Early Experience with a Novel Treatment for Menière's Disease: A Long Acting Dexamethasone Formulation for Precise Delivery to the Round Window Membrane.

OBJECTIVE: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease. STUDY DESIGN: Prospective, unblinded, cohort study. SETTING: Tertiary care neurotology clinic. PATIENTS: Adults 18 to 85 years with a diagnosis of unilateral definite Menière's disease per Barany society criteria. INTERVENTIONS: A single injection of a long-acting gel formulation under direct visualization into the round window niche. MAIN OUTCOME MEASURES: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer. RESULTS: Ten subjects with unilateral Menière's disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment. CONCLUSIONS: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy.

Cannabidiol-Loaded Solid Lipid Nanoparticles Ameliorate the Inhibition of Proinflammatory Cytokines and Free Radicals in an In Vitro Inflammation-Induced Cell Model.

Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa. It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability. This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained. The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD. In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.

Therapeutic Potential of Nanocarrier Mediated Delivery of Peptides for Wound Healing: Current Status, Challenges and Future Prospective.

Wound healing presents a complex physiological process that involves a sequence of events orchestrated by various cellular and molecular mechanisms. In recent years, there has been growing interest in leveraging nanomaterials and peptides to enhance wound healing outcomes. Nanocarriers offer unique properties such as high surface area-to-volume ratio, tunable physicochemical characteristics, and the ability to deliver therapeutic agents in a controlled manner. Similarly, peptides, with their diverse biological activities and low immunogenicity, hold great promise as therapeutics in wound healing applications. In this review, authors explore the potential of peptides as bioactive components in wound healing formulations, focusing on their antimicrobial, anti-inflammatory, and pro-regenerative properties. Despite the significant progress made in this field, several challenges remain, including the need for standardized characterization methods, optimization of biocompatibility and safety profiles, and translation from bench to bedside. Furthermore, developing multifunctional nanomaterial-peptide hybrid systems represents promising avenues for future research. Overall, the integration of nanomaterials made up of natural or synthetic polymers with peptide-based formulations holds tremendous therapeutic potential in advancing the field of wound healing and improving clinical outcomes for patients with acute and chronic wounds.

Effects of prednisolone tapering on effectiveness of infliximab in patients with ulcerative colitis: data from a retrospective cohort.

BACKGROUND AND OBJECTIVE: The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. RESULTS: There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. CONCLUSION: In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy.

Nanotechnology in inflammation: cutting-edge advances in diagnostics, therapeutics and theranostics.

Inflammatory dysregulation is intimately associated with the occurrence and progression of many life-threatening diseases. Accurate detection and timely therapeutic intervention on inflammatory dysregulation are crucial for the effective therapy of inflammation-associated diseases. However, the clinical outcomes of inflammation-involved disorders are still unsatisfactory. Therefore, there is an urgent need to develop innovative anti-inflammatory strategies by integrating emerging technological innovations with traditional therapeutics. Biomedical nanotechnology is one of the promising fields that can potentially transform the diagnosis and treatment of inflammation. In this review, we outline recent advances in biomedical nanotechnology for the diagnosis and treatment of inflammation, with special attention paid to nanosensors and nanoprobes for precise diagnosis of inflammation-related diseases, emerging anti-inflammatory nanotherapeutics, as well as nanotheranostics and combined anti-inflammatory applications. Moreover, the prospects and challenges for clinical translation of nanoprobes and anti-inflammatory nanomedicines are highlighted.

Nanofiber Hydrogel Drug Delivery System for Prevention of Postsurgical Intestinal Adhesion.

Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic-co-glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

Unleashing the power of chlorogenic acid: exploring its potential in nutrition delivery and the food industry.

In the contemporary era, heightened emphasis on health and safety has emerged as a paramount concern among individuals with food. The concepts of "natural" and "green" have progressively asserted dominance in the food consumption market. Consequently, through continuous exploration and development, an escalating array of natural bioactive ingredients is finding application in both nutrition delivery and the broader food industry. Chlorogenic acid (CGA), a polyphenolic compound widely distributed in various plants in nature, has garnered significant attention. Abundant research underscores CGA's robust biological activity, showcasing notable preventive and therapeutic efficacy across diverse diseases. This article commences with a comprehensive overview, summarizing the dietary sources and primary biological activities of CGA. These encompass antioxidant, anti-inflammatory, antibacterial, anti-cancer, and neuroprotective activities. Next, a comprehensive overview of the current research on nutrient delivery systems incorporating CGA is provided. This exploration encompasses nanoparticle, liposome, hydrogel, and emulsion delivery systems. Additionally, the article explores the latest applications of CGA in the food industry. Serving as a cutting-edge theoretical foundation, this paper contributes to the design and development of CGA in the realms of nutrition delivery and the food industry. Finally, the article presents informed speculations and considerations for the future development of CGA.

Vitiligo in a Patient Receiving Adalimumab for Idiopathic Uveitis.

In recent years, adalimumab has been increasingly used in the chronic treatment of non-infectious uveitis. This case report aimed to describe a drug-induced adverse event in a 34-year-old man who presented with blurred vision and floaters in the right eye and was being treated for intermediate uveitis. The patient had started topical treatment with a diagnosis of uveitis at another center. Best corrected visual acuity at presentation was 0.8 (decimal) in the right eye and 1.0 in the left eye. On examination, the anterior chamber in the right eye was clear, with anterior vitreous cells and mild haze, and snow banking and vitreous opacities in the inferior periphery. Fluorescein angiography (FA) showed hyperfluorescence in the right disc and leakage in the inferior periphery. As the inflammation did not resolve with local treatment, systemic cyclosporine was administered, after which the patient exhibited vomiting and weakness. Cyclosporine was discontinued and adalimumab treatment was started. On examination 5 months later, bilateral vitreous cells and mild vitreous opacity were noted, and FA showed mild leakage in the inferior periphery bilaterally. In addition, a depigmented patchy vitiligo lesion was observed on the chin. Due to the persistence of intraocular inflammation and on the recommendation of the dermatology clinic, adalimumab treatment was continued and topical tacrolimus was started for the lesion. On examination 3 months later, the inflammatory findings had resolved and there was no progression of the vitiligo lesion. The patient's treatment was continued. Taken together with the previous literature findings, no pathology was found in the patient's systemic examination, suggesting that this lesion was a side effect of the treatment. Ophthalmologists should be alert for this side effect in patients receiving adalimumab.

Methyl jasmonate ameliorates pain-induced learning and memory impairments through regulating the expression of genes involved in neuroinflammation.

OBJECTIVE: Orofacial pain with high prevalence is one of the substantial human health issues. The importance of this matter became more apparent when it was revealed that orofacial pain, directly and indirectly, affects cognition performances. Currently, researchers have focused on investigating pharmaceutics to alleviate pain and ameliorate its subsequent cognitive impairments. DESIGN: In this study, the rats were first treated with the central administration of methyl jasmonate (MeJA), which is an antioxidant and anti-inflammatory bio-compound. After 20 min, orofacial pain was induced in the rats by the injection of capsaicin in their dental pulp. Subsequently, the animals' pain behaviors were analyzed, and the effects of pain and MeJA treatments on rats learning and memory were evaluated/compared using the Morris water maze (MWM) test. In addition, the expression of tumor necrosis factor-α (TNF-α), IL-1ß, BDNF, and COX-2 genes in the rats' hippocampus was evaluated using real-time polymerase chain reaction. RESULTS: Experiencing orofacial pain resulted in a significant decline in the rats learning and memory. However, the central administration of 20 µg/rat of MeJA effectively mitigated these impairments. In the MWM, the performance of the MeJA-treated rats showed a two- to threefold improvement compared to the nontreated ones. Moreover, in the hippocampus of pain-induced rats, the expression of pro-inflammatory factors TNF-α, IL-1ß, and COX-2 significantly increased, whereas the BDNF expression decreased. In contrast, MeJA downregulated the pro-inflammatory factors and upregulated the BDNF by more than 50%. CONCLUSIONS: These findings highlight the notable antinociceptive potential of MeJA and its ability to inhibit pain-induced learning and memory dysfunction through its anti-inflammatory effect.

Cytotoxicity, anti-inflammatory effect, and acute oral toxicity of a novel Attalea phalerata kernel oil-loaded nanocapsules.

The kernel oil of the Attalea phalerata Mart. Ex Spreng (Acurí) is traditionally used in several Latin American countries to treat respiratory problems, inflammation, and fever. However, it cannot be found on the literature any attend to use this oil in pharmaceutical formulation. In this paper, it was developed Acurí oil-loaded nanocapsules, and it was evaluated the cytotoxicity against cancer cells, the antinflammatory activity and the oral acute toxicity in rats. Acurí oil contains lauric acid as the predominant saturated fatty acid (433.26 mg/g) and oleic acid as the main unsaturated fatty acid (180.06 mg/g). The Acurí oil-loaded nanocapsules showed a size of 237 nm, a polydispersity index of 0.260, and a high ζ-potential of -78.75 mV. It was obtained an encapsulation efficiency of 88.77%, and the nanocapsules remain stable on the shelf for 180 days. The nanocapsules showed a rapid release profile (98.25% in 40 minutes). Nanocapsules at a dose of 10 mg/kg exhibit an anti-inflammatory effect similar to indomethacin at the same dose. The nanocapsules showed excellent antiproliferative effect and selectivity index against prostate tumor cells (IC50 2.09 µg/mL, SI=119.61) and kidney tumor cells (IC50 3.03 µg/mL, SI=82.50). Both Acurí oil and Acurí oil-loaded nanocapsules are nontoxic at a dose of 2000 mg/kg. Additionally, they reduce serum triglyceride and total cholesterol levels in rat and could find application in nutraceutical formulations. The Acurí oil-loaded nanocapsules emerge as a promising candidate for new antitumor therapies.

Ginkgo biloba attenuated detrimental inflammatory and oxidative events due to Trypanosoma brucei rhodesiense in mice treated with melarsoprol.

BACKGROUND: The severe late stage Human African Trypanosomiasis (HAT) caused by Trypanosoma brucei rhodesiense (T.b.r) is characterized by damage to the blood brain barrier, severe brain inflammation, oxidative stress and organ damage. Melarsoprol (MelB) is currently the only treatment available for this disease. MelB use is limited by its lethal neurotoxicity due to post-treatment reactive encephalopathy. This study sought to assess the potential of Ginkgo biloba (GB), a potent anti-inflammatory and antioxidant, to protect the integrity of the blood brain barrier and ameliorate detrimental inflammatory and oxidative events due to T.b.r in mice treated with MelB. METHODOLOGY: Group one constituted the control; group two was infected with T.b.r; group three was infected with T.b.r and treated with 2.2 mg/kg melarsoprol for 10 days; group four was infected with T.b.r and administered with GB 80 mg/kg for 30 days; group five was given GB 80mg/kg for two weeks before infection with T.b.r, and continued thereafter and group six was infected with T.b.r, administered with GB and treated with MelB. RESULTS: Co-administration of MelB and GB improved the survival rate of infected mice. When administered separately, MelB and GB protected the integrity of the blood brain barrier and improved neurological function in infected mice. Furthermore, the administration of MelB and GB prevented T.b.r-induced microcytic hypochromic anaemia and thrombocytopenia, as well as T.b.r-driven downregulation of total WBCs. Glutathione analysis showed that co-administration of MelB and GB prevented T.b.r-induced oxidative stress in the brain, spleen, heart and lungs. Notably, GB averted peroxidation and oxidant damage by ameliorating T.b.r and MelB-driven elevation of malondialdehyde (MDA) in the brain, kidney and liver. In fact, the co-administered group for the liver, registered the lowest MDA levels for infected mice. T.b.r-driven elevation of serum TNF-α, IFN-γ, uric acid and urea was abrogated by MelB and GB. Co-administration of MelB and GB was most effective in stabilizing TNFα levels. GB attenuated T.b.r and MelB-driven up-regulation of nitrite. CONCLUSION: Utilization of GB as an adjuvant therapy may ameliorate detrimental effects caused by T.b.r infection and MelB toxicity during late stage HAT.

The Anti-inflammatory Potential of a Strain of Probiotic Bifidobacterium pseudocatenulatum G7: In Vitro and In Vivo Evidence.

The genus Bifidobacterium has been widely used in functional foods for health promotion due to its beneficial effects on human health, especially in the gastrointestinal tract (GIT). In this study, we characterize the anti-inflammatory potential of the probiotic strain Bifidobacterium pseudocatenulatum G7, isolated from a healthy male adult. G7 secretion inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Moreover, oral administration of bacteria G7 alleviated the severity of colonic inflammation in dextran sulfate sodium (DSS)-treated colitis mice, which was evidenced by a decreased disease activity index (DAI) and enhanced structural integrity of the colon. The 16S rRNA gene sequencing result illustrated that the G7 alleviated DSS-induced gut microbiota dysbiosis, accompanied by the modulated bile acids and short-chain fatty acid (SCFA) levels. Overall, our results demonstrated the potential anti-inflammatory effects of Bifidobacterium pseudocatenulatum G7 on both in vitro and in vivo models, which provided a solid foundation for further development of a novel anti-inflammatory probiotic.

Feruloylated Oligosaccharides Prevented Influenza-Induced Lung Inflammation via the RIG-I/MAVS/TRAF3 Pathway.

Uncontrolled inflammation contributes significantly to the mortality in acute respiratory infections. Our previous research has demonstrated that maize bran feruloylated oligosaccharides (FOs) possess notable anti-inflammatory properties linked to the NF-kB pathway regulation. In this study, we clarified that the oral administration of FOs moderately inhibited H1N1 virus infection and reduced lung inflammation in influenza-infected mice by decreasing a wide spectrum of cytokines (IFN-α, IFN-ß, IL-6, IL-10, and IL-23) in the lungs. The mechanism involves FOs suppressing the transduction of the RIG-I/MAVS/TRAF3 signaling pathway, subsequently lowering the expression of NF-κB. In silico analysis suggests that FOs have a greater binding affinity for the RIG-I/MAVS signaling complex. This indicates that FOs have potential as promising targets for immune modulation. Moreover, in MAVS knockout mice, we confirmed that the anti-inflammatory function of FOs against influenza depends on MAVS. Comprehensive analysis using 16S rRNA gene sequencing and metabolite profiling techniques showed that FOs have the potential to restore immunity by modulating the gut microbiota. In conclusion, our study demonstrates that FOs are effective anti-inflammatory phytochemicals in inhibiting lung inflammation caused by influenza. This suggests that FOs could serve as a potential nutritional strategy for preventing the H1N1 virus infection and associated lung inflammation.

Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.

Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.

Development of a hydrogel containing bisabolol-loaded nanocapsules for the treatment of atopic dermatitis in a Balb/c mice model.

α-Bisabolol (αBIS), a plant-derived compound with anti-inflammatory properties, is potentially a therapeutic agent for Atopic dermatitis. However, its poor water solubility and photoinstability limit its topical application. Therefore, the present study, aimed to develop cationic polymeric nanocapsules of αBIS to improve its skin delivery, photostability, and therapeutic efficacy. The αBIS-loaded nanocapsules were prepared using the solvent displacement technique. A Box-Behnken (BB) design was employed to statistically optimize formulation variables and αBIS-loaded nanocapsules characterized by particle size, surface charge and encapsulation efficiency. The optimal formulation was selected, and the spherical shape of the nanocapsules was confirmed by scanning electron microscopy (SEM). Furthermore, hydrogel containing αBIS-loaded nanocapsules was prepared by thickening of nanocapsule suspension with Carbopol 934 and evaluated for rheology, in vitro drug release and skin permeation. Furthermore, a mice model of atopic dermatitis was used to evaluate the anti-inflammatory potential of the hydrogels. The optimal formulation displayed a spherical morphology under scanning electron microscopy (SEM) with an optimum particle size of 133.00 nm, polydispersity index (PDI) of 0.12, high EE% of 93 %, and improved optical stability of αBIS in the prepared nanocapsules compared to the free drug. The nano-based hydrogels demonstrated non-Newtonian pseudoplastic behavior and an increased αBIS in vitro release profile without causing skin irritation in rabbits. Drug retention within the dermis and epidermis layers significantly surpassed that of drug-free hydrogel. Moreover, in vivo histopathological studies and myeloperoxidase (MPO) enzyme activity, revealed that hydrogel containing bisabolol nanocapsules exhibited The best anti-inflammatory effect. The results showed that hydrogels containing bisabolol nanocapsules markedly alleviated dermatitis-related inflammation and reduced skin thickness in Balb/c mice. Our findings support nanocapsules as an effective drug delivery system to enhance αBIS stability, bioavailability, and therapeutic efficacy in AD treatment.

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)-1ß, 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.