Evaluating the spectrum-effect profiling and pharmacokinetics of Tieshuang Anshen Prescription with better sedative-hypnotic effect based on Fe2+ than Hg2+

• Main Authors: Manhuayun Zhai, Dandan Gong, Qiannan Gao, Hong Zhang, Guoxiang Sun
• Format: Article
• Language: English
• Published: Elsevier 2021-09-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Sedative-hypnotic effect; Fingerprint; Spectrum-effect relationship; Tieshuang Anshen Prescription; Pharmacokinetics
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332221007058

Although Zhusha Anshen Pill (ZSASP) is a commonly used traditional prescription for insomnia, the safety of cinnabar in the formula has always been controversial since its initial application in medical fields. Here, we developed a new prescription, Tieshuang Anshen Prescription (TSASP), by improving ZSASP with Fe2+ instead of Hg2+. Besides, TSASP was further optimized by establishing and testing the HPLC fingerprint and its sedative-hypnotic effect of formulas with different compatibility ratios and performing correlation spectrum analysis. The safety of TSASP was also evaluated by HE staining of liver and kidney. In addition, a validated and robust UHPLC-MS/MS method was established to demonstrate the pharmacokinetic characteristics of berberine, palmatine, jatrorrhizine, ligustilide, catalpol, loganin, liquiritin and liquiritigenin after oral administration of TSASP. Our study originally provides a new non-toxic prescription, TSASP, with better sedative-hypnotic effect in comparison with ZSASP, revealing that Fe2+ could replace Hg2+ to eliminate its toxicity and play a sedative role. Meanwhile, we believe that our pharmacokinetics results may contribute valuable reference to both TSASP’s specific mechanism of action and its further clinical efficacy and effectiveness research.