Recent advances on cyanidin-3-O-glucoside in preventing obesity-related metabolic disorders: A comprehensive review.

Anthocyanins, found in various pigmented plants as secondary metabolites, represent a class of dietary polyphenols known for their bioactive properties, demonstrating health-promoting effects against several chronic diseases. Among these, cyanidin-3-O-glucoside (C3G) is one of the most prevalent types of anthocyanins. Upon consumption, C3G undergoes phases I and II metabolism by oral epithelial cells, absorption in the gastric epithelium, and gut transformation (phase II & microbial metabolism), with limited amounts reaching the bloodstream. Obesity, characterized by excessive body fat accumulation, is a global health concern associated with heightened risks of disability, illness, and mortality. This comprehensive review delves into the biodegradation and absorption dynamics of C3G within the gastrointestinal tract. It meticulously examines the latest research findings, drawn from in vitro and in vivo models, presenting evidence underlining C3G's bioactivity. Notably, C3G has demonstrated significant efficacy in combating obesity, by regulating lipid metabolism, specifically decreasing lipid synthesis, increasing fatty acid oxidation, and reducing lipid accumulation. Additionally, C3G enhances energy homeostasis by boosting energy expenditure, promoting the activity of brown adipose tissue, and stimulating mitochondrial biogenesis. Furthermore, C3G shows potential in managing various prevalent obesity-related conditions. These include cardiovascular diseases (CVD) and hypertension through the suppression of reactive oxygen species (ROS) production, enhancement of endogenous antioxidant enzyme levels, and inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway and by exercising its cardioprotective and vascular effects by decreasing pulmonary artery thickness and systolic pressure which enhances vascular relaxation and angiogenesis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are also managed by reducing gluconeogenesis via AMPK pathway activation, promoting autophagy, protecting pancreatic ß-cells from oxidative stress and enhancing glucose-stimulated insulin secretion. Additionally, C3G improves insulin sensitivity by upregulating GLUT-1 and GLUT-4 expression and regulating the PI3K/Akt pathway. C3G exhibits anti-inflammatory properties by inhibiting the NF-κB pathway, reducing pro-inflammatory cytokines, and shifting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. C3G demonstrates antioxidative effects by enhancing the expression of antioxidant enzymes, reducing ROS production, and activating the Nrf2/AMPK signaling pathway. Moreover, these mechanisms also contribute to attenuating inflammatory bowel disease and regulating gut microbiota by decreasing Firmicutes and increasing Bacteroidetes abundance, restoring colon length, and reducing levels of inflammatory cytokines. The therapeutic potential of C3G extends beyond metabolic disorders; it has also been found effective in managing specific cancer types and neurodegenerative disorders. The findings of this research can provide an important reference for future investigations that seek to improve human health through the use of naturally occurring bioactive compounds.

Two New Compounds Isolated from the Itea omeiensis and Their Anti-oxidant Activities.

Two new compounds (1-2) together with ten known compounds (3-12) were isolated for the first time from the 95 % EtOH extract of aerial parts of Itea omeiensis. Their structures were elucidated based on extensive spectroscopic analyses and comparison with published data. The structure of 1 was further confirmed through single-crystal X-ray diffraction analysis, and circular dichroism (CD) spectrum in combination with acid hydrolysis was employed for the absolute configuration determination of 2. Compound 1 was the first 2-arylbenzo[b]furan with an extra six-membered lactone ring from Itea plants. Anti-oxidant assays indicated that compound 1 possessed significant radical scavenging effects on 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS⋅+ ) with IC50 values of 0.14 and 0.06 mg/mL, respectively, which were comparable to the positive control of ascorbic acid. However, no obvious anti-hepatocellular carcinoma activity was observed for compounds 1 and 2.

Olea europaea L. leaf extract mitigates pulmonary inflammation and tissue destruction in Wistar rats induced by concurrent exposure to noise and toluene.

This study aimed to investigate the effects of combined exposure to noise (85 dB(A)) and inhaled Toluene (300 ± 10 ppm) on rat lung health. It also aimed to assess the potential therapeutic effects of Olea europaea L. leaves extract (OLE) (40 mg/kg/day) using biochemical, histopathological, and immunohistochemical (IHC) analyses, as well as determination of pro-inflammatory cytokines (TNF-α and IL-1ß), and in silico Docking studies. The experiment involved forty-two male Wistar rats divided into seven groups, each exposed to a 6-week/6-hour/day regimen of noise and Toluene. The groups included a control group, rats co-exposed to noise and Toluene, and rats co-exposed to noise and Toluene treated with OLE for different durations. The results indicated that noise and Toluene exposure led to structural damage in lung tissue, oxidative harm, and increased levels of pro-inflammatory cytokines (TNF-α and IL-1ß). However, the administration of OLE extract demonstrated positive effects in mitigating these adverse outcomes. OLE treatment reduced lipid peroxidation and enhanced the activities of catalase and superoxide dismutase, indicating its anti-oxidant properties. Furthermore, OLE significantly decreased the levels of pro-inflammatory cytokines compared to the groups exposed to noise and Toluene without OLE treatment. Moreover, the in silico investigation substantiated a robust affinity between COX-2 and OLE components, affirming the anti-inflammatory activity. Overall, our findings suggest that OLE possesses anti-inflammatory and anti-oxidative properties that mitigate the adverse effects of concurrent exposure to noise and Toluene.

Design and Synthesis of Dimethylaminomethyl-Substituted Curcumin Derivatives: Potent Anti-Inflammatory, Anti-Oxidant, and Radioprotection Activity, Improved Aqueous Solubility Compared with Curcumin.

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1-15). Acetate of these derivatives were prepared (compounds 1a-15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.

Development of Lipid Polymer Hybrid Nanoparticles of Abietic Acid: Optimization, In-Vitro and Preclinical Evaluation.

The objective of the current research was to develop abietic acid (AA)-loaded hybrid polymeric nanoparticles (HNPs) for anti-inflammatory and antioxidant activity after oral administration. AAHNPs were developed by microinjection technique and optimized by 3-factor 3-level Box-Behnken design. The AAHNPs were evaluated for morphology, FTIR, X-ray diffraction, in-vitro release, ex-vivo permeation, in-vitro antioxidant, and in-vivo anti-inflammatory activity. The optimized AAHNPs (AAHNPsopt) displayed 384.5 ± 6.36nm of PS, 0.376 of PDI, 23.0 mV of ZP, and 80.01 ± 1.89% of EE. FTIR and X-ray diffraction study results revealed that AA was encapsulated into a HNPs matrix. The AAHNPsopt showed significant (P < 0.05) high and sustained release of AA (86.72 ± 4.92%) than pure AA (29.87 ± 3.11%) in 24h. AAHNPsopt showed an initial fast release of AA (20.12 ± 3.07% in 2h), which succeeded in reaching the therapeutic concentration. The AAHNPsopt showed 2.49-fold higher ex-vivo gut permeation flux than pure AA due to the presence of lipid and surfactant. The AAHNPsopt exhibited significantly (P < 0.05, P < 0.01, P < 0.001) higher antioxidant activity as compared to pure AA at each concentration. AAHNPsopt formulation displayed a significantly (P < 0.05) higher anti-inflammatory effect (21.51 ± 2.23% swelling) as compared to pure AA (46.51 ± 1.74% swelling). From the in-vitro and in-vivo finding, it was concluded that HNPs might be a suitable carrier for the improvement of the therapeutic efficacy of the drug.

Quercetin extraction from small onion skin (Allium cepa L. var. aggregatum Don.) and its antioxidant activity.

In the present study, the maximum yield of quercetin was optimized for the ethanol extraction of small onions (Allium cepa L. var. aggregatum Don.), and the antioxidant activity was investigated in vitro. The extraction of quercetin from the small onion skin was carried out through ethanol solvent extraction with different ratios of ethanol and water. Ethanol: water ratio produced the highest quercetin from the onion skin. RP-HPLC analysis of the extracted material showed 2, 122 mg/g of quercetin and 0.34 mg/g of isorhamnetin. A total of 301.03 mg GAE/g dry weight and 156 mg/g quercetin equivalents were found in the onion skin extract. DPPH and ABTS free radical scavenging potentials of the tested extract (90:10 v/v) were dose-dependent, with IC50 values of 62.27 µg/mL and 53.65 µg/mL, respectively. Therefore, the present study reports that small onion skin extract rich in quercetin may serve as a promising antioxidant and anticancer agent.

Biological applications of green synthesized lanthanum oxide nanoparticles via Couroupita guianensis abul leaves extract.

In this work, extract from leaves of Couroupita guianensis (C.guianensis) abul was used as a potential reducing agent for the synthesis of lanthanum oxide (La2O3) nanoparticles (NPs). In addition, the morphology and several physicochemical properties of the La2O3 NPs were improved by introducing the ionic liquid of 1-butyl 3-methyl imidazolium tetra fluoroborate (BMIM BF4) as a stabilizing agent. The structure of the La2O3 (without ionic liquid) and IL-La2O3 (with ionic liquid) NPs were analyzed by X-ray diffraction (XRD). The chemical composition of the synthesized NPs was analyzed using the energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) studies. Optical and morphological studies were also performed. The antibacterial, antioxidant, anti-inflammatory, anti-diabetic and anticancer properties of the La2O3 and IL-La2O3 NPs were evaluated.

Therapeutic potential of dietary flavonoid hyperoside against non-communicable diseases: targeting underlying properties of diseases.

Non-communicable diseases (NCDs) are a global epidemic with diverse pathogenesis. Among them, oxidative stress and inflammation are the most fundamental co-morbid features. Therefore, multi-targets and multi-pathways therapies with significant anti-oxidant and anti-inflammatory activities are potential effective measures for preventing and treating NCDs. The flavonol glycoside compound hyperoside (Hyp) is widely found in a variety of fruits, vegetables, beverages, and medicinal plants and has various health benefits, especially excellent anti-oxidant and anti-inflammatory properties targeting nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. In this review, we summarize the pathogenesis associated with oxidative stress and inflammation in NCDs and the biological activity and therapeutic potential of Hyp. Our findings reveal that the anti-oxidant and anti-inflammatory activities regulated by Hyp are associated with numerous biological mechanisms, including positive regulation of mitochondrial function, apoptosis, autophagy, and higher-level biological damage activities. Hyp is thought to be beneficial against organ injuries, cancer, depression, diabetes, and osteoporosis, and is a potent anti-NCDs agent. Additionally, the sources, bioavailability, pharmacy, and safety of Hyp have been established, highlighting the potential to develop Hyp into dietary supplements and nutraceuticals.

Bioluminescence Sensing in 3D Spherical Microtissues for Multiple Bioactivity Analysis of Environmental Samples.

The development of predictive in vitro sensing tools able to provide rapid information on the different bioactivities of a sample is of pivotal importance, not only to monitor environmental toxicants, but also to understand their mechanisms of action on diverse molecular pathways. This mechanistic understanding is highly important for the characterization of toxicological hazards, and for the risk assessment of chemicals and environmental samples such as surface waters and effluents. Prompted by this need, we developed and optimized a straightforward bioluminescent multiplexed assay which enables the measurement of four bioactivities, selected for their relevance from a toxicological perspective, in bioluminescent microtissues. The assay was developed to monitor inflammatory, antioxidant, and toxic activity, and the presence of heavy metals, and was successfully applied to the analysis of river water samples, showing potential applicability for environmental analyses. The assay, which does not require advanced equipment, can be easily implemented in general laboratories equipped with basic cell culture facilities and a luminometer.

Analysis of Components and Properties of Extractives from Alnus cremastogyne Pods from Different Provenances.

Chemical components with anti-oxidant, anti-inflammatory, and anti-cancer properties extracted from Alnus bark and leaves have been extensively studied. However, less attention has been paid to extractives from Alnus pods, which are mostly treated as waste. Here, extractives of Alnus cremastogyne pods from 12 provenances in Sichuan Province were studied for high value-added utilization of Alnus waste. The extractives were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS), Ultraviolet-visible spectroscopy (UV-Vis spectra), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity. A total of 58, 49, and 51 chemical components were found when the organic solvents of ethanol, petroleum ether, and ethyl acetate were used to collect extractives, respectively. These chemical components including Phytol, CIS-5,8,11,14,17-eicosapentaenoic acid, Germacrene D, Lupeol, and ß-sitosterol, etc., have wide applications in the fields of pharmacy and cosmetics. Moreover, it was also found that extractives in ethanol and ethyl acetate had impressive UV resistance, especially for UV-C and UV-B blocking. The results showed that the maximum block ratio towards UV-C and UV-B could reach 99%. In addition, the ethanol extract showed good anti-oxidant activity with a maximum free radical scavenging rate of 96.19%. This comprehensive and systematic study on extractives from Alnus cremastogyne pods promotes the development of high-value utilization of Alnus components.

Purification, secondary structure and antioxidant activity of metallothionein zinc-binding proteins from Arca subcrenata.

Zinc-binding proteins named MT-M-I and MT-M-II were obtained after purification from metal-exposed hairy clams (Arca subcrenata) using gel permeation and ion-exchange chromatography. MT-M-I and MT-M-II were resolved by ion-exchange chromatography, and they were found to have similar molecular weights. MT-M-I and MT-M-II can bind 6 and 7 equivalents of Zn2+ in vitro, and they showed unusual migration behaviors in Tricine sodium dodecyl sulfate polyacrylamide gel electrophoresis (Tricine-SDS-PAGE). Such migration behaviors may be due to themetal thiolate clusters in these proteins. In terms of amino acid composition, the proportion of cysteine in MT-M-I and MT-M-II was approximately 30%, and glycine accounted for approximately 15%, where as aromatic amino acids were absent. Considering the performance in Tricine-SDS-PAGE and the amino acid compositions, MT-M-I and MT-M-II conform to the molecular characteristics of the metallothionein proteins. The structures were explored using circular dichroism (CD) and Fourier-transform infrared spectroscopy (FTIR). Also determined the antioxidant activities in terms of DPPH radical scavenging ability, hydroxyl radical (·OH) scavenging ability, and ferric-reducing/antioxidant power. The antioxidant activities of MT-M-I were found to be stronger than those of MT-M-II.

Bioactive prenylated C6-C3 derivatives from the stems and leaves of Illicium fargesii.

Seventeen new prenylated C6-C3 derivatives, namely, illifargeins A-M (1-13), including three pairs of enantiomers (1, 5, and 12) and one norillifargeal A (14), together with eight known analogues (15-22), were isolated from the stems and leaves of Illicium fargesii. The structures of the new compounds were elucidated using spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). Their absolute configurations were determined by using experimental and calculated ECD data analysis, as well as a modified Mosher's method. Compounds 1a, 1b, 2, 3, 5a, 7, 10, 11, 15, 16, 19, and 20 showed potential activity against Coxsackie virus B3, with IC50 values ranging from 6.23 to 33.33 µM. Compounds 9 and 15 exhibited potential activity against influenza virus A, with IC50 values of 11.11 and 19.24 µM, respectively. Compounds 2, 3, and 18 exhibited potential anti-oxidant activity, with IC50 values ranging from 1.43 to 6.71 µM.

Serum Albumin: A Multifaced Enzyme.

Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrier of fatty acids, recognizes metal ions, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays esterase, enolase, glucuronidase, and peroxidase (pseudo)-enzymatic activities. HSA-based catalysis is physiologically relevant, affecting the metabolism of endogenous and exogenous compounds including proteins, lipids, cholesterol, reactive oxygen species (ROS), and drugs. Catalytic properties of HSA are modulated by allosteric effectors, competitive inhibitors, chemical modifications, pathological conditions, and aging. HSA displays anti-oxidant properties and is critical for plasma detoxification from toxic agents and for pro-drugs activation. The enzymatic properties of HSA can be also exploited by chemical industries as a scaffold to produce libraries of catalysts with improved proficiency and stereoselectivity for water decontamination from poisonous agents and environmental contaminants, in the so called "green chemistry" field. Here, an overview of the intrinsic and metal dependent (pseudo-)enzymatic properties of HSA is reported to highlight the roles played by this multifaced protein.

Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention.

Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

Anti-Cancer Activity and Phenolic Content of Extracts Derived from Cypriot Carob (Ceratonia siliqua L.) Pods Using Different Solvents.

Extracts derived from the Ceratonia siliqua L. (carob) tree have been widely studied for their ability to prevent many diseases mainly due to the presence of polyphenolic compounds. In this study, we explored, for the first time, the anti-cancer properties of Cypriot carobs. We produced extracts from ripe and unripe whole carobs, pulp and seeds using solvents with different polarities. We measured the ability of the extracts to inhibit proliferation and induce apoptosis in cancer and normal immortalized breast cells, using the MTT assay, cell cycle analysis and Western Blotting. The extracts' total polyphenol content and anti-oxidant action was evaluated using the Folin-Ciocalteu method and the DPPH assay. Finally, we used LC-MS analysis to identify and quantify polyphenols in the most effective extracts. Our results demonstrate that the anti-proliferative capacity of carob extracts varied with the stage of carob maturity and the extraction solvent. The Diethyl-ether and Ethyl acetate extracts derived from the ripe whole fruit had high Myricetin content and also displayed specific activity against cancer cells. Their mechanism of action involved caspase-dependent and independent apoptosis. Our results indicate that extracts from Cypriot carobs may have potential uses in the development of nutritional supplements and pharmaceuticals.

Synthesis, biological evaluation of benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety as potential anti-oxidant and anti-inflammatory agents.

Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+ bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.

Characterization of a New Chitosanase from a Marine Bacillus sp. and the Anti-Oxidant Activity of Its Hydrolysate.

Chitooligosaccharide (COS) has been recognized to exhibit efficient anti-oxidant activity. Enzymatic hydrolysis using chitosanases can retain all the amino and hydroxyl groups of chitosan, which are necessary for its activity. In this study, a new chitosanase encoding gene, csnQ, was cloned from the marine Bacillus sp. Q1098 and expressed in Escherichia coli. The recombinant chitosanase, CsnQ, showed maximal activity at pH 5.31 and 60 °C. Determination of CsnQ pH-stability showed that CsnQ could retain more than 50% of its activity over a wide pH, from 3.60 to 9.80. CsnQ is an endo-type chitosanase, yielding chitodisaccharide as the main product. Additionally, in vitro and in vivo analyses indicated that chitodisaccharide possesses much more effective anti-oxidant activity than glucosamine and low molecular weight chitosan (LMW-CS) (~5 kDa). Notably, to our knowledge, this is the first evidence that chitodisaccharide is the minimal COS fragment required for free radical scavenging.

A study of the hepatoprotective effect of Plantago psyllium L. seed extract against Carbon tetrachloride induced hepatic injury in rats.

BACKGROUND: The liver is the main metabolic organ involved in disposal and detoxification of various molecules. Plantago psyllium L. seed has been reported to exert positive effects in some pathological conditions. The current study aims to assess the hepatoprotective effect of Plantago psyllium L. seed extract against carbon tetrachloride-induced hepatotoxicity. METHODS: Male albino Wistar rats were randomly divided into five groups of 10 rats each. Hepatotoxicity was induced by orally administered carbon tetrachloride (CCl4) for nine weeks with or without the different treatments which were utilized daily for the whole nine weeks. Serum and tissue samples were then withdrawn and different liver biomarkers were investigated. RESULTS: Treatment of rats with Psyllium seed ethanolic extract significantly alleviated the toxic effects of CCl4. This was evidenced by its ability to restore liver biomarkers levels. Moreover, treatment with Psyllium seed extract normalized levels of oxidative biomarkers such as lipid peroxidation, hepatic content of reduced glutathione and catalase activity, as well as the expression level of the inflammatory marker TNF-α. Histopathological examination reflected the protective effect of the extract on liver architecture and confirmed the observed biochemical data. CONCLUSIONS: The presented data demonstrates a potential hepatoprotective effect of Psyllium seed extract compared to the standard hepatoprotective drug silymarin. This effect can be attributed to the antioxidant and anti-inflammatory effects of Psyllium extract.

Bio-preservative effect of blends of essential oils: natural anti-oxidant and anti-microbial agents for the shelf life enhancement of emulsion based chicken sausages.

This work explores the efficacy and potential of four different blends of essential oils as bio-preservative for enhancement of shelf life of emulsion based ready-to-eat chicken sausages. Pre-optimized levels of four different blends of essential oils: 0.25% each of B-1, B-2, B-3 and 0.125% of B-4, were tried in the chicken sausages. Four different treatments along with control were then aerobically packaged and stored under refrigerated (4 ± 1 °C) conditions. An increase in pH and TBARS value was found to be significantly lower in the case of B-2 products. Significantly higher values for DPPH activity (% inhibition) and total phenolic content (µg/g) were also observed for B-2 products which indicated that B-2 products had better oxidative stability. Further, B-1 and B-2 products were observed with significantly lower microbial count; however, B-4 products received slightly higher sensory scores than B-2. It was found that B-1, 2 and 3 (each at 0.25%) and B-4 (0.125%) enhanced the shelf life of chicken sausages by 13-14 days, 16-17 days, 10-11 days and 6-7 days, respectively under refrigerated (4 ± 1 °C) storage.

A retinoid X receptor partial agonist attenuates pulmonary emphysema and airway inflammation.

BACKGROUND: Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signalling by 9-cis retinoic acid, a vitamin A derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners, e.g., for retinoic acid receptors, vitamin D receptors, and peroxisome proliferator-activated receptors. The NR family may also play important roles in the development of emphysema. However, the role of RXRs in the pathogenesis of emphysema is not well defined. METHODS: We developed a novel RXR partial agonist (NEt-4IB) and investigated its effect and mechanism compared to a full agonist (bexarotene) in a murine model of emphysema. For emphysema induction, BALB/c mice received intraperitoneal cigarette smoke extract (CSE) or intratracheal porcine pancreas elastase (PPE). Treatment with RXR agonists was initiated before or after emphysema induction. RESULTS: Treatment with NEt-4IB significantly suppressed the increase in static lung compliance and emphysematous changes in CSE-induced emphysema and PPE-induced established and progressive emphysema. NEt-4IB significantly suppressed PPE-induced neutrophilic airway inflammation and the levels of keratinocyte chemoattractant (KC), C-X-C motif ligand5 (CXCL5), interferon (IFN)-γ and IL-17. NEt-4IB also improved the matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and the reduced anti-oxidant activity in bronchoalveolar lavage (BAL) fluid. NEt-4IB suppressed PPE-induced vascular endothelial growth factor (VEGF) expression in the airway. Treatment with NEt-4IB and bexarotene significantly suppressed the increase in static lung compliance and emphysematous changes. However, adverse effects of RXR agonists, including hypertriglyceridemia and hepatomegaly, were observed in bexarotene-treated mice but not in NEt-4IB-treated mice. CONCLUSION: These data suggest that RXRs play crucial roles in emphysema and airway inflammation, and novel partial RXR agonists could be potential therapeutic strategies for the treatment of PPE- and CSE-induced emphysema.