Americanin B inhibits pyroptosis in lipopolysaccharide-induced septic encephalopathy mice through targeting NLRP3 protein.

BACKGROUND: Sepsis is considered as a severe illness due to its high mortality. Sepsis can cause septic encephalopathy, thus leading to brain injury, behavioral and cognitive dysfunction. Pyroptosis is a type of regulated cell death (RCD) and takes a crucial part in occurrence and development of sepsis. Americanin B (AMEB) is a lignan compounds, which is extracted from Vernicia fordii. In our previous study, AMEB could inhibit microglial activation in inflammatory cell model. However, the function of AMEB in septic encephalopathy mice is uncertain. It would be worthwhile to ascertain the role and mechanism of AMEB in sepsis. PURPOSE: Current study designs to certify the relationship between pyroptosis and septic encephalopathy, and investigate whether AMEB can restrain NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and restrict pyroptosis by targeting NLRP3 in septic mice model. STUDY DESIGN: C57BL/6 mice were utilized to perform sepsis model in vivo experiments. BV-2 cell lines were used for in vitro experiments. METHODS: In vivo sepsis model was established by lipopolysaccharide (LPS) intraperitoneal injection in male C57BL/6 J mice and in vitro model was exposed by LPS plus ATP in BV-2 cells. The survival rate was monitored on the corresponding days. NLRP3, apoptosis associated Speck-like protein (ASC), caspase-1, GasderminD (GSDMD), interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) level were detected by western blotting and immunofluorescence analysis. Molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) experiments, RNAi transfection and quantitative real-time PCR were applied to confirm the potential target of AMEB. RESULTS: The results suggested that AMEB could rise survival percentage and lighten brain injury in LPS-induced sepsis mice. In addition, AMEB could inhibit pyroptosis and the activiation of NLRP3 inflammasome. The inhibiting function of AMEB on the activiation of NLRP3 inflammasome is weakened following si-NLRP3 transfection. Moreover, AMEB exerted anti-pyroptosis effect via targeting NLRP3 protein. CONCLUSIONS: Our findings first indicate NLRP3 is an effective druggable target for septic encephalopathy related brain injury, and also provide a candidate-AMEB for the treatment of septic encephalopathy. These emerging findings on AMEB in models of sepsis suggest an innovative approach that may be beneficial in the prevention of septic encephalopathy.

Palmatine ameliorated lipopolysaccharide-induced sepsis-associated encephalopathy mice by regulating the microbiota-gut-brain axis.

BACKGROUND: Sepsis-associated encephalopathy (SAE), a common neurological complication from sepsis, is widespread among patients in intensive care unit and is linked to substantial morbidity and mortality rates, thus posing a substantial menace to human health. Due to the intricate nature of SAE's pathogenesis, there remains a dearth of efficacious therapeutic protocols, encompassing pharmaceutical agents and treatment modalities, up until the present time. Palmatine exhibits distinctive benefits in the regulation of inflammation for the improvement of sepsis. Nevertheless, the precise functions of palmatine in treating SAE and its underlying mechanism have yet to be elucidated. PURPOSE: This study aimed to evaluate efficiency of palmatine in SAE mice and its underlying mechanisms. STUDY DESIGN AND METHODS: Behavioral experiments, percent survival rate analysis, histological analysis, immunofluorescence staining, ELISA analysis, were performed to evaluate the efficiency of palmatine in SAE mice. Quantibody® mouse inflammation array glass chip was performed to observe the effects of palmatine on inflammation storm in SAE mice. Real-time quantitative and western blotting analyzes were employed to examine the expression of relevant targets in the Notch1/nuclear factor-kappa B (NF-κB) pathway. Finally, brain tissues metabolomics-based analyzes were performed to detect the differentially expressed metabolites and metabolic pathways. The fecal samples were subjected to microbial 16S rRNA analysis and untargeted metabolomics analysis in order to identify the specific flora and metabolites associated with SAE, thereby further investigating the mechanism of palmatine in SAE mice. RESULTS: Our results showed that palmatine significantly improved nerve function, reduced cell apoptosis in brain tissue, and decreased inflammatory cytokine levels in SAE induced-LPS mice. Meanwhile, our results demonstrate the potential of palmatine in modulating key components of the Notch1/NF-κB pathway, enhancing the expression of tight junction proteins, improving intestinal permeability, promoting the growth of beneficial bacteria (such as Lachnospiraceae_NK4A136_group), inhibiting the proliferation of harmful bacteria (such as Escherichia-Shigella), and mitigating metabolic disorders. Ultimately, these observed effects contribute to the therapeutic efficacy of palmatine in treating SAE. CONCLUSION: The findings of our study have provided confirmation regarding the efficacy of palmatine in the treatment of SAE, thereby establishing a solid foundation for further exploration into SAE therapy and the advancement and investigation of palmatine.

Puerarin prevents sepsis-associated encephalopathy by regulating the AKT1 pathway in microglia.

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.

USP8 mitigates cognitive dysfunction of mice with sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis which results from neuroinflammation and could lead to cognitive dysfunction. Ubiquitin-specific peptidase 8 (USP8) is involved in cognitive dysfunction. This study investigated the mechanism by which USP8 plays a role in cognitive dysfunction of SAE mice. METHODS: The SAE models were established by performing cecal ligation and puncture in the mice. Subsequently, a series of tests and procedures were conducted to assess the cognitive dysfunction and pathological impairment of mice, including the Morris water maze test, Y-maze test, open field test, tail suspension test, fear conditioning test, and haematoxylin-eosin staining. The levels of USP8 and Yin Yang 1 (YY1) in brain tissues of mice were detected. In order to determine the effects of USP8 or YY1 on cognitive function, SAE mice were injected with an adenovirus-packaged vector that had overexpressed levels of USP8 or YY1 short hairpin RNA. The binding of USP8 to YY1 and the ubiquitination level of YY1 were analyzed using immunoprecipitation and ubiquitination experiments. Lastly, chromatin immunoprecipitation was carried out to analyze enrichment of YY1 on the USP8 promoter. RESULTS: In SAE models, USP8 and YY1 were downregulated and cognitive functions were impaired. USP8 overexpression upregulated YY1 and attenuated the brain histopathological damage and cognitive dysfunction in SAE mice. USP8 upregulated YY1 protein level through deubiquitination, while YY1 was enriched on the USP8 promoter and activated USP8 transcription. The effects of USP8 overexpression on SAE mice was reversed secondary to YY1 silencing. CONCLUSION: USP8 upregulated YY1 protein level through deubiquitination and YY1 activated USP8 transcription, and USP8-YY1 feedback loop attenuated cognitive dysfunction in SAE mice, which could potentially serve as a novel theoretical foundation for the management of SAE.

YY1 PROMOTES MICROGLIA M2 POLARIZATION THROUGH THE MIR-130A-3P/TREM-2 AXIS TO ALLEVIATE SEPSIS-ASSOCIATED ENCEPHALOPATHY.

ABSTRACT: Purpose: Sepsis-associated encephalopathy (SAE) induces cognitive dysfunction via mechanisms that commonly involve neuroinflammation. Yin Yang 1 (YY1) is an important transcription factor that acts as a key role in sepsis and neuroepithelium development. However, the function of YY1 in SAE remains unclear. Our study aimed to probe the intrinsic and concrete molecular mechanism of YY1 in SAE. Methods: SAE cell model and SAE animal model were constructed by lipopolysaccharide (LPS) treatment and cecal ligation and puncture surgery, respectively. Behavioral tests were performed to analyze the cognitive function. The polarization state of mouse microglia (BV-2 cells) was assessed by flow cytometry assay. The mRNA and protein expressions were assessed by qRT-PCR and western blot. Finally, the binding relationships between YY1, miR-130a-3p, andTREM-2were verified by dual luciferase reporter gene assay and/or ChIP assay. Results: Here our results described that YY1 and TREM-2 were downregulated and miR-130a-3p was upregulated in SAE. YY1 overexpression could promote M2 polarization of microglia, and alleviate neuroinflammation and behavioral deficits in vitro and in vivo. YY1 could inhibit miR-130a-3p promoter activity. As expected, miR-130a-3p overexpression abolished the effects of YY1 overexpression on LPS-treated BV-2 cells. Besides, TREM-2 was identified as the target of miR-130a-3p. TREM-2 silencing could reverse the effects of miR-130a-3p inhibition on LPS-treated BV-2 cells. Conclusion: Taken together, YY1 promoted microglia M2 polarization via upregulating TREM-2 by interacting with miR-130a-3p promoter, suggesting YY1 overexpression might be a novel therapeutic strategy of SAE.

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis-associated encephalopathy.

BACKGROUND: Fisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role in sepsis-associated encephalopathy (SAE) remains unclarified. METHODS: Cecal ligation and puncture (CLP) operation was performed to establish a rat model of SAE. Rats were grouped according to the surgery operation and fisetin administration. Cognitive impairment was assessed by Morris water maze test. Disruption of blood-brain barrier (BBB) integrity was detected by Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, and pro-inflammatory cytokines levels were measured through western blot and double immunofluorescence labeling. A transmission electron microscope was applied for the observation of mitochondrial autophagosomes. RESULTS: Rats in the CLP group presented increased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglial cells, indicating severe inflammation in the central nervous system (CNS). Nevertheless, there was no increase in BBB permeability. Meanwhile, NLRP3 inflammasome was activated in cerebral microvascular endothelial cells (CMECs), presented with an elevation of caspase-1 expression and IL-1ß secretion into CNS. In addition, we found fisetin significantly improved cognitive dysfunction in rats with SAE. Neuroprotective effects of fisetin might be associated with inhibition of neuroinflammation, represented with decreased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglia. Furthermore, fisetin induced mitophagy, scavenged ROS, blocked NLRP3 inflammasome activation of CMECs, as evidenced by decreased expression of caspase-1 and reduced release of IL-1ß into CNS. CONCLUSION: Collectively, fisetin-blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL-1ß into CNS, reduce neuroinflammation, and contribute to the amelioration of cognitive impairment.

[Protective effect and mechanism of Angong Niuhuang pill in sepsis-associated brain dysfunction of rats].

OBJECTIVE: To observe the protective effect of Angong Niuhuang pill on brain function of rats with sepsis, explore its protective mechanism, and provide the experimental basis for clinical application of Angong Niuhuang pill in the treatment of sepsis-associated encephalopathy (SAE). METHODS: Thirty male Sprague-Dawley (SD) rats were divided into sham operation group, sepsis model group and Angong Niuhuang pill group according to random number table method, with 10 rats in each group. The sepsis model was established by cecal ligation and puncture (CLP); rats in sham operation group received open and closed abdomen. The rats in the Angong Niuhuang pill group were given Angong Niuhuang pill (0.3 g/kg) by gastric irrigation daily for 3 days before CLP, and the drugs were administrated 12 hours after modeling again. After 24 hours of CLP, the neuroreflex scores were evaluated, white blood cell count (WBC), the levels of serum neuron-specific enolase (NSE) and S100ß were detected. Then the brain tissue was harvested. After hematoxylin-eosin (HE) staining, the pathological changes of brain tissue were observed under the light microscope. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in brain tissue were detected by polymerase chain reaction. RESULTS: Compared with the sham operation group, the total score of neuroreflex scores in the sepsis model group and the Angong Niuhuang pill group were significantly reduced (4.43±1.40, 6.57±1.90 vs. 9.40±0.84, both P < 0.05), WBC, serum NSE, S100ß were significantly increased [WBC (×109/L): 8.07±1.32, 5.84±0.94 vs. 3.60±0.32; NSE (µg/L): 1.04±0.14, 0.61±0.07 vs. 0.16±0.04; S100ß (ng/L): 255.624±30.25, 97.72±15.41 vs. 46.88±12.03, all P < 0.05], and the mRNA expressions of IL-6 and TNF-α in brain tissue were significantly increased [IL-6 mRNA (2-ΔΔCt): 5.668±2.195, 3.605±1.014 vs. 0.997±0.329; TNF-α mRNA (2-ΔΔCt): 18.996±0.913, 1.746±0.710 vs. 0.674±0.132, all P < 0.05]. Compared with the sepsis model group, the total score of neuroreflex scores in the Angong Niuhuang pill group was significantly increased (6.57±1.90 vs. 4.43±1.40, P < 0.05), WBC, serum NSE, S100ß concentration, and the mRNA expressions of IL-6 and TNF-α in the brain were significantly reduced [WBC (×109/L): 5.84±0.94 vs. 8.07±1.32, NSE (µg/L): 0.61±0.07 vs. 1.04±0.14, S100ß (ng/L): 97.72±15.41 vs. 255.62±30.25, IL-6 mRNA (2-ΔΔCt): 3.605±1.014 vs. 5.668±2.195, TNF-α mRNA (2-ΔΔCt): 1.746±0.710 vs. 18.996±0.913, all P < 0.05]. Brain histopathological observation showed that the hippocampal neurons in the sepsis model group were disordered arrangement, a large number of neuronal nuclei were contracted, and the tissue was loose with obvious edema. Compared with the sepsis model group, the Angong Niuhuang pill group had less nuclear shrinkage and tissue edema. CONCLUSIONS: The pretreatment of the Angong Niuhuang pill can improve the brain dysfunction of septic rats and reduce the expression of pro-inflammatory cytokines in the brain. It is speculated that the Angong Niuhuang pill can protect the brain function in sepsis by inhibiting the inflammatory reaction in the brain.

Electroacupuncture Improves Cognition in Rats With Sepsis-Associated Encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common complication of sepsis. Although sepsis is effectively managed with the administration of antibiotics and source control, which may include surgical intervention, SAE usually leads to prolonged cognitive dysfunction affecting the quality of life of the patients. In this study, we investigated the possible effect of electroacupuncture (EA) on cognition in a model of SAE induced by cecal ligation and puncture (CLP). MATERIALS AND METHODS: The rats were randomly divided into four groups: the control group, the CLP group, the CLP with EA treatment group (CLP + EA), and the CLP with sham EA treatment group (CLP + sham EA). EA at DU20, LI11, and ST36 or sham EA was performed 30 min daily for 10 consecutive days starting from 2 days before CLP. Then cognitive function was examined by the Morris water maze test. On day 14 after CLP surgery, the synaptic injury, neuron loss, and oxidative stress were studied. RESULTS: Rats with EA treatment showed improved survival rate, spatial learning, and memory abilities. The dendritic spine density, the synaptic proteins, and the hippocampal neuron number were also increased after EA treatment. Furthermore, EA suppressed oxidative stress through regulating the level of malondialdehyde and superoxide dismutase and enhanced the expression of antioxidant nuclear factor erythroid-2-related factor-2 and hemeoxygenase-1. But sham EA did not have the same effect. CONCLUSIONS: EA may protect against SAE-induced cognitive dysfunction by inhibiting synaptic injury, neuronal loss, and oxidative stress, and the nuclear factor erythroid-2-related factor-2/hemeoxygenase-1 signaling pathway may be involved in this effect.

[Clinical effect of electroacupuncture at Baihui and Shuigou points in treatment of brain injury in patients with sepsis-associated encephalopathy].

OBJECTIVE: To investigate the clinical effect of electroacupuncture at Baihui (GV20) and Shuigou (GV26) points in the treatment of brain injury in patients with sepsis-associated encephalopathy(SAE). METHODS: A total of 70 patients with SAE were randomly divided into control group and treatment group, with 35 patients in each group. The patients in the control group were given routine western medicine treatment, including anti-infective therapy, nerve nutrition, and mechanical ventilation, and those in the treatment group were given electroacupuncture at GV20 and GV26 in addition to the treatment in the control group. The course of treatment was 1 week for both groups. Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and neuron-specific enolase (NSE) were measured for both groups, the Montreal Cognitive Assessment (MoCA) scale was used to assess the change in cognitive function, and Glasgow Coma Scale (GCS) score was determined before and after treatment and was used to evaluate treatment outcome after treatment. RESULTS: Both groups had significant reductions in the serum levels of CRP, IL-6, and NSE after 24 h and one week of treatment (P<0.05), and compared with the control group, the treatment group had significant reductions in the levels of CRP, IL-6 and NSE after treatment (P<0.05). The treatment group had significant increases in the total score of MoCA and the scores of all dimensions except attention after one week of treatment (P<0.05), and the treatment group had significantly higher scores than the control group after treatment (P<0.05). Both groups had a significant increase in GCS score after one week of treatment (P<0.05), and the treatment group had a significantly higher GCS score than the control group after treatment (P<0.05). The treatment group had a significantly higher total effective rate than the control group ï¼»88.6% (31/35) vs 57.1% (20/35), P<0.05ï¼½. CONCLUSION: Electroacupuncture at GV20 and GV26 can effectively improve brain injury and effective rate in SAE patients.

Brain Volume Changes in Patients with Acute Brain Dysfunction Due to Sepsis.

BACKGROUND: Sepsis-induced brain dysfunction (SIBD) is often encountered in sepsis patients and is related to increased morbidity. No specific tests are available for SIBD, and neuroimaging findings are often normal. In this study, our aim was to analyze the diagnostic value of volumetric analysis of the brain structures and to find out its significance as a prognostic measure. METHODS: In this prospective observational study, brain magnetic resonance imaging (MRI) sections of 25 consecutively enrolled SIBD patients (17 with encephalopathy and 8 with coma) and 22 healthy controls underwent volumetric evaluation by an automated segmentation method. RESULTS: Ten SIBD patients had normal MRI, and 15 patients showed brain lesions or atrophy. The most prominent volume reduction was found in cerebral and cerebellar white matter, cerebral cortex, hippocampus, and amygdala, whereas deep gray matter regions and cerebellar cortex were relatively less affected. SIBD patients with normal MRI showed significantly reduced volumes in hippocampus and cerebral white matter. Caudate nuclei, putamen, and thalamus showed lower volume values in non-survivor SIBD patients, and left putamen and right thalamus showed a more pronounced volume reduction in coma patients. CONCLUSIONS: Volumetric analysis of the brain appears to be a sensitive measure of volumetric changes in SIBD. Volume reduction in specific deep gray matter regions might be an indicator of unfavorable outcome.

[Effect of "Tongdu Tiaoshen" needling on cognitive dysfunction in patients with sepsis asso-ciated encephalopathy and its mechanism].

OBJECTIVE: To observe the efficacy of "Tongdu Tiaoshen" (dredging Governor Vessel and regula-ting mind,needling on the cognitive function of patients with sepsis associated encephalopathy (SAE). METHODS: A total of 64 patients with SAE were enrolled in the present study, and randomly and equally divided into a control group and a treatment group. Patients in the control group received conventional medicines and conventional needling treatment. The patients of the treatment group received conventional medicines and "Tongdu Tiaoshen" needling treatment. The treatment was conducted once daily for 10 days. The Montreal Cognitive Assessment (MoCA) scale was used to assess the therapeutic effect after the treatment. Serum interleukin-6 (IL-6) was detected by radioimmunoassay, serum C-reactive protein (CRP) was detected by immuno-scattering method, and arterial blood lactic acid (Lac) content was detected by blood gas analyzer. RESULTS: The effective rate in the treatment group was obviously higher than that in the control group (P<0.01). After the treatment, the MoCA scores were considerably increased in both groups compared with their own pre-treatment (P<0.01), and the MoCA scores in the treatment group were obviously higher than those of the control group in the visual space and executive function, attention and computational power, language, abstraction and delayed recall dimensions (P<0.01). The contents of IL-6, CRP and Lac in both groups were significantly decreased after the treatment relevant to those of their own pre-treatment (P<0.01), and were obviously lower in the treatment group than those in the control group (P<0.01). CONCLUSION: "Tongdu Tiaoshen" needling can significantly improve the cognitive function of SAE patients, which may be associated with its effect in reducing inflammatory reaction of sepsis.

Effects of Ecballium elaterium on brain in a rat model of sepsis-associated encephalopathy.

Despite recent advances in antibiotic therapy, sepsis remains a major clinical challenge in intensive care units. Here we examined the anti-inflammatory and antioxidant effects of Ecballium elaterium (EE) on brain, and explored its therapeutic potential in an animal model of sepsis-associated encephalopathy (SAE) [induced by cecal ligation and puncture (CLP)]. Thirty rats were divided into three groups of 10 each: control, sepsis, and treatment. Rats were subjected to CLP except for the control group, which underwent laparatomy only. The treatment group received 2.5 mg/kg EE while the sepsis group was administered by saline. Twenty-four hours after laparotomy, animals were sacrificied and the brains were removed. Brain homogenates were prepared to assess interleukin 1beta (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), total antioxidant capacity (TAC), and total oxidant status (TOS). Brain tissue sections were stained by hematoxylin and eosin (H&E) to semi-quantitatively examine the histopathologic changes such as neuron degeneration, pericellular/perivascular edema and inflammatory cell infiltration in the cerebral cortex. We found a statistically significant reduction in brain tissue homogenate levels of TNF-α 59.5 ± 8.4/50.2 ± 6.2 (p = 0.007) and TOS 99.3 ± 16.9/82.3 ± 7.8 (p = 0.01) in rats treated with EE; although interleukin 6 levels were increased in the treatment group compared to the sepsis group, this was not statistically significant. Neuronal damage (p = 0.00), pericellular/perivascular edema and inflammatory cell infiltration (p = 0.001) were also significantly lower in the treatment group compared to those in the sepsis group. These data suggest that Ecballium elaterium contains some components that exert protective effects against SAE in part by attenuating accumulation of proinflammatory cytokines, which may be important contributors to its anti-inflammatory effects during sepsis.

Ginsenoside Rg1 protects against sepsis-associated encephalopathy through beclin 1-independent autophagy in mice.

BACKGROUND: Sepsis-associated encephalopathy (SAE), a commonly complicated syndrome, is associated with increased mortality in patients with sepsis. Currently, no specific diagnostic test or effective intervention exists to improve long-term consequences on cerebral function. Ginsenoside Rg1 (Rg1), a major component in ginseng, was reported to have pleiotropic properties including anti-inflammation and neuroprotection. The aim of our study was to investigate the protective effect of Rg1 on SAE and the potential mechanism. MATERIALS AND METHODS: SAE model was prepared by inducing cecal ligation and puncture (CLP) in mice. Rg1 was injected 1 h before the CLP operation. Survival rate within 7 d after operation was analyzed. Surviving mice were subjected to Morris water maze tests and the brains were collected for histopathologic evaluation and immunohistochemistry. The hippocampus was obtained for Western blot, real time polymerase chain reaction, and enzyme-linked immunosorbent assay analysis. RESULTS: Rg1 improved the postoperative survival rate and protected against sepsis-associated learning and memory impairments (Morris water maze). Besides, Rg1 was able to attenuate brain histopathologic changes (hematoxylin and eosin staining), suppress Iba1 activation, decrease the expressions of inflammatory cytokines (tumor necrosis factor α, interleukin 1ß, and interleukin 6), and reduce neuronal apoptosis (cleaved caspase 3 activation) in hippocampus. Furthermore, the mechanism study showed that Rg1 suppressed the expressions of light chain 3-II and p62 in hippocampus but not beclin 1. CONCLUSIONS: These findings suggested that Rg1 improved the survival rate and ameliorated cognitive impairments partially through regulating cerebral inflammation and apoptosis. In addition, the action mechanism might be noncanonical beclin 1-independent autophagy pathway. Rg1 may be a promising treatment strategy for SAE.

[Treatment of Sepsis-associated Encephalopathy by Xingnaojing Injection: a Clinical Observation].

OBJECTIVE: To observe the efficacy of Xingnaojing Injection (XI) in treatment of sepsis-associated encephalopathy (SAE). METHODS: Totally 65 SAE patients were retrospectively analyzed at EICU from September 2010 to September 2013. They were assigned to the control group (32 cases) and the treatment group (33 cases) according to whether they received XI. Patients in the control group received anti-infection and symptomatic support, while those in the treatment group were intravenously injected with XI at 20 mL per day for additional 7-10 days. The fever clearance time, Glasgow coma scale (GCS), C-reactive protein (CRP), neuron-specific enolase (NSE), and improvement of electroen-cephalogram (EEG) were observed in the two groups. RESULTS: Compared with the control group, the fever clearance time was shortened, CRP levels decreased, GCS score and efficacy of EEG was alleviated in the treatment group after treatment with statistical difference (P < 0.05). No adverse reaction occurred during medication. CONCLUSION: X1 was safe and effective in treatment of SAE.

Treatment of Sepsis-associated Encephalopathy by Xingnaojing Injection: a Clinical Observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the efficacy of Xingnaojing Injection (XI) in treatment of sepsis-associated encephalopathy (SAE).</p><p><b>METHODS</b>Totally 65 SAE patients were retrospectively analyzed at EICU from September 2010 to September 2013. They were assigned to the control group (32 cases) and the treatment group (33 cases) according to whether they received XI. Patients in the control group received anti-infection and symptomatic support, while those in the treatment group were intravenously injected with XI at 20 mL per day for additional 7-10 days. The fever clearance time, Glasgow coma scale (GCS), C-reactive protein (CRP), neuron-specific enolase (NSE), and improvement of electroen-cephalogram (EEG) were observed in the two groups.</p><p><b>RESULTS</b>Compared with the control group, the fever clearance time was shortened, CRP levels decreased, GCS score and efficacy of EEG was alleviated in the treatment group after treatment with statistical difference (P < 0.05). No adverse reaction occurred during medication.</p><p><b>CONCLUSION</b>X1 was safe and effective in treatment of SAE.</p>