San-Huang-Xie-Xin-Tang Constituents Exert Drug-Drug Interaction of Mutual Reinforcement at Both Pharmacodynamics and Pharmacokinetic Level: A Review

Abstract

Inflammatory disorders underlie varieties of human diseases. San-Huang-Xie-xin-Tang (SHXXT), composed with Rhizoma Rhei (Rheum palmatum L.), Rhizoma Coptidis (Coptis chinensis Franch), and Radix Scutellaria (Scutellaria baicalensis Georgi), is a famous formula which has been widely used in the fight against inflammatory abnormalities. Mutual reinforcement is one of the basic theories of traditional Chinese medicine. Here this article reviewed and analyzed the recent research on (1) How the main constituents of SHXXT impact on inflammation-associated signaling pathway molecules. (2) The interaction between the main constituents and efflux pumps or intestinal transporters. The goal of this work was to, (1) Provide evidence to support the theory of mutual reinforcement. (2) Clarify the key targets of SHXXT and suggest which targets need further investigation. (3) Give advice for the clinical use of SHXXT to elevated the absorption of main constituents and eventually promote oral bioavailability. We search literatures in scientific databases with key words of "each main SHXXT constituent," in combination with "each main inflammatory pathway target molecule" or each main intestinal transporter, respectively. We report the effect of five main constituents on target molecules which lies in three main inflammatory signaling pathways, we as well investigate the interaction between constituents and intestinal transporter. We conclude, (1) The synergistic effect of constituents at both levels confirm the mutual reinforcement theory of TCM as it is proven in this work. (2) The effect of main constituents on downstream targets in nuclear need more further investigation. (3) Drug elevating the absorption of rhein, berberine and baicalein can be employed to promote oral bioavailability of SHXXT.

Keywords: JAK/STAT; MAPK; NF-κB; San-Huang-Xie-Xin-Tang; anti-inflammatory; constituents; intestinal transporter.

Figure 1

The effect of SHXXT alkaloids on inflammatory pathway molecules. 1. The green ellipse represents kinase. 2. The purple ellipse represents transcription factor. 3. The red ellipse represents GTpase. 4. The brown ellipse represents phosphatase. 5. The solid arrow represents direct stimulatory modification. 6. The dotted arrow represents translocation. 7. The dotted “T” represents direct inhibitory modification. 8. The red, yellow and blue cross represents the target influenced by RC, RS, and RR constituents, respectively.

Figure 2

The effect of SHXXT constituents on ITs. Ber, berberine; Cop, coptisine; Pal, palmatine; Jat, jatrorrhizine; Bai, baicalin; Bae, baicalein; Emo, emodin; Aem, aloe-emodin; Rhe, rhein.