A metabonomic analysis reveals novel regulatory mechanism of Huangqi injection on leucopenia mice

<p><i>Context</i>: Huangqi injection (HQI), extracted from Astragali Radix, which has capability on treating the leucopenia. However, the potential metabolic mechanism is poorly understood.</p> <p><i>Objective</i>: To investigate the effect of HQI on cyclophosphamide (Cy)-induced leucopenia in mice, the nuclear magnetic resonance (NMR)-based metabolomic profiling technique coupled with multivariate statistical analysis was applied.</p> <p><i>Materials and methods</i>: NMR analysis was used to identify the various compounds of HQI, and high-performance liquid chromatography was applied to determine the contents of major compounds. A experimental mice model of leucopenia induced by Cy and NMR-based metabolomic approach was used to evaluate the pharmacological effect of HQI and to investigate its probable acting mechanism on leucopenia.</p> <p><i>Results</i>: HQI increased body weight and elevated the white blood cell (WBC), monocytes (MO), neutrophils (NE), and lymphocyte (LY) levels of Cy-treated mice. In addition, the levels of most perturbed endogenous metabolites could be reversed after HQI treatment. Correlations between WBC, MO, NE, LY, and altered metabolite profiles in spleen were greater than that in serum, and the correlation in MO was more evident than those for WBC, NE, and LY.</p> <p><i>Discussion and conclusion</i>: HQI showed obvious efficacy on the mice model of leucopenia. And the drug action of HQI on leucopenia was probably related with regulating metabolic pathways of energy metabolism, amino acids metabolism, oxidative stress, and choline metabolism. However, various compounds were present in the HQI, and the bioactive compounds responsible for the drug actions should be further investigated.</p

Information of the data exploited in this study.

<p>Information of the data exploited in this study.</p

Beta-diversity consistency across studies and 16s rRNA regions.

<p>Samples of (a-b) CF baseline, (c-d) Exacerbated CF, and (e-f) Uninfected control (NIC) were compared with queries of studies (a, c, e) and 16s rRNA regions (b, d, f).</p

Beta-diversity consistency across studies and 16s rRNA regions.

<p>Samples of (a-b) CF baseline, (c-d) Exacerbated CF, and (e-f) Uninfected control (NIC) were compared with queries of studies (a, c, e) and 16s rRNA regions (b, d, f).</p

Effects of Baicalein on Cortical Proinflammatory Cytokines and the Intestinal Microbiome in Senescence Accelerated Mouse Prone 8

Baicalein, a flavonoid derived from the roots of <i>Scutellariae baicalensis</i> Georgi, has shown health benefits for an array of human diseases including dementia. The senescence-accelerated mouse prone 8 (SAMP8) strain is extensively used as a senile dementia model. To further investigate the effects of baicalein in SAMP8 mice, behavioral testing, biochemical detection, and gut microbiota analysis were performed. The results demonstrated that treatment with baicalein ameliorated the senescence status of the SAMP8 mice, as manifested by reducing the grading score of senescence. Additionally, baicalein improved the cognitive functions of the SAMP8 mice, including spatial learning and memory abilities, object recognition memory, and olfactory memory. Furthermore, baicalein significantly inhibited the release of proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α) in the brain cortex of SAMP8 mice. Gut microbiota analysis revealed that treatment with baicalein markedly altered the abundance of six genera in SAMP8 mice. Correlation analysis indicated that the abundances of <i>Mucispirillum</i>, <i>Bacteroides</i>, and <i>Sutterella</i> were negatively correlated with cognitive abilities and that <i>Christensenellaceae</i> was positively correlated with cognition. Furthermore, the abundance of <i>Christensenellaceae</i> was negatively correlated with the levels of IL-6 and TNF-α, while [<i>Prevotella</i>] was positively correlated with the levels of IL-1β and IL-6. In addition, <i>Mucispirillum</i> and <i>Bacteroides</i> were positively correlated with the level of IL-6 in the brain cortex. These data indicated that baicalein ameliorates senescence status and improves cognitive function in SAMP8 mice and that this effect might be attributable to suppression of cortical proinflammatory cytokines and modulation of the intestinal microbiome

Information of the data exploited in this study.

<p>Information of the data exploited in this study.</p

Boxplots for alpha diversity measurements of the microbiota of CF subgroups.

<p>Chao1 and Shannon indices were used to determine the richness and diversity of the bacterial community, respectively. Chao1 (a) and Shannon (b) measurements of the microbiota of Uninfected Control (NIC), CF baseline, and Exacerbated CF, Chao1 (c) and Shannon (d) measurements of the microbiota of Before, During and AfterTreatment of exacerbated CF. The upper edge of each box represents the 75% line, the lower edge represents the 25% line, and the inner line of each box represents the 50% line. ** refers to statistically highly significant as <i>p</i> < 0.01.</p

Dynamic variance of the relative abundances for the various bacteria in microbiota of exacerbated CF generated from individual studies.

<p>The relative abundances of the top two opportunistic and commensal bacteria are shown. The blank, zebra crossing, and solid column represent the Before, During and After Treatment of Exacerbated CF, respectively. (a) Data from SRP025173, (b) PC02, and (c) SRP044880. Detailed information for these three studies is listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164510#pone.0164510.t001" target="_blank">Table 1</a>. * refers to statistically significant as <i>p</i> < 0.05, ** refers to statistically highly significant as <i>p</i> < 0.01.</p

Unweighted UniFrac PCoA plot of healthy and CF microbiota.

<p>Distance comparisons were made for microbiota of: (a) Uninfected control (NIC) and CF baseline, (b) NIC and Exacerbated CF, (c) NIC and After Treatment of Exacerbated CF, (d) NIC and On Treatment of Exacerbated CF, (e) NIC and Before Treatment of Exacerbated CF, (f) CF baseline and Exacerbated CF, (g) Before, During and After Treatment of Exacerbated CF, (h) CF baseline and Before, During, After Treatment of Exacerbated CF. Each point represents a sample from the studies listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0164510#pone.0164510.t001" target="_blank">Table 1</a>. The color for each sample group can be found on the figure.</p

Venn diagrams for the microbiota of healthy individuals and patients in the various CF subgroups.

<p>Comparisons were made for: (a) Uninfected control (NIC), CF baseline, and Exacerbated CF; (b) Before, During and After Treatment of Exacerbated CF; (c) NIC and Before, During, After Treatment of Exacerbated CF; (d) CF baseline and Before, During, After Treatment of Exacerbated CF. The number inside each circle represents the amounts of OTUs observed.</p