Chlorogenic Acid Treatment Research Articles

Chlorogenic Acids Inhibit Adipogenesis: Implications of Wnt/β-Catenin Signaling Pathway

In our previous in vitro study, we found that chlorogenic acid (CGA) inhibited adipocyte differentiation and triglyceride (TG) accumulation, but the underlying mechanism is still unclear. Accumulative genetic evidence supports that canonical Wnt signaling is a key modulator on adipogenesis. Methods. In this study, 3T3-L1 cells were induced adipogenic differentiation and then treated with CGA. We investigate the effect of CGA in inhibiting adipogenesis and evaluate its role in modulating Wnt10b (wingless integration1 10b), β-catenin, glycogen synthase kinase-3β (GSK-3β), and peroxisome proliferator-activated receptor γ (PPAR-γ) involved in the Wnt (wingless integration1)/β-catenin signaling pathway. Results. The result showed that after CGA treatment, lipid accumulation and TG level decreased significantly in 3T3-L1 cells, indicating that CGA could inhibit adipogenesis. In addition, CGA repressed the induction of adipocyte differentiation biomarkers as PPAR-γ, adipocyte protein 2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL), and the secretion of GSK-3β in a dose-dependent manner upregulated the expression of β-catenin and Wnt10b both in gene and protein levels. Moreover, CGA induced phosphorylation of GSK-3β and promoted the accumulation of free cytosolic β-catenin in 3T3-L1 adipocytes. Conclusion. Overall, these findings gave us the implications that CGA inhibits adipogenesis via the canonical Wnt signaling pathway.

Impact of chlorogenic acid on modulation of significant genes in dermal fibroblasts and epidermal keratinocytes

Chlorogenic acid is one of the most abundant polyphenols found in human diet. It is well-documented that chlorogenic acid has a significant impact on human cells, especially in the regulation of inflammation and metabolic processes. However, its role in regulating skin functions, especially with respect to the dermal collagen network or epidermal skin barrier, has not yet been elucidated. Here, we report that chlorogenic acid treatment can induce production of procollagen type I in human dermal fibroblast, Hs68 cell lines. Moreover, this treatment can stimulate upregulation of skin barrier genes, including the ones encoding filaggrin (FLG), involucrin (IVL), and envoplakin (EVPL), in epidermal keratinocytes. Chlorogenic acid also triggered a multifaceted response in the cytokine profile of keratinocytes. Therefore, we suggest that chlorogenic acid can be used to restore the impaired dermal matrix network as well as the epidermal skin barrier.

The combination of ultrasound and chlorogenic acid to inactivate Staphylococcus aureus under planktonic, biofilm, and food systems

This study aimed to investigate the mechanism of different treatments, namely, ultrasound (US), chlorogenic acid (CA), and ultrasound combined with chlorogenic acid (US plus CA) on the inactivation of Staphylococcus aureus planktonic and biofilm cells. Results showed that the combined treatment of US and CA exhibited remarkable synergistic antibacterial and antibiofilm effects. Scanning electron microscopy images indicated that the combined treatment of US and CA caused the most serious damage to the cell morphology. Confocal laser scanning microscopy images revealed that the combined treatment led to sharp increase and severe damage to the permeability of the cell membrane, causing the release of ATP and nucleic acids and decreasing the exopolysaccharide contents in S. aureus biofilm. Finally, the combined treatment of US plus 1% CA for 60 min inactivated S. aureus cells by 1.13 lg CFU/g on mutton. Thus, the combined treatment of US and CA had synergistic effect against S. aureus under planktonic, biofilm, and food systems.

The mechanism of molecular cross-linking against nonenzymatic degradation in the body wall of ready-to-eat sea cucumber

Ready-to-eat sea cucumbers (RSC) treated by high pressure steam were easily degraded during storage. Celery (Apium graveolens, AG) and chlorogenic acid (CA) were screened for enhancing the stability of RSC. After RSC cross-linked by AG or CA, the hardness was significantly increased by 108% or 254% at 30 d, and the relaxation time decrease by 31.90 or 39.89 ms, and the proportion of T23 reduced by 0.40% or 1.15%. The crosslinked RSC exhibited smaller pore size with finer collagen fibrils. CA treatment caused the secondary structure changes in RSC. In addition, it also inhibited the break of peptide bonds in RSC collagen, observing the decrease of free hydroxyproline level from 46.63 to 34.53 μg/g, and the reduction of free ammonia nitrogen from 20.96 to 15.30 μmol/g. Therefore, AG and CA will have an important application in RSC processing industry.

Chlorogenic acid protects human chondrocyte C28/I2 cells from oxidative stress-induced cell death through activation of autophagy

AimsThe development of osteoarthritis (OA), the most common form of arthritis, is commonly associated with oxidative stress. Indeed, the lack of antioxidant responses largely increases OA incidence. OA is a leading cause of disability in the elderly, which reduces the quality of life and places high socioeconomic burdens on them. Several polyphenolic compounds, including chlorogenic acid (CGA), have shown cytoprotective effects via their antioxidant activity, but the exact mechanism (s) remain elusive. In this study, we demonstrated how CGA protects human chondrocytes against H2O2-induced apoptosis. Materials and methodsThe cytoprotective effect by CGA in 500 μM hydrogen peroxide-treated C28/I2 cells was evaluated by cell viability, TUNEL assay, and Western blotting analyses, and autophagy assessment was further performed by AO and MDC staining and tandem mRFP-GFP fluorescence analyses. Key findingsTreatment of CGA to the human chondrocytes under oxidative stress significantly decreased apoptosis markers, such as cleaved caspase 3 and cleaved PARP, and increased anti-apoptotic marker Bcl-xL and the antioxidant response proteins NRF2 and NF-κB. Furthermore, CGA-dependent activation of antioxidant response proteins NRF2 and NF-κB and its protective effects in chondrocytes depended on autophagy. Indeed, CGA treatment and autophagy induction significantly decreased reactive oxygen species (ROS)–induced apoptosis. SignificanceCGA exhibited the protective effect to human chondrocyte C28/I2 cells against oxidative stress-induced cell death by activating autophagy. These findings indicate that CGA is a potential therapeutic agent for the development of OA drugs.

Effect of thermal treatment on the molecular-level interactions and antioxidant activities in β-casein and chlorogenic acid complexes

The interaction between β-casein (β-CN) and chlorogenic acid (CA) following treatments at 25, 65, 100, and 121 °C and their effects on the antioxidant capacity of resultant complexes were investigated. Fluorescence spectroscopy indicated that CA bound to β-CN mainly via hydrophobic interactions, and thermal treatment at 121 °C weakened the binding affinity. Circular dichroism showed that CA and thermal treatment did not affect the secondary structure of β-CN. Fourier transform infrared spectroscopy indicated that, except for excessive CA, CA did not cause a significant change in the vibrational wavenumber of the amide II of β-CN. According to the results of matrix-assisted laser desorption and ionization tandem time-of-flight mass spectrometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no covalent bond was observed in the complexes formed between β-CN and CA after thermal treatments. Assessments of antioxidant capacity indicated a synergistic effect observed between β-CN and CA in FRAP and an antagonistic effect in ABTS. After 30 min of thermal treatment at 65 °C, β–CN–CA complexes exhibited rather strong antioxidant capacity. These results support the use of CA in functional dairy beverages and maintaining their antioxidant capacity by modulating processing conditions.

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells.

Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. Unlike other dietary polyphenols, only few studies recognize chlorogenic acid (CGA) as a potential partner in combination therapy, while, conversely, its anticancer evidence is steadily growing, ultimately in OS. On this basis, herein we examine the cooperating effects between CGA and Doxo in U2OS and MG-63 human OS cells. With respect to Doxo alone, the concomitant administration of CGA further decreased cell viability and growth, promoting cell death potentially via apoptosis induction. Furthermore, a longer-lasting reduction in clonogenic potential deeply supported the CGA ability to improve Doxo efficacy in those cells. Remarkably, CGA treatment ameliorated Doxo-induced cytotoxicity in H9c2 rat cardiomyocyte cells instead. Although inactivation of p44/42 MAPK was detected in response to CGA plus Doxo, PD98059-mediated p44/42 MAPK impairment enhanced the combination outcome in OS cells. These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility.

Beneficial effects of chlorogenic acid treatment on neuroinflammation after deep hypothermic circulatory arrest may be mediated through CYLD/NF-κB signaling

Deep hypothermic circulatory arrest (DHCA) during heart surgery may induce neuroinflammation leading to neurocognitive dysfunction. Chlorogenic acid (CA) is a common phytochemical, which can attenuate neuroinflammation. Nevertheless, the underlying mechanism involved in the anti-inflammatory effect of CA after DHCA is unknown. The present study therefore characterized the anti-inflammatory functions of CA after DHCA using in vivo and in vitro DHCA models. The activation of microglia, inflammatory cytokine levels, and the NF-κB pathway were measured. The results showed that CA treatment ameliorated neurocognitive function and reduced the inflammatory cytokine levels in the brain and circulation. Furthermore, the microglial and NF-κB activations were suppressed after DHCA. CA exerted the same anti-inflammatory effect in hypothermia OGD microglial cells as the in vivo study. Additional studies indicated that the regulation of ubiquitin ligase activity of TRAF6 and RIP1 by CYLD was related to the mechanism involving inhibition of CA in the NF-κB pathway. Together, the results showed that CA may attenuate neuroinflammation after DHCA by modulating the signaling of CYLD/NF-κB.

Chlorogenic acid alleviates neurobehavioral disorders and brain damage in focal ischemia animal models

Cerebral ischemia leads to neuronal cell death, causes neurological disorder and permanent disability. Chlorogenic acid has antioxidant, anti-inflammatory, and anti-apoptotic properties. This study investigated the neuroprotective effects of chlorogenic acid against cerebral ischemia. Focal cerebral ischemia was induced in male adult rats via middle cerebral artery occlusion (MCAO). Chlorogenic acid (30 mg/kg) or vehicle was injected in the intraperitoneal cavity 2 h after MCAO operation. Neurological behavior tests were performed 24 h after MCAO, brain edema and infarction were measured. Oxidative stress was assessed by investigating the levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. MCAO damage leaded to severe neurobehavioral deficits, increased ROS and LPO levels, and induced brain edema and infarction. MCAO damage caused histopathological damages and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the cerebral cortex. However, chlorogenic acid treatment improved neurological behavioral deficits caused by MCAO and attenuated the increase in ROS and LPO levels. It also alleviated MCAO-induced brain edema, infarction, and histopathological lesion. Chlorogenic acid treatment attenuated the increase in the number of TUNEL-positive cells in the cerebral cortex of MCAO animals. We also investigated caspase proteins expression to elucidate the neuroprotective mechanism of chlorogenic acid. Caspase-3, caspase-7, and poly ADP-ribose polymerase expression levels were increased in the MCAO damaged cortex, while chlorogenic acid mitigated these increases. These results showed that MCAO injury leads to severe neurological damages and chlorogenic acid exerts neuroprotective effects by regulating oxidative stress and caspase proteins expressions. Thus, our findings suggest that chlorogenic acid acts as a potent neuroprotective agent by modulating the apoptotic-related proteins.

Chlorogenic Acid Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Wnt Signaling.

Periodontal disease (PD) is one of the main causes of periodontal bone resorption and tooth loss in adults. How to repair the alveolar bone effectively has always been a challenge. This study was designed to clarify the effects and the underlying molecular mechanisms of chlorogenic acid (CGA) on osteogenic differentiation of human dental pulp stem cells (hDPSCs). In this study, we used CGA to treat hDPSCs. The osteogenic experiment showed that CGA can promote hDPSCs osteogenic differentiation. RNA-Seq and quantitative real-time polymerase chain reaction showed that CGA treatment enhanced the expression of the osteogenesis genes for frizzled-related protein (FRZB) and pyruvate dehydrogenase kinase 4 (PDK4) and inhibit the expression of the osteoclastogenesis genes such as those for asporin (ASPN) and cytokine-like 1 (CYTL1). Western blot analysis showed that besides FRZB, CGA treatment also caused reduction of both active and total β-catenin, while increased the total calcium/calmodulin-dependent kinase II (CamKII), the phosphorylated CamKII (pCamKII) and the phosphorylated cAMP-response element-binding protein (pCREB). Likely, the increased osteogenesis was associated with reduced canonical Wnt/β-catenin signaling but increased noncanonical Wnt/Ca2+ signaling. The results suggested that CGA can promote the osteogenic differentiation of hDPSCs by regulating Wnt signaling. These findings will serve as a foundation for further studies on how to repair defective alveolar bone for the patients with PD.

Evaluation of antidiabetic activity of dietary phenolic compound chlorogenic acid in streptozotocin induced diabetic rats: Molecular docking, molecular dynamics, in silico toxicity, in vitro and in vivo studies

BackgroundChlorogenic acid is amongst the well-known polyphenolic compounds being used in human food and beverages. Its presence has been reported in tea leaves, roasted green beans, coffee, cocoa, berry fruits, apples, citrus fruits, and pears. ObjectiveThe present study aims to elucidate the effectiveness of chlorogenic acid on in silico and in vitro inhibition of glucose metabolising enzymes (α-amylase and α-glucosidase) and on blood-based markers associated with diabetic complications in vivo. MethodsDocking and molecular dynamics studies were performed using GLIDE (Schrodinger, LLC, NY, 2019-2) and Maestro-Desmond Interoperability Tools, version 4.1 (Schrödinger, NY, 2015), respectively. α-Amylase and α-glucosidase inhibitory activities of chlorogenic acid were measured in vitro. Diabetes was induced in adult Wistar rats by injecting streptozotocin (50 mg/kg). Biochemical assays were performed using standard kits. ResultThe in silico studies for α-amylase and α-glucosidase with chlorogenic acid suggested that the ligand was stable and strongly bound with the above-mentioned proteins. During in vitro studies, chlorogenic acid inhibited both the enzymes in a dose-dependent manner (5–30 μg/mL). In addition, chlorogenic acid treatment for 28 days significantly suppressed the increase in blood glucose, total cholesterol, triglyceride, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, γ-glutamyl transferase, alkaline phosphatase, total bilirubin, creatinine, urea, uric acid, and feed intake levels in diabetic rats. Chlorogenic acid also caused significant improvement in body weight, serum HDL-cholesterol, total protein, and albumin levels leading to betterment in atherogenic indices related to diabetes-associated cardiovascular risks. ConclusionThe findings indicated that chlorogenic acid inhibited α-amylase and α-glucosidase and significantly decreased diabetes associated hyperglycemia, hyperlipidemia, and hepatorenal damage, making it a possible functional food ingredient and drug candidate for the management of diabetes and related complications.

Chlorogenic acid ameliorates mice clinical endometritis by activating Keap1/Nrf2 and inhibiting NFκB signalling pathway.

Clinical endometritis is a common reproductive disorder in mammals that seriously endangers animal health and causes economic losses worldwide. This study aims to use lipopolysaccharide and Trueperella pyogenes exotoxin as modelling reagents (LC) to perfuse the mouse uterus in order to establish a model of clinical endometritis and to investigate the anti-inflammatory and antioxidant effects of chlorogenic acid (CGA). In this study, five LC uterine perfusions were selected to model clinical endometritis. The anti-inflammatory and antioxidant effects of CGA were clarified. Through HE staining, proinflammatory cytokines, blood testing, NFκB and Keap1/Nrf2 signalling pathways and other index changes to explore the protection mechanism of CGA. After CGA treatment, the appearance, inflammatory damage and blood indicators of the mouse uterus returned to normal. Simultaneously, CGA could inhibit the activation of NFκB and reduce the release of inflammatory cytokines; CGA could also activate Keap1/Nrf2, promote the dissociation of Keap1 and Nrf2 and significantly increase the expression of the downstream genes HO-1 and NQO1. The above results together explain that five LC uterine perfusions can be used to establish a mouse model of clinical endometritis. CGA can treat clinical endometritis by activating Keap1/Nrf2 and inhibiting the NFκB signalling pathway.

Chlorogenic Acid retards cartilaginous endplate degeneration and ameliorates intervertebral disc degeneration via suppressing NF-κB signaling

AimsIntervertebral Disc Degeneration (IDD) is a key factor involved in low back pain (LBP) which affects approximately 540 million individuals worldwide. Chlorogenic Acid (CGA), a natural compound, exerts anti-inflammatory property in several diseases. Here, we aim to investigate the biological effect of CGA on IDD and explore the underlying mechanism. Materials and methodsLumbar spine instability (LSI) model in mice was utilized to mimic process of IDD. The effects of CGA in response to LSI were evaluated by luminescent imaging, micro-CT, histomorphology, and immunohistochemistry in vivo. Besides, the cytotoxicity of CGA on chondrocytes was detected by cell counting kit-8 (CCK-8) and the biological effects were assessed by polymerase chain reaction (PCR) in vitro. Key findingsWe found that CGA treatment dramatically suppressed the NF-κB activity in LSI mice. Moreover, administration of CGA mitigated cartilaginous endplate degeneration and postponed IDD development accompanying a decrease of inflammatory and catabolic mediators. Specifically, CGA ameliorated endplate degeneration might be related to its protective effects against endplate chondrocytes apoptosis and trans-differentiation. We further elucidated that CGA exerted these biological effects mainly by repressing NF-κB signaling in cartilage endplate. SignificanceOur study has illustrated, for the first time, the curative effects as well as the latent mechanism of CGA in IDD and our results suggested that CGA administration might be used as an alternative therapy for IDD.

Chlorogenic acid inhibits proliferation in human hepatoma cells by suppressing noncanonical NF-κB signaling pathway and triggering mitochondrial apoptosis.

Chlorogenic acid (CGA), a phenylpropanoid derived from Eucommia ulmoides Oliver, has been shown to exhibit potent cytotoxic and anti-proliferative activities against several human cancers. However, the effects of CGA on hepatocellular carcinoma (HCC) and the underlying mechanisms have not been intensively studied. In this study, the CGA treatment effects on the viability of human hepatoma cells were investigated by MTT assay. Our data showed that CGA could dose-dependently inhibit the activity of human hepatoma cells Hep-G2 and Huh-7, but did not affect the activity and growth of normal human hepatocyte QSG-7701. The genes and pathways influenced by CGA treatment were explored by RNA sequencing and bioinformatics analysis, which identified 323 differentially expressed genes (DEGs) involved in multiple pharmacological signaling pathways such as MAPK, NF-κB, apoptosis and TGF-β signaling pathways. Further analyses by real-time quantitative PCR, Western blot and flow cytometry revealed that CGA effectually suppressed the noncanonical NF-κB signaling pathway, meanwhile it activated the mitochondrial apoptosis of HCC by upregulation of the BH3-only protein Bcl-2 binding component 3 (BBC3). Our findings demonstrated the potential of CGA in suppressing human hepatoma cells and provided a new insight into the anti-cancer mechanism of CGA.

Protection Mechanisms Underlying Oral Administration of Chlorogenic Acid against Cadmium-Induced Hepatorenal Injury Related to Regulating Intestinal Flora Balance

Cadmium (Cd) is a heavy metal, which is widely used in the industry and daily life. It has a long half-life, so large amounts of Cd can accumulate in humans and become toxic. Chlorogenic acid (CGA) can eliminate free radicals and inhibit lipid peroxidation and is mainly used to prevent metal toxicity. In the present study, mice are given CGA by intraperitoneal injection or gavage, respectively, to explore the mechanism of preventing Cd toxicity. In acute Cd-exposed mice, CGA treatment (ip) alleviated Cd-induced oxidative damage and reduced the production of NO and MPO in the liver and kidney tissues, while TLR4 expression levels did not change significantly. After 8 weeks of Cd exposure, CGA administration (gavage) significantly alleviated gut dysbiosis by decreasing the Firmicutes to Bacteroidetes ratio, enhancing the relative abundances of bacteria, including Ruminiclostridium_9, Alloprevotella, and Rikenella, and inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway. These findings suggested that protection mechanisms underlying the oral administration of CGA against the Cd-induced hepatorenal injury was related to the regulation of the intestinal flora balance. CGA can be used as an effective component in daily diet to prevent Cd toxicity.

Chlorogenic acid co-administration abates tamoxifen-mediated reproductive toxicities in male rats: An experimental approach.

Reports over the years have demonstrated toxic side effect-including reproductive toxicity- of tamoxifen (TAM), a drug of choice in the management of primary breast cancer. Chlorogenic acid (CGA), a dietary polyphenol, reportedly elicits beneficial pharmacological effects. However, the impact of CGA on TAM-associated reproductive toxicity is absent in the literature. We, therefore, experimented on CGA's effect and TAM-mediated reproductive toxicity in rats. Cohorts of rats were treated with TAM (50mg/kg) or co-treated with CGA (25 or 50mg/kg) for 14 consecutive days. The result showed that treatment of CGA significantly increases testosterone, LH, and FSH levels compared to the TAM group. However, prolactin level was markedly decreased after pretreatment of CGA in TAM-treated rats. CGA abated TAM-induced decreases acid phosphatase, alkaline phosphatase, and antioxidant enzymes in the testis. CGA alleviated TAM-facilitated surges of reactive oxygen and nitrogen species, myeloperoxidase, nitric oxide, interleukin-1β, and tumor necrosis factor-alpha in rats epididymis and testes. Additionally, CGA increased anti-inflammatory cytokine -interleukin-10-, suppressed caspase-3 activity, and reduced pathological lesions in the examined organs of rats co-treated with CGA and TAM. CGA phytoprotective effect improved reproductive function occasioned by TAM-mediated toxicities in rats, by abating oxido-inflammatory damages and downregulating apoptotic responses. PRACTICAL APPLICATIONS: CGA protects against the damaging oxido-inflammatory responses incumbent on TAM metabolism. As an antioxidant abundant in plant-derived foods, CGA reportedly protects against inflammatory damage, hypertension, and neurodegenerative diseases. We present evidence that CGA ameliorates TAM-induced reproductive dysfunction by suppressing oxidative and inflammation stress downregulate apoptosis and improve reproductive function biomarker in rats.

Anti-acne vulgaris effects of chlorogenic acid by anti-inflammatory activity and lipogenesis inhibition.

Chlorogenic acid (CGA) exhibits substantial biological function in antioxidant, antibacterial, anti-lipogenesis and anti-inflammatory activities. Increased sebum production and inflammation are considered important for the development of acne. However, the therapeutic effects of CGA on acne vulgaris remain unexplored. In this study, to assess the effects and underlying mechanisms of CGA on acne, a model of skin inflammation in ears of ICR mouse induced by living Propionibacterium acnes was used. 24 hours after 1.0×107CFU, P.acnes were intradermally injected into the ears of the ICR mouse. 1, 5 and 10mg of CGA mixed with vaseline were applied to the surface of the skin every 12 hours for 3days. Then, skin inflammation in the ears was assessed and the change of SREBP1 and TNF-α expression was analysed after CGA treatment. The mechanisms of CGA in anti-inflammatory activity and lipogenesis were also studied in primary sebocytes and HaCaT cells. We found that CGA treatment effectively rescued ear swelling, redness and erythema skin in ears of ICR mouse induced by P.acnes and significantly downregulated the expression of inflammatory cytokines by reducing the activity of the NF-κB signalling pathway. Furthermore, CGA could inhibit lipogenesis at the protein secretion and transcription level by decreasing the AKT/mTOR/SREBP signalling pathway. Our findings suggest that CGA could become a potential alternative drug for the treatment of acne vulgaris.

Chlorogenic Acid Alleviates Colon Mucosal Damage Induced by a High-Fat Diet via Gut Microflora Adjustment to Increase Short-Chain Fatty Acid Accumulation in Rats.

A high-fat diet (HFD) has been previously associated with the development of diseases such as chronic colitis. While chlorogenic acid (CGA) is known to exhibit potent antioxidant, antibacterial, and anti-inflammatory properties, little is known about its effects on intestinal inflammation. In this study, we investigated the effects of CGA on intestinal inflammation in an HFD-induced obesity rat model and assessed whether these effects were related to changes in gut microbiota composition. This was achieved by examining physiological and biochemical indicators, the liver transcriptome, and the structure of the fecal microflora. CGA treatment significantly reduced HFD-induced internal organ weight gain, promoted colon tissue repair, downregulated the expression of inflammatory cytokines, and promoted the accumulation of the tight junction protein. KEGG enrichment analysis of differentially expressed genes, applied to data from the RNA-seq of rat liver tissue, revealed that CGA treatment significantly affected amino acid and lipid metabolism in the liver. Furthermore, CGA decreased the abundance of bacteria belonging to the genera Blautia, Sutterella, and Akkermansia and increased butyric acid levels, which were positively correlated with the abundance of Ruminococcus (butyric acid producer). Moreover, the beneficial changes observed in the HFD group were not as pronounced as those in the CGA treatment group. In summary, CGA can alleviate colitis in HFD-induced obesity through its anti-inflammatory effects associated with changes in gut microbiota composition and an increase in the production of short-chain fatty acids and thus can be used as a potential drug for the treatment of this pathology.

Dietary chlorogenic acid ameliorates oxidative stress and improves endothelial function in diabetic mice via Nrf2 activation.

ObjectivesChlorogenic acid (CGA) is an antioxidant dietary factor. We investigated the effects of CGA on endothelial cell dysfunction in diabetic mice and the mechanistic role of nuclear factor erythroid-related factor 2 (Nrf2) in the antioxidant effect of CGA.MethodsDiabetic (db/db) mice were fed normal chow or chow containing 0.02% CGA for 12 weeks. Human umbilical vein endothelial cells (HUVECs) and mouse aortas were treated with normal or high glucose.ResultsCGA treatment induced upregulation of Nrf2 in HUVECs in a dose-dependent manner. CGA pretreatment prevented reactive oxygen species generation and preserved nitric oxide bioavailability in HUVECs and aortas from wild-type but not Nrf2−/− mice. CGA improved endothelium-dependent relaxation in high glucose-treated aortas from wild-type and db/db mice, but not Nrf2−/− mice. Dietary CGA improved endothelium-dependent relaxation in db/db mice.ConclusionsCGA ameliorates endothelial dysfunction in diabetic mice through activation of the Nrf2 anti-oxidative pathway.

Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway.

BackgroundSalmonella typhimurium (ST) causes several intestinal diseases. Polyphenols including chlorogenic acid (CGA) inhibit pathogenesis.ObjectiveThis study aimed to investigate the mechanisms of CGA in ST infection.MethodsThe intestinal pathological changes and survival rate of ST-infected mice were measured to verify the protection of CGA on ST infection. The antibacterial effects of CGA in vitro on the invasion to intestinal epithelial cells and autophagy was evaluated. The relationships among GAS5, miR-23a, and PTEN were verified. Expression of inflammation- and autophagy-related proteins was detected.ResultsCGA treatment alleviated pathological damage, improved the secretion disturbance of intestinal cytokines caused by ST infection, and reduced the mortality of mice. Intestinal GAS5 was upregulated after CGA treatment. LncRNA GAS5 competitively bound to miR-23a to upregulate PTEN and inhibit the p38 MAPK pathway. CGA regulated the p38 MAPK pathway through lncRNA GAS5/miR-23a/PTEN axis to promote autophagy in ST infection. The functional rescue experiments of miR-23a and PTEN further identified these effects.ConclusionCGA promotes autophagy and inhibits ST infection through the GAS5/miR-23a/PTEN axis and the p38 MAPK pathway.