System pharmacology-based determination of the functional components and mechanisms in chronic heart failure treatment: an example of Zhenwu decoction.

Chronic heart failure (CHF) is the primary cause of death among patients with cardiovascular diseases, representing the advanced stage in the development of several cardiovascular conditions. Zhenwu decoction (ZWD) has gained widespread recognition as an efficacious remedy for CHF due to its potent therapeutic properties and absence of adverse effects. Nevertheless, the precise molecular mechanisms underlying its actions remain elusive. This study endeavors to unravel the intricate pharmacological underpinnings of five herbs within ZWD concerning CHF through an integrated approach. Initially, pertinent data regarding ZWD and CHF were compiled from established databases, forming the foundation for constructing an intricate network of active component-target interactions. Subsequently, a pioneering method for evaluating node significance was formulated, culminating in the creation of core functional association space (CFAS). To discern vital components, a novel dynamic programming algorithm was devised and used to determine the core component group (CCG) within the CFAS. Enrichment analysis of the CCG targets unveiled the potential coordinated molecular mechanisms of ZWD, illuminating its capacity to ameliorate CHF by modulating genes and related signaling pathways involved in pathological remodeling. Notable pathways encompass PI3K-Akt, diabetic cardiomyopathy, cAMP and MAPK signaling. Concluding the computational analyses, in vitro experiments were executed to assess the effects of vanillic acid, paradol, 10-gingerol and methyl cinnamate. Remarkably, these compounds demonstrated efficacy in reducing the production of ANP and BNP within isoprenaline-induced AC 16 cells, further validating their potential therapeutic utility. This investigation underscores the efficacy of the proposed model in enhancing the precision and reliability of CCG selection within ZWD, thereby presenting a novel avenue for mechanistic inquiries, compound refinement and the secondary development of TCM herbs.

Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia.

BACKGROUND: Propofol is a safe and effective intravenous anesthetic that is widely used for the induction and maintenance of anesthesia during surgery. However, the mechanism by which propofol exerts its anesthetic effect remains unknown. The rapid onset of phosphorylation modifications coincides with that of propofol anesthesia. METHODS: Propofol-anesthetized rat models were built and phosphorylated proteins in the thalamus, hippocampus and frontal lobe were enriched the to analyze the changes in these phosphoproteins after propofol anesthesia. RESULTS: Sixteen of these phosphoprotein spots were successfully identified using MALDI-TOF MS and a subsequent comparative sequence search in the Mascot database. Of these proteins, keratin 18 and the tubulin 2c chain are cytoskeletal proteins; keratin 18 and gelsolin are relevant to alcohol drowsiness. Based on Western blot analysis, we also confirmed that the phosphorylation of these proteins is directly induced by propofol, indicating that propofol anesthesia may be relevant to cytoskeletal proteins and alcohol drowsiness. CONCLUSIONS: These identified propofol-induced phosphorylations of proteins provide meaningful contributions for further studying the anesthetic mechanism of propofol.

[GAT-1 and GAD65 mRNA expressions in different brain regions in dogs at brain propofol uptake equilibrium].

OBJECTIVE: To investigate the expressions of gamma aminobutyric acid transporter 1 (GAT-1) and glutamate decarboxylase 65 (GAD65) mRNA in different brain regions at brain propofol uptake equilibrium in dogs. METHODS: Eighteen 12- to 18-month-old healthy hybrid dogs were randomized equally into control group (group C), low dose group (group L), and high dose group (group H). In groups L and H, anesthesia was administered by intravenous injection of 5.5 and 7.0 mg/kg propofol followed by propofol infusion at a constant rate of 55 and 70 mg·kg(-1)·h(-1) for 50 min, respectively. Blood samples were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations, and the brain tissues of the hypothalamus, sub thalamus, dorsal thalamus, hippocampus, pons, parietal lobe and frontal lobe were examined for GAT-1 and GAD65 mRNA expressions using quantitative real-time PCR. RESULTS: In groups L and H, propofol infusion at a constant rate for 50 min resulted in comparable plasma propofol concentrations between the internal carotid artery and jugular vein (P>0.05), but the concentrations differed significantly between the two groups (P<0.01). GAT-1 mRNA levels in the hypothalamus and hippocampus were significantly higher in groups L and H than in group C (P<0.05 and P<0.01), but comparable between the former two groups. The variations of GAT-1 mRNA levels between the hypothalamus and hippocampus were similar in both group L [(61.26∓7.17)% and (79.34∓39.95)%, P>0.05] and group H [(74.64∓19.63)% and (97.12∓32.31)%, P>0.05]. GAT-1 mRNA levels in other brain regions showed no significant difference among the 3 groups. GAD65 mRNA levels were similar between group L and group H, but both significantly higher than that in group C (P<0.01). GAD65 mRNA in other brain regions had no significant difference among the 3 groups. CONCLUSION: GAT-1 mRNA in the hypothalamus and hippocampus and GAD65 mRNA in the dorsal thalamus are upregulated when propofol uptake reaches an equilibrium in the brain of dogs.

[Prophylactic effect of acupuncture on nausea and vomiting after laparoscopic operation].

OBJECTIVE: To explore the prophylactic effect of acupuncture Neiguan (PC 6) on nausea and vomiting after laparoscopic operation. METHODS: One hundred patients with laparoscopic gastrointestinal operation were randomly divided into an acupuncture group and a control group, 50 patients in each group. The operation was carried out with the combined infusion and inhalation anesthesia. The patients in the acupuncture group were being punctured at bilateral Neiguan (PC 6) before anesthesia and during the operation. The needles were extracted after operation, and the acupoints were covered with opaque tape. In contrast, the patients in the control group only accepted tape covering without acupuncture. After operation, all patients were given the self-controlled intravenous analgesia, and followed up at 6 h, 12 h, 24 h, 48 h for recording the incidence rate of the nausea, retching and vomiting, then scoring with VAS. RESULTS: At 6 h, 12 h, 24 h, 48 h after operation, in the acupuncture group, the incidence rates of the nausea were 12.0%, 6.0%, 6.0% and 2.0%, and the incidence rates of the retching were 0, 0, 2.0% and 2.0%, respectively; in the control group, the incidence rates of the nausea were 28.0%, 20.0%, 12.0% and 2.0%, and the incidence rates of the retching were 2.0%, 6.0%, 2.0% and 0, respectively. At 6 h, 12 h after operation, the incidence rates of the nausea and retching in the acupuncture group were lower than those of the control group (P < 0.05, P < 0.001). The vomiting was not happened in both groups. There was no difference between the two groups according to the scoring with VAS. CONCLUSION: Acupuncturing at Neiguan (PC 6) can reduce the incidence rates of the patients' nausea and retching after laparoscopic operation, especially in 24 h.

[Cerebral uptake and regional cerebral distribution of propofol under concentration equilibrium condition in the internal carotid artery and internal jugular vein in dogs].

OBJECTIVE: To investigate the cerebral uptake and regional distribution of propofol when plasma propofol concentration reaches equilibrium in the internal carotid artery and internal jugular vein in dogs. METHODS: Eight male hybrid dogs aged 12-18 months weighing 10-12 kg were anesthetized with propofol at a single bolus (7 mg/kg) in 15 s followed by propofol infusion at a constant rate of 70 mg.kg(-1).h(-1) via the great saphenous vein of the right posterior limb. Blood samples were taken from the internal carotid artery and internal jugular vein at 30 min (T30) after propofol infusion for measurement of plasma propofol concentrations by high-pressure liquid chromatography (HPLC). The thalamus, epithalamus, metathalamus, hypothalamus, subthalamus, frontal lobe, parietal lobe, temporal lobe, hippocampus, cingulate gyrus, cerebellum, midbrain, pons, medulla oblongata and cervical cord were then dissected to determine propofol concentrations in these tissues by HPLC. RESULTS: The propofol concentrations in the internal carotid artery and internal jugular vein blood plasma were comparable at T30 (6.16-/+1.02 vs 6.17-/+1.00 microg/ml, P>0.05). The propofol concentration was 6.11-/+1.07 microg/g in the epithalamus, 6.14-/+0.98 microg/g in the metathalamus, 6.12-/+1.02 microg/g in the hypothalamus, 6.15-/+1.00 microg/g in the subthalamus, 6.20-/+1.03 microg/g in the frontal lobe, 6.18-/+1.02 microg/g in the parietal lobe, 6.13-/+1.00 microg/g in the temporal lobe, 6.07-/+0.99 microg/g in the hippocampus, 6.14-/+1.06 microg/g in the cingulate gyrus, 6.15-/+1.00 microg/g in the cerebellum, 6.13-/+1.05 microg/g in the midbrain, 6.18-/+1.01 microg/g in the pons, 6.15-/+0.93 microg/g in the medulla oblongata, and 6.13-/+1.00 microg/g in the cervical cord, showing no significant differences in the distributions (P>0.05). Propofol concentration in the thalamus (8.68-/+0.88 microg/g) was significantly higher than those in the other brain tissues (P<0.05). CONCLUSIONS: At the constant intravenous propofol injection rate of 70 mg.kg(-1).h(-1), plasma propofol concentration reaches equilibrium 30 min after the injection in the internal carotid artery and internal jugular vein with even distribution in the cerebral tissues in dogs, but the thalamus contains high propofol concentration.