Comparative pharmacokinetic study of nine bioactive components in osteoarthritis rat plasma using ultra-performance liquid chromatography–tandem mass spectrometry after single and combined oral administration of Epimedii Folium and Chuanxiong Rhizoma extracts

The herb pair Epimedii Folium–Chuanxiong Rhizoma (EF–CR), derived from the classical traditional Chinese medicine ‘Xian Ling Pi San’, has a distinctive compatibility therapeutic profile and is clinically safe and effective. This study aimed to investigate and compare the pharmacokinetic characteristics of nine analytes in osteoarthritis (OA) rat plasma after the oral administration of EF, CR or a combination of these two herbs. We developed an ultra-performance liquid chromatography method coupled with quadrupole linear ion-trap mass spectrometry to simultaneously quantify and assess the pharmacokinetics of icariin, epimedin A, epimedin B, epimedin C, icariside I, icariside II, ferulic acid, ligustilide and senkyunolide A of the EF–CR pair in the plasma of osteoarthritic rats. The pharmacokinetic parameters showed that the absorption of multiple components was significantly enhanced and residence time was prolonged in the EF–CR group (P < 0.05) compared to the single-herb group. These parameters revealed that the combination of EF and CR exhibited synergistic effects of the nine bioactive components, suggesting the potential application of the EF–CR combination for the treatment of OA.     

Authentication of Cyathulae Radix and Cyathulae Capitatae Radix based on the strength of the characteristic component achybidensaponin I

Because of the immense difficulty in identifying Cyathulae Capitatae Radix adulteration in Cyathulae Radix, this research aims at fortifying the quality control of Cyathulae Radix and its decoction pieces to guarantee the effectiveness and safety of its clinical use in terms of source material. A method was devised to identify Cyathulae Capitatae Radix adulteration in Cyathulae Radix and its decoction pieces. This research takes achybidensaponin I, that is, the characteristic component of Cyathulae Capitatae Radix, as reference substance and adopts HPLC for detection. The results revealed that, among all samples collected, no trace of achybidensaponin I was found in the 21 batches of Cyathulae Radix, whereas achybidensaponin I was found in all the 14 batches of Cyathulae Capitatae Radix. The research sets 5% as the adulteration limit, that is, 1.45 mg/g Cyathulae Capitatae Radix was detected in 57.14% of the 49 batches of market samples collected and the ratio was 51.02% in the case of 5% adulteration limit. The method is not only precise and reliable but can also be used as a supplement for provisions regarding quality control of Cyathulae Radix and its decoction pieces in Pharmacopoeia of the People's Republic of China, to effectively crack down on Cyathulae Capitatae Radix adulteration in the market.     

Kinetic features of Gualou-Xiebai-Banxia decoction,a classical traditional Chinese medicine formula,in rat plasma and intestine content based on its metabolic profile

Gualou-Xiebai-Banxia decoction (GXB) is a famous classical traditional Chinese medicine (TCM) formula for the treatment of coronary heart disease (CHD, namely chest stuffiness and pain syndrome in Chinese medicine). Compared with Gualou-Xiebai-Baijiu decoction, which only consists of Trichosanthis Pericarpium (TP), Allii Macrostemonis Bulbus (AMB) and wine, GXB comprises one additional herbal medicine, Pinellinae Rhizoma Praeparatum (PRP). However, due to a lack of kinetic profile studies on GXB, its in vivo components with high exposure remain unknown, making it difficult to interpret bioactive components likely linked to its efficacy, but also fails to provide substance-related evidence for reflecting the compatibility in GXB. The goal of this study was to systematically characterize the kinetic features of GXB in rat plasma and intestine content for revealing its in vivo high-exposure components on the basis of their metabolic fates, and to compare the kinetic differences between GXB and GXB-dePRP (GXB deducted PRP) for describing the chemical contribution of PRP to the compatibility in GXB. Firstly, the metabolic profile of GXB was systematically investigated by UPLC-Q/TOF-MS. Subsequently, quantitative methods for representative xenobiotics in rat plasma and intestine content were respectively validated and developed by UPLC-TQ-MS. Then, the established approaches were successfully applied to characterize the kinetic features of GXB through estimating pharmacokinetic parameters. These results showed that only a few kinds of xenobiotics at low exposure levels were observed in plasma, while various xenobiotics possessed high exposure in intestine content. Among them, steroidal saponins and triterpenoid saponins displayed relatively high exposure in plasma and intestine content, which are likely associated with the therapeutic effects of GXB. Moreover, there were no significant differences between metabolic profiles of GXB and GXB-dePRP, whereas the pharmacokinetic parameters, including area under the concentration–time curve (AUC) and C_max (p < 0.05) for most xenobiotics in GXB were significantly larger than those in GXB-dePRP, implying that the introduction of PRP improved the bioavailability of constituents from TP and AMB. Altogether, this study laid a solid foundation and provided theoretical guidance for further clarification of bioactive components of GXB, as well as the synergistic effect of PRP to the compatibility in GXB.