Molecular evidence of herbal formula: a network-based analysis of Si-Wu decoction.

INTRODUCTION: Emerging network pharmacology (NP) combines phytochemical information with bioinformatics tools allowing herbal formulae to be illustrated holistically in the context of phytochemical basis and therapeutic mechanisms. OBJECTIVE: This study attempted to explore the holistic molecular evidence of herbal formula Si-Wu decoction (SWD) by using the method of NP. MATERIAL AND METHOD: Databases of traditional medicines combined with PubChem, SciFinder, SEA, STRING, and KEGG were employed to gather information for establishing the "compound similarity" (CS) network and the "target-(pathway)-target" (TPT) network. Gephi software was applied to visualise the networks, with further module-based and node-based network topological analysis. Moreover, the approved drugs and shortest path analysis were used to validate the TPT network. RESULTS: The CS network presented the phytochemical profile of SWD, including the major compound groups of iridoid glycosides, glycosides, phthalide lactones, phenylpropanoids, and monoterpenoids. Furthermore, the topological analysis of TPT network depicted the holistic property of SWD in interpretable neuroendocrine immunomodulation (NIM) perspective, and the node degree analysis indicated a closer connection of SWD with endocrine or metabolism system. Moreover, by combing the analysis of the CS network and TPT network, potential active ingredients could be primarily identified. CONCLUSION: The phytochemical profile and molecular target profile, which might pave the way for an understanding of SWD in modern science and provide a reference for relevant quality research and evaluation, were demonstrated by network analysis. Moreover, the methods could be further applied to discover the phytochemical or biomolecular evidence with distinct advantages in dealing with the tremendous separated information.

Knowledge-Based Neuroendocrine Immunomodulation (NIM) Molecular Network Construction and Its Application.

Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling molecules based on our knowledge and obtained 611 NIM signaling molecules. Then, we built a NIM molecular network based on the MetaCore database and analyzed the signaling transduction characteristics of the core network. We found that the endocrine system played a pivotal role in the bridge between the nervous and immune systems and the signaling transduction between the three systems was not homogeneous. Finally, employing the forest algorithm, we identified the molecular hub playing an important role in the pathogenesis of rheumatoid arthritis (RA) and Alzheimer's disease (AD), based on the NIM molecular network constructed by us. The results showed that GSK3B, SMARCA4, PSMD7, HNF4A, PGR, RXRA, and ESRRA might be the key molecules for RA, while RARA, STAT3, STAT1, and PSMD14 might be the key molecules for AD. The molecular hub may be a potentially druggable target for these two complex diseases based on the literature. This study suggests that the NIM molecular network in this paper combined with the forest algorithm might provide a useful tool for predicting drug targets and understanding the pathogenesis of diseases. Therefore, the NIM molecular network and the corresponding online tool will not only enhance research on complex diseases and system biology, but also promote the communication of valuable clinical experience between modern medicine and Traditional Chinese Medicine (TCM).

LW-AFC, a new formula from the traditional Chinese medicine Liuwei Dihuang decoction, as a promising therapy for Alzheimer's disease: Pharmacological effects and mechanisms.

LW-AFC is a new formula derived from the Liuwei Dihuang decoction, a classical traditional Chinese medicine prescription. Based on our research, LW-AFC is a promising drug for Alzheimer's disease (AD). The studies were conducted primarily in two typical AD mouse models: SAMP8 and APP/PS1 mice. The results showed that LW-AFC could improve many cognitive behaviors, such as spatial learning and memory ability, passive and active avoidance response, and object recognition memory capability. In addition, LW-AFC could also alleviate the AD-like pathology in animal models, such as neuron loss and Aß deposition. Subsequent studies found that LW-AFC could rebalance hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis, and modulate the disturbance of immune system and gut flora. These data suggested that the anti-AD effects of LW-AFC might be mainly via modulating the neuroendocrine immunomodulation (NIM) network. As inhibiting the immune function by immunosuppressant could abolish the protective effects of LW-AFC against long-term potentiation (LTP) impairment model, it is likely that LW-AFC balancing the NIM network is initiated by modulating the immune system.

Effect of Liuwei Dihuang decoction, a traditional Chinese medicinal prescription, on the neuroendocrine immunomodulation network.

Liuwei Dihuang decoction (LW) has been used in traditional Chinese medicine (TCM) for more than 900years to prevent and treat various diseases with characteristic features of kidney yin deficiency. To date, LW has been commonly prescribed in TCM as therapy or adjuvant therapy against various diseases. To elucidate the pharmacological characteristics and mechanism of action of this formula, studies have been conducted on the pharmacological effects and chemical profiles (including bioactive ingredients) to investigate the role of LW in the neuroendocrine immunomodulation (NIM) network. In this review, we provide an overview of the pharmacological effects of LW on the NIM network, particularly on learning and memory, immunomodulation, and neuroendocrine-immune interactions, including the effects of LW on the central nervous system, endocrine system, and immune system. We also discuss advances in related chemical studies, especially those identifying the bioactive components of LW and their unique combinational effects on the immune system. Our experimental results indicate that LW exerts a broad spectrum of pharmacological effects, by modulating and restoring the balance of the NIM network disturbed by several pathological factors.

Neuroendocrine immunomodulation network dysfunction in SAMP8 mice and PrP-hAßPPswe/PS1ΔE9 mice: potential mechanism underlying cognitive impairment.

Senescence-accelerated mouse prone 8 strain (SAMP8) and PrP-hAßPPswe/PS1ΔE9 (APP/PS1) mice are classic animal models of sporadic Alzheimer's disease and familial AD respectively. Our study showed that object recognition memory, spatial learning and memory, active and passive avoidance were deteriorated and neuroendocrine immunomodulation (NIM) network was imbalance in SAMP8 and APP/PS1 mice. SAMP8 and APP/PS1 mice had their own specific phenotype of cognition, neuroendocrine, immune and NIM molecular network. The endocrine hormone corticosterone, luteinizing hormone and follicle-stimulating hormone, chemotactic factor monocyte chemotactic protein-1, macrophage inflammatory protein-1ß, regulated upon activation normal T cell expressed and secreted factor and eotaxin, pro-inflammatory factor interleukin-23, and the Th1 cell acting as cell immunity accounted for cognitive deficiencies in SAMP8 mice, while adrenocorticotropic hormone and gonadotropin-releasing hormone, colony stimulating factor granulocyte colony stimulating factor, and Th2 cell acting as humoral immunity in APP/PS1 mice. On the pathway level, chemokine signaling and T cell receptor signaling pathway played the key role in cognition impairments of two models, while cytokine-cytokine receptor interaction and natural killer cell mediated cytotoxicity were more important in cognitive deterioration of SAMP8 mice than APP/PS1 mice. This mechanisms of NIM network underlying cognitive impairment is significant for further understanding the pathogenesis of AD and can provide useful information for development of AD therapeutic drug.