Shumei Wang

Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction.

1H NMR-based metabonomic analysis of the effect of optimized rhubarb aglycone on the plasma and urine metabolic fingerprints of focal cerebral ischemia–reperfusion rats

ETHNOPHARMACOLOGICAL RELEVANCE The ischemia cerebrovascular disease is one of leading causes of death and long-term disability in modern society. Rhubarb is one of the common traditional Chinese medicine with many effects, and the main pharmacodynamic ingredients are aloe-emodin, rhein, emodin, chrysophanol and physcion. The five components are also known as rhubarb aglycone. Rhubarb aglycone has been confirmed to play a remarkable curative effect on cerebral ischemia, but the mechanism is not clear. In this study, (1)H NMR-based metabonomics approach has been used to investigate the protective effect of the optimized rhubarb aglycone on rats of cerebral ischemia-reperfusion. MATERIALS AND METHODS Male Wistar rats were divided into four groups: sham operation group, model group, Nimodipine group and the optimized rhubarb aglycone group. Based on (1)H-NMR spectra of plasma and urine, principal component analyses were performed to identify different metabolic markers and explore the changes of associated biochemical pathways. Behavior research and brain histopathology examinations were also performed. RESULTS It was showed that the optimized rhubarb aglycone treatment improved neurological deficits, cerebral infarction and neuronal apoptosis. Principal component analysis scores plots demonstrated that the cluster of model rats was separated from those of sham operation group; rats of the optimized rhubarb aglycone group were classified from model group, but the optimized rhubarb aglycone group closed to the sham operation group. Optimized rhubarb aglycone regulated the associated amino acid, energy and lipid metabolisms disturbed in model rats. CONCLUSION Our results suggested that the optimized rhubarb aglycone had protective effect on rats of cerebral ischemia-reperfusion and explored the metabolic regulation mechanism. This work showed that the NMR-based metabonomics approach might be a promising approach to study mechanisms of traditional Chinese medicines.

A support vector machine based pharmacodynamic prediction model for searching active fraction and ingredients of herbal medicine: Naodesheng prescription as an example

The complex chemical composition of herbal medicine leads to the lack of appropriate method for identifying active compounds and optimizing the formulation of herbal medicine. One of the most commonly used method is bioassay-guided fractionation. However, if the herbal medicine was divided into many fractions, it would cost much money and time in carrying out such a full bioassay. So, can we just perform the bioassay of a few fractions, and then develop a method to predict the bioactivities of other fractions? This study is designed to try to answer the question. In this work, a support vector machine (SVM) pharmacodynamic prediction model was introduced to search active fraction and ingredients of Naodesheng prescription. The prescription was first divided into five extracts, yielding a total of 2⁵=32 combinations. Anti-platelet aggregation experiment with SD rats was just carried out on 16 combinations. The effects of the remained 32-16=16 combinations were then predicted by the SVM model. The prediction quality was evaluated by both the rigorous jackknife test and the independent dataset validation test. Furthermore, the present method was compared with the frequently used MLR, PCR and PLSR. The present method outperforms the other 3 methods, yielding: RMSECV=2.40, R=0.895 by the jackknife test and RMSEP=7.41, R=0.910 by the independent dataset test. It indicates that the SVM prediction model has good accuracy and generalization ability. The active fraction and ingredients of Naodesheng prescription were then predicted by the model. It is believed that the present model can be extended to help search the active fraction and ingredients of other herbal medicines.

Plasma metabonomic analysis reveals the effects of salvianic acid on alleviating acute alcoholic liver damage

Acute alcoholic liver damage is a common illness and poses a potential health risk for humans presently. Salvianic acid (SA) has been found to be effective in liver protection. However, the mammalian systems responses to acute alcohol exposure and the underlying biochemical mechanism of SA treatment are not clear. In this study, we systematically analysed the acute alcohol-induced metabonomic changes and the therapeutic effect of SA by using a 1H NMR-based metabonomics approach together with histopathological and clinical biochemistry assessments. The rats in the treatment and model groups were gavaged with 5 g kg−1 BW edible alcohol once every 12 h three times to establish the acute alcoholic liver damage model. SA-treated rats were gavaged with 20 mg kg−1 SA for five days before alcohol administration. The model rats presented acute alcoholic injury with centrilobular inflammation and necrosis. SA treatment not only alleviated the hepatic damage but also promoted the recovery of liver function. We found that acute alcohol exposure induced significant elevation of lactate, glycerol, acetate, creatine and ketone bodies but reduction of glycine and TMAO/betaine. SA reversed the metabolic changes in multiple metabolic pathways, including anaerobic glycolysis, fatty acid oxidation, lipolysis, oxidative stress, creatinine and methylation metabolism. These findings provide an overview of the biochemical consequences of acute alcohol intake and new insights into the SA effects on acute alcoholic liver injury, demonstrating metabonomics as a powerful approach for examining the molecular mechanisms of Traditional Chinese Medicine.

Investigation into the anti-thrombosis effect and contents of total saponins and flavonoids in the bioactive fraction of Naodesheng prescription

ETHNOPHARMACOLOGICAL RELEVANCE Naodesheng prescription is a widely used traditional Chinese medicine (TCM), and mainly applied in clinics to treat cerebral arteriosclerosis, ischemic stroke, sequelae of cerebral hemorrhage etc. AIM OF THE STUDY The present study was designed to investigate the anti-thrombosis effects of this prescription, and to search its bioactive fraction. MATERIALS AND METHODS We evaluated the anti-thrombotic effects by measuring platelet aggregation in rats, and the clotting time and protection rate in mice. The contents of total saponins and flavonoids in the bioactive fraction were determined by UV-vis spectrophotometry. RESULTS The results showed that Naodesheng has significant anti-thrombotic and anticoagulation effects. The contents of total saponins and flavonoids in the bioactive fraction were 7.885% and 8.434%, respectively. CONCLUSIONS Such study will contribute to further exploration of Naodesheng in the therapy of thrombosis diseases and to its re-development based on the bioactive fraction and ingredients.

Multiple information contents derived from the chromatograms and their application to the modeling of quantitative profile-efficacy relationship.

Herbal medicine has been successfully applied in clinical therapeutics throughout the world. In this paper, various information contents in addition to a best-first search strategy are proposed for improving prediction quality of quantitative profile-efficacy relationship (QPER). As a demonstration, a QPER model was constructed to predict the blood-clotting time increasing effect of Naodesheng prescription, a widely used herbal medicine in China. Evaluated by both the self-consistency test and the rigorous jackknife test, the predictive accuracy was increased by feeding the model with the merged information contents compared to only with the common chromatographic peak areas. The confirmation experiment exhibited that the predicted blood-clotting time were well consistent with the observed values. Furthermore, it has not escaped from our notice that the important potential application of the current QPER model is to be extended to help search active fractions, which has attracted more and more attention in the re-developments of herbal medicines based on the active compounds.

(1)H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.

ETHNOPHARMACOLOGICAL RELEVANCE Stroke is a leading cause of death and disability in the world. However, current therapies are limited. Naodesheng, a widely used traditional Chinese medicine prescription, has shown a good clinical curative effect on ischemic stroke. Also, Naodesheng has been suggested to have neuroprotective effect on focal cerebral ischemia rats, but the underlying molecular mechanism remains unclear. AIM OF THE STUDY The present study was designed to evaluate the effect of Naodesheng bioactive extract on the metabolic changes in brain tissue, plasma and urine induced by cerebral ischemia perfusion injury, and explore the possible metabolic mechanisms by using a (1)H NMR-based metabonomics approach. MATERIALS AND METHODS A middle cerebral artery occlusion rat model was established and confirmed by the experiments of neurobehavioral abnormality evaluation, brain tissue TTC staining and pathological examination. The metabolic changes in brain tissue, plasma and urine were then assessed by a (1)H NMR technique combined with multivariate statistical analysis method. RESULTS These NMR data showed that cerebral ischemia reperfusion induced great metabolic disorders in brain tissue, plasma and urine metabolisms. However, Naodesheng bioactive extract could reverse most of the imbalanced metabolites. Meanwhile, it was found that both the medium and high dosages of Naodesheng bioactive extract were more effective on the metabolic changes than the low dosage, consistent with histopathological assessments. CONCLUSIONS These results revealed that Naodesheng had protective effect on ischemic stroke rats and the underlying mechanisms involved multiple metabolic pathways, including energy metabolism, amino acid metabolism, oxidative stress and inflammatory injury. The present study could provide evidence that metabonomics revealed its capacity to evaluate the holistic efficacy of traditional Chinese medicine and explore the underlying mechanisms.

The electrochemical behaviors of tetrahydropalmatine at a nickel nanoparticles/sulfonated graphene sheets modified glassy carbon electrode

A novel electrochemical sensor was designed to determine tetrahydropalmatine (THP) by using a nickel nanoparticles deposited on sulfonated graphene sheets-modified glassy carbon electrode (NiNPs/SGS/GCE). The components and morphological properties of the NiNPs/SGS nanocomposites were investigated by scanning electron microscopy. The anodic peak current (Ipa) of THP at the GCE modified with NiNPs/SGS was much higher than those at the bare GCE and SGS/GCE due to the enhanced effect of the modified nanomaterials. Differential pulse voltammetry (DPV) disclosed a good linear relationship between Ipa and concentrations of THP (0.50–20.0 μM), with a limit of detection of 0.17 μM. Finally, the modified electrode was successfully applied for the determination of THP in Yuanhu Zhitong capsules.

Study on material base and action mechanism of compound Danshen dripping pills for treatment of atherosclerosis based on modularity analysis.

ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine (TCM) has been widely used in China and its surrounding countries in clinical treatments for centuries-long time. However, due to the complexity of TCM constituents, both action mechanism and material base of TCM remain nearly unknown. AIM OF THE STUDY The present study was designed to uncover the action mechanism and material base of TCM in a low-cost manner. MATERIALS AND METHODS Compound Danshen dripping pills (DSP) is a widely used TCM for treatment of atherosclerosis, and was researched here to demonstrate the effectiveness of our method. We constructed a heterogeneous network for DSP, identified the significant network module, and analyzed the primary pharmacological units by performing GO and pathways enrichment analysis. RESULTS Two significant network modules were identified from the heterogeneous network of DSP, and three compounds out of four hub nodes in the network were found to intervene in the process of atherosclerosis. Moreover, 13 out of 20 enriched pathways that were ranked in top 10 corresponding to both the two pharmacological units were found to be involved in the process of atherosclerosis. CONCLUSIONS Quercetin, luteolin and apigenin may be the main active compounds which modulate the signaling pathways, such as metabolism of xenobiotics by cytochrome P450, retinol metabolism, etc. The present method helps reveal the action mechanism and material base of DSP for treatment of atherosclerosis.

Simultaneous measurement of contents of liquirtin and glycyrrhizic acid in liquorice based on near infrared spectroscopy

OBJECTIVE To establish calibration models for simultaneous determination of contents of liquirtin and glycyrrhizic acid, and to investigate the variable selection methods. METHODS The contents of liquirtin and glycyrrhizic acid determined by HPLC were as the reference values, which were associated with samples spectra by using near infrared spectrum (NIR) analysis technology. Calibration models were developed using partial least squares (PLS) regression algorithm, and evaluated by the independent dataset test with calculating the metrics of coefficients of determination of calibration and prediction (R2c, R2p), the root mean square errors of calibration and prediction (RMSEC, RMSEP), the mean absolute errors of calibration and prediction (MAEC, MAEP), and the residual prediction deviation (RPD). Five variable selection methods including variable importance in projection (VIP), competitive adaptive reweighted sampling (CARS), Monte Carlo uninformative variable elimination (MCUVE), particle swarm optimization (PSO) and genetic algorithm (GA), were investigated. RESULTS Compared to the original full spectra, both quantification models for liquirtin and glycyrrhizic acid performed better with a clear ranking of GA>PSO>CARS>MCUVE≅VIP>Full. Especially for GA-PLS models, RMSEC and RMSEP were <0.05%, R2c and R2p were >0.94, and RPD were both >4, indicating that both the models had good robustness and excellent prediction accuracy. CONCLUSION The present calibration models can be utilized to simultaneously determine the contents of liquirtin and glycyrrhizic acid in liquorice samples, and thus are of great help for rapid quality evaluation and control of liquorice.