Zian Xia

Xuefu Zhuyu decoction, a traditional Chinese medicine, provides neuroprotection in a rat model of traumatic brain injury via an anti-inflammatory pathway

Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Xuefu Zhuyu decoction (XFZY) is an effective traditional Chinese medicine to treat TBI. To elucidate its potential molecular mechanism, this study aimed to demonstrate that XFZY functions as an anti-inflammatory agent by inhibiting the PI3K-AKT-mTOR pathway. Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received XFZY (9 g/kg and 18 g/kg), Vehicle group and Sham group were gavaged with equal volumes of saline. The modified neurologic severity score (mNSS) and the Morris water maze test were used to assess neurological deficits. Arachidonic acid (AA) levels in brain tissue were measured using tandem gas chromatography-mass spectrometry. TNF-α and IL-1β levels in injured ipsilateral brain tissue were detected by ELISA. AKT and mTOR expression were measured by western blot analysis. The results indicated that XFZY significantly enhanced spatial memory acquisition. XFZY (especially at a dose of 9 g/kg) markedly reduced the mNSS and levels of AA, TNF-α and IL-1β. Significant downregulation of AKT/mTOR/p70S6K proteins in brain tissues was observed after the administration of XFZY (especially at a dose of 9 g/kg). XFZY may be a promising therapeutic strategy for reducing inflammation in TBI.

Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments

Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment.

Protective Effects of Chinese Herbal Medicine Rhizoma drynariae in Rats After Traumatic Brain Injury and Identification of Active Compound

Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. Effective therapeutic strategies for TBI are needed, and increasing attention is turning toward traditional herbal medicine. Rhizoma drynariae is a traditional Chinese medicine that has immunomodulatory and anti-inflammatory effects. Here, using the controlled cortical impact model of TBI in rats, we examined whether oral administration of R. drynariae can reduce TBI-induced brain injury in rats. We also identified the likely active compound among its four major phytochemicals in decoction. We found that post-treatment with R. drynariae decreased brain lesion volume, improved neurologic and cognitive function, and reduced anxiety- and depression-like behaviors. These changes were accompanied by reduced blood levels of IL-6 and increased IL-10. R. drynariae treatment also reversed the TBI-induced decrease in blood monocyte numbers and percentage of blood CD3 and CD4 T lymphocytes while inhibiting microglial/macrophage activation. Furthermore, by using ultra performance liquid chromatography and comparing retention times with authentic standards, we identified eriodictyol as the putative active compound of R. drynariae extract in the blood of rats with TBI. These novel findings indicate that the traditional Chinese herbal medicine R. drynariae protects brain against TBI-induced brain injury, possibly via immune-promoting, anti-inflammatory, and neuroprotective effects. Eriodictyol could be its active compound.

A potential tool for diagnosis of male infertility: Plasma metabolomics based on GC-MS

Male infertility has become an important public health problem worldwide. Nowadays the diagnosis of male infertility frequently depends on the results of semen quality or requires more invasive surgical intervention. Therefore, it is necessary to develop a novel approach for early diagnosis of male infertility. According to the presence or absence of normal sexual function, the male infertility is classified into two phenotypes, erectile dysfunction (ED) and semen abnormalities (SA). The aim of this study was to investigate the GC-MS plasma profiles of infertile male having erectile dysfunction (ED) and having semen abnormalities (SA) and discover the potential biomarkers. The plasma samples from healthy controls (HC) (n=61) and infertility patients with ED (n=26) or with SA (n=44) were analyzed by gas chromatography-mass spectrometry (GC-MS) for discrimination and screening potential biomarkers. The partial least squares-discriminant analysis (PLS-DA) was performed on GC-MS dataset. The results showed that HC could be discriminated from infertile cases having SA (AUC=86.96%, sensitivity=78.69%, specificity=84.09%, accuracy=80.95%) and infertile cases having ED (AUC=94.33%, sensitivity=80.33%, specificity=100%, accuracy=87.36%). Some potential biomarkers were successfully discovered by two commonly used variable selection methods, variable importance on projection (VIP) and original coefficients of PLS-DA (β). 1,5-Anhydro-sorbitol and α-hydroxyisovaleric acid were identified as the potential biomarkers for distinguishing HC from the male infertility patients. Meanwhile, lactate, glutamate and cholesterol were the found to be the important variables to distinguish between patients with erectile dysfunction from those with semen abnormalities. The plasma metabolomics may be developed as a novel approach for fast, noninvasive, and acceptable diagnosis and characterization of male infertility.

The impact of ginsenosides on cognitive deficits in experimental animal studies of Alzheimer's disease: a systematic review

BackgroundThe efficacy of ginsenoside treatment on cognitive decline in individuals with Alzheimer’s disease (AD) has yet to be investigated. In this protocal, we conducted a systematic review to evaluate the effect of ginsenosides on cognitive deficits in experimental rodent AD models.MethodsWe identified eligible studies by searching seven electronic databases spanning from January 1980 to October 2014. We assessed the study quality, evaluated the efficacy of ginsenoside treatment, and performed a stratified meta-analysis and meta-regression analysis to assess the influence of the study design on ginsenoside efficacy.ResultsTwelve studies fulfilled our inclusion criteria from a total of 283 publications. The overall methodological quality of these studies was poor. The meta-analysis revealed that ginsenosides have a statistically significant positive effect on cognitive performance in experimental AD models. The stratified analysis revealed that ginsenoside Rg1 had the greatest effect on acquisition and retention memory in AD models. The effect size was significantly higher for both acquisition and retention memory in studies that used female animals compared with male animals.ConclusionsWe conclude that ginsenosides might reduce cognitive deficits in AD models. However, additional well-designed and well-reported animal studies are needed to inform further clinical investigations.

Enhanced antitumoral efficacy and immune response following conditionally replicative adenovirus containing constitutive HSF1 delivery to rodent tumors.

BackgroundOncolytic adenoviruses are promising as anticancer agents but have limited clinical responses. Our previous study showed that heat shock transcription factor 1 (HSF1) overexpression could increase the anti-tumor efficacy of E1B55kD deleted oncolytic adenovirus through increasing the viral burst. Due to the important roles of heat shock proteins (HSPs) in eliciting innate and adaptive immunity, we reasoned that besides increasing the viral burst, HSF1 may also play a role in increasing tumor specific immune response.MethodsIn the present study, intra-dermal murine models of melanoma (B16) and colorectal carcinoma (CT26) were treated with E1B55kD deleted oncolytic adenovirus Adel55 or Adel55 incorporated with cHSF1, HSF1i, HSP70, or HSP90 by intra-tumoral injection. Tumors were surgically excised 72 h post injection and animals were analyzed for tumor resistance and survival rate.ResultsApproximately 95% of animals in the Adel55-cHSF1 treated group showed sustained resistance upon re-challenge with autologous tumor cells, but not in PBS, Adel55, or Adel55-HSF1i treated groups. Only 50–65% animals in the Adel55-HSP70 and Adel55-HSP90 treated group showed tumor resistance. Tumor resistance was associated with development of tumor type specific cellular immune responses. Adel55-cHSF1 treatment also showed higher efficacy in diminishing progression of the secondary tumor focus than Adel55-HSP70 or Adel55-HSP90 treatment.ConclusionsBesides by increasing its burst in tumor cells, cHSF1 could also augment the potential of E1B55kD deleted oncolytic adenovirus by increasing the tumor-specific immune response, which is beneficial to prevent tumor recurrence. cHSF1 is a better gene for neoadjuvant immunotherapy than other heat shock protein genes.

Hydroxysafflor yellow A exerts antioxidant effects in a rat model of traumatic brain injury

Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography-tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI.

Qualitative analysis of major constituents from Xue Fu Zhu Yu Decoction using ultra high performance liquid chromatography with hybrid ion trap time-of-flight mass spectrometry

Xue Fu Zhu Yu Decoction, a famous formula that has been used for treating many blood stasis-caused diseases for many centuries, comprises 11 kinds of traditional Chinese medicines. A convenient, efficient, and rapid analytical method was developed to simultaneously determine the major compounds in this decoction. An ultra-high performance liquid chromatography with hybrid ion trap time-of-flight mass spectrometry method was used to rapidly separate and detect the major constituents of the decoction. Using this technique, we identified or tentatively identified 34 compounds, including 21 flavonoids, 5 terpenoids, 3 organic acids, 2 lactones, 1 alkaloid, 1 amino acid, and 1 cyanogenic glycoside. The MS analysis of these constituents was described in detail. Findings may contribute to future metabolic and pharmacokinetic studies of this medicine.

Determination of hydroxysafflor yellow A in biological fluids of patients with traumatic brain injury by UPLC-ESI-MS/MS after injection of Xuebijing

A simple, novel, specific, rapid and reproducible ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for the determination of hydroxysafflor yellow A (HSYA) in biological fluids (plasma, urine and cerebrospinal fluid) of patients with traumatic brain injury after intravenous injection of Xuebijing (XBJ). Liquid-liquid extraction was performed, and separation was carried out on an Acquity UPLC™ BEH C18 column, with gradient elution using a mobile phase composed of methanol and 0.1% formic acid at a flow rate of 0.3 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization was used for the detection of HSYA. The mass transition followed was m/z 611.0 → 491. The retention time was less than 3.0 min. The calibration curve was linear in the concentration range from 2 to 6125 ng/mL for cerebrospinal fluid, plasma and urine. The intra- and inter-day precisions were <10%, and the relative standard deviation of recovery was <15% for HSYA in biological matrices. The method was successfully applied for the first time to quantify HSYA in the biological fluids (especially in cerebrospinal fluid) of patients with traumatic brain injury following intravenous administration of XBJ.

Naoling decoction restores cognitive function by inhibiting the neuroinflammatory network in a rat model of Alzheimer's disease.

Neuroinflammation is central to the pathogenesis of Alzheimers disease (AD). We previously showed that Naoling decoction (NLD), a traditional Chinese medicine, was effective against AD, acting by inhibiting expression of IL-1β and IL-6. In the present study, we generated the rat model of AD by injecting Aβ1–42 peptide intracerebroventricularly and evaluated the dose-dependent effects of NLD treatment. The NLD-treated rats exhibited significant improvements in cognitive function as evaluated by the Morris water maze test. Golgi-Cox staining revealed that NLD treatment dose-dependently increased dendritic spines in the CA1 region, which were diminished in vehicle-treated rats. Further, NLD treatment normalized hippocampal Chromogranin A levels, which were elevated by Aβ1-42 induction. NLD also attenuated activation of microglia and astrocytes induced by Aβ1-42. Subsequently, NLD dose-dependently reduced levels TNF-α, IL-1β and IL-6 by inhibiting the NF-κB signaling pathway and the ASC-dependent inflammasome in the hippocampus. These findings reveal that NLD is a promising therapeutic agent that exerts inhibitory effects at multiple sites within the neuroinflammatory network induced in AD.