In Vitro Evaluation of the Interaction of Seven Biologically Active Components in Anemarrhenae rhizoma with P-gp

Abstract

The efficacy and pharmacokinetics of the biologically active components in Anemarrhenae rhizoma (AR) would be affected by the interaction of P-glycoprotein(P-gp) and effective components in AR. However, little is known about the interaction between them. The goal of this research was to examine the transmembrane absorption of timosaponin AIII(TAIII), timosaponin BII(TBII), sarsasapogenin (SSG), mangiferin(MGF), neomangiferin(NMGF), isomangiferin(IMGF), and baohuosideI(BHI) in AR and their interaction with P-gp. Seven effective components in AR(TAIII, TBII, SSG, MGF, NMGF, IMGF, and BHI) were investigated, and MDCK-MDR1 cells were used as the transport cell model. CCK-8 assays, bidirectional transport assays, and Rhodamine-123 (Rh-123) transport assays were determined in the MDCK-MDR1 cells. LC/MS was applied to the quantitative analysis of TAIII, TBII, MGF, NMGF, IMGF, SSG, and BHI in transport samples. The efflux ratio of MGF, TAIII, TBII, and BHI was greater than 2 and significantly descended with the co-administration of Verapamil, indicating MGF, TAIII, TBII, and BHI as the substrates of P-gp. The efflux ratio of the seven effective components in the extracts (10 mg/mL) of AR decreased from 3.00~1.08 to 1.92~0.48. Compared to the efflux ratio of Rh-123 in the control group (2.46), the efflux ratios of Rh-123 were 1.22, 1.27, 1.25, 1.09, 1.31, and 1.47 by the addition of TAIII, TBII, MGF, IMGF, NMGF, and BHI, respectively, while the efflux ratio of Rh-123 with the co-administration of SSG had no statistical difference compared to the control group. These results indicated that MGF, TAIII, TBII, and BHI could be the substrates of P-gp. TAIII, TBII, MGF, IMGF, NMGF, and BHI show the effect of inhibiting P-gp function, respectively. These findings provide important basic pharmacological data to assist the therapeutic development of AR constituents and extracts.

Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) <i>via</i> dephosphorylation of the EGFR signaling pathway

“…These findings suggest that T-AⅢ may influence the metabolism of clinically used substrate drugs by up-regulating CYP2B6, CYP3A4, and MDR1, thereby impacting the efficacy and toxicity of the drugs. The literature indicates that T-AⅢ has been reported to induce multidrug resistance (MDR) reversal by inhibiting the expression of MDR1 and MRP1 in human chronic myelogenous leukemia K562/ADM cells [28] . Additionally, recent findings by Dai et al suggest that T-AⅢ may serve as both a substrate and an inhibitor of MDR1 in MDCK-MDR1 cells [29] .…”

The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment

“…This indicates that TSAIII can be either a substrate or an inhibitor of P-gp. Furthermore, TSAIII can decrease the efflux ratio of Rh-123 from 2.46 to 1.22 [ 88 ].…”

Network pharmacology analysis and experimental validation of &lt;italic&gt;Anemarrhenae Rhizoma&lt;/italic&gt; in treating Alzheimer&lt;bold&gt;&rsquo;&lt;/bold&gt;s disease

“…知母（ Anemarrhenae Rhizoma ）为百合科植物知母 Anemarrhena asphodeloides Bge. 的干燥根茎，传统医学将其药物作用归纳为清热泻火、滋阴润燥 ［ 6 ］ ，现代药理学认为知母及其活性成分具有抗痴呆、抗凋亡、抗氧化、抗炎、抗病毒、免疫调节等药理作用 ［ 5 ， 7 - 8 ］ ，是治疗AD的中草药之一。本研究通过网络药理学及实验验证探讨知母改善AD的作用机制。…”