Protective Effect Of Chlorogenic Acid Research Articles

Protective Effects of Chlorogenic Acid Against Amyloid-Beta-Induced Oxidative Stress and Ion Transport Dysfunction in SH-SY5Y Cells.

Caloric restriction mimetics mimic the beneficial effects of dietary restriction approaches, such as caloric restriction approaches, without limiting the dietary intake. Chlorogenic acid (CGA) acts as a caloric restriction mimetic; however, its neuroprotective mechanisms remain ambiguous. Therefore, in this study, we aimed to elucidate the neuroprotective effects of CGA on SH-SY5Y cells treated with amyloid-beta (Aβ)1-42. Aβ1-42 (1.25 μM) induced oxidative stress by significantly increasing the pro-oxidant levels and decreasing the antioxidant levels in the cells. Additionally, it decreased the Na+/K+-ATPase and Ca2+-ATPase ion transporter activities and enhanced the acetylcholinesterase activity. However, CGA (100 μM) reversed these Aβ1-42-induced changes in SH-SY5Y cells. Overall, CGA exerted neuroprotective effects against Aβ1-42-induced oxidative stress and impaired ion transporter and acetylcholinesterase activities, serving as a promising therapeutic candidate for neurodegenerative diseases, such as Alzheimer's disease.

Potential protective role of chlorogenic acid against cyclophosphamide-induced reproductive damage in male mice.

Cyclophosphamide (CP) is an anticancer drug; however, clinical utilization of CP is limited, resulting from its considerable toxicities. This research was performed to explore the protective effects of Chlorogenic acid (CGA) on reproductive damage induced by CP in mice. Blood samples were collected for analysis of hormone content subsequently; semen samples were evaluated for quality, and testis samples were used for histopathological evaluation and analysis of oxidative stress biomarkers, protein and gene expression levels of steroid regulatory factors, and steroid synthase. The results noted that CGA increased serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) activity; increased SOD, GPx, and GSH oxidative stress levels in testis tissue; and decreased MDA content in testis tissue. Testicular cells in the CGA treatment group gradually returned to normal morphology, and CYP11A1 and CYP17A1 levels increased after CGA treatment. The mRNA levels of CYP11A1, CYP17A1, StAR, 3β-HSD, and 17β-HSD were significantly raised in the CGA dose group. In the test dose range, CGA can improve sperm quality, quantitative abnormality, and serum T synthesis disorder caused by CP. This mechanism may be correlated with the inhibition of oxidative stress and antioxidation levels. Therefore, CGA has a protective impact on testicular injuries arising from CP in mice.

Amelioration effects of chlorogenic acid on mice colitis: Anti-inflammatory and regulation of gut flora

This research endeavors to investigate the potential preventive and protective effects of chlorogenic acid (CGA), a bioactive component found in various foods, in the context of dextran sodium sulfate (DSS)-induced colitis in mice. The study reveals that CGA administration, at dosages of 150 and 300 mg/kg, significantly retards the progression of colitis. This is substantiated by observable enhancements in colon length, reduction in the disease activity index, and mitigation of colon tissue damage. Meanwhile, CGA acts as an antioxidant by reducing the oxidative stress associated with colitis inflammation and increasing the activity of antioxidant enzymes. Furthermore, CGA demonstrates anti-inflammatory properties by inhibiting the inflammatory response associated with colitis and regulating the excessive expression of cytokines. Notably, CGA contributes to the restoration of intestinal barrier function by augmenting the levels of claudin-1 and ZO-1. Moreover, the investigation uncovers CGA's capacity to modulate the gut microbiota composition in colitic mice, fostering the proliferation of beneficial bacteria, notably Lactobacillus, while concurrently impeding the growth of detrimental bacteria like Bacteroides, Enterobacteriaceae, and Escherichia_Shigella. To conclude, these findings substantiate the viability of CGA for diverse applications in the realms of food and medicine, thereby bolstering its potential as a therapeutic strategy within dietary interventions.

Chlorogenic acid mitigates potassium dichromate-induced acute hepato-nephrotoxicity by attenuating the NF-κB signalling pathway.

Hexavalent chromium (CrVI) is known to be a potentially hepatotoxic and nephrotoxic contaminant in humans and other animals, whose toxicity is associated with oxidative stress and inflammation. The aim of this study was to evaluate the potential protective effect of chlorogenic acid (CGA), which has known anti-inflammatory and antioxidant effects, on potassium dichromate (PDC)-induced acute hepatotoxicity and nephrotoxicity in rats. Thirty-six Wistar albino rats were treated with CGA (10, 20, or 40mg/kg, intraperitoneally) and/or PDC (15mg/kg/day, intraperitoneally) as a single dose. Serum, liver, and kidney tissues were examined biochemically, histopathologically, and immunohistochemically. Compared to the control group, a significant increase in interleukin-6 (IL-6) levels and a significant decrease in serum and renal reduced glutathione (GSH) levels, liver catalase (CAT), tumour necrosis factor-alpha (TNF-α), and interleukin 1β (IL-1β) levels were observed in the PDC group. The administration of PDC led to histopathological and immunohistochemical changes in rat liver and kidney tissues. With the administration of CGA, especially at the 10mg/kg dosage, the above-mentioned parameters approached normal levels. CGA had antioxidant and anti-inflammatory effects that alleviated PDC-induced acute hepato- and nephrotoxicity.

Protective effects of chlorogenic acid on the intestinal barrier of broiler chickens: an immunological stress model study

This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on inflammatory responses and intestinal health of lipopolysaccharide (LPS)-challenged broilers. One hundred and forty-four 1-day-old male broiler chicks were divided into 3 groups with 6 replicates of 8 birds each. The groups were as follows: 1) Control group: birds fed a basal diet; 2) LPS group: LPS-challenged birds fed a basal diet; 3) CGA group: LPS-challenged birds fed a CGA-supplemented diet. The LPS was intraperitoneally administered at a dose of 1 mg/kg of body weight. CGA increased the weight gain and feed intake of LPS-challenged birds by 37.05% and 24.29%, respectively (P < 0.05). CGA also alleviated LPS-induced inflammation, as evidenced by lower levels of pro-inflammatory cytokines in the serum and jejunum (tumor necrosis factor-α, interferon-γ, interleukin-1β, and interleukin-6), and the decreased myeloperoxidase activity in the jejunum (P < 0.05). These effects were accompanied by a decrease in the mRNA abundance of toll-like receptor 4 and myeloid differentiation factor 88 and an inhibition of nuclear factor kappa-B translocation in the jejunum (P < 0.05). CGA reduced circulating diamine oxidase activity and levels of D-lactate and endotoxin, and positively regulated the expression of jejunal claudin-3 and zonula occludens-1 in LPS-challenged broilers (P < 0.05). Compared to the LPS group, CGA reduced the apoptotic rate of epithelial cells and cytochrome c concentration in the jejunum, and normalized the expression of genes responsible for proliferation and apoptosis in jejunal epithelial cells, including cysteine aspartate-specific protease-9, B cell lymphoma-2, and proliferating cell nuclear antigen (P < 0.05). Furthermore, CGA normalized the altered phosphorylation of protein kinase B and glycogen synthase kinase-3β, as well as the translocation of nuclear β-catenin in the jejunum of LPS-challenged broilers (P < 0.05). These results suggested that CGA supplementation improved growth performance, alleviated inflammation, and helped maintain intestinal integrity and barrier function in LPS-challenged broilers, possibly through the regulation of the toll-like receptor 4/nuclear factor kappa-B and protein kinase B/Wnt/β-catenin pathways.

Protective effect of chlorogenic acid on liver injury in heat‐stressed meat rabbits

AbstractThis study investigated the protective effects of chlorogenic acid (CGA) on production performance and liver function of rabbits under heat stress (HS) condition. A total of 120 healthy New Zealand weaned rabbits with similar initial body weight, were randomly divided into 3 treatments with 20 replicates per treatment and 2 weaned rabbits per replicate: control (CON) group (rabbits were housed at 25 ± 1°C and fed a basal diet), HS group (rabbits were housed at 35 ± 1°C and fed a basal diet), and HS + CGA group (rabbits were housed at 35 ± 1°C and fed a basal diet supplemented with 800 mg/kg CGA). The trial lasted for 28 days. The results showed that HS challenge decreased (p &lt; 0.05) growth performance, induced oxidative stress and hepatic apoptosis, and caused liver damage in rabbits. However, dietary CGA supplementation increased (p &lt; 0.05) body weight gain and feed efficiency, and enhanced (p &lt; 0.05) antioxidative capacity in serum and liver in HS‐challenged rabbits; attenuated HS‐induced increases in urea nitrogen (p = 0.03), alanine aminotransferase (p = 0.03), aspartate aminotransferase (p = 0.01), caspase‐8 (p = 0.02), and caspase‐3 (p = 0.04) as well as decrease albumin (p = 0.04). Moreover, supplementation with CGA upregulated Nrf2/HO‐1 pathway‐related genes expressions, including Nrf2 (p = 0.009), HO‐1 (p = 0.03) and SOD1 (p = 0.04) in HS‐challenged rabbits. Our findings demonstrated that dietary CGA supplementation could alleviate HS‐induced decline in growth performance, and protect against HS‐induced liver damage partially through enhancing antioxidant capacity via acting Nrf2/HO‐1 pathway and inhibiting hepatic apoptosis in rabbits.

Chlorogenic acid regulates the expression of protein phosphatase 2A subunit B in the cerebral cortex of a rat stroke model and glutamate-exposed neurons

BackgroundIschemic stroke is a serious neurological disorder caused by blockages in cerebral artery. Protein phosphatase 2A (PP2A) is a phosphatase that performs a critical role in cell signaling and growth. PP2A subunit B acts as a neuroprotective agent in the nerve system. Chlorogenic acid, which is mainly found in roasted coffee, has antioxidant, anti-inflammatory, and anti-apoptotic effects. We hypothesized that chlorogenic acid modulates PP2A subunit B expression in ischemic stroke models and glutamate-mediated neurons. Middle artery occlusion (MCAO) surgery was operated and chlorogenic acid (30 mg/kg) or phosphate buffer saline was treated 2 h after MCAO. The cerebral cortex was collected 24 h after surgery and the change of PP2A subunit B expression was analyzed. Glutamate and/or chlorogenic acid were treated in cultured neurons, further study was performed.ResultsA decrease in PP2A subunit B expression in MCAO animals was identified. Chlorogenic acid alleviated this decrease due to ischemic injury. Moreover, the number of PP2A subunit B-positive cells in the ischemic cerebral cortex was significantly decreased, chlorogenic acid alleviated this decrease. We also found protective effects of chlorogenic acid in neurons exposed to glutamate. Glutamate decreased the expression of PP2A subunit B and chlorogenic acid mitigated this decrease. Our results elucidated that chlorogenic acid performs neuroprotective functions and attenuates the reduction of PP2A subunit B by brain damage and glutamate-mediated excitotoxicity.ConclusionsWe showed that chlorogenic acid attenuated the decrease of PP2A subunit B in ischemic injury and neurons exposed to glutamate. Since PP2A subunit B contributes to the protection of brain tissue, we can suggest that chlorogenic acid preserves neurons by modulating PP2A subunit B during ischemic damage.

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

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

Protective Effects of Chlorogenic Acid on Cerebral Ischemia/Reperfusion Injury Rats by Regulating Oxidative Stress-Related Nrf2 Pathway [Retraction

[This retracts the article DOI: 10.2147/DDDT.S228751.].

Protective effects of chlorogenic acid against cyclophosphamide induced liver injury in mice

ABSTRACT We investigated possible protective effects of chlorogenic acid (CGA) against cyclophosphamide (CP) induced hepatic injury in mice. We measured aminotransferase alanine transaminase (ALT) and aspartate transaminase (AST) levels in the serum. We assayed catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in hepatic tissue. We assessed expression of nuclear transcription factor 2 (Nrf2) and Kelch sample related protein-1 (keap1) proteins in hepatic tissues using immunohistochemistry. The relative mRNA expression levels of heme oxygenase-1 (HO-1), NADH quinone oxidoreductase 1 (NQO1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Hematoxylin & eosin staining was used to assess liver histopathology. We found that administration of CGA prior to induction of injury by CP decreased serum ALT, AST and MDA expressions in hepatic tissue, while CAT, SOD, GSH and GSH-Px concentrations were increased. We found that hepatocytes of animals administered CGA gradually returned to normal morphology. CGA increased the protein expression of Nrf2 in murine hepatic tissue. Administration of CGA up-regulated mRNA expression levels of HO-1, NQO1, TNF-α and IL-6 in hepatic tissue. CGA exhibited a marked protective effect on CP induced liver injury in mice.

Involvement of miR-27a/smurf1/ TNF-α and mitochondrial apoptotic pathway in apoptosis induced by cerebral ischemia–reperfusion injury in rats: The protective effect of chlorogenic acid

AimsApoptosis may contribute to a considerable proportion of neuron death after acute cerebral ischemia, although the underlying mechanisms remain unknown. The purpose of this research is to investigate the effect of cerebral ischemia–reperfusion on miR-27a/smurf1 axis in rat cerebral cortex alone and in combination with chlorogenic acid. MethodsTo create a model of ischemic brain injury, nylon monofilament occlusion of the common carotid artery (CCAO) was used for 20 min. Chlorogenic acid (30 mg/kg) was given intraperitoneally (ip) 10 min before ischemia and 10 min before reperfusion. ResultsTUNEL staining of cerebral cortex neurons revealed an increase in the number of apoptotic neurons 24 h after reperfusion. At the molecular level, IR damage lowered bcl2 protein expression while simultaneously increasing bax levels and the bax/bcl2 ratio. Also, we observed higher miR-27a gene expression and higher TNF-α protein level as well as lower smurf1 protein expression after 24 h following CCAO. Treatment with chlorogenic acid significantly reduced the apoptotic damage and reversed molecular alterations in cerebral cortex neurons after IR. ConclusionOur findings indicate that miR-27a/smurf1/TNF-α axis may play a regulatory function in cerebral cortex cell death, providing a new target for novel therapeutic approaches during transit ischemic stroke. It was also shown that chlorogenic acid could restore these molecular changes, demonstrating that it is an effective agent against cerebral cortex apoptotic damage after acute IR injury.

Chlorogenic acid enhances PPARγ-mediated lipogenesis through preventing Lipin 1 nuclear translocation in Staphylococcus aureus-exposed bovine mammary epithelial cells

Chlorogenic acid (CGA) as one of the most ubiquitously dietary polyphenolic compounds, has been reported to have various antimicrobial effects and exhibit strong anti-inflammatory ability. Staphylococcus aureus is a gram-positive bacterium that can induce mastitis. However, the mechanism through which S. aureus infection affects lipid synthesis and whether CGA have protective effect on S. aureus reduced lipid synthesis is not fully understood. In this study, the internalization of S. aureus reduced intracellular lipid droplet formation, decreased the levels of intracellular triacylglycerol, total cholesterol and 7 types of fatty acid and downregulated the expression of lipogenic genes FAS, ACC, and DGAT1 in bovine mammary epithelial cells (BMECs). In addition, we found that S. aureus intracellular infection attenuated mTORC1 activation resulting in Lipin 1 nuclear localization. Remarkablely, S. aureus infection-mediated repression of lipid synthesis related to the mTORC1 signaling and Lipin 1 nuclear localization can be alleviated by CGA. Thus, our findings provide a novel mechanism by which lipid synthesis is regulated under S. aureus infection and the protective effects of CGA on lipid synthesis in BMECs.

Chlorogenic Acid Inhibits Ceramide Accumulation to Restrain Hepatic Glucagon Response.

Chlorogenic acid (CGA), a dietary natural phenolic acid, has been widely reported to regulate glucose and lipid metabolism. However, the protective effects and the underlying mechanisms of CGA on glucagon-induced hepatic glucose production remain largely uncharacterized. Herein, we investigated the efficacy of CGA on hepatic gluconeogenesis both in vivo and in vitro. The elevated levels of endogenous glucose production induced by infusion of glucagon or pyruvate were lowered in mice administered with CGA. Furthermore, chronic CGA treatment ameliorated the accumulation of glucose and ceramide in high-fat diet (HFD)-fed mice. CGA also attenuated HFD-fed-induced inflammation response. The protective effect of CGA on glucose production was further confirmed in primary mouse hepatocytes by inhibiting accumulation of ceramide and expression of p38 MAPK. Moreover, CGA administration in HFD-fed mice preserved the decreased phosphorylation of Akt in the liver, resulting in the inhibition of FoxO1 activation and, ultimately, hepatic gluconeogenesis. However, these protective effects were significantly attenuated by the addition of C2 ceramide. These results suggest that CGA inhibits ceramide accumulation to restrain hepatic glucagon response.

Chlorogenic Acid Protects DNA against Double-strand Breaks: Evidence from Single Molecule Observation

A natural polyphenol chlorogenic acid (CGA) is regarded as an antioxidant by preventing oxidative damage. Among the oxidative damages, DNA double-strand breaks (DSBs) are considered the most severe. To study the protective effect of CGA against DSBs, we measured the time-dependent increase of DSBs caused by photo-irradiation through a single molecule observation of DNA (166 kbp) using fluorescence microscopy. The results have been analyzed in relation to the two-step mechanism with single-strand breaks. A major beneficial effect of polyphenols is to prevent oxidative damage in living cells by suppressing the production of reactive oxygen species (ROS). We quantified the protective effect of Chlorogenic acid (Polyphenol) against ROS by calculating the amount of DSBs generated in a genome-size DNA molecule using a single molecular observation technique.

Targeting TLR4/3 using Chlorogenic acid ameliorates LPS+POLY I:C-induced acute respiratory distress syndrome via alleviating oxidative stress-mediated NLRP3/NF-κB axis.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a life-threatening condition caused due to significant pulmonary and systemic inflammation. Chlorogenic acid (CGA) has been shown to possess potent antioxidant, anti-inflammatory, and immunoprotective properties. However, the protective effect of CGA on viral and bacterial-induced ALI/ARDS is not yet explored. Hence, the current study is aimed to evaluate the preclinical efficacy of CGA in lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (POLY I:C)-induced ALI/ARDS models in vitro and in vivo. Human airway epithelial (BEAS-2B) cells exposed to LPS+POLY I:C significantly elevated oxidative stress and inflammatory signaling. Co-treatment with CGA (10 and 50 µM) prevented inflammation and oxidative stress mediated by TLR4/TLR3 and NLRP3 inflammasome axis. BALB/c mice, when chronically challenged with LPS+POLY I:C showed a significant influx of immune cells, upregulation of pro-inflammatory cytokines, namely: IL-6, IL-1β, and TNF-α, and treatment with intranasal CGA (1 and 5 mg/kg) normalized the elevated levels of immune cell infiltration as well as pro-inflammatory cytokines. D-Dimer, the serum marker for intravascular coagulation, was significantly increased in LPS+ POLY I:C challenged animals which was reduced with CGA treatment. Further, CGA treatment also has a beneficial effect on the lung and heart, as shown by improving lung physiological and cardiac functional parameters accompanied by the elevated antioxidant response and simultaneous reduction in tissue damage caused by LPS+POLY I:C co-infection. In summary, these comprehensive, in vitro and in vivo studies suggest that CGA may be a viable therapeutic option for bacterial and viral-induced ALI-ARDS-like pathology.

Chlorogenic acid attenuates liver apoptosis and inflammation in endoplasmic reticulum stress-induced mice.

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER)results in a state known as "ER stress". It can affect the fate of proteins and play a crucial role in the pathogenesis of several diseases. In this study, we investigated the protective effect of chlorogenic acid (CA) on the inflammation and apoptosis of tunicamycin-induced ER stress in mice. We categorized mice into six groups: Saline, Vehicle, CA, TM, CA 20-TM, and CA 50-TM. The mice received CA (20 or 50 mg/kg) before intraperitoneal tunicamycin injection. After 72 hr of treatment, serum biochemical analysis, histopathological alterations, protein and/or mRNA levels of steatosis, and inflammatory and apoptotic markers were investigated by ELISA and/or RT-PCR. We found that 20 mg/kg CA decreased mRNA levels of Grp78, Ire-1, and Perk. Moreover, CA supplementation prevented TM-induced liver injury through changes in lipid accumulation and lipogenesis markers of steatosis (Srebp-1c, Ppar- α , and Fas), and exerted an inhibitory effect on inflammatory (NF- κ B, Tnf- α , and Il-6) and apoptotic markers (caspase 3, p53, Bax, and Bcl2), of liver tissue in ER stress mice. These data suggest that CA ameliorates hepatic apoptosis and inflammation by reducing NF-κB and Caspase 3 as related key factors between inflammation and apoptosis.

Effects of dietary supplementation with chlorogenic acid on growth performance, antioxidant capacity, and hepatic inflammation in broiler chickens subjected to diquat-induced oxidative stress

This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on broilers subjected to (DQ)-induced oxidative stress. In experiment 1, one hundred and ninety-two male one-day-old Ross 308 broiler chicks were distributed into 4 groups and fed a basal diet supplemented with 0, 250, 500, or 1,000 mg/kg CGA for 21 d. In experiment 2, an equivalent number of male one-day-old chicks were allocated to 4 treatments for a 21-d trial: 1) Control group, normal birds fed a basal diet; 2) DQ group, DQ-challenged birds fed a basal diet; and 3) and 4) CGA-treated groups: DQ-challenged birds fed a basal diet supplemented with 500 or 1,000 mg/kg CGA. The intraperitoneal DQ challenge was performed at 20 d. In experiment 1, CGA administration linearly increased 21-d body weight, and weight gain and feed intake during 1 to 21 d (P < 0.05). CGA linearly and/or quadratically increased total antioxidant capacity, catalase, superoxide dismutase, and glutathione peroxidase activities, elevated glutathione level, and reduced malondialdehyde accumulation in serum, liver, and/or jejunum (P < 0.05). In experiment 2, compared with the control group, DQ challenge reduced body weight ratio (P < 0.05), which was reversed by CGA administration (P < 0.05). DQ challenge increased serum total protein level, aspartate aminotransferase activity, and total bilirubin concentration (P < 0.05), which were normalized when supplementing 500 mg/kg and/or 1,000 mg/kg CGA (P < 0.05). DQ administration elevated hepatic interleukin-1β, tumor necrosis factor-α, and interleukin-6 levels (P < 0.05), and the values of interleukin-1β were normalized to control values when supplementing CGA (P < 0.05). DQ injection decreased serum superoxide dismutase activity, hepatic catalase activity, and serum and hepatic glutathione level, but increased malondialdehyde concentration in serum and liver (P < 0.05), and the values of these parameters (except hepatic catalase activity) were reversed by 500 and/or 1,000 mg/kg CGA. The results suggested that CGA could improve growth performance, alleviate oxidative stress, and ameliorate hepatic inflammation in DQ-challenged broilers.

Protective effects of chlorogenic acid on growth, intestinal inflammation, hepatic antioxidant capacity, muscle development and skin color in channel catfish Ictalurus punctatus fed an oxidized fish oil diet

Under oxidative stress condition, the protective effects of dietary chlorogenic acid (CGA) supplementation on liver antioxidant capacity, intestinal inflammation and barrier function, muscle development and skin coloration in channel catfish Ictalurus punctatus were explored in the current study. With that purpose, I. punctatus were fed five experimental diets containing 2% fresh fish oil (FFO, 9.2 meqO2/kg) or 2% oxidized fish oil (OFO, 897.4 meqO2/kg) without or with CGA supplementation (0.02%, 0.04% and 0.08%) for 8 weeks. Upon comparative analysis, the oxidized fish oil consumption significantly lowered weight gain rate, decreased intestinal villi length and muscular thickness values and the tight junction proteins mRNA abundance, augmented the intestinal proinflammatory factors, attenuated hepatic antioxidant enzymes activities and related genes mRNA expression levels, influenced the myogenic regulatory factors expression profile and impacted the myocyte density, myocyte area values as well as the skin pigments contents compared to the FFO treatment. Collectively, long-term feeding of the oxidized fish oil diet suppressed the growth performance, destroyed intestinal structural integrity, caused intestinal inflammation and hepatic oxidative stress, impacted the skeletal development and skin color of I. punctatus. Whereas CGA supplementation in oxidized fish oil diets partially counteracted the negative effects of the oxidized fish oil on I. punctatus in terms of increasing the growth performance, improving the intestinal mucosal structure, alleviating hepatic oxidative stress and intestinal inflammation, recompiling the myogenic regulatory factors expression and improving skin color. In conclusion, CGA has great potential to be an aquatic feed additive.

Chlorogenic acid ameliorates chronic stress-induced prefrontal cortex injury through activating the 5-HT/BDNF signaling pathway in rats

The chlorogenic acid (CGA) has a strong neuroprotective ability and cognitive improvement. The purpose of this study was to investigate the effect and mechanism of CGA on chronic restraint stress (CRS)-induced prefrontal cortex (PFC) injury and depression-like behavior. Rats were restrained for 6 h each day to create a CRS paradigm that lasted for 21 days. One hour prior to constraint, CGA (50 mg/kg, 100 mg/kg and 150 mg/kg) was intragastrically delivered. The results showed that CGA could reduce serum corticosterone (CORT) levels in rats and 100 mg/kg CGA could prevent CRS-induced depression-like behaviors. Histopathological revealed that 100 mg/kg CGA ameliorated CRS-induced PFC microstructural. Furthermore, 5-HT content was also increased. Therefore, 100 mg/kg of CGA will be used to further probe the molecular mechanism of regulating 5-HT. Observations using transmission electron microscopy demonstrated that CGA reduced CRS-induced PFC synaptic damage. CGA promotes cAMP-CREB-BDNF signaling pathway and inhibits indoleamine 2,3-dioxygenase (IDO) and serotonin transporter (SRET). Cellular thermal shift assays (CETSA) and molecular docking studies have shown that IDO, SERT and CGA docking have priority potential targets. Together, a protective effect of CGA is seen in rats with CRS-induced PFC by regulating the expression of IDO and SERT and then affecting the effect of 5-HT on the cAMP-CREB-BDNF signaling pathway.

Efficacy of chlorogenic acid against ethylene glycol-induced renal stone model: The role of NFKB-RUNX2-AP1-OSTERIX signaling pathway

Background and objectiveRenal tissue injuries by free radicals are an essential reason in pathogenesis of urinary tract stones. Ethylene glycol is one of the toxic agents which can causes to the increases in biosynthesis of reactive oxygen species and oxidative stress condition. Natural antioxidants have been reported to protective efficacy against renal stones formation. Accordingly, the aim of the current experiment was to identify the renal protective effect of chlorogenic acid as a well-prominent antioxidant on ethylene glycol-induced renal stone model targeting the NFKB-RUNX2-AP1-OSTERIX signaling pathway. Materials and methodsRenal stones model were established by ethylene glycol (Percent: 0.75) within the daily drinking water for rats. Treatment groups received cystone (750 mg/kg) and chlorogenic acid (100, 200, and 400 mg/kg, day: 15th to 28th, gavage). After 4 weeks, the renal function parameters (calcium, uric acid, creatinine, total protein, oxalate, and citrate) in plasma, urine, and renal tissue were measured. Moreover, oxidative stress factors and gene expression of NFKB, RUNX2, AP1, and OSTERIX were also evaluated. ResultsThe results showed improved renal function in chlorogenic acid-treated groups. The total proteins and creatinine excretion were decreased. Also the gene expression of oxidative stress pathway (NFKB-RUNX2-AP1-OSTERIX) were decreased which caused to increases of antioxidant enzymes. Conclusionsthe antioxidant activity increases by chlorogenic acid treatment may have a critical role in prevention of calcium oxalate formation via inhibition of the NFKB-RUNX2-AP1-OSTERIX signaling pathway.