pivotal pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-12 (IL-12), utilizing the RAW 264.7 cell line as a model system.Our findings illuminate the exceptional antioxidant prowess of PS extracts, with EEPS, EAPS, and nhPS displaying noteworthy DPPH scavenging activities. These results underscore their potential in quenching harmful free radicals and mitigating oxidative stress. Furthermore, our investigation unveils the promising anti-inflammatory attributes of EEPS and EAPS, as evidenced by their capacity to preserve cellular viability, dampen NO production, and suppress the secretion of critical pro-inflammatory mediators (TNF-α, IL-6, IL-1β, and IL-12) in RAW 264.7 cells. These remarkable anti-inflammatory effects hint at the therapeutic potential of PS in ameliorating chronic inflammatory conditions and bolstering the body’s immune response.In conclusion, Polyscias scutellaria stands as an emerging botanical champion, offering a wealth of natural antioxidants and anti-inflammatory compounds that hold great promise for optimizing health and well-being. This study opens exciting avenues for future research to elucidate the precise bioactive constituents within PS and unravel their intricate mechanisms of action, paving the way for the development of innovative therapeutic interventions and wellness-enhancing products. The remarkable properties of PS underscore its potential as a cornerstone of holistic health and a valuable asset in the pursuit of a vibrant and balanced life. Graphical abstract

Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway.

JOURNAL/nrgr/04.03/01300535-202408000-00034/figure1/v/2023-12-16T180322Z/r/image-tiff Spinal cord injury-induced motor dysfunction is associated with neuroinflammation. Studies have shown that the triterpenoid lupenone, a natural product found in various plants, has a remarkable anti-inflammatory effect in the context of chronic inflammation. However, the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown. In this study, we established an impact-induced mouse model of spinal cord injury, and then treated the injured mice with lupenone (8 mg/kg, twice a day) by intraperitoneal injection. We also treated BV2 cells with lipopolysaccharide and adenosine 5'-triphosphate to simulate the inflammatory response after spinal cord injury. Our results showed that lupenone reduced IκBα activation and p65 nuclear translocation, inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B, and enhanced the conversion of proinflammatory M1 microglial cells into anti-inflammatory M2 microglial cells. Furthermore, lupenone decreased NLRP3 inflammasome activation, NLRP3-induced microglial cell polarization, and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway. These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

Comparison of RCI001 and corticosteroid on the effects on intraocular pressure in mice.

RCI001, a novel therapeutic candidate for the treatment of ocular inflammatory diseases, have demonstrated remarkable anti-inflammatory and antioxidant effects in various ocular experimental models. This study was to evaluate the effects of RCI001 on intraocular pressure (IOP) and compare them with those of corticosteroids in experimental mouse models. Experimental mice were randomly divided into naïve, phosphate-buffered saline (PBS), 0.1% dexamethasone (DEX-1), and 1% RCI001 (RCI) groups, and each reagent was pipetted into the right eye of the mouse at 10 μL thrice daily for 5 weeks. In addition, 20 μL of 0.1% dexamethasone was injected subconjunctivally into the right eye once weekly for 5 weeks in the DEX-2 group. The IOP was measured under anesthesia at baseline and twice weekly for 5 weeks. The △IOP (%) was defined as the change in IOP from baseline [△IOP (%) = (IOPweek5-IOPbaseline)/IOPbaseline × 100%]. The anterior segments were clinically and histologically examined. There was no significant increase in IOP and △IOP (%) [values by week 3 (day 21) in any of the groups]. However, IOP and △IOP (%) in the DEX-2 group tended to increase slightly after day 10 compared with baseline. Compared with baseline IOP values, the DEX-1 group showed a statistically significant increase in IOP at weeks 4 and 5, and the DEX-2 group at week 5. The △IOP (%) of the DEX-1 and DEX-2 groups (%) at week 5 were 38.2% ± 5.8% and 38.4 ± 4.6%, respectively. However, the IOP in the RCI group did not increase significantly until week 5. The RCI group did not show notable corneal changes, such as epithelial defects or stromal opacities, at week 5. In addition, hematoxylin and eosin (H&E) staining of corneas in the RCI group revealed healthy corneal epithelial, stromal, and endothelial integrity. Long-term use of RCI001 did not induce significant IOP elevation or ocular surface changes, whereas topical corticosteroids significantly increased the IOP. Therefore, RCI001 may be an effective anti-inflammatory agent with a low risk of drug-induced IOP elevation.

Active fraction of Polyrhachis vicina (Roger) alleviated cerebral ischemia/reperfusion injury by targeting SIRT3-mediated mitophagy and angiogenesis

BackgroundDamaged mitophagy and impaired angiogenesis involve in the pathogenic development of ischemic stroke. Active fraction of Polyrhachis vicina (Roger) (AFPR) showed great potential on neurological disease with it's remarkable anti-inflammatory and anti-oxidative effects. PurposeThis study designed to clarify the correlation between Pink1/Parkin-mediated mitophagy and angiogenesis after stroke, and to elucidate the role of SIRT3 in regulating mitophagy and angiogenesis, and to address the mechanism of AFPR on promoting mitophagy and angiogenesis in microvessels endothelium of ischemic brain. Study designA cerebral ischemia/reperfusion (CIR) rat model was developed by middle cerebral artery occlusion procedure. bEnd.3 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic CIR process. Neurological function, mitophagy and angiogenesis related indicators were measured. SIRT3 siRNA and 3-MA were used to verify the interaction between SIRT3-mediated mitophagy and angiogenesis. MethodsCIR rats were orally treated with AFPR (8 and 4 g raw drug /kg) and Nimodipine (10.8 mg/kg) for 12 days to mimic the recovery phase post-stroke. The neurological function assessment, TTC staining, HE staining, TUNEL staining and Nissl staining were performed to assess neuroprotective effects of AFPR against CIR. Then CD31-labeled microvessel density in brain was visualized and quantified by immunofluorescence staining. Mitochondrial ultrastructure was assessed by transmission electron microscope scanning. Expressions of relative proteins,e.g. SIRT3, Pink1, Parkin, LC3-II, p62, VEGFA, involving in mitophagy and angiogenesis, were detected by Western blotting analysis. In vitro, bEnd.3 cells were cultured with AFPR or in combination of autophagy inhibitor 3-MA during the reoxygenation. Then cell viability, and LDH releasing were measured. Angiogenic indicators,such as migration and tube formation activity, VEGFA level were determined. To assess effects of AFPR on mitophagy, mitophagy-related proteins were detected, as well as the autophagosome engulfment and lysosome degradation of mitochondria. To address the role of SIRT3, deacetylation activity of SIRT3 was validated by detecting acetylated FOXO3A level with co-immunoprecipitation (Co-IP) assay. Pre-treatment of siRNA or combination use of 3-MA were used to verify the detailed mechanism. ResultsAFPR remarkably reduced neurological scores and infarct size, alleviated neuron apoptosis in cortex, and increased Nissl density in hippocampus of CIR rats. In addition, AFPR significantly promoted angiogenesis by increasing microvessels density and VEGFA expressions, increased SIRT3 expression, and activated Pink1/Parkin mediated mitophagy. In bEnd.3 cells, the combination use of 3-MA and AFPR further demonstrated that AFPR might promote angiogenesis after OGD/R injury through activating Pink1/Parkin mediated mitophagy. Co-IP assay suggested AFPR reduced acetylated FOXO3A level. This might be correlated with an elevation of SIRT3 expression and it's deacetylation activity. SIRT3 siRNA pretreatment significantly abolished the activation of mitophagy through Pink1/Parkin axis, eventually inhibited angiogenesis. ConclusionAFPR promoted angiogenesis through activating mitophagy after cerebral ischemia reperfusion, which might partially involved in the amelioration of SIRT3-mediated regulation on Pink1/Parkin axis. Our study will shed new light on the role of SIRT3 in ischemic brain, especially in regulating mitophagy and angiogenesis after stroke.

Octominin: An antimicrobial peptide with antibacterial and anti-inflammatory activity against carbapenem-resistant Escherichia coli both in vitro and in vivo

The emergence of carbapenem-resistant Escherichia coli (CREC) is a global concern as its prevalence restricts treatment options and poses a considerable threat to public health. In this study, in vitro and in vivo activity of the antimicrobial peptide Octominin against CREC was investigated to reveal possible mechanisms of action. Furthermore, its safety and factors influencing its antibacterial effect were assessed. Additionally, the anti-inflammatory effects of Octominin were examined. The antimicrobial activity of Octominin against 11 strains of CREC was determined using the broth microdilution method, growth curve, and time-kill assay. Its possible mechanism of action was unraveled using the propidium iodide and N-phenyl-1-naphthylamine fluorochrome and lipopolysaccharide-binding assays. To understand the safety and stability of Octominin, its cytotoxicity, hemolysis, and antibacterial activity under various conditions (i.e, temperature, ions) were estimated. Additionally, a Galleria mellonella infection model was utilized to evaluate the efficacy of Octominin in vivo, and qRT-PCR was performed to assess its effect on the expression of proinflammatory cytokines. Octominin displayed a significant antibacterial effect, with MICs of 4-8 µg/mL and MBCs of 8-16 µg/mL. Octominin exerted its antibacterial effect by disrupting bacterial membranes. Cytotoxicity and hemolysis tests demonstrated the potential application of Octominin in vivo. The G. mellonella infection model asserted the in vivo efficacy of Octominin. Furthermore, Octominin inhibited the expression of proinflammatory cytokines. Although the temperature had little effect on its the activity, serum and ions reduced activity. Octominin is a promising alternative agent with remarkable antibacterial and anti-inflammatory effects for treating infections caused by CREC.

Low intensity pulsed ultrasound ameliorates Adriamycin-induced chronic renal injury by inhibiting ferroptosis

ABSTRACTObjectiveIt is very important to develop a new therapeutic strategy to cope with the increasing morbidity and mortality of chronic kidney disease (CKD). As a kind of physical therapy, low intensity pulsed ultrasound (LIPUS) has remarkable anti-inflammatory and repair-promoting effects and is expected to become a new therapeutic method for CKD. This study aims to clarify the treatment effect of LIPUS on CKD-related renal inflammation and fibrosis, and to further explore the potential signal network of LIPUS treatment for ameliorating chronic renal injury.MethodsA rat model simulating the progress of CKD was established by twice tail-vein injection of Adriamycin (ADR). Under anesthesia, bilateral kidneys of CKD rats were continuously stimulated by LIPUS for four weeks. The parameters of LIPUS were 1.0 MHz, 60 mW/cm2, 50% duty cycle and 20 min/d.ResultsLIPUS treatment effectively inhibited ADR-induced renal inflammation and fibrosis, and improved CKD-related to oxidative stress and ferroptosis. In addition, the therapeutic effect of LIPUS is closely related to the regulation of TGF-β1/Smad and Nrf2/keap1/HO-1 signalling pathways.DiscussionThis study provides a new direction for further mechanism research and lays an important foundation for clinical trials.

Quality variation and biosynthesis of anti-inflammatory compounds for Capparis spinosa based on the metabolome and transcriptome analysis.

Capparis spinosa L. fruits as edible and medicinal plant, has anti-inflammatory activities. The different morphological characteristics of C. spinosa fruits from Ili, Turpan, and Karamay may affect their anti-inflammatory components and functions. The anti-inflammatory activity of C. spinosa fruit was assessed using an LPS-induced inflammatory cell model. Furthermore, the differences in anti-inflammatory compounds were analyzed by metabolome and RNA-seq. Additionally, the anti-inflammatory mechanism was elucidated using network pharmacology. In the study, we found that the 95% ethanol extracts (CSE) obtained from the three kinds of fruits showed remarkable anti-inflammatory effects both in vivo and in vitro. However, the CSE derived from Ili fruits significantly reduced CD86 levels on DCs. As a result of metabolomic analysis, the metabolic profiles of Ili fruits differed significantly from those of the other two habitats, which were consistent with transcriptome analysis. A total of 15 compounds exhibiting anti-inflammatory activity were subjected to screening, revealing a greater accumulation of flavonoids in the Turpan and Karamay districts. Notably, phenolic compounds were identified as the principal anti-inflammatory components in C. spinosa. There were significant differences in the morphology, metabolites, transcriptional levels, and anti-inflammatory activity of C. spinosa from the three districts.

1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation. Currently, there is no effective treatment for the disease. According to our preliminary data, 1,8-cineole, which is the main active compound of Amomum compactum Sol. ex Maton volatile oil and an effective drug for the treatment of pneumonia, showed remarkable anti-inflammatory effects on colitis pathogenesis. However, its mechanism of action and direct targets remain unclear. This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate sodium salt-induced colitis mouse model. The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells. In addition, 1,8-cineole targets were revealed by drug affinity responsive target stability, thermal shift assay, cellular thermal shift assay, and heat shock protein 90 (HSP90) adenosine triphosphatases (ATPase) activity assays. The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function. Mechanistically, 1,8-cineole directly interacted with HSP90 and decreased its ATPase activity, also inhibited nucleotide-binding and oligomerization domain-, leucine rich repeat-, and pyrin domain-containing 3 (NLRP3) binding to HSP90 and suppressor of G-two allele of SKP1 (SGT1) and suppressed NLRP3 inflammasome activation in macrophages. These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.

Therapeutic effect of melatonin-loaded chitosan/lecithin nanoparticles on hyperglycemia and pancreatic beta cells regeneration in streptozotocin-induced diabetic rats

Nanotechnology is used to overcome fundamental flaws in today's marketed pharmaceuticals that obstruct therapy, like restricted solubility and quick release of drugs into the bloodstream. In both human and animal researches, melatonin was demonstrated to regulate glucose levels. Despite the fact that melatonin is quickly transported through the mucosa, its sensitivity to be oxidized creates a difficulty in achieving the required dose. Additionally, due to its variable absorption and poor oral bioavailability necessitates the development of alternative delivery methods. The study aimed to synthesize melatonin loaded chitosan/lecithin (Mel-C/L) nanoparticles to be assessed in the treatment of streptozotocin (STZ)-induced diabetes in rats. The antioxidant, anti-inflammatory, and cytotoxicity properties of nanoparticles were estimated to determine the safety of manufactured nanoparticles for in vivo studies. In addition, Mel-C/L nanoparticles were administered to rats for eight weeks after inducing hyperglycemia. The therapeutic effect of Mel-C/L nanoparticles was assessed in all experimental groups by detecting insulin and blood glucose levels; observing improvements in liver and kidney functions as well as histological and immunohistochemical evaluation of rats’ pancreatic sections. The results proved that Mel-C/L nanoparticles showed remarkable anti-inflammatory, anti-coagulant, and anti-oxidant effects, in addition to its efficiency in reducing blood glucose levels of STZ-induced diabetic rats and great ability to promote the regeneration of pancreatic beta (β)-cells. Furthermore, Mel-C/L nanoparticles elevated the insulin level; and decreased the elevated levels of urea, creatinine and cholesterol. In conclusion, nanoparticles application decreased the administrated melatonin dose that in turn can diminish the side effects of free melatonin administration.

Liquid chromatography-tandem mass spectrometry analysis of a ratio-optimized drug pair of Sophora flavescens Aiton and Coptis chinensis Franch and study on the mechanism of anti-colorectal cancer effect of two alkaloids thereof.

The drug pair consisting of Sophora flavescens Aiton (Sophorae flavescentis radix, Kushen) and Coptis chinensis Franch. (Coptidis rhizoma, Huanglian), as described in Prescriptions for Universal Relief (Pujifang), is widely used to treat laxation. Matrine and berberine are the major active components of Kushen and Huanglian, respectively. These agents have shown remarkable anti-cancer and anti-inflammatory effects. A mouse model of colorectal cancer was used to determine the most effective combination of Kushen and Huanglian against anti-colorectal cancer. The results showed that the combination of Kushen and Huanglian at a 1:1 ratio exerted the best anti-colorectal cancer effect versus other ratios. Moreover, the anti-colorectal cancer effect and potential mechanism underlying the effects of matrine and berberine were evaluated by the analysis of combination treatment or monotherapy. In addition, the chemical constituents of Kushen and Huanglian were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 67 chemical components were identified from the Kushen-Huanglian drug pair (water extraction), and the levels of matrine and berberine were 129 and 232 µg/g, respectively. Matrine and berberine reduced the growth of colorectal cancer and relieved the pathological conditions in mice. In addition, the combination of matrine and berberine displayed better anti-colorectal cancer efficacy than monotherapy. Moreover, matrine and berberine reduced the relative abundance of Bacteroidota and Campilobacterota at phylum level and that of Helicobacter, Lachnospiraceae_NK4A136_group, Candidatus_Arthromitus, norank_f_Lachnospiraceae, Rikenella, Odoribacter, Streptococcus, norank_f_Ruminococcaceae, and Anaerotruncus at the genus level. Western blotting results demonstrated that treatment with matrine and berberine decreased the protein expressions of c-MYC and RAS, whereas it increased that of sirtuin 3 (Sirt3). The findings indicated that the combination of matrine and berberine was more effective in inhibiting colorectal cancer than monotherapy. This beneficial effect might depend on the improvement of intestinal microbiota structure and regulation of the RAS/MEK/ERK-c-MYC-Sirt3 signaling axis.

Dynamics of CD68 receptor expression in macrophages of the interstitial space of the rat testis under triptorelin prolonged administration

Testosterone, the production of which is stimulated by the release of luteinizing hormone (LH) has a remarkable anti-inflammatory and immunomodulatory effect, and in conditions of testosterone deficiency tissue damage can occur due to excessive differentiation of macrophages into a pro-inflammatory M1 phenotype. The aim of this study was to determine the spread of CD68 receptorn as the marker of inflammation on the cells in the interstitial space and testicular vessels under LH synthesis blockade with tryptorelin. Sexually mature white male rats were randomly divided into control (10 animals) and experimental (25 animals) groups. Animals in the experimental group were injected with a tryptorelin acetate solution (0.3 mg/kg). Immunochemical analysis of CD68+ expression was estimated at Olympus FV10i-LIV laser scanning confocal microscope using fluorescent labeling dye hilyte flour 488. It was shown that luteinizing hormone deprivation led to an increase in the distribution of the CD68 receptor in the interstitial space and in the testicular vessels from day 30 to 180 of the experiment, associated with the increase of inducible NO synthase activity in testis tissue. Keywords: CD68, luteinizing hormone, macrophage M1 phenotype, testis, testosterone, tryptorelin

Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.

Methyl gallate nanomicelles impairs neutrophil accumulated in zymosan-induced arthritis

Arthritis is a chronic disease that affects, approximately, 1 % of the total global population. It is characterized by chronic inflammation, accompanied in most of the cases of motor disability and sever pain. The main therapies available have high risk of failure and advanced treatments are scarce and highly cost. In this scenario, search for effective, safe and low-cost treatments is quite desirable. Methyl gallate (MG) is a plant-derived phenolic compound described to present remarkable anti-inflammatory effect in experimental models of arthritis. Thus, in this study we formulated nanomicelles of MG using Pluronic (F-127) as matrix and evaluated in vivo the pharmacokinetic, biodistribution and its effect in the mice model of zymosan-induced arthritis. The nanomicelles were formed with a size 126 nm. The biodistribution showed a ubiquitous tissue deposition with a renal excretion. The pharmacokinetics showed elimination half-life of 1.72 h and a clearance of 0.006 L/h. The oral pretreatment with nanomicelles containing MG (3.5 or 7 mg/kg) demonstrated a reduction in total leukocytes, neutrophils, and mononuclear cells from the inflammation site. The data supports the use of methyl gallate nanomicelles as an alternative drug for arthritis. Data availabilityAll the data of this study are transparent.

Design and dermatokinetic appraisal of lornoxicam-loaded ultrafine self-nanoemulsion hydrogel for the management of inflammation: In vitro and in vivo studies

The present study aimed to evaluate the impact of ultrafine nanoemulsions on the transdermal delivery of lornoxicam (LOR) for management of the inflammation. The transdermal administration of LORNE could increase the efficacy of LOR with a reduction in side effects. Merging the beneficial properties of ultrafine nanoemulsions and their components (penetration enhancers) can lead to good solubilization, a small droplet size, and more effective LOR carriers. Therefore, this study aims to develop and evaluate the potential use of ultrafine nanoemulsions of LOR (LORNE) to elucidate their skin targeting for the treatment of inflammation. Based on solubility and pseudo ternary phase diagram tests, ultrafine LORNE composed of Labrafil M 2125 CS, Cremophor RH40, and Transcutol HP to deliver LOR was developed and characterized for its physicochemical properties, emulsification, and in vitro release. The selected LORNE was incorporated into carbopol gel (LORNE-Gel) and examined for ex vivo skin permeation, retention, dermatokinetics, anti-inflammatory efficacy, and skin irritation. The selected LORNE12-Gel could improve skin permeation, retention, and dermatokinetic results significantly (p < 0.05) with enhanced CSkin max and AUC0-48h compared to LOR-Gel. Moreover, LORNE12-Gel showed a remarkable anti-inflammatory effect compared to LOR-Gel after topical application. No signs of skin irritation were observed following treatment, indicating the safety of LORNE12-Gel. Thus, this study demonstrated that LOR-loaded LORNE12-Gel could be promising as an efficient transdermal nanocarrier for an anti-inflammatory alternative.

Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides.

Polygonati Rhizoma, a typical homology of medicine and food, possesses remarkable anti-fatigue, anti-aging, metabolic regulatory, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetes, and anti-cancer effects. Among bioactive phytochemicals in Polygonati Rhizoma, polysaccharides play important roles in the health-promoting activities through the mechanisms mentioned above and potential synergistic effects with other bioactives. In this review, we briefly introduce the updated biosynthesis of polysaccharides, the purification method, the structure characterization, and food applications, and discuss in detail the biological activities of Polygonati Rhizoma polysaccharides and associated mechanisms, aiming at broadening the usage of Polygonati Rhizoma as functional food and medicine.

The anti-inflammatory and analgesic activities of 2Br-Crebanine and Stephanine from Stephania yunnanenses H. S.Lo.

Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy. Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved. Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels. Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1β and TNF-α) by LPS-induced RAW264.7 macrophages (p < .01). Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.

A local dark tea - Liubao tea - extract exhibits remarkable performance in oral tissue regeneration, inflammation relief and oral microbiota reconstruction.

The prevalence of oral health problems is ubiquitous in contemporary society, with particular emphasis placed on the central role of oral flora in mitigating this issue. Both ancient literature and modern research have highlighted the promising application of tea with substantial bioactive properties, particularly dark tea, in preserving and promoting oral health. Liubao tea, a widely consumed dark tea with increasing popularity in recent years, has been reported to possess abundant bioactive constituents, exhibit remarkable antioxidant and anti-inflammatory effects, modulate the flora structure and so on. It may be a promising candidate for addressing oral health problems. In this study, Liubao tea was meticulously extracted, purified and identified, followed by an investigation of its potential to modulate oral microecology by virtue of an acetic acid-induced oral disorder murine model. The results revealed that Liubao tea extract (LTE) application commendably reconstructed the oral mucosal barrier, promoted tissue regeneration and mitigated micro-inflammation. Furthermore, LTE treatment could also ameliorate the oral flora composition by decreasing the abundance of Proteobacteria and increasing the abundance of Firmicutes and Actinobacteria at the phylum level, as well as inhibiting pernicious bacteria such as Streptococcus and Delftia acidovorans. So, it could promote the generation of a beneficial microenvironment and regulate the immune process. Overall, LTE demonstrated remarkable potential in regulating the balance of oral microecology, suggesting that it may represent a promising therapeutic strategy for oral health concerns.

Evaluation of Curcumin Nanoparticles against Rabbit Skin Infection

Curcumin is a polyphenolic compound with multiple beneficial effects in human health. It has shown a remarkable anti-inflammatory, antibacterial, antifungal, anticancer, and antioxidant effects. The limitations of curcumin are primarily in its bioavailability. Curcumin nanoparticles is suggested to reduce the limitation of bulk curcumin and probably enhance its desired effect. Curcumin was turned into nanoparticles by using simple wet-milling method. The characterization of curcumin nanoparticles indicated the presence of curcumin in size less than 100 nm. The effect of both curcumin and curcumin nanoparticles on wound healing was investigated in rabbits, in paraffin wax. Rabbits whom under curcumin and curcumin nanoparticles have shown faster healing from day 5 compared to control rabbits whom showed a proximate advancement after day 7. On day 14, rabbits whom treated with bulk and nanosized curcumin have shown a perfect healing with no sign of infection. Furthermore, both bulk and nanosized curcumin have shown a comparable antioxidant effect with ascorbic acid. Furthermore, curcumin nanoparticles were exhibited a slightly powerful antioxidant effect compared to curcumin.

A Review on Unleashing the Potentials of Natural Products in Managing Dengue

Background/Aims: Dengue virus (DENV) spreads widely in many tropical and sub-tropical countries by Aedes sp. In recent decades, dengue has been alarmingly on the rise and affects approximately half of the world population. The current dengue treatments are still mainly supportive without any approved vaccines or effective anti-dengue drugs. This leads to an urgency to seek alternative solutions in reducing dengue morbidity and mortality. Methods: A total of 94 articles describing in vitro and in vivo studies were screened and selected through curated databases. The selected articles underpinned the potentials of natural products as alternative anti-dengue compounds. Results: Those compounds have been employed as larvicide, mosquitocide, mosquito repellents, agents in sticky traps and non-specific interventions for dengue. In this review, their direct and indirect effects on dengue virus replication and dengue diseases were deliberated. Inteestingly, the majority of them demonstrated remarkable anti-inflammatory effects on dengue diseases. Several phytochemical contents such as luteolin, coumarins and geraniin were shown to inhibit DENV replication in vitro. Conclusion: Natural product-based anti-dengue agents are believed to be less costly, easy to derive, biologically effective and less toxic. This review, therefore, aims to provide current updates and insights on the benefits of natural products in preventing, managing and treating dengue.