Systems pharmacology uncovers serotonergic pathway mediated psychotherapeutic effects of Lonicerae Japonicae Flos

Abstract 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.