Chronic heart failure (CHF) is characterized by insufficient blood supply from heart to meet the body's metabolic demands. Integrating Western and traditional Chinese medicine to treat CHF has proved a validated therapeutic approach. In recent years, metabolomics has been regarded as a potential platform to provide biomarkers for disease-subtypes. To examine 38 patients, combined NMR plasma metabolomics and traditional Chinese medicine diagnosis in order to identify diagnostic biomarkers for two CHF syndrome subtypes. After processing the spectra, orthogonal partial least square discriminant analysis was performed, and the contributing NMR signals were analyzed using Y-scrambling statistical validation with good reliability. Plasma metabolic patterns of yin deficiency and yang deficiency patients were clearly discriminated. The yin-deficiency group had increased level of lactate, glycoprotein, lipoprotein and lower levels of glucose, valine and proline. The yang-deficiency group had higher levels of lactate, glycoprotein and pyruvic acid, and lower levels of glucose and lipoprotein. Potential biomarkers of CHF based on the two traditional Chinese medicine syndromes indicated alternative modes of metabolites and metabolic pathways in the disease, e.g. dysfunction of energy utilization and disturbance in fatty acids, amino acids. This study suggests that combining metabolomics with traditional Chinese medicine diagnosis can reveal metabolic signatures for CHF syndrome subtypes. The plasma metabolites identified might be of special clinical relevance for subtypes of CHF, which could lead to further understanding of mechanisms involved and an improvement in personalized treatment for CHF.
Abstract One of the most difficult problems that hinder the development and application of herbal medicine is how to illuminate the global effects of herbs on the human body. Currently, the chemo-centric network pharmacology methodology regards herbs as a mixture of chemical ingredients and constructs the ‘herb-compound-target-disease’ connections based on bioinformatics methods, to explore the pharmacological effects of herbal medicine. However, this approach is severely affected by the complexity of the herbal composition. Alternatively, gene-expression profiles induced by herbal treatment reflect the overall biological effects of herbs and are suitable for studying the global effects of herbal medicine. Here, we develop an online transcriptome-based multi-scale network pharmacology platform (TMNP) for exploring the global effects of herbal medicine. Firstly, we build specific functional gene signatures for different biological scales from molecular to higher tissue levels. Then, specific algorithms are designed to measure the correlations of transcriptional profiles and types of gene signatures. Finally, TMNP uses pharmacotranscriptomics of herbal medicine as input and builds associations between herbs and different biological scales to explore the multi-scale effects of herb medicine. We applied TMNP to a single herb Astragalus membranaceus and Xuesaitong injection to demonstrate the power to reveal the multi-scale effects of herbal medicine. TMNP integrating herbal medicine and multiple biological scales into the same framework, will greatly extend the conventional network pharmacology model centering on the chemical components, and provide a window for systematically observing the complex interactions between herbal medicine and the human body. TMNP is available at http://www.bcxnfz.top/TMNP.
Traditional Chinese medicine (TCM) not only maintains the health of Asian people but also provides a great resource of active natural products for modern drug development. Herein, we developed a Database of Constituents Absorbed into the Blood and Metabolites of TCM (DCABM-TCM), the first database systematically collecting blood constituents of TCM prescriptions and herbs, including prototypes and metabolites experimentally detected in the blood, together with the corresponding detailed detection conditions through manual literature mining. The DCABM-TCM has collected 1816 blood constituents with chemical structures of 192 prescriptions and 194 herbs and integrated their related annotations, including physicochemical, absorption, distribution, metabolism, excretion, and toxicity properties, and associated targets, pathways, and diseases. Furthermore, the DCABM-TCM supported two blood constituent-based analysis functions, the network pharmacology analysis for TCM molecular mechanism elucidation, and the target/pathway/disease-based screening of candidate blood constituents, herbs, or prescriptions for TCM-based drug discovery. The DCABM-TCM is freely accessible at http://bionet.ncpsb.org.cn/dcabm-tcm/. The DCABM-TCM will contribute to the elucidation of effective constituents and molecular mechanism of TCMs and the discovery of TCM-derived drug-like compounds that are both bioactive and bioavailable.
To explore the onset cycle of scarlet fever in Beijing and its association with theory of five evolutive phases and six climatic factors (FEPSCF).Based on the monthly scarlet fever data from 1970 to 2004, Complex Morlet wavelet was adopted to analyze the annual incidence and the incidence of six climatic factors in the past 35 years. Its association with the cycles of FEP-SCF was explored. The features of heavenly stems and earthly branches in the year that the wave peak corresponded and their correlations with doctrine of FEPSCF were analyzed.The annual incidence of scarlet fever and the incidence of FEPSCF had two main cycles, i.e., 5 years and 28 years. The 5-year primary cycle was consistent with 5-year cycle of FEPSCF theory. The high incidence year of 5-year primary cycle was Jinyun.The cycle of five evolutive phases was consistent with the onset cycle of scarlet fever. The quasi-periodic phenomenon and multi-cycle superimposed phenomenon of FEPSCF theory existed in the incidence of scarlet fever.
Abstract Background Chronic heart failure (CHF) is characterized by insufficient blood supply from heart to meet the body's metabolic demands. Integrating Western and traditional Chinese medicine to treat CHF has proved a validated therapeutic approach. In recent years, metabolomics has been regarded as a potential platform to provide biomarkers for disease-subtypes. Objective To examine 38 patients, combined NMR plasma metabolomics and traditional Chinese medicine diagnosis in order to identify diagnostic biomarkers for two CHF syndrome subtypes. Methods After processing the spectra, orthogonal partial least square discriminant analysis was performed, and the contributing NMR signals were analyzed using Y-scrambling statistical validation with good reliability. Results Plasma metabolic patterns of yin deficiency and yang deficiency patients were clearly discriminated. The yin-deficiency group had increased level of lactate, glycoprotein, lipoprotein and lower levels of glucose, valine and proline. The yang-deficiency group had higher levels of lactate, glycoprotein and pyruvic acid, and lower levels of glucose and lipoprotein. Potential biomarkers of CHF based on the two traditional Chinese medicine syndromes indicated alternative modes of metabolites and metabolic pathways in the disease, e.g. dysfunction of energy utilization and disturbance in fatty acids, amino acids. Conclusion This study suggests that combining metabolomics with traditional Chinese medicine diagnosis can reveal metabolic signatures for CHF syndrome subtypes. The plasma metabolites identified might be of special clinical relevance for subtypes of CHF, which could lead to further understanding of mechanisms involved and an improvement in personalized treatment for CHF.
Objective: Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs. Materials and Methods: First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula. Results: The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales. Conclusions: Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.
Longshengzhi capsule (LSZC) is an optimized preparation based on the traditional Chinese Medicine formula Buyanghuanwu Decoction (BYHWD), and is approved by the China Food and Drug Administration for treating stroke-induced disability and vascular diseases. Herein, we examined the pharmacodynamics, anti-apoptotic and anti-oxidant actions, and potential mechanisms of action of LSZC following stroke in rats. Permanent middle cerebral artery occlusion (MCAO) was used as an ischemic stroke model. LSZC was administered intragastrically. We examined the survival rate, bodyweight, and neurological deficits in stroke rats. Brain infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Brain pathology was examined using hematoxylin and eosin staining, Nissl staining, and TdT-mediated dUTP Nick-End Labeling staining. Malondialdehyde, catalase, superoxide dismutase, and glutathione levels were examined by commercial kits. Expression of Nrf2, heme oxygenase-1, Bax, Bcl-2, cleaved caspase-3, and caspase-3 proteins in brain tissue was measured by Western blot. LSZC markedly improved the survival rate and bodyweight, and reduced infarct volume and neurological deficit scores, in MCAO stroke rats. LSZC also significantly attenuated oxidative stress, as indicated by decreased expression of malondialdehyde, and upregulation of Nrf2, heme oxygenase-1, catalase, superoxide dismutase, and glutathione. Moreover, LSZC significantly decreased apoptosis, including a decrease in Bax and cleaved caspase-3 expression, and an increase in Bcl-2, as well as a reduction in numbers of apoptotic neurons. LSZC treatment is neuroprotective against ischemic stroke, potentially via reducing oxidative stress and apoptosis. The Nrf2 and apoptotic signaling pathways may play important roles in the antioxidant and anti-apoptotic actions of LSZC.
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