Exploration of TCM syndrome types of the material basis and risk prediction of Wilson disease liver fibrosis based on 1H NMR metabolomics.

Wilson disease (WD) is an autosomal recessive disorder characterized by abnormal copper metabolism. The accumulation of copper in the liver can progress to liver fibrosis and, ultimately, cirrhosis, which is a primary cause of death in WD patients. Metabonomic technology offers an effective approach to investigate the traditional Chinese medicine (TCM) syndrome types of WD-related liver fibrosis by monitoring the alterations in small molecule metabolites within the body. In this study, we employed 1H-Nuclear Magnetic Resonance (1H NMR) metabonomics to assess the metabolic profiles associated with five TCM syndrome types of WD-related liver fibrosis and analyzed the diagnostic and predictive capabilities of various metabolites. The study found a variety of metabolites, each with varying levels of diagnostic and predictive capabilities. Furthermore, the discerned differential metabolic pathways were primarily associated with various pathways involving carbohydrate metabolism, amino acid metabolism, and lipid metabolism. This study has identified various characteristic metabolic markers and pathways associated with different TCM syndromes of liver fibrosis in WD, providing a substantial foundation for investigating the mechanisms underlying these TCM syndromes.

Qualitative analysis on the transdermal absorption from the dichloromethane extract of the Sambucus adnata wall. based on UPLC-Q-Exactive Orbitrap/MS.

Sambucus adnata Wall.(SAW) has been used to treat osteoarthritis by the Yi nationality in China. The present study established an overall identification strategy based on ultra-high performance liquid chromatography-tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method to characterize the multiple chemical constituents of SAW before and after percutaneous penetration. Nineteen compounds, including triterpenoids, fatty acids, lignans, flavonoid, and amide, were tentatively identified in the dichloromethane extract of SAW, while fourteen ingredients penetrated the skin. Among them, eleven components were reported for the first time in SAW.

The Influence of Stomach Back-Shu and Front-Mu Points on Insular Functional Connectivity in Functional Dyspepsia Rat Models.

Functional Dyspepsia (FD) is a common functional gastrointestinal disease, which can reduce the quality of life in patients. Prior research has indicated that insula is closely related to FD and that acupuncture can regulate the functional connectivity (FC) of FD. Therefore, we hypothesized that acupuncture on FD was effected through the insular pathway. To test our hypothesis, we performed electroacupuncture (EA) on FD rat models and then examined the FC between insula and other brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). Seven-day-old male infant Sprague-Dawley (SD) rats were randomly divided into control group, FD model group, and FD acupuncture group, with twelve rats per group (n = 36). Upon establishing successful models, the FD acupuncture group was subjected to EA intervention using Stomach back-shu (BL-21) and front-mu (RN-12) points for ten consecutive days for durations of 20 minutes each day. After intervention, each group was subject to rs-fMRI. The digital image data obtained were analyzed using FC analysis methods. Subsequently, gastric ligation was performed to measure gastric emptying rates. Before EA intervention, the FD model group exhibited decreased functional connections between the insula and a number of brain regions. After EA intervention, FD acupuncture group exhibited increasing FC between insula and regions when compared to the FD model group, such as the primary somatosensory cortex (S1), hippocampal CA3 (CA3), polymorphic layer of dentate gyrus (PoDG), caudate putamen (CPu), and oral pontine reticular nuclei (PnO) (P < 0.05); decreasing FC was also exhibited between insula and regions such as the bilateral primary and secondary motor cortexes (M1/2), paraventricular hypothalamic nucleus (PVA), and limbic cortex (LC). These findings indicate that the effective treatment of FD using EA may be through regulating the abnormal FC between insula and several brain regions, in particular CA3, PoDG, and PVA.

ZnO, TiO(2), SiO(2,) and Al(2)O(3) nanoparticles-induced toxic effects on human fetal lung fibroblasts.

OBJECTIVE: This study aims to investigate and compare the toxic effects of four types of metal oxide (ZnO, TiO(2), SiO(2,) and Al(2)O(3)) nanoparticles with similar primary size (∼20 nm) on human fetal lung fibroblasts (HFL1) in vitro. METHODS: The HFL1 cells were exposed to the nanoparticles, and toxic effects were analyzed by using MTT assay, cellular morphology observation and Hoechst 33 258 staining. RESULTS: The results show that the four types of metal oxide nanoparticles lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the concentration range of 0.25-1.50 mg/mL and the toxic effects are obviously displayed in dose-dependent manner. ZnO is the most toxic nanomaterials followed by TiO(2), SiO(2), and Al(2)O(3) nanoparticles in a descending order. CONCLUSION: The results highlight the differential cytotoxicity associated with exposure to ZnO, TiO(2), SiO(2), and Al(2)O(3) nanoparticles, and suggest an extreme attention to safety utilization of these nanomaterials.

[Effects of Cinnabar and Realgar in Angong Niuhuang powder on heat shock protein, nitric oxide synthase and inflammatory cytokines in contusion cerebral edema].

OBJECTIVE: To explore the pharmacological mechanism of Cinnabar and Realgar in Angong Niuhuang powder (ANP). METHODS: SD rats were randomly divided into six groups (12 rats/group): normal controls group (NS group), contusion cerebral edema model group( CCE group) , cerebral edema rats administrated by cinnabar 0. 15 g/kg 1h (CA group), cerebral edema rats administrated by realgar 0.15 g/kg 1h (RG group), cerebral edema rats administrated by Angong Niuhuang powder 1.5 g/kg 1h (ANP I group), cerebral edema rats administrated by Angong Niuhuang powder substracted cinnabar and realgar 1.2 g/kg 1h (ANP II group). Each group was divided into two subgroups (6 rats/subgroup). The rats in subgroups were killed at 8h and 24h after modeling respectively. Expression of heat shock protein 70 ( HSP 70) mRNA in brain tissues was measured by RT-PCR. Activities of nitric oxide synthase (NOS) and its isoenzymes (iNOS, cNOS) in brain tissues were tested by colorimetry. Levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in serum were determined by radioimmunoassay (RIA). RESULTS: Expression of HSP 70 mRNA in ANP I group and ANP II group significantly increased as compared with CCE group 8h after being modeled (P < 0.05), and increase range in ANP I group were singificantly higher than that in ANP II group (P < 0.05). Activities of iNOS in CA group, RG group, ANP I group and ANP II group were lower than that in CCE group 8h after being modeled (P < 0.05) , and the activities in ANP I group were the lowest in the four groups. Levels of TNF-alpha in RG group, ANP I group and ANP II group decreased obviously as compared with CCE group 8h after being modeled (P < 0.05) , so did levels of IL-1beta in ANP I group and ANP II group (P < 0.05). But no significant difference was shown between ANP I group and ANP 11 group. CONCLUSION: HSP 70, iNOS, TNF-alpha and IL-1beta are involved in contusion cerebral edema. ANP and CA, RG in ANP are protective against CCE in rats. It may be associated with the increase of HSP 70 mRNA expression, inhibition of iNOS activity, and the decreasae of inflammatory cytokines (TNF-alpha, IL-1beta) levels.

[Effects of cinnabar and realgar in angong niuhuang powder on lactate dehydrogenase and its isoenzymes in rats with infectious cerebral edema].

OBJECTIVE: To explore the pharmacologic mechanism of cinnabar (CA) and realgar (RG) in Angong Niuhuang powder (ANP) by way of studying the characteristics of their effects on organism under physiologic and pathologic states. METHODS: SD rats were randomly divided into six groups, 8-10 rats in each group. Group A: untreated normal rats; Group B: normal rats administered by ANP (drug I) 278 mg/kg; Group C: normal rats administered by ANP subtracted CA and RG (drug II) 222.7 mg/kg; Group D: brain edema model rats established by unilateral common carotid artery injection of Bacillus pertussis 250 million/kg; Group E: model rats administered by ANP 278 mg/kg 1 hr before modeling; Group F: model rats administered by drug II 222.7 mg 1 hr before modeling. Blood sample and brain tissue in Group D were obtained 4 hrs after modeling and those in other groups obtained 5 hrs after drug administration. The total activity of lactate dehydrogenase (LDH) in serum and brain tissue was determined by colorimetry and that of serum LDH isoenzymes (LDH(1-5)) were determined by gel electrophoresis. RESULTS: As compared with Group A, LDH, LDH1 and LDH2 activities increased in Group D (P < 0.01), and increased also in Group B and C (P < 0.05), while LDH4 and LDH5 decreased obviously in Group B and C. But except that of LDH5, no significant difference of LDH(1-4) in brain tissue and serum was shown in comparison of Group B and C. As compared with Group D, LDH was lower (P < 0.01) and LDH5 was higher (P < 0.01) in Group E and F without significant difference, LDH2, LDH3 were lower in Group E (P < 0.01) but unchanged in Group F, LDH1 and LDH4 were not changed in Group E but significantly lowered in Group F (P < 0.05 and P < 0.01). CONCLUSION: Administration of ANP in normal physiologic condition would cause damage on myocardium and kidney to certain extent, administration of ANP and drug II in pathologic (infectious brain edema) would suppress the hyper-activated LDH, with no significant difference between the effects of drug II and ANP. However, CA and RA in ANP are proven to have influence on the serum LDH isoenzymes, indicating that the two ingredients may have some potential pharmacological effects.

Effects of cinnabar and realgar in angong niuhuang powder on lactate dehydrogenase and its isoenzymes in rats with infectious cerebral edema / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the pharmacologic mechanism of cinnabar (CA) and realgar (RG) in Angong Niuhuang powder (ANP) by way of studying the characteristics of their effects on organism under physiologic and pathologic states.</p><p><b>METHODS</b>SD rats were randomly divided into six groups, 8-10 rats in each group. Group A: untreated normal rats; Group B: normal rats administered by ANP (drug I) 278 mg/kg; Group C: normal rats administered by ANP subtracted CA and RG (drug II) 222.7 mg/kg; Group D: brain edema model rats established by unilateral common carotid artery injection of Bacillus pertussis 250 million/kg; Group E: model rats administered by ANP 278 mg/kg 1 hr before modeling; Group F: model rats administered by drug II 222.7 mg 1 hr before modeling. Blood sample and brain tissue in Group D were obtained 4 hrs after modeling and those in other groups obtained 5 hrs after drug administration. The total activity of lactate dehydrogenase (LDH) in serum and brain tissue was determined by colorimetry and that of serum LDH isoenzymes (LDH(1-5)) were determined by gel electrophoresis.</p><p><b>RESULTS</b>As compared with Group A, LDH, LDH1 and LDH2 activities increased in Group D (P < 0.01), and increased also in Group B and C (P < 0.05), while LDH4 and LDH5 decreased obviously in Group B and C. But except that of LDH5, no significant difference of LDH(1-4) in brain tissue and serum was shown in comparison of Group B and C. As compared with Group D, LDH was lower (P < 0.01) and LDH5 was higher (P < 0.01) in Group E and F without significant difference, LDH2, LDH3 were lower in Group E (P < 0.01) but unchanged in Group F, LDH1 and LDH4 were not changed in Group E but significantly lowered in Group F (P < 0.05 and P < 0.01).</p><p><b>CONCLUSION</b>Administration of ANP in normal physiologic condition would cause damage on myocardium and kidney to certain extent, administration of ANP and drug II in pathologic (infectious brain edema) would suppress the hyper-activated LDH, with no significant difference between the effects of drug II and ANP. However, CA and RA in ANP are proven to have influence on the serum LDH isoenzymes, indicating that the two ingredients may have some potential pharmacological effects.</p>