Integrated pharmacokinetics of ginsenosides after intravenous administration of YiQiFuMai powder injection in rats with chronic heart failure by UFLC-MS/MS.

YiQiFuMai powder injection (YQFM), derived from the classical traditional Chinese medicine (TCM) formula Shengmai San, is a modern preparation widely used to combat cardiovascular diseases, chronic heart failure (CHF) for example, in clinical practice in China. Ginsenosides are the major components of YQFM, which are responsible for its therapeutic effect. In this research, we developed a rapid, sensitive and simple method for simultaneous determination of ten ginsenosides from YQFM in CHF rat plasma with ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS). After solid phase extraction (SPE), chromatography was done on an Acquity UPLC HSS T3 column (1.8µm, 100mm×2.1mm, i.d.) through an 8.0min gradient elution with acetonitrile and 0.1% formic acid in water, while mass spectrometry was performed in the positive ion electrospray ionization (ESI) mode. A good linearity was achieved for each analyte with correlation coefficient (r) >0.9920. The lower limits of quantification (LLOQ) were 1.25ng/mL for ginsenoside Rg1, Rd, Re and Rh1, 2.5ng/mL for ginsenoside Rf, Rg3, Rb2 and Rb3 and 5.0ng/mL for ginsenoside Rb1 and Rc, respectively. All the precision (RSD) data ranged from 1.7-14.5% and the accuracy (RE) data was within ±13.73%. Moreover, the validated method has been applied to investigate the integrated pharmacokinetic profiles of ginsenosides in CHF rats following intravenous administration of YQFM successfully.

Influence of ultrafiltration membrane on ophiopogonins and homoisoflavonoids in Ophiopogon japonicus as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry.

Ultrafiltration is one of the most fascinating technologies, which makes it possible to improve the quality of traditional medicines for application in the pharmaceutical industry. However, researchers have paid little attention to the effect of ultrafiltration membrane on traditional medicines chemical constituents. In this work, Ophiopogon japonicus (L.f) Ker-Gawl. was used as an example to illuminate the influence of ultrafiltration with different material and molecular weight cut-off (MWCO) membrane on natural chemical constituents as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT-TOF/MS). Our results indicated that ultrafiltration membrane significantly impacted homoisoflavonoids, especially homoisoflavonoids that were almost completely retained on the polyethersulfone (PES) membrane. We also found that the larger number of aglycone hydroxy and sugar moiety in steroid saponins, the higher the transmittance. Furthermore, the passage rate (%) of ophiogenin type saponins was higher than that of others. The possible adsorptive mechanisms were hydrogen bonding, hydrophobic interactions, and benzene ring interaction by π-π stacking. In conclusion, it is crucial to choose appropriate ultrafiltration membrane based on the characteristics of produce products for application of ultrafiltration technique.

YiQiFuMai Powder Injection attenuates coronary artery ligation-induced myocardial remodeling and heart failure through modulating MAPKs signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: YiQiFuMai Powder Injection (YQFM), a traditional Chinese medicine prescription re-developed based on Sheng-Mai-San, is a classical and traditional therapeutic for clinical heart failure (HF) and angina. However, its potential mechanism against HF remains unclear. AIM OF THE STUDY: The present study observes the therapeutic role of YQFM and mechanisms underlying its effects on coronary artery ligation (CAL)-induced myocardial remodeling (MR) and HF. METHODS: MR and HF were induced by permanent CAL for 2 weeks in ICR mice. Then mice were treated with YQFM (0.13g/kg, 0.26g/kg and 0.53g/kg) once a day until 2 weeks later. Cardiac structure and function were evaluated by echocardiography. Serum lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) were measured by biochemical kits and cardiomyocyte morphology was assessed by hematoxylin-eosin (HE) staining. Myocardial hydroxyproline (HYP), serum amino-terminal pro-peptide of pro-collagen type III (PIIINP), and Masson's trichrome staining were employed to evaluate cardiac fibrosis. Circulating level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was tested by ELISA kit to predict prognosis of CAL-induced HF. Effects of YQFM on the mitogen-activated protein kinases (MAPKs) pathway after CAL operation was evaluated by Western blotting and immunohistochemistry assay. RESULTS: YQFM (0.53g/kg) improved the left ventricular (LV) function and structure impairment after 2 weeks in CAL mice. YQFM administration also decreased LDH and CK activities, circulating levels of MDA, PIIINP, NT-proBNP, and HYP contents. Moreover, YQFM ameliorated cardiac injury and fibrosis. Furthermore, YQFM (0.53g/kg) inhibited the myocardial phosphorylation of MAPKs in HF mice. CONCLUSION: Our findings suggest that YQFM attenuates CAL-induced HF via improving cardiac function, attenuating structure damage, oxidative stress, necrosis, collagen deposition, and fibrosis. In addition, YQFM ameliorates cardiac remodeling and HF, partially through inhibiting the MAPKs signaling pathways. These data provide insights and mechanisms into the widely application of YQFM in patients with HF, MI and other ischemic heart diseases.

Protective effect of the extract of Yi-Qi-Fu-Mai preparation on hypoxia-induced heart injury in mice.

Yi-Qi-Fu-Mai (YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation (EYQFM), the EYQFM (1.4, 2.8, and 5.5 g·kg(-1)·d(-1)) was assessed for its heart-protective effect in a chronic intermittent hypoxia (CIH) animal model (oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc (0.151 6 g·kg(-1)·d(-1)) was used as a positive control. The histopathological analyses of heart in CIH mice were conducted. Several cardiac state parameters, such as left ventricular ejection fractions (EF), stroke volume (SV), expression of creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when compared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial contractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.

[Construction of NIRS-based process analytical system for production of salvianolic acid for injection and relative discussion].

Currently, near infrared spectroscopy (NIRS) has been considered as an efficient tool for achieving process analytical technology(PAT) in the manufacture of traditional Chinese medicine (TCM) products. In this article, the NIRS based process analytical system for the production of salvianolic acid for injection was introduced. The design of the process analytical system was described in detail, including the selection of monitored processes and testing mode, and potential risks that should be avoided. Moreover, the development of relative technologies was also presented, which contained the establishment of the monitoring methods for the elution of polyamide resin and macroporous resin chromatography processes, as well as the rapid analysis method for finished products. Based on author's experience of research and work, several issues in the application of NIRS to the process monitoring and control in TCM production were then raised, and some potential solutions were also discussed. The issues include building the technical team for process analytical system, the design of the process analytical system in the manufacture of TCM products, standardization of the NIRS-based analytical methods, and improving the management of process analytical system. Finally, the prospect for the application of NIRS in the TCM industry was put forward.

[Monitoring method for macroporous resin column chromatography process of salvianolic acids based on near infrared spectroscopy].

To study and establish a monitoring method for macroporous resin column chromatography process of salvianolic acids by using near infrared spectroscopy (NIR) as a process analytical technology (PAT).The multivariate statistical process control (MSPC) model was developed based on 7 normal operation batches, and 2 test batches (including one normal operation batch and one abnormal operation batch) were used to verify the monitoring performance of this model. The results showed that MSPC model had a good monitoring ability for the column chromatography process. Meanwhile, NIR quantitative calibration model was established for three key quality indexes (rosmarinic acid, lithospermic acid and salvianolic acid B) by using partial least squares (PLS) algorithm. The verification results demonstrated that this model had satisfactory prediction performance. The combined application of the above two models could effectively achieve real-time monitoring for macroporous resin column chromatography process of salvianolic acids, and can be used to conduct on-line analysis of key quality indexes. This established process monitoring method could provide reference for the development of process analytical technology for traditional Chinese medicines manufacturing.