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Spermatogenesis process plays a major role in male fertility. Quercetin, a flavonoid, is found in daily food or traditional Chinese medicine, which has a significant effect on treating inflammatory diseases. Several studies have shown that quercetin can improve male spermatogenesis. However, the intrinsic mechanism has not been systematically investigated. The network pharmacology approaches were utilized to investigate the mechanisms of quercetin against spermatogenesis impairment (SI). 78 potential therapeutic targets of quercetin against SI were identified. The enrichment analysis showed that the mechanism of quercetin on SI is closely related to its anti-inflammatory pharmacological effects. It is indicated that quercetin could be used for treating SI through inflammation-related targets or pathways including NF-κB, MAPK, JAK-STAT and Toll-like receptor signaling pathways. [ABSTRACT FROM AUTHOR]

Different studies have confirmed that P2X purinergic receptors play a key role in inflammation. Activation of P2X purinergic receptors can release inflammatory cytokines and participate in the progression of inflammatory diseases. In an inflammatory microenvironment, cells can release a large amount of ATP to activate P2X receptors, open non-selective cation channels, activate multiple intracellular signaling, release multiple inflammatory cytokines, amplify inflammatory response. While P2X4 and P2X7 receptors play an important role in the process of inflammation. P2X4 receptor can mediate the activation of microglia involved in neuroinflammation, and P2X7 receptor can mediate different inflammatory cells to mediate the progression of tissue-wide inflammation. At present, the role of P2X receptors in inflammatory response has been widely recognized and affirmed. Therefore, in this paper, we discussed the role of P2X receptors-mediated inflammation. Moreover, we also described the effects of some antagonists (such as A-438079, 5-BDBD, A-804598, A-839977, and A-740003) on inflammation relief by antagonizing the activities of P2X receptors. [Display omitted] • The biological characteristics of P2X receptors were described. • Provided up-to-date data support for the intrinsic link between P2X receptors and inflammation response. • Provided some data of P2X antagonists for the treatment of inflammation. • P2X receptors as a potential target for the treatment of inflammation was discussed. [ABSTRACT FROM AUTHOR]

(7 R,8 S)-Dehydrodiconiferyl alcohol (DDA), a lignan isolated from the dried stems of Clematis armandii, has been found to exert potential anti-inflammatory activity in vitro. In the present study, we investigated the effects and possible mechanisms of DDA on lipopolysaccharide (LPS)-mediated inflammatory response in murine BV2 microglia. Our results revealed that non-toxic concentrations (6.25-25 μM) of DDA markedly suppressed LPS-induced production of nitric oxide, expression of inducible nitric oxide synthase and cyclooxygenase-2, and release of inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in a concentration dependent manner. In addition, DDA time- and concentration-dependently attenuated LPS-induced phosphorylation of c-Jun N-terminal kinase 1/2 (JNK), but not protein kinase B, p38, or extracellular signal-regulated kinase 1/2. Moreover, DDA significantly suppress LPS-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. Collectively, our results demonstrated that DDA inhibited LPS-stimulated inflammatory response in BV2 cell, at least in part, through inhibition of NF-κB activation and modulation of JNK signaling. [ABSTRACT FROM AUTHOR]

Neuroinflammation underlies the pathogenesis and progression of neurodegenerative diseases. 2׳-hydroxy-4,3׳,4׳,6׳-tetramethoxychalcone (HTMC) is a known chalcone derivative isolated from Chloranthus henryi with anti-inflammatory activities in BV2 macrophages. However, its pharmacological effects on microglial cells have not been demonstrated. To this end, we examined the effects of HTMC on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells. HTMC concentration-dependently inhibited LPS-induced expression of inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nitric oxide (NO) production, and the secretion of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In addition, HTMC inhibited reactive oxygen species (ROS) production by reducing NADPH oxidase (Nox) 2 and Nox4 expression. In addition, HTMC interfered LPS-induced c-Jun N-terminal kinase 1/2 (JNK) phosphorylation in a time- and concentration-dependent manner. By inhibiting phosphorylation and nuclear translocation of Jun, HTMC suppressed LPS-induced activator protein-1 (AP-1) activation. Taken together, our data indicate that HTMC suppresses inflammatory responses in LPS-stimulated BV2 microglial cells by modulating JNK-AP-1 and NADPH oxidases-ROS pathways. HTMC represents a promising therapeutic agent for neurodegenerative and related aging-associated diseases. [ABSTRACT FROM AUTHOR]

Inflammatory processes are often accompanied by oxidative stress and lipid peroxidation, which might lead to cellular and organ damage. Carnosic acid (CA), an active component found in rosemary, exhibits pharmacological properties including antioxidative, anti-inflammatory, and antiviral effects. The aim of this research was to investigate whether CA can mitigate lipopolysaccharide (LPS)-induced oxidative stress and inflammatory responses in poultry and to understand its underlying mechanisms. We administered CA to broiler chickens via oral gavage and treated them with LPS, followed by analysis of the effects of different dosages of CA on body weight, antioxidative capacity, and inflammatory factors. Carnosic acid had no significant impact on the body weight of broiler chickens. However, serum analysis indicated that the middle dose of CA effectively enhanced the antioxidative capacity and reduced levels of oxidative stress and inflammation-related factors. Moreover, in the liver, CA demonstrated the ability to regulate the expression of proteins such as heat shock protein 60 (HSP60), heat shock protein 70 (HSP70), and P38 mitogen-activated protein kinase (P38), suggesting its protective role against liver damage induced by LPS. In the intestinal tract of broiler chickens, CA regulated the expression and localization of proteins including HSP60, HSP70, NFE2 like bZIP transcription factor 2 (Nrf2), and P38, while also influencing the expression of inflammatory markers such as protein tyrosine phosphatase receptor type C (CD45), and connexin (Cx). These findings revealed the potential protective mechanisms of CA in alleviating oxidative stress and inflammatory damage induced by LPS in poultry. Carnosic acid notably enhanced the chickens' antioxidative capacity by modulating the expression of key proteins, thereby reducing oxidative stress and inflammatory response levels. This study provides a deeper comprehension of the protective mechanisms of CA and its potential impact on avian health. [ABSTRACT FROM AUTHOR]

Adrenomedullin (ADM) is a novel cardiovascular peptide with anti-inflammatory and antioxidant properties. Chronic inflammation, oxidative stress and calcification play pivotal roles in the pathogenesis of vascular dysfunction in obesity-related hypertension (OH). Our study aimed to explore the effects of ADM on the vascular inflammation, oxidative stress and calcification in rats with OH. Eight-week-old Sprague Dawley male rats were fed with either a Control diet or a high fat diet (HFD) for 28 weeks. Next, the OH rats were randomly subdivided into two groups as follows: (1) HFD control group, and (2) HFD with ADM. A 4-week treatment with ADM (7.2 μg/kg/day, ip) not only improved hypertension and vascular remodeling, but also inhibited vascular inflammation, oxidative stress and calcification in aorta of rats with OH. In vitro experiments, ADM (10 nM) in A7r5 cells (rat thoracic aorta smooth muscle cells) attenuated palmitic acid (PA, 200 μM) or angiotensin II (Ang II, 10 nM) alone or their combination treatment-induced inflammation, oxidative stress and calcification, which were effectively inhibited by the ADM receptor antagonist ADM22-52 and AMP-activated protein kinase (AMPK) inhibitor Compound C, respectively. Moreover, ADM treatment significantly inhibited Ang II type 1 receptor (AT1R) protein expression in aorta of rats with OH or in PA-treated A7r5 cells. ADM improved hypertension, vascular remodeling and arterial stiffness, and attenuated inflammation, oxidative stress and calcification in OH state partially via receptor-mediated AMPK pathway. The results also raise the possibility that ADM will be considered for improving hypertension and vascular damage in patients with OH. [ABSTRACT FROM AUTHOR]

Nickel (Ni), one of hazardous environmental chemicals, is known to cause liver injury. Accumulating evidence showed that puerarin (PU) possessed comprehensive biological effects. The purpose of the current study was to test the hypothesis that the puerarin protects against enhanced liver injury caused by Ni in mice. ICR mice received intraperitoneally nickel sulfate (20 mg/kg/body weight, daily) for 20 days, and puerarin (200 and 400 mg/kg/body weight) was applied before Ni exposure. The results indicated that puerarin markedly inhibited Ni-induced liver injury, which was characterized by decreased aminotransferase activities and inflammation. Puerarin also inhibited the oxidative stress and decreased the metallothionein (MT) levels. Puerarin decreased the level of pro-inflammatory cytokines TNF-α and IL-6 in livers. Puerarin significantly inhibited the TLR4 activation and p38 MAPK phosphorylation, which in turn inhibited NF-κB activity. Likewise, Ni-induced inflammatory responses were diminished by puerarin as observed by a remarkable reduction in the levels of phosphorylated CREB. Furthermore, puerarin also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) levels in livers. Data from this study suggested that the inhibition of Ni-induced oxidative stress and inflammatory responses by puerarin is due to its ability to modulate the TLR4/p38/CREB signaling pathway. [ABSTRACT FROM AUTHOR]

Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases. [Display omitted] • The potential of Chuanminshen violaceum stems and leaves to be used as agricultural by-products is exploited. • Ultrasound-assisted extraction was efficient to extract polysaccharide from the stems and leaves of Chuanminshen violaceum. • A polysaccharide (CVP-AP-Ⅰ) was obtained and characterized as a typical pectic polysaccharide. • CVP-AP-Ⅰ exhibited potent anti-inflammatory and antioxidant effects in vitro. [ABSTRACT FROM AUTHOR]

N -acetylcysteine (NAC) plays a beneficial role in improving animal growth and health. The current study evaluated the impact of dietary supplementation with NAC on the growth performance, physiological status and intestinal health of juvenile Cyprinus carpio. The experiment involved 5 groups, with 3 replicates in each group, and each replicate group containing 30 juvenile Cyprinus carpio (average weight 2.06 ± 0.01 g). Five experimental diets (36% crude protein and 9% crude lipid) were prepared by supplementing graded levels (0, 0.15%, 0.30%, 0.45% and 0.60%) of NAC in the basal diet. Subsequently, these 5 diets were utilized for an 56 d feeding trial with Cyprinus carpio. During the feeding trial, the water temperature was maintained between 24 and 28 °C, and the feeding rate was 3%–5% of body weight. After the feeding trial, fish were fasted for 24 h, anesthetized, and dissected on ice trays to collect samples for subsequent analysis. Results showed that NAC (0.30%, 0.45% and 0.60% diets) significantly improved the growth performance and intestinal mucosa development in Cyprinus carpio , and inhibited apoptosis. Similarly, NAC (0.30%, 0.45% and 0.60% diets) could enhance the homeostasis of the redox defense system in intestine of Cyprinus carpio , which is linked to enhanced glutathione metabolism, scavenging of reactive oxygen species and activation of Nrf2 pathway. Furthermore, dietary NAC improved anti-inflammatory and immunomodulatory functions, and involved in the regulation of MAPK/NF-κB signaling pathway. Summary, NAC (0.30%, 0.45% and 0.60% diets) could significantly promote the growth and intestinal health in Cyprinus carpio. These findings provide partial available information for promoting the utilization of NAC in aquafeed and improving the ecological and healthy cultivation of Cyprinus carpio. [Display omitted] • N -acetylcysteine (NAC) can improve intestinal development and inhibit apoptosis in fish. • NAC exerts anti-inflammatory and antioxidant effects by modulating the MAPK/NF-κB/Nrf2 signaling pathway. • Dietary supplementation with appropriate levels of NAC improved the growth and health status of juvenile Cyprinus carpio. [ABSTRACT FROM AUTHOR]

Proanthocyanidins (PCs), a class of naturally occurring flavonoids, had been reported to possess a variety of biological activities, including anti-oxidant, anti-tumor and anti-inflammatory. In this study, we examined the protective effect of PCs against lead-induced inflammatory response in the rat brain and explored the potential mechanism of its action. The results showed that PCs administration significantly improved behavioral performance of lead-exposed rats. One of the potential mechanisms was that PCs decreased reactive oxygen species production and increased the total antioxidant capacity in the brains of lead-exposed rats. Furthermore, the results also showed that PCs significantly decreased the levels of tumor necrosis factor-α, interleukin 1β and cyclooxygenase-2 in the brains of lead-exposed rats. Moreover, PCs significantly decreased the levels of beta amyloid and phosphorylated tau in the brains of lead-treated rats, which in turn inhibited endoplasmic reticulum (ER) stress. PCs also decreased the phosphorylation of protein kinase RNA-like ER kinase, eukaryotic translation initiation factor-2, inositol-requiring protein-1, c-Jun N-terminal kinase, p38 and inhibited nuclear factor-κB nuclear translocation in the brains of lead-exposed rats. In conclusion, these results suggested that PCs could improve cognitive impairments by inhibiting brain oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]

N-acetylcysteine (NAC) positively contributes to enhancing animal health, regulating inflammation and reducing stress by participating in the synthesis of cysteine, glutathione, and taurine in the body. The present study aims to investigate the effects of dietary different levels of NAC on the morphology, function and physiological state of hepatopancreas in juvenile common carp (Cyprinus carpio). 450 common carps were randomly divided into 5 groups: N1 (basal diet), N2 (1.5 g/kg NAC diet), N3 (3.0 g/kg NAC diet), N4 (4.5 g/kg NAC diet) and N5 (6.0 g/kg NAC diet), and fed for 8 weeks. The results indicated that dietary 3.0–6.0 g/kg NAC reduced hepatopancreas lipid vacuoles and nuclear translocation, and inhibited apoptosis in common carp. Simultaneously, the activities of hepatopancreas alanine aminotransferase and aspartate aminotransferase progressively increased with rising dietary NAC levels. Dietary NAC enhanced the non-specific immune function of common carp, and exerted anti-inflammatory effects by inhibiting the MAPK/NF-κB signaling pathway. Additionally, dietary 3.0–6.0 g/kg NAC significantly improved the antioxidant capacity of common carp, which was associated with enhanced glutathione metabolism, clearance of ROS and the activation of Nrf2 signaling pathway. In summary, NAC has the potential to alleviate inflammation, mitigate oxidative stress and inhibit apoptosis via the MAPK/NF-κB/Nrf2 signaling pathway, thereby improving hepatopancreas function and health of common carp. The current findings provide a theoretical basis for promoting the application of NAC in aquaculture and ecological cultivation of aquatic animals. [Display omitted] • N-acetylcysteine (NAC) could improve the morphology and health of hepatopancreas in common carp. • The anti-inflammatory and antioxidant effects of NAC via the MAPK/NF-κB/Nrf2 signalling pathway. • We recommend adding 3.0 g/kg NAC to the diets of juvenile common carp. [ABSTRACT FROM AUTHOR]

Two Cu(II)-based coordination polymers with the chemical formula of [Cu(bibb)(1,4-NDC)](DMF) (1, bibb = 1,4-bis(benzimidazol-1-yl)−2-butylene, 1,4-H2NDC = 1,4-naphthalenedicarboxylic acid, DMF = N,N-dimethylformamide) and [Cu(bibb)(1,4-NDC)](DMA) (2, N,N-dimethylacetamide) have been prepared. The structural solution and refinement results based on the crystal data show that complex 1 exhibits a rarely 2-fold interpenetrating 3D (4,5)-connected xah framework, and complex 2 possesses an unusual 3D (3,4)-connected dmc topology. Furthermore, the protective activity of compounds 1 and 2 on Viral myocarditis (VMC) was detected on CVB3-induced mouse viral myocarditis model. The relative expression of the inflammatory factors nf-κb and p38 in myocardial cells after compounds 1 and 2 treatment was measured with reverse transcription-polymerase chain reaction (RT-PCR). The release level of the inflammatory cytokines IL-1 and MCP-1 by myocardial cells was determined with enzyme linked immunosorbent assay (ELISA) detection kit. [ABSTRACT FROM AUTHOR]

Cordyceps is a parasitic edible fungus, which is a unique Chinese medicinal material. It has been reported to have immunomodulatory effects and use in kidney disease. Especially, Cordyceps has been used in the treatment of lupus nephritis (LN). Cordyceps proteins (CP) have a favorable bidirectional immunomodulatory functions and may have therapeutic potential for LN. However, the underlying molecular mechanism remains unknown. So this study aimed to examine the activities of CP in LN and possible mechanism. So proteomics was performed to detect proteins components of Cordyceps, and analysis it. In addition, MRL/lpr mice were used to study the progression of LN. The MRL/lpr mice were fed either CP (i.g, 0.5, 1.0, 1.5 g/kg/d), prednisolone acetate (PA, i.g, 6 mg/kg/d), or Bailing capsule (BC, i.g, 0.75 g/kg/d) for 8 weeks. Hematoxylin-eosin (H&E), Periodic Acid Schif (PAS) and Masson's stainings, Immunofluorescence, and Immunohistochemistry were performed to verify the therapeutic effect of CP on MRL/lpr mice. The mechanism by CP alimerated LN was uncovered by Western blotting (WB) and Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) methods. Our results revealed that CP blocked proteinuria production and renal inflammatory infiltratation in MRL/lpr mice to reduce the renal fibrosis. In addition, CP worked better than BC which is artificial Cordyceps fungus powder in regulating proteinuria to urine creatinine ratio and interleukin-4(IL-4) protein amount. Especially, CP modulated the STAT3/mTOR/NF-кB signaling pathway in LN mice and brought a more pronounced lowering effect on the contents of IL-6 and IL-1β than the PA. CP could be a potential anti-inflammatory immune product with strong regulatory effects and potency than BC and PA in nephritis therapeutics. [Display omitted] • For the first time, Cordyceps protein has been shown to improve proteinuria in lupus nephritis. • The inhibitor prednisolone acetate improved renal inflammatory infiltration in lupus nephritis. • Trichospora chinensis powder is involved in the regulation of renal fibrosis in lupus nephritis. • Cordyceps protein has a negative regulatory effect on STAT3/mTOR/NF-кB signaling pathway. [ABSTRACT FROM AUTHOR]

Quercetin (QE), a natural flavonoid, has many medical beneficial effects. However, its protective effects against carbon tetrachloride (CCl 4 ) induced injury in liver have not been clarified. The aim of the present study is to illustrate the effects of QE on hepatic oxidative injury and inflammation in mice exposed to CCl 4 . ICR (Institute of Cancer Research) mice were exposed to CCl 4 with or without QE co-administration for one week. Our results showed that QE administration significantly inhibited CCl 4 -induced liver injury. One of the potential mechanisms of QE action was decreasing the oxidative stress, which is consistent with decreasing of lipid peroxidation level and increasing the antioxidant enzyme activities in livers of mice. Furthermore, QE significantly decreased cytochrome P450 2E1 (CYP2E1) expression and production of pro-inflammatory markers such as inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and nitric oxide (NO) in livers of CCl 4 -treated mouse. In the process of exploring the underlying mechanisms of QE action, we found that QE significantly inhibited the Toll-like receptor 2 (TLR2) and the Toll-like receptor 4 (TLR4) activation and mitogen-activated protein kinase (MAPK) phosphorylation, which in turn inactivated NF-κB and the inflammatory cytokines in livers of the CCl 4 -treated mice. In conclusion, these results suggested that the inhibition of CCl 4 -induced inflammation by QE is due to its anti-oxidant activity and its ability to modulate the TLR2/TLR4 and MAPK/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Quercetin (QE), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against nickel (Ni) induced injury in liver have not been clarified. The aim of the present study was to investigate the effects of quercetin on hepatic DNA methylation and inflammation in mice exposed to nickel. ICR mice were exposed to nickel sulfate with or without quercetin co-administration for 20 days. Our results showed that quercetin administration significantly inhibited nickel-induced liver injury, which was indicated by diagnostic indicators. In exploring the underlying mechanisms of quercetin action, we found that quercetin decreased total DNA methyltransferases (DNMTs) activity and DNA methylation level of the NF-E2 related factor 2 (Nrf2) DNA in livers of nickel-treated mice. Quercetin also induced Nrf2 nuclear translocation and heme oxygenase-1 (HO-1) activity. Moreover, quercetin decreased production of pro-inflammatory markers including TNF-α, IL-1β and iNOS. Quercetin significantly inhibited the p38 and signal transducer and activator of transcription 1 (STAT1) activation, which in turn inactivated NF-κB and the inflammatory cytokines in livers of the nickel-treated mice. In conclusion, these results suggested that the inhibition of nickel-induced inflammation by quercetin is associated with its ability to modulate Nrf2/HO-1 and p38/STAT1/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease activity was scored by a disease activity index (DAI). Histological changes were evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1, interleukin (IL)-1β, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group). In addition, LMWH significantly decreased the expression of both IL-1β and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa. [ABSTRACT FROM AUTHOR]

Dysregulated long non-coding RNA (lncRNA) expression is closely related to neuroinflammation, leading to multiple neurodegenerative diseases. In this study, we investigated the function and regulation of lncRNA AK148321 in neuroinflammation using an in vitro lipopolysaccharide (LPS)-stimulated BV2 microglial cell system. Expression of AK148321 was analyzed by qPCR. Inflammatory cytokine expression levels were determined by ELISA assay. The interaction between AK148321, microRNA (miRNA), and its target gene was validated by luciferase reporter assay and RNA immunoprecipitation (RIP). Cell apoptosis was analyzed by Annexin V/PI staining. LPS treatment suppressed AK148321 expression in BV2 cells. Overexpression of AK148321 inhibited LPS-induced BV2 microglial cell activation and decreased the expression of inflammatory cytokine TNF-α and IL-1β. AK148321 function as a competing endogenous RNA (ceRNA) by sponging microRNA-1199-5p (MiR-1199-5p). In LPS-stimulated BV2 cells, AK148321 exerted its inhibitory function via negatively modulating miR-1199-5p expression. Moreover, we identified that Heat Shock Protein Family A Member 5 (HSPA5) was a direct target of miR-1199-5p. RIP assay using the anti-Ago2 antibody further validated the relationship among AK148321, miR-1199-5p and HSPA5. The AK148321/miR-1199-5p/HSPA5 axis regulated the neuroinflammation in LPS-induced BV2 microglial cells. Microglial cell culture supernatant from LPS-stimulated, AK148321-overexpressing BV2 cells suppressed the cell apoptosis of mouse hippocampal neuronal cell HT22, while HSPA5 knockdown abrogated the suppression effect. Our findings suggest that AK148321 alleviates neuroinflammation in LPS-stimulated BV2 microglial cells through miR-1199-5p/HSPA5 axis. • LPS stimulation inhibited the expression of lncRNA AK148321 in microglial cells. • LncRNA AK148321/miR-1199-5p/HSPA5 axis regulates microglial cell activation, inflammatory cytokine production, and modulates neuron cell apoptosis. • LncRNA AK148321 inhibits LPS-induced BV2 microglial cell activation and inflammation [ABSTRACT FROM AUTHOR]