Xuefu Zhuyu decoction promotes synaptic plasticity by targeting miR-191a-5p/BDNF-TrkB axis in severe traumatic brain injury.

BACKGROUND: Xuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal formula known for its ability to eliminate blood stasis and improve blood circulation, providing neuroprotection against severe traumatic brain injury (sTBI). However, the underlying mechanism is still unclear. PURPOSE: We aim to investigate the neuroprotective effects of XFZYD in sTBI from a novel mechanistic perspective of miRNA-mRNA. Additionally, we sought to elucidate a potential specific mechanism by integrating transcriptomics, bioinformatics, and conducting both in vitro and in vivo experiments. METHODS: The sTBI rat model was established, and the rats were treated with XFZYD for 14 days. The neuroprotective effects of XFZYD were evaluated using a modified neurological severity score, hematoxylin and eosin staining, as well as Nissl staining. The anti-inflammatory effects of XFZYD were explored using quantitative real-time PCR (qRT-PCR), Western blot analysis, and immunofluorescence. Next, miRNA sequencing of the hippocampus was performed to determine which miRNAs were differentially expressed. Subsequently, qRT-PCR was used to validate the differentially expressed miRNAs. Target core mRNAs were determined using various methods, including miRNA prediction targets, mRNA sequencing, miRNA-mRNA network, and protein-protein interaction (PPI) analysis. The miRNA/mRNA regulatory axis were verified through qRT-PCR or Western blot analysis. Finally, morphological changes in the neural synapses were observed using transmission electron microscopy and immunofluorescence. RESULTS: XFZYD exhibited significant neuroprotective and anti-inflammatory effects on subacute sTBI rats' hippocampus. The analyses of miRNA/mRNA sequences combined with the PPI network revealed that the therapeutic effects of XFZYD on sTBI were associated with the regulation of the rno-miR-191a-5p/BDNF axis. Subsequently, qRT-PCR and Western blot analysis confirmed XFZYD reversed the decrease of BDNF and TrkB in the hippocampus caused by sTBI. Additionally, XFZYD treatment potentially increased the number of synaptic connections, and the expression of the synapse-related protein PSD95, axon-related protein GAP43 and neuron-specific protein TUBB3. CONCLUSIONS: XFZYD exerts neuroprotective effects by promoting hippocampal synaptic remodeling and improving cognition during the subacute phase of sTBI through downregulating of rno-miR-191a-5p/BDNF axis, further activating BDNF-TrkB signaling.

Baihe Extracts Reduce the Activation and Apoptosis of Microglia in the Hippocampus of Mice with Depression-like Behaviors by Downregulating MYC.

The purpose of our investigation is to identify the potential effects and key molecular targets of Baihe extracts in depression treatment. Network meta-analysis was applied for the synthesis of efficacy outcomes of fluoxetine and three traditional Chinese medicine Baihe prescriptions in depression. Depression-related target genes were screened using "GeneCards" database and "Comparative Toxicogenomics Database (CTD)". The major active components and targets of Baihe were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The identified depression-related genes and the target genes of Baihe were intersected, an interaction network was constructed using the "String" database, and key target genes were determined based on their degree value. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) profiles was performed using the "ClusterProfiler" R package. A mouse model with depression-like behaviors was constructed to verify the putative roles of the in silico identified key genes. Microglia were isolated from the mouse hippocampus, and the effects of Baihe extract-containing serum on microglia activation and apoptosis by targeting the key genes were examined in vitro. The meta-analysis results revealed no obvious differences in depression treatment efficacy between fluoxetine and the three Baihe prescriptions, suggesting Baihe extracts as a safe and effective alternative treatment for depression. Using network pharmacology and bioinformatics analysis, Baihe extracts were found to modulate depression by regulating 15 key genes, with MYC as the key gene. Subsequent animal experiments demonstrated that Baihe extracts reduced depression-related behavior, microglial activation, and inflammatory mediator release in mice by inhibiting MYC. Serum containing Baihe extracts could inhibit the activation of microglia and the release of inflammatory mediators by downregulating MYC. In summary, Baihe extracts were found to diminish MYC expression to reduce microglial activation and inflammatory factor release, thereby exerting antidepressant effects.

Supplementing conjugated linoleic acid in breeder hens diet increased conjugated linoleic acid incorporation in liver and alters hepatic lipid metabolism in chick offspring.

This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (control (CT)) or 0·5 % CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 d. CLA treatment had no significant influence on development, egg quality and fertility of breeder hens but darkened the egg yolks in shade and increased yolk sac mass compared with the CT group. Addition of CLA resulted in increased body mass and liver mass and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum TAG and total cholesterol levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in the liver of chick offspring, accompanied by the decreased hepatic TAG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC and sterol regulatory element-binding protein-1c) and induced the expression of genes related to ß-oxidative (CPT1, AMP-activated protein kinase and PPARα) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased the incorporation of CLA in the liver of chick offspring, which further regulate hepatic lipid metabolism.

Development of a sensitive and rapid UHPLC-MS/MS method for simultaneous quantification of nine compounds in rat plasma and application in a comparative pharmacokinetic study after oral administration of Xuefu Zhuyu Decoction and nimodipine.

Xuefu Zhuyu Decoction (XFZYD) is a traditional Chinese medicine prescription used for the clinical treatment of traumatic brain injury (TBI). The purpose of this work was to develop a sensitive and rapid UHPLC-MS/MS method to simultaneously study the pharmacokinetics of nimodipine and eight components of XFZYD, namely, amygdalin, hydroxysafflor yellow A, rutin, liquiritin, narirutin, naringin, neohesperidin and saikosaponin A, in rats with and without TBI. Multiple reaction monitoring was highly selective in the detection of nine analytes and the internal standard without obvious interference. The calibration curves displayed good linearity (r > 0.99) over a wide concentration range. The mean absolute recoveries of the nine analytes were 85-106%, and all matrix effects were in the range 80-120%. The intra- and inter-day precision and accuracy were acceptable (RSD, <15%; RE%, ±20%). The validated method was successfully applied to compare the pharmacokinetics in four experimental groups, including control rats orally administered XFZYD and TBI model rats orally administered XFZYD, XFZYD and nimodipine, or nimodipine alone. The results showed that herb-drug interactions occurred between XFZYD and nimodipine in the treatment of TBI, nimodipine affected the pharmacokinetics of XFZYD, and XFZYD affected the absorption, distribution and excretion of nimodipine in vivo.

Maternal conjugated linoleic acid alters hepatic lipid metabolism via the AMPK signaling pathway in chick embryos.

The effects of maternal conjugated linoleic acid (CLA) on embryonic development and hepatic lipid metabolism were investigated in chick embryos. A total of 180 Arbor Acres female broiler breeders (36 wk old) were randomly divided into the following 3 dietary treatment groups: a basic diet (control), a basic diet containing 0.5% CLA (CLA1), and a basic diet containing 1.0% CLA (CLA2). The females were fed for 8 wk, and the eggs from each group were collected and hatched during the last 2 wk. The results showed that the addition of dietary CLA increased the broken egg rate and reduced the fertilization rate and the egg hatchability (P < 0.05). CLA enrichment decreased the polyunsaturated and monounsaturated fatty acids and increased the saturated fatty acids in the yolk sac (P < 0.05). The yolk sac weight, body weight, and body length had a linear decrease with CLA supplementation (P < 0.05). In the developing chick embryo (at E14) and newly hatched chick (D0), the serum triglyceride concentration decreased with maternal CLA supplementation and was accompanied by a reduction in subcutaneous adipose tissue deposition. In addition, maternal CLA supplementation mediated the hepatic lipid metabolism by decreasing the mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), fatty acid synthase and acetyl-CoA carboxylase, and increasing the mRNA expression of adenosine 5'-monophosphate-activated protein kinase α (AMPKα), peroxisome proliferator-activated receptors α (PPARα), liver fatty acid-binding protein, adipose triglyceride lipase and carnitine palmitoyltransferase in embryonic chick livers (P < 0.05). A drop in SREBP-1c protein expression and an increase in the protein expression of p-AMPKα and PPARα were also observed in the liver of chick embryo (P < 0.05). In conclusion, maternal CLA supplementation regulated the fatty acid composition in the yolk sac, and mediated embryonic chick development and hepatic lipometabolism, and these effects may be related to the AMPK pathway. These findings suggest the potential ability of maternal CLA supplementation to reduce fat deposition in chick embryos.

UPLC-ESI-IT-TOF-MS metabolomic study of the therapeutic effect of Xuefu Zhuyu decoction on rats with traumatic brain injury.

It has been widely reported that Xuefu Zhuyu decoction (XFZYD), a traditional Chinese medicine, is effective in the treatment of traumatic brain injury (TBI). However, the mechanism of the therapeutic process is still not fully understood. Metabolomic technique can be used to explore the mechanisms underlying the treatment of TBI with XFZYD. The purpose of this work was to investigate the metabolic characteristics of blood samples from rats with and without XFZYD treatment and the dynamic changes in metabolite profiles on days 1, 3, 7, 14 and 21 after injury (within the severe phase of TBI) based on untargeted UPLC-ESI-IT-TOF-MS analysis. Pattern recognition, clustering analysis and metabolic pathway analysis were used to analyse the metabolomic data of three groups (a sham-operated group, a TBI model, and an XFZYD-treated TBI model). The results showed that XFZYD reversed the abnormalities in the levels of small-molecule metabolites (such as L-acetylcarnitine, L-tryptophan, indoleacrylic acid, γ-aminobutyric acid, hypotaurine, LysoPC(18:1)(11Z), creatine, L-phenylalanine and L-leucine) in TBI rats through six metabolic pathways (including phenylalanine, tyrosine and tryptophan biosynthesis; phenylalanine metabolism; valine, leucine and isoleucine biosynthesis; taurine and hypotaurine metabolism; tryptophan metabolism; and alanine, aspartate and glutamate metabolism) involved in the therapy process. XFZYD regulated the metabolic disorders of endogenous markers by the possible mechanisms of neuroprotection, energy metabolism, inflammatory response and oxidative stress. This study revealed the holistic and dynamic metabolic changes caused by XFZYD in rats with TBI and provided important research methods and approaches for exploring the multiple metabolites and metabolic pathways involved in the therapeutic effect of XFZYD on 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.

Dietary Niacin Supplementation Suppressed Hepatic Lipid Accumulation in Rabbits.

An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32) were allocated to two equal treatment groups: Fed basal diet (control) or fed basal diet with additional 200 mg/kg niacin supplementation (niacin). The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p<0.05), but significantly decreased the hepatic fatty acid synthase activity and adiponectin receptor 2, insulin receptor and acetyl-CoA carboxylase mRNA levels (p<0.05). Plasma insulin had a decreasing tendency in the niacin treatment group compared with control (p = 0.067). Plasma very low density lipoproteins, leptin levels and the hepatic adiponectin receptor 1 and carnitine palmitoyl transferase 1 genes expression were not significantly altered with niacin addition to the diet (p>0.05). However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (p<0.05). In conclusion, niacin treatment can decrease hepatic fatty acids synthesis, but does not alter fatty acids oxidation and triacylglycerol export. And this whole process attenuates lipid accumulation in liver. Besides, the hormones of insulin, leptin and adiponectin are associated with the regulation of niacin in hepatic lipid metabolism in rabbits.

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-1ß 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-1ß. 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.

Steroidal and phenolic glycosides from the bulbs of Lilium pumilum DC and their potential Na+/K+ ATPase inhibitory activity.

A new steroidal saponin, named pumilum A (1), and a new phenolic glycoside, threo-1-(4'-hydroxy-2'-methoxyphenyl)-2-(2",4"-dihydroxyphenyl)-1,3-propanediol-4'-O-ß-D-glucopyranoside (7) were isolated from the methanolic extract of the bulbs of Lilium pumilum DC, along with five known steroidal saponins. Their chemical structures were elucidated on the basis of detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical methods. In addition, the inhibitory activity of all the isolates on Na(+)/K(+) ATPase was evaluated.

Sex differences in blood pressure response to antihypertensive therapy in Chinese patients with hypertension.

BACKGROUND: Sex-specific responses to antihypertensive drugs are not very well understood. OBJECTIVE: To investigate sex-related differences in blood pressure response to antihypertensive drugs in a community-based prospective clinical trial. METHODS: We recruited 3535 untreated hypertensive patients (2326 women), aged 40-75 years, from 7 rural communities in China. Subjects were randomized to 1 of 4 drug groups: atenolol, hydrochlorothiazide (HCTZ), captopril, or sustained-released nifedipine; duration of the study was 8 weeks. Mean blood pressure reduction, blood pressure control rates, and frequency of adverse events were compared between men and women. RESULTS: Women had a better response to HCTZ in relation to diastolic blood pressure (1.8 mm Hg lower) than did men (p < 0.05) and were 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). In the atenolol group, mean systolic blood pressure decreased 3.9 mm Hg more in women than in men (p < 0.05), and women were 65% more likely to reach the control goal of systolic blood pressure and 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). Significant sex-related differences were also found in drug-related adverse events in the nifedipine group (15.8% in women vs 9.8% in men; p = 0.017) and in the captopril group (14.3% in women vs 8.4% in men; p = 0.005), but no differences were seen with HCTZ or atenolol. CONCLUSIONS: Women have better blood pressure responses to HCTZ and atenolol and experience more adverse effects with sustained-release nifedipine and captopril than do men, indicating that sex should be taken into account when selecting antihypertensive drugs.

[Studies on the aporphine alkaloids from Fissistigma oldhamii (Hemsl.) Merr].

OBJECTIVE: To study aporphine alkaloids from Fissistigma oldhamii (Hemsl.) Merr. which is a characteristic plant of Guangxi. METHODS: Various chromatographic techniques were used to separate and purify the aporphine alkaloids. Their physical and chemical properties and spectral data were measured for structural elucidation. RESULTS: Four aporphine alkaloids were isolated from the fraction of total alkaloids of Fissistigma oldhamii (Hemsl.) Merr. They were identified as romucosine(I), xylopine(II), O-methylmoschatolineIII), oxoxylopine(IV). CONCLUSION: Compounds I is obtained from this plant for the first time.