Study on chemical constituents and fingerprints of Phellodendron amurense Rupr. based on ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry.

The chemical constituents from Phellodendron amurense Rupr. were characterized systematically by ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry method for collecting mass spectrometry data, and the fingerprints method was established, providing reference for its quality control. The chromatographic column was ACQUITY UPLC BEH-C18 (100 mm×2.1 mm, 1.7 µm). The mobile phase was acetonitrile-0.1% formic acid aqueous solution and the compounds from P. amurense Rupr. were identified by Qualitative Analysis 10.0 software, reference substance, retention time, mass spectrometry fragmentation pattern and database retrieval. Meanwhile, liquid chromatography-mass spectrometry fingerprint methods of P. amurense Rupr. and Phellodendron chinense Schneid. were established by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine (2012 edition), and the differences were analyzed by multivariate statistical analysis methods. A total of 105 compounds were identified, including 102 alkaloids, two phenolic acids, and one lactone compound. Liquid chromatography-mass spectrometry fingerprint method was established with ideal precision, stability and repeatability, and 12 quality differential markers were recognized between the above two herbs. Liquid chromatography-mass spectrometry method can be used for qualitative analysis of the constituents of Phellodendron amurense Rupr., providing reference for clarifying the material basis and promoting the clinical precision medication and quality evaluation of P. amurense Rupr.

Structural modification and antihypertensive activity study of formononetin derivatives.

A series of formononetin derivatives with substituted benzyloxy groups on the 4' position of isoflavone were designed and synthesized. Their vasodilative activities were evaluated by wire myograph system on isolated rat mesenteric arterial ring. The preliminary SAR of target compounds was thus discussed. Compounds 3d and 3e exhibited potent vasodilative activities against the rat mesenteric arterial rings induced contraction with K+. Compounds 3d and 3e also showed antihypertensive effects in SHRs by oral administration.

Gasdermin D Drives the Nonexosomal Secretion of Galectin-3, an Insulin Signal Antagonist.

The inflammasomes play critical roles in numerous pathological conditions largely through IL-1ß and/or IL-18. However, additional effectors have been implied from multiple studies. In this study, through two independent mass spectrometry-based secretome screening approaches, we identified galectin-3 as an effector protein of the NLRP3 inflammasome. Although the activation of AIM2 or NLRC4 inflammasome also led to galectin-3 secretion, only the NLRP3 inflammasome controlled the serum galectin-3 level under physiological condition. Mechanistically, active gasdermin D drove the nonexosomal secretion of galectin-3 through the plasma membrane pores. In vivo, high-fat diet-fed Nlrp3-/- mice exhibited decreased circulating galectin-3 compared with wild-type animals. Of note, the improved insulin sensitivity in such Nlrp3-/- mice was aggravated by infusion of recombinant galectin-3. Moreover, galectin-3 was essential for insulin resistance induction in mice harboring the hyperactive Nlrp3A350V allele. Thus, the inflammasome-galectin-3 axis has been demonstrated as a promising target to intervene inflammasome and/or galectin-3 related diseases.

Hyperactivation of the NLRP3 inflammasome protects mice against influenza A virus infection via IL-1ß mediated neutrophil recruitment.

Host innate immune system is critical for combating invading microbes including Influenza A virus (IAV). As an important arm of the innate immunity, the NLRP3 inflammasome has been found essential for protecting host against IAV challenge, while the mechanism remained elusive. Here we found that mice carrying a gain-of-function mutation in the Nlrp3 gene (Nlrp3R258W) are strongly resistant to IAV infection. Upon H1N1 IAV infection, the Nlrp3R258W mice exhibited decreased weight loss, increased survival rate and attenuated lung damage compared with WT littermate controls. Mechanistically, the resistance of Nlrp3R258W mice to IAV infection was dependent on IL-1ß-mediated neutrophil recruitment. Upon IAV infection, mice carrying the Nlrp3R258W mutation produced more IL-1ß than WT mice in the lung, which enhanced neutrophil recruitment locally. The recruited neutrophils facilitated IAV clearance, so that the viral load in Nlrp3R258W mice was lower than that in control mice. Conversely, neutrophil depletion in Nlrp3R258W mice compromised IAV clearance. Taken together, our results demonstrate a previously undescribed mechanism by which hyperactivation of the NLRP3 Inflammasome protects mice from IAV infection through IL-1ß mediated neutrophil recruitment, thus suggest that positively fine tuning the physiological function of NLRP3 inflammasome can be beneficial for a mammalian host against IAV challenge.

Cutting Edge: TRAF6 Mediates TLR/IL-1R Signaling-Induced Nontranscriptional Priming of the NLRP3 Inflammasome.

NLRP3 inflammasome activiation requires two sequential signals. The priming signal 1 from TLRs or cytokine receptors induces the transcription of NLRP3 and IL-1ß, and concomitantly promotes transcription-independent activation of caspase-1. The activating signal 2 can be provided by microbial products or danger signals. In this study we found that TRAF6 is necessary for the nontranscriptional priming of NLRP3 inflammasome by TLR/IL-1R derived signals. Deficiency of TRAF6 specifically inhibited TLR/IL-1R priming-initiated caspase-1 cleavage, pyroptosis, and secretion of presynthesized IL-18. Mechanistically, TRAF6 promoted NLRP3 oligomerization as well as the interaction between NLRP3 and apoptosis-associated speck-like protein containing a CARD. Of note, the nontranscriptional priming via TRAF6 did not involve mitochondrial reactive oxygen species or the phosphorylation of Jnk, Erk, and Syk, whereas the ubiquitin E3 ligase activity of TRAF6 was required. Our findings thus extended cognition on the mechanism of NLRP3 inflammasome activation, and provided a novel target for controlling NLRP3-related diseases.

Hyperactivation of the NLRP3 Inflammasome in Myeloid Cells Leads to Severe Organ Damage in Experimental Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model. It was discovered that more severe lupus-like syndrome developed in Nlrp3-R258W mice carrying the gain-of-function mutation. Nlrp3-R258W mutant mice exhibited significantly higher mortality upon pristane challenge. Moreover, prominent hypercellularity and interstitial nephritis were evident in the glomeruli of Nlrp3-R258W mice. In addition, hyperactivation of the NLRP3 inflammasome in this mouse line resulted in proteinuria and mesangial destruction. Importantly, all of these phenotypes were largely attributed to the Nlrp3-R258W mutation expressed in myeloid cells, because Cre recombinase-mediated depletion of this mutant from such cells rescued mice from experimental lupus. Taken together, our study demonstrates a critical role for NLRP3 in the development of SLE and suggests that modulating the inflammasome signal may help to control the inflammatory damage in autoimmune diseases, including lupus.

Interleukin-18 protects mice from Enterovirus 71 infection.

Previous study has demonstrated that the NLRP3 inflammasome is essential for protecting murine host against Enterovirus 71 (EV71) infection. However, the underlying mechanism remained unknown. Here we discovered that the pleiotropic cytokine interleukin-18 (IL-18), an NLRP3 inflammasome-dependent effector protein, exhibits a protective capability against EV71 challenge. Deficiency of IL-18 in mice exacerbated EV71 infection, which was reflected by increased viral replication, elevated production of interferons (IFN-ß, IFN-γ), proinflammatory cytokines (TNF-α, IL-6) and chemokine CCL2,as well as decreased survival of experimental animals. Conversely, administration of recombinant IL-18 considerably restrained EV71 infection in IL-18 deficient mice. Thus, our results revealed a protective role for IL-18 against EV71 challenge, and indicated a novel therapeutic application for IL-18 in EV71 associated hand, foot, and mouth disease (HFMD).

Transgene-based, female-specific lethality system for genetic sexing of the silkworm, Bombyx mori.

Transgene-based genetic sexing methods are being developed for insects of agricultural and public health importance. Male-only rearing has long been sought in sericulture because males show superior economic characteristics, such as better fitness, lower food consumption, and higher silk yield. Here we report the establishment of a transgene-based genetic sexing system for the silkworm, Bombyx mori. We developed a construct in which a positive feedback loop regulated by sex-specific alternative splicing leads to high-level expression of the tetracycline-repressible transactivator in females only. Transgenic animals show female-specific lethality during embryonic and early larval stages, leading to male-only cocoons. This transgene-based female-specific lethal system not only has wide application in sericulture, but also has great potential in lepidopteran pest control.

HIRA is essential for the development of gibel carp.

HIRA is one of the chaperones of histone H3.3. Mutation of Hira results in embryonic lethality in mice, suggesting a critical role in embryogenesis. However, Hira-mutated Drosophila may survive to adults, indicating that it is dispensable in Drosophila development. The role of Hira in fish development is unknown. In this study we first investigated the expression of Hira during embryogenesis of gibel carp (Carassius auratus gibelio) by whole-mount in situ hybridization. We found that Hira signal appeared ubiquitously in the early embryos. After gastrulation, it appeared mainly along the anterior-posterior axis, including the tail bud. In hatching period, the signal was detected in head, heart, and the endoderm region on the back of yolk. Then by microinjection with morpholino-HIRA at the beginning of development, we observed delayed gastrulation and abnormal somitogenesis in gibel carp embryos. The HIRA morphants exhibited short trunk, limited yolk extension, and twisted tail. Most of the mutants died during embryogenesis or shortly after hatching. The rest of the HIRA morphants could survive to larvae but with severe defects in organogenesis. These data suggest that HIRA may be essential for the development of gibel carp, and this function is conserved in vertebrates.

Anti-influenza activity of CPAVM1 protease secreted by Bacillus subtilis LjM2.

Bacillus spp. has been considered a promising source for identifying new antimicrobial substances, including anti-viral candidates. Here, we successfully isolated a number of bacteria strains from aged dry citrus peel (Chenpi). Of note, the culture supernatant of a new isolate named Bacillus subtilis LjM2 demonstrated strong inhibition of influenza A virus (IAV) infection in multiple experimental systems in vitro and in vivo. In addition, the anti-viral effect of LjM2 was attributed to its direct lysis of viral particles. Further analysis showed that a protease which we named CPAVM1 isolated from the culture supernatant of LjM2 was the key component responsible for its anti-viral function. Importantly, the therapeutic effect of CPAVM1 was still significant when applied 12 hours after IAV infection of experimental mice. Moreover, we found that the CPAVM1 protease cleaved multiple IAV proteins via targeting basic amino acid Arg or Lys. Furthermore, this study reveals the molecular structure and catalytic mechanism of CPAVM1 protease. During catalysis, Tyr75, Tyr77, and Tyr102 are important active sites. Therefore, the present work identified a special protease CPAVM1 secreted by a new strain of Bacillus subtilis LjM2 against influenza A virus infection via direct cleavage of critical viral proteins, thus facilitates future biotechnological applications of Bacillus subtilis LjM2 and the protease CPAVM1.

Comparative methylomics between domesticated and wild silkworms implies possible epigenetic influences on silkworm domestication.

BACKGROUND: In contrast to wild species, which have typically evolved phenotypes over long periods of natural selection, domesticates rapidly gained human-preferred agronomic traits in a relatively short-time frame via artificial selection. Under domesticated conditions, many traits can be observed that cannot only be due to environmental alteration. In the case of silkworms, aside from genetic divergence, whether epigenetic divergence played a role in domestication is an unanswered question. The silkworm is still an enigma in that it has two DNA methyltransferases (DNMT1 and DNMT2) but their functionality is unknown. Even in particular the functionality of the widely distributed DNMT1 remains unknown in insects in general. RESULTS: By embryonic RNA interference, we reveal that knockdown of silkworm Dnmt1 caused decreased hatchability, providing the first direct experimental evidence of functional significance of insect Dnmt1. In the light of this fact and those that DNA methylation is correlated with gene expression in silkworms and some agronomic traits in domesticated organisms are not stable, we comprehensively compare silk gland methylomes of 3 domesticated (Bombyx mori) and 4 wild (Bombyx mandarina) silkworms to identify differentially methylated genes between the two. We observed 2-fold more differentiated methylated cytosinces (mCs) in domesticated silkworms as compared to their wild counterparts, suggesting a trend of increasing DNA methylation during domestication. Further study of more domesticated and wild silkworms narrowed down the domesticates' epimutations, and we were able to identify a number of differential genes. One such gene showing demethyaltion in domesticates correspondently displays lower gene expression, and more interestingly, has experienced selective sweep. A methylation-increased gene seems to result in higher expression in domesticates and the function of its Drosophila homolog was previously found to be essential for cell volume regulation, indicating a possible correlation with the enlargement of silk glands in domesticated silkworms. CONCLUSIONS: Our results imply epigenetic influences at work during domestication, which gives insight into long time historical controversies regarding acquired inheritance.

Disruption of an N-acetyltransferase gene in the silkworm reveals a novel role in pigmentation.

The pigmentation of insects has served as an excellent model for the study of morphological trait evolution and developmental biology. The melanism (mln) mutant of the silkworm Bombyx mori is notable for its strong black coloration, phenotypic differences between larval and adult stages, and its widespread use in strain selection. Here, we report the genetic and molecular bases for the formation of the mln morphological trait. Fine mapping revealed that an arylalkylamine N-acetyltransferase (AANAT) gene co-segregates with the black coloration patterns. Coding sequence variations and expression profiles of AANAT are also associated with the melanic phenotypes. A 126 bp deletion in the mln genome causes two alternatively spliced transcripts with premature terminations. An enzymatic assay demonstrated the absolute loss of AANAT activity in the mutant proteins. We also performed RNA interference of AANAT in wild-type pupae and observed a significant proportion of adults with ectopic black coloration. These findings indicate that functional deletion of this AANAT gene accounts for the mln mutation in silkworm. AANAT is also involved in a parallel melanin synthesis pathway in which ebony plays a role, whereas no pigmentation defect has been reported in the Drosophila model or in other insects to date. To the best of our knowledge, the mln mutation is the first characterized mutant phenotype of insects with AANAT, and this result contributes to our understanding of dopamine metabolism and melanin pattern polymorphisms.

Endothelin receptors in augmented vasoconstrictor responses to endothelin-1 in chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) contributes to the development of cardiovascular diseases in patients with obstructive sleep apnoea. Many studies have shown an association between increased circulating endothelin (ET)-1 levels and CIH. The aim of the present study was to determine the role of ET receptors in altered aortic function in an animal model of CIH. Rats were subjected to CIH (Fi o2 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/week) for 3 weeks. After 3 weeks, the rats were killed and their aortas retrieved for use in in vitro experiments (isometric force measurement), histological analysis, immunohistochemistry and western blotting. Aortas from rats subjected to CIH exhibited marked endothelial dysfunction and increased responsiveness to ET-1. Furthermore, CIH induced increased ET-1 and ETA receptor expression, whereas ETB receptor expression was decreased. Aortic contractile responses to ET-1 were inhibited by the ETA and ETB receptor antagonists BQ-123 and BQ-788, respectively. Acetylcholine-induced relaxation responses were significantly attenuated in aortas from rats subjected to CIH, whereas CIH had no significant effect on aortic responses to sodium nitroprusside. The results of the present study suggest that increased expression of ETA receptors, which mediate a potent vasoconstrictor response, plays an important role in the pathogenesis of CIH. In addition, decreased endothelial ETB receptor expression, which is associated with the functional decline of endothelium-dependent vasodilation, also contributes to the pathogenesis of CIH. It appears that the ETB receptor-induced buffering of ET-1 responsiveness is mediated via a nitric oxide-dependent mechanism.

Microbiota-derived acetate enhances host antiviral response via NLRP3.

Pathogenic viral infections represent a major challenge to human health. Host immune responses to respiratory viruses are closely associated with microbiome and metabolism via the gut-lung axis. It has been known that host defense against influenza A virus (IAV) involves activation of the NLRP3 inflammasome, however, mechanisms behind the protective function of NLRP3 are not fully known. Here we show that an isolated bacterial strain, Bifidobacterium pseudolongum NjM1, enriched in the gut microbiota of Nlrp3-/- mice, protects wild-type but not Nlrp3 deficient mice against IAV infection. This effect depends on the enhanced production of type I interferon (IFN-I) mediated by NjM1-derived acetate. Application of exogenous acetate reproduces the protective effect of NjM1. Mechanistically, NLRP3 bridges GPR43 and MAVS, and promotes the oligomerization and signalling of MAVS; while acetate enhances MAVS aggregation upon GPR43 engagement, leading to elevated IFN-I production. Thus, our data support a model of NLRP3 mediating enhanced induction of IFN-I via acetate-producing bacterium and suggest that the acetate-GPR43-NLRP3-MAVS-IFN-I signalling axis is a potential therapeutic target against respiratory viral infections.

Shengxian decoction protects against chronic heart failure in a rat model via energy regulation mechanisms.

BACKGROUND: Chronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats' serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LA、FFA、MDA、SOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium. RESULTS: HPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT. CONCLUSION: SXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.

Three new species of the genus Sulcolotis Miyatake (Coleoptera, Coccinellidae, Sticholotidini) from the Philippines.

The genus Sulcolotis Miyatake, 1994 is reviewed. Three new species (S. threadis sp. n., S. ovalis sp. n., and S. xanthomarginalis sp. n.) from the Philippines are described and illustrated in the present paper. A key to species of the genus Sulcolotis is also provided.

First complete mitochondrial genome from the genus Coptodryas (Coleoptera: Curculionidae: Scolytinae) and its phylogenetic implications.

The complete mitochondrial genome (mitogenome) of Coptodryas elegans was determined, which represents the first sequenced mitogenome from Coptodryas. This mitogenome is 15,959 bp in size and comprises 36 typical coding genes and a control region, the tRNAIle was not detected in this mitogenome, as observed in other species of Curculionidae. The monophyly of the family Scolytinae and the sister relationship between C. elegans and Cyclorhipidion bodoanus is supported by maximum likelihood analysis derived from the protein-coding gene sequences.

Preparation, characterization and in vitro study of bellidifolin nano-micelles.

Bellidifolin (BEL), a xanthone compound, has significant therapeutic effectiveness in cardiac diseases such as arrhythmias. However, BEL is limited in clinical applications by its hydrophobicity. In this work, we used BEL as the active pharmaceutical ingredient (API), and polyethylene glycol 15-hydroxy stearate (Kolliphor HS15) as the carrier to prepare BEL nano-micelles by a solvent-volatilization method. According to an analysis by differential scanning calorimetry (DSC), BEL was successfully encapsulated in HS15 as BEL nano-micelles with a 90% encapsulation rate, and particle size was 12.60 ± 0.074 nm in the shape of a sphere and electric potential was -4.76 ± 4.47 mV with good stability and sustained release characteristics. In addition, compared with free drugs, these nano-micelles can increase cellular uptake capacity, inhibit the proliferation of human cardiac fibroblasts, and down-regulate the expression of Smad-2, α-SMA, Collagen I, and Collagen III proteins in myocardial cells to improve myocardial fibrosis. In conclusion, the BEL nano-micelles can provide a new way for the theoretical basis for the clinical application of anti-cardiac fibrosis.

Gentianella acuta improves TAC-induced cardiac remodelling by regulating the Notch and PI3K/Akt/FOXO1/3 pathways.

Cardiac remodelling mainly manifests as excessive myocardial hypertrophy and fibrosis, which are associated with heart failure. Gentianella acuta (G. acuta) is reportedly effective in cardiac protection; however, the mechanism by which it protects against cardiac remodelling is not fully understood. Here, we discuss the effects and mechanisms of G. acuta in transverse aortic constriction (TAC)-induced cardiac remodelling in rats. Cardiac function was analysed using echocardiography and electrocardiography. Haematoxylin and eosin, Masson's trichrome, and wheat germ agglutinin staining were used to observe pathophysiological changes. Additionally, real-time quantitative reverse transcription polymerase chain reaction and western blotting were used to measure protein levels and mRNA levels of genes related to myocardial hypertrophy and fibrosis. Immunofluorescence double staining was used to investigate the co-expression of endothelial and interstitial markers. Western blotting was used to estimate the expression and phosphorylation levels of the regulatory proteins involved in autophagy and endothelial-mesenchymal transition (EndMT). The results showed that G. acuta alleviated cardiac dysfunction and remodelling. The elevated levels of myocardial hypertrophy and fibrosis markers, induced by TAC, decreased significantly after G. acuta intervention. G. acuta decreased the expression of LC3 II and Beclin1, and increased p62 expression. G. acuta upregulated the expression of CD31 and vascular endothelial-cadherin, and prevented the expression of α-smooth muscle actin and vimentin. Furthermore, G. acuta inhibited the PI3K/Akt/FOXO1/3a pathway and activated the Notch signalling. These findings demonstrated that G. acuta has cardioprotective effects, such as alleviating myocardial fibrosis, inhibiting hypertrophy, reducing autophagy, and blocking EndMT by regulating the PI3K/Akt/FOXO1/3a and Notch signalling pathways.

Shashen-Maidong Decoction improved chronic intermittent hypoxia-induced cognitive impairment through regulating glutamatergic signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which is associated with cognitive impairment. Previous study suggested CIH exposure could induce similar symptoms and signs to the clinical features of Deficiency of both Qi and Yin Syndrome (DQYS) in Traditional Chinese Medicine (TCM). Shashen-Maidong Decoction (SMD) has been applied clinically for DQYS for hundred years. However, SMD treatment could be beneficial to CIH induced cognitive impairment is still unclear. AIM OF THE STUDY: Therefore, the aim of this study was to investigate the effect of SMD treatment on CIH induced cognitive impairment, and to explore the related neuroprotective mechanism. MATERIALS AND METHODS: Mice were exposed to CIH for 5 weeks (8 h/day) and were orally treated with either vehicle or SMD (5.265 g/kg/day) 30 min before CIH exposure. Spatial memory was evaluated by Morris Water Maze and Y-Maze test. Synaptic morphology in hippocampus was observed by Golgi-Cox staining and Electron microscope, and NR2B-ERK signaling pathway were detected by western blotting. RESULTS: Our results showed that SMD treatment improved performance in either Morris Water Maze or Y-Maze test in mice exposed to CIH, increased spine density and postsynaptic density (PSD) thickness in hippocampus. SMD treatment suppressed the over-activation of NR2B/CaMKII/SynGAP induced by CIH exposure, enhanced ERK/CREB phosphorylation and increased PSD-95 and BDNF expression. CONCLUSION: SMD attenuates the CIH-induced cognitive impairment through regulating NR2B-ERK signaling pathway. Additionally, our findings provided that DQYS may be the potential therapeutic target for neurocognitive diseases in patients with OSA.