Identification of interactions between multiple components in Socheongryong‐tang using a plant profiling approach

Abstract

Traditional herbal medicine consists of multiple components. There are interactions among the components, which affect both potency and toxicity. The preparation of herbal medicines can be a cause of interactions between multicomponents in herbs.To demonstrate the differences in multiherb interactions based on the preparation methods, the changes in the active components in the different preparations of Socheongryong-tang (SCRT) were evaluated using metabolomics profiling. We performed multicomponent profiling of the decoction of SCRT (SCRTD) and individual herb mixture (SCRTM) using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Active compounds from SCRTD and SCRTM were identified using multivariate analysis, and the activities between the two groups were compared. We also evaluated the antiinflammatory effect of SCRT through investigating the protein expression of iNOS and COX-2 in lipopolysaccharide-induced macrophage RAW 264.7 cells in both groups. From the multivariate analysis, 53 active compounds that have different intensities between SCRTD and SCRTM were identified. The intensities of those components, such as ephedrines, glycyrrhizic acid, 6-gingerol and (2E,4E,8Z,10E)-Nisobutyl-2,4,8,10-dodecatetraenamide, which is newly identified in Asiasarum heterotropoides, were mostly higher in SCRTD than in SCRTM, which was related to the anti-inflammatory effect. From the iNOS inhibition test, it was found that SCRTD had a stronger anti-inflammatory effect than SCRTM. It was demonstrated that multicomponent interactions can be changed by the preparation method, and finally the anti-inflammatory effect in SCRT can be affected. KEYWORDS multicomponent interactions, plant profiling approach, Socheongryong-tang, UPLC-QTOF-MS Abbreviations: AP-1, activator protein-1; GC, gas chromatography; IRF-3, interferon regulatory factor-3; LC, lipid chromatography; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MyD88, myeloid differentiation factor 88; NF-κB, activation of nuclear factor-kappa B; PCA, principal component analysis; PLS-DA, partial least square discriminant analysis; QTOF, ultra-high performance liquid chromatography quadrupole time-of-flight; SCRT, Socheongryong-tang; SCRT_PM, mixture of original plants; SCRTD, decoction of Socheongryong-tang; SCRTM, individual herb mixture of Socheongryong-tang; SHXXT, San-Huang-Xie-Xin-Tang; STAT1, single transducers and activators of transcription 1; TRIF, toll-interleukin-1R domain-containing adapter inducing interferon-β

Pharmacokinetic Changes According to Single or Multiple Oral Administrations of Socheongryong-Tang to Rats: Presented as a Typical Example of Changes in the Pharmacokinetics Following Multiple Exposures to Herbal Medicines

“…Socheongryong-tang (SCRT), a remedy for respiratory diseases well-known in Korea, Japan, and China, consists of eight herbal medicines: Ephedrae Herba, Paeoniae Radix, Asari Herba, Zingiberis Rhizoma, Glycyrrhizae Radix, Cinnamoni Ramulus, Pinelliae Rhizoma, and Schisandrae Fructus [1]. SCRT, also known as Sho-Seiryu-to or Xiao-Qing-Long-tang, has been used to treat respiratory diseases such as colds, allergic rhinitis, and bronchial asthma for several centuries in Asian countries [2][3][4].…”

“…The main pharmacologically active ingredients of SCRT are ephedrine, paeoniflorin, and cinnamic acid [7,9]. Although, as described above, SCRT is composed of 8 kinds of herbal medicines, so there may be various components in SCRT as follows: Ephedrine (for Ephedrae Herba), cinnamic acid (for Cinnamoni Ramulus), gingerol (for Zingiberis Rhizoma), methyl eugenol (for Asari Herba), schizandrin (for Schisandrae Fructus), paeoniflorin (for Paeoniae Radix), sitosterol (for Pinelliae Rhizoma), and glycyrrhizin (for Glycyrrhizae Radix) [1]. Nevertheless, the reasons why ephedrine, paeoniflorin, and cinnamic acid were selected as target substances for the pharmacokinetic study of SCRT in this study were as follows: In the content analysis results of the SCRT tablets used in this study, the major contents were ephedrine, paeoniflorin, and cinnamic acid; in addition, access to information on ephedrine, paeoniflorin, and cinnamic acid was most realistically possible in accessing the dose information for each component, which is one of the most important information in pharmacokinetic analysis.…”

“…As mentioned, the efficacies of SCRT and its individual components are well known, but pharmacokinetic studies on SCRT are still very scarce. Although SCRT has been used for a long time and is listed in the herbal medicine standard book [1,7], it is an herbal medicine that has been recognized empirically. However, its safety and effectiveness have not been adequately verified scientifically, like other herbal medicines.…”