Background: Ligusticum striatum DC. (LDC) is often prescribed for Cerebral Ischemia (CI) and is commonly combined with Borneolum (BO) to enhance therapeutic outcomes. However, its specific active ingredients and underlying mechanisms remain unclear. Objective: This study aimed to identify the active ingredients and mechanisms of LDC and BO combination therapy against CI using network pharmacology, molecular docking, and in vivo experiments. Methods: Potential active ingredients and targets were sourced from relevant databases, and a drug-component-target-disease network was constructed to pinpoint key ingredients. Subsequently, a protein-protein interaction analysis was conducted to confirm the key targets. Following enrichment analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular docking was employed to evaluate binding energies. Finally, the therapeutic effects and mechanisms of the combination against CI were validated through in vivo experiments using male ICR mice Results: Venn analysis identified a total of 41 components and 292 potential targets. The drugcomponent-target-disease network revealed that the key components in LDC were palmitic acid, tetramethylpyrazine, and (Z)-ligustilide, while those in BO were (+)-borneol, β-elemene, and (-)- borneol. The PPI analysis highlighted seven crucial targets. Docking results confirmed a stable affinity between these components and their targets. KEGG enrichment analysis indicated that the mechanism involved the PI3K/AKT signaling pathway. Subsequently, in vivo experiments confirmed that the combination ameliorated abnormal hippocampus morphology and reduced the release of inflammatory factors through the activation of the PI3K/AKT signaling pathway Conclusion: The combination of LDC and BO markedly improved CI and inhibited inflammation response via activating the PI3K/AKT pathway
The relationship between major depressive disorder (MDD) and dysthymia, a form of chronic depression, is complex. The two conditions are highly comorbid and it is unclear whether they are two separate disease entities. We investigated the extent to which patients with dysthymia superimposed on major depression can be distinguished from those with recurrent MDD.We examined the clinical features in 1970 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and dysthymia and between dysthymia and disorders comorbid with major depression.The 354 cases with dysthymia had more severe MDD than those without, with more episodes of MDD and greater co-morbidity for anxiety disorders. Patients with dysthymia had higher neuroticism scores and were more likely to have a family history of MDD. They were also more likely to have suffered serious life events.Results were obtained in a clinically ascertained sample of Chinese women and may not generalize to community-acquired samples or to other populations. It is not possible to determine whether the associations represent causal relationships.The additional diagnosis of dysthymia in Chinese women with recurrent MDD defines a meaningful and potentially important subtype. We conclude that in some circumstances it is possible to distinguish double depression from recurrent MDD.
Background: Ligusticum chuanxiong Hort (LCH) is a famous ethnomedicine in Asia known for its excellent output on stroke treatment, and borneol usually acts as an assistant for its reducing permeability of the blood–brain barrier (BBB) after stroke. Although their synergy against brain ischemia was verified in previous studies, the potential mechanism is still unknown. Methods: The research aimed to explore the exact synergic mechanisms between LCH and borneol on neurogenesis within the areas of the dentate gyrus and subventricular zone. After treating middle cerebral artery occlusion rats with LCH (0.1 g/kg) and/or borneol (0.08 g/kg), the neurological severity score, brain infarct ratio, Nissl staining, Evans blue permeability, BBB ultrastructure, and expressions of von Willebrand factor and tight junction–associated proteins were measured. Co-localizations of Nestin + /BrdU + and doublecortin + /BrdU + , and expressions of neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) were observed under a fluorescence microscope. Moreover, astrocyte polarization markers of complement component 3 and pentraxin 3, and relevant neurotrophins were also detected by immunoblotting. Results: Basically, LCH and borneol had different focuses, although both of them decreased infarct areas, and increased quantity of Nissl bodies and expression of brain-derived neurotrophic factor. LCH increased the neurological severity score, NeuN + cells, and the ratios of Nestin + /BrdU + and doublecortin + /BrdU + , and decreased GFAP + cells and ciliary neurotrophic factor expression. Additionally, it regulated the expressions of complement component 3 and pentraxin 3 to transform astrocyte phenotypes. Borneol improved BBB ultrastructure and increased the expressions of von Willebrand factor, tight junction–associated proteins, vascular endothelial growth factor, and vascular endothelial growth factor receptor 2. Unexpectedly, their combined therapy showed more obvious regulations on the Nissl score, Evans blue permeability, doublecortin + /BrdU + , NeuN + cells, brain-derived neurotrophic factor, and vascular endothelial growth factor than both of their monotherapies. Conclusions: The results indicated that LCH and borneol were complementary to each other in attenuating brain ischemia by and large. LCH mainly promoted neural stem cell proliferation, neurogenesis, and mature neuron preservation, which was probably related to the transformation of reactive astrocytes from A1 subtype to A2, while borneol preferred to maintain the integrity of the BBB, which provided neurogenesis with a homeostatic environment.
To observe the effect of electroacupuncture (EA) on the expression of blood-brain barrier (BBB)-related functional protein, ATP-binding cassette protein and gene in the cerebral cortex of depression rats.Forty SD rats were equally and randomly divided into control group, EA group, depressive (model) group and depression + EA group. The depression model was established by chronic unpredictable mild stress. EA (2 Hz, 1 mA) was applied to "Baihui"(GV 20) and "Yamen"(GV 15) for 20 min, once daily for 14 days. The expression levels of multidrug resistance (Mdr) 1a, Mdr 1b, multidrug resistance-associated protein (Mrp) 1, Mrp 4, Mrp 5, and breast cancer resistance protein (Bcrp) gene and proteins in the cerebral cortex tissue were detected by RT-PCR semi-quantitative analysis and Western blot, respectively.In comparison with the control group, no obvious changes were found in the expression levels of cerebral Mdr la, Mdr 1b, Mrp 1, Mrp 4, Mrp 5 and Bcrp genes and proteins in the model group (P > 0.05), and only cerebral Mdr 1a gene and protein expression levels in the EA group were evidently down-regulated (P < 0.01, P < 0.05). Compared with the model group, only cerebral Mdr la gene and protein expression levels were obviously decreased in the depression+ EA group (P < 0.01, P < 0.05). No significant changes were found in the Mdr 1b, Mrp 1, Mrp 4, Mrp 5 and Bcrp genes and proteins after EA intervention in depression rats (P > 0.05).EA of GV 20 and GV 15 can obviously down-regulate the expression of cerebral Mdr 1a in depression rats which might be involved in the opening activity of blood-brain barrier.
OBJECTIVE To explore the haemodynamics effect of Xin'anling on anesthetized dogs.METHODS We observed Xin'anling's influence on blood pressure,heartbeat,cardiac output,coronary blood flow,oxygen consumption,etc.of anesthetized dogs after being taken mid-sternal thoracotomy.RESULTS Xin'anling significantly reduced diastolic blood pressure,pulse pressure difference,heartbeat,total peripheral vascular resistance,and total oxygen consumption of the dogs.CONCLUSION Xin'anling can bring down afterload,reduce cardiac work,and improve cardiac function without decreasing blood supply by heart,which indicates that this medicine is able to better cardiovascular system.
Objective: To examine the influence of Yiqiyangyinhuoxue Decoction on endothelin-l(ET-1) and angiotensinⅡ(ANGⅡ)in patients with diastolic heart failure(DHF).Methods: 160 patients with DHF were randomly divided into the control group and the treatment group(80 patients).The control group were treated with routine western medicine.The treatment group were treated with decoction besides the control group therapy.Results: The ET-1 and ANGⅡ of the treatment group were decreased more obviously than those of the control group.The effect of the treatment group was superior to that of the control group.Conclusion: Expressions including ET-1 and ANGⅡ are lowered remarkably when used the Yiqiyangyinhuoxue decoction.
Objective To observe the effect of combined administration of intragastric perfusion of extract of Hypericum Perforatum L(HP-L) and electroacupuncture(EA) of Baihui(GV 20) and Yamen(GV 15) on behavior and brain microcirculation in depression rats.Methods Female SD rats were randomized into control,model,lower-dose of HP-L(lower-dose in short,10 mg/kg),lower-dose+EA,higher-dose(20 mg/kg) and higher-dose+EA groups(n=10/group).Depression model was established by lonely raising and chronic unpredictable mild stress(tail cramping,water-deprivation,fasting,electrical shock stimulation,etc.) for 21 days.EA(2 Hz,1 mA) was applied to Baihui(GV 20) and Yamen(GV 15) for 20 min,once daily for 14 days.Changes of ethology including glucose-consumption during 1 h,crossing and rearing scores of open-field test during 3 min(for assessing the rats' locomoto)and laser Doppler flowmetry values of cortical regional cerebral bloodflow(r CBF) were detected,and Morris water maze test(for assessing the rats' learning-memory ability) was conducted.Results In comparison with the control group,the sucrose consumption,crossing and rearing scores of open-field test,the average swimming velocity(ASV),the ratios of path length and swimming duration near the hidden-platform and the path length and swimming duration far from the platform of Morris water maze test during 70 seconds,and the cortical r CBF value in the model group were decreased significantly(P0.01),while the total swimming distance and escape latency in the model group increased apparently(P0.01).Compared to the model group,the average sucrose consumption,crossing and rearing scores of open-field test,the ASV,and the ratios of path length and swimming duration near the platform and those far from the platform in the lower-dose,lower-dose+EA,higher-dose and higher-dose+EA groups,and the cortical r CBF in the lower-dose+EA and higher-dose+EA groups were increased considerably(P0.05,P0.01).The total swimming distances and escape latencies of lower-dose,lower-dose+EA,higher-dose and higher-dose+EA groups were significantly shortened in comparison with the model group(P0.05,P0.01).The sucrose consumption and crossing score were significantly higher in the higher-dose+EA group than in the lower-dose group(P0.05).The escape latency was significantly shorter in the higher-dose+EA group than in the lower-dose group(P0.05).No significant differences were found among the lower-dose,lower-dose+EA and higher-dose groups in the sucrose consumption,crossing score and escape latency;among the lower-dose,lower-dose+EA,higher-dose and higher-dose+EA groups in the rearing score and ASV;among the lower-dose,higher-dose and model groups in the cortical r CBF(P0.05).Conclusion EA can enhance the effect of extract of HP-L in increasing sucrose consumption,crossing score and cerebral blood flow,and in shortening escape latency in depression rats,which may contribute to their effect in improving depression.But HP-L itself has no effect on cortical microcirculation.
Background and Objective: Ligusticum Chuanxiong Hort (LC) is often prescribed with borneol (BO) for a better effect in treating ischemic stroke in Asia.However, the mechanism of their combination is unclear till now.This study was aim to explore the synergy between BO and extract of LC (ELC) in protecting cortex and striatum against ischemia attack.Materials and Methods: The rats were divided into sham, model, ELC, BO and ELC+BO groups.Four-vessel occlusion surgery was employed for rat global cerebral ischemia/reperfusion (GCIR) model.After the treatment, the microcirculation, anti-oxidative ability, apoptosis index (AI), levels of apoptosis-related genes, intracellular [Ca 2+ ] and autophagy-related proteins expressions were measured respectively.Results: In cortex, the superiority of ELC was on anti-oxidation, while that of BO was on improvement of brain microcirculation.Both of them inhibited Ca 2+ overload and apoptosis in cortex via regulating p53, caspase-3, Bcl-2 and Bax.In striatum, ELC had the superiorities in regulating AI, mTOR, LC3 II/I, besides their common modulation on p53, Beclin 1 and [Ca 2+ ]. Surprisingly, the combined group produced some new targets, including ULK1 in cortex and including CAT, GSH-Px, MDA, iNOS, NO, Bcl-2, Bax, caspase-3 and ULK1in striatum.Conclusion: The superiorities of ELC against cerebral ischemia were in inhibiting oxidation and apoptosis and promoting autophagy, while those of BO were in improving microcirculation and autophagy and inhibiting apoptosis.Their combinative therapy brought some new mechanisms in treating brain ischemia.
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