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The concrete implementation process of systems pharmacology approach in treating psychiatric disorder with LJF (Lonicerae Japonicae Flos) is described as follows: firstly, the active ingredients of LJF were screened out by an in silico ADME system, and secondly, of those with satisfactory pharmacokinetic properties were used as baits to fish their biological targets. Thirdly, the obtained targets contribute to psychiatric disease were then mapped to relational databases to identify their corresponding pathways, followed by network analysis to elucidate the psychopharmacological mechanisms of LJF. Finally, combined application of systems pharmacology with the RNA-seq technique, we explored the pathophysiological mechanisms induced by chronic mild stress in rats, and demonstrated our prediction about psychotherapeutic effects of LJF and its active ingredient in treatment of depressive/anxiety-like behavior. • Systems pharmacology revealed psychotherapeutic properties of LJF (Lonicerae Japonicae Flos). • LJF treatment can reversed depressive/anxiety-like behavior in CMS (chronic mild stress) rats. • LJF treatment can globally restored abnormal gene expression changes in the striatum of CMS rats. • Psychotherapeutic effects of LJF were mediated by the HTR2A/PLCγ/ERK/CREB pathway. Psychiatric disorders have become the biggest cause of non-fatal health burden and are the major contributor to suicide worldwide. The currently limitations of standard psychotherapy lead to an increasing attention in complementary and alternative therapies, in particular the traditional herbal medicine. Lonicerae Japonicae Flos (LJF) is one of the most consumed herbal tea beverages for medical purposes. LJF contains flavonoids and phenolic acid as the major constituents, hence the anti-inflammatory and anti-oxidative properties reported earlier. Nevertheless, the neuro-pharmacological properties of LJF are largely unknown. In this study, combined systems pharmacology strategy and RNA-Seq technology, we uncovered psychotherapeutic effects of LJF. In brief, LJF and its active ingredient luteolin can reversed depressive/anxiety-like behavior in rats exposed to chronic mild stress (CMS), restored abnormal gene expression changes and neurotransmission in the striatum of CMS rats, these effects were mediated through triggering the activation of the HTR2A/PLCγ/ERK/CREB pathway. [ABSTRACT FROM AUTHOR]

Chronic hepatitis is a general designation class of diseases, which results in different degrees of liver necrosis and inflammatory reaction, followed by liver fibrosis, may eventually develop into cirrhosis. However, the molecular pathogenesis of chronic hepatitis is too complex to elucidate. Herbal medicines, featured with multiple targets and compounds, have long displayed therapeutic effect in treating chronic hepatitis, though their molecular mechanisms of contribution remain indistinct. This research utilized the network pharmacology to confirm the molecular pathogenesis of chronic hepatitis through providing a comprehensive analysis of active chemicals, drug targets and pathways’ interaction of Sinisan formula for treating chronic hepatitis. The outcomes showed that 80 active ingredients of Sinisan formula interacting with 91 therapeutic proteins were authenticated. Sinisan formula potentially participates in immune modulation, anti-inflammatory and antiviral activities, even has regulating effects on lipid metabolism. These mechanisms directly or indirectly are involved in curing chronic hepatitis by an interaction way. The network pharmacology based analysis demonstrated that Sinisan has multi-scale curative activity in regulating chronic hepatitis related biological processes, which provides a new potential way for modern medicine in the treatment of chronic diseases. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Vitiligo is a depigmentation disorder, which results in substantial cosmetic disfigurement and poses a detriment to patients' physical as well as mental. Now the molecular pathogenesis of vitiligo still remains unclear, which leads to a daunting challenge for vitiligo therapy in modern medicine. Herbal medicines, characterized by multi-compound and multi-target, have long been shown effective in treating vitiligo, but their molecular mechanisms of action also remain ambiguous. Materials and methods Here we proposed a systems pharmacology approach using a clinically effective herb formula as a tool to detect the molecular pathogenesis of vitiligo. This study provided an integrative analysis of active chemicals, drug targets and interacting pathways of the Uygur medicine Qubaibabuqi formula for curing Vitiligo. Results The results show that 56 active ingredients of Qubaibabuqi interacting with 83 therapeutic proteins were identified. And Qubaibabuqi probably participate in immunomodulation, neuromodulation and keratinocytes apoptosis inhibition in treatment of vitiligo by a synergistic/cooperative way. Conclusions The drug-target network-based analysis and pathway-based analysis can provide a new approach for understanding the pathogenesis of vitiligo and uncovering the molecular mechanisms of Qubaibabuqi, which will also facilitate the application of traditional Chinese herbs in modern medicine. [ABSTRACT FROM AUTHOR]

[Display omitted] Quinolizidine alkaloids, as essential active ingredients extracted from Sophora alopecuroides Linn (SAL), have been proven to be pharmacologically active in a variety of cancers including non-small cell lung cancer (NSCLC). However, whether these alkaloids have substantial benefits in combination with immune checkpoint blockade (ICB) for the treatment of NSCLC is unknown. Here, we explore the potential of these alkaloids in combination with ICB therapy based on a systems pharmacology and bioinformatics approach. We found that 37 alkaloids in SAL have highly similar characteristics in the molecular skeleton, pharmacological properties, and targets. The expression of targets of these alkaloids are significantly correlated with the infiltration level of tumor infiltrating lymphocytes and the expression levels of multiple immune checkpoints in NSCLC. They share similar molecular mechanisms in antitumor immunity. Sophocarpine (Sop) is one of the most representative constituents of these alkaloids. We demonstrated that the Sop promotes PD-L1 expression to improve the effects of PD-L1 blockade treatment via the ADORA1-ATF3 axis. In conclusion, our study identified these alkaloids as promising candidates for the treatment of NSCLC, either alone or in combination with ICB, with potential value for drug development and may provide a promising strategy for improving the survival of NSCLC patients. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy (CH) is an incurable heart disease, contributing to an increased risk of heart failure due to the lack of safe and effective strategies. Therefore, searching for new approaches to treat CH is urgent. Centella asiatica (L.) Urb. (CA), a traditional food and medicinal natural plant, has been turned out to be effective in the treatment of cardiovascular disease, but its efficacy and potential mechanisms in alleviating CH have not yet been investigated. In this study, we aimed to elucidate the multi-level mechanisms underlying the effect of CA against CH. A systems pharmacology approach was employed to screen active ingredients, identify potential targets, construct visual networks and systematically investigate the pathways and mechanisms of CA for CH treatment. The cardiac therapeutic potential and mechanism of action of CA on CH were verified with in vivo and in vitro experiments. Firstly, we demonstrated the therapeutic effect of CA on CH and then screened 13 active compounds of CA according to the pharmacokinetic properties. Then, asiatic acid (AA) was identified as the major active molecule of CA for CH treatment. Afterwards, network and functional enrichment analyses showed that CA exerted cardioprotective effects by modulating multiple pathways mainly involved in anti-apoptotic, antioxidant and anti-inflammatory processes. Finally, in vivo, the therapeutic effects of AA and its action on the YAP/PI3K/AKT axis and NF-κB signaling pathway were validated using an isoproterenol-induced CH mouse model. In vitro, AA decreased ROS levels in hydrogen peroxide-treated HL-1 cells. Overall, the multi-level mechanisms of CA for CH treatment were demonstrated by systems pharmacology approach, which provides a paradigm for systematically deciphering the mechanisms of action of natural plants in the treatment of diseases and offers a new idea for the development of medicinal and food products. [Display omitted] • The multi-level mechanisms of Centella asiatica (L.) Urb. against cardiac hypertrophy was proposed. • A systems pharmacology approach was employed to reveal molecular mechanisms. • Centella asiatica (L.) Urb. exerted cardioprotective effects by modulating multiple processes. • The therapeutic effects and mechanisms were validated with in vivo and in vitro experiments. [ABSTRACT FROM AUTHOR]

Cardiomyopathy is a common cause of heart failure and may lead to increased risk of sudden cardiac death, lacking simple, safe and effective treatment strategies due to unclear pathogenesis. Ginkgo biloba L. leaves (GBLs), a traditional Chinese medicine (TCM), has been widely used in clinical medicine for improving blood circulation, and was demonstrated to be effective on cardiomyopathy in preclinical studies. However, because of the widely known holistic therapeutic philosophy via multi-target and multi-pathway effect for most TCMs, to explore its underlying molecular mechanisms of action (MoA) remains a great challenge. Decipher the underlying MoA of GBLs for cardiomyopathy treatment: Study design and methods: An integrated systems pharmacology framework was employed to screen potential active compounds, identify therapeutic targets, explore the action pathways and verify mechanisms of GBLs with in vitro experiments. We firstly confirmed the therapeutic effect of GBLs on cardiomyopathy and subsequently screened 27 active compounds from GBLs according to their pharmacokinetic properties. Then Probability Ensemble Approach was applied to identify the compound combinations that exert synergetic effect from GBLs. Network analysis and functional enrichment analysis demonstrated that these compounds exhibit synergistic therapeutic effect by acting on multiple targets and thereby regulating multiple pathways mainly involved in pro-survival, anti-apoptotic and anti-inflammatory processes. Finally, using a doxorubicin-induced myocardial injury model, therapeutic effect of ginkgolide A, ginkgolide B, isorhamnetin, as well as their synergistic effect on PI3K-AKT and NF-κB signaling pathways were validated in vitro. Importantly, we demonstrated that Ginkgo diterpene lactone meglumine injection (GDJ), an approved injection derived from GBLs, could be a promising agent for cardiomyopathy treatment. Collectively, the multi-level synergetic mechanism of GBLs on cardiomyopathy treatment was demonstrated with systems pharmacology approach, providing a paradigm for deciphering the complicated MoA of TCMs. Image 1 [ABSTRACT FROM AUTHOR]