Inhibitory Influence of Panax notoginseng Saponins on Aspirin Hydrolysis in Human Intestinal Caco-2 Cells

Abstract

Herb-drug interactions are important safety concerns in clinical practice. The interactions occur firstly in the intestinal absorption for orally administered drugs. Aspirin and Panax notoginseng saponins (PNS)-based drugs are often combined in China to prevent larger-artery atherosclerosis. Here, we aimed to characterize the aspirin transport across Caco-2 cell monolayers, a model of the intestinal absorption, and further to evaluate the influence of PNS on aspirin hydrolysis and the relating mechanisms. Transcellular transport of aspirin and the influence of PNS were explored using Caco-2 cell monolayers. The protein expression of human carboxylesterase 1 (hCE1) and hCE2 in Caco-2 cells after PNS treatment was analyzed by ELISA, and the mRNA level were determined by qRT-PCR. In the study, Caco-2 cells showed high level of hydrolase activity, and most aspirin was hydrolyzed inside the cells during the transport process. Interestingly, PNS were demonstrated to inhibit the esterase activities responsible for aspirin hydrolysis in Caco-2 cells. PNS could also decrease the protein expression of hCE1 and hCE2, whereas exhibited minor effect on the mRNA expression. These results indicated that oral administration of PNS-based drugs might inhibit the hydrolysis of aspirin during intestinal absorption thus promoting its bioavailability.

Inhibition of human carboxylesterases by ginsenosides: structure–activity relationships and inhibitory mechanism

“…Considering that the intestinal hCES2A is a crucial target to ameliorate irinotecan-triggered intestinal toxicity, and the local exposure of ginsenosides in the gastrointestinal system may reach to a high level when the patients repeatedly take ginseng products orally, the ginsenosides may block the over-production of SN-38 in the gastrointestinal system and thereby ameliorate irinotecan-triggered gut toxicity. Of note, a recent study revealed that Panax notoginseng saponins could inhibit both hCES1A and hCES2A and down-regulate the protein levels of these two enzymes in Caco-2 cells, therefore affecting hCES-mediated aspirin hydrolysis in Caco-2 cells [66]. This result combined with our findings suggests that the ginseng products may modulate the activity and expression of hCES2A and then affect the pharmacokinetic behaviors of hCES2A substrates, which may be beneficial to patients receiving irinotecan.…”

Caco-2 Cell Permeability of Flavonoids and Saponins from Gynostemma pentaphyllum: the Immortal Herb

“…However, reports suggest that the other class of saponins, the steroidal saponins, can pass through Caco-2 monolayers. These saponins are actively transported by suitable transport proteins, such as sugar transporters, or can be effluxed across the monolayers by efflux pumps such as P-gp and MRP-2. ,− We know that Caco-2 cells express active transporters including sugar transporters such as SGLT1 (responsible for the transport of glycosides), GLUT2 and GLUT5 . Analysis of our permeability assay data in light of these literature reports suggests that the glycosylated saponins assessed here may be actively transported by sugar transporters across Caco-2 monolayers.…”

A systematic review of possible interactions for herbal medicines and dietary supplements used concomitantly with disease‐modifying or symptom‐alleviating multiple sclerosis drugs

“…The mechanism responsible for this was further evaluated in vitro, where decreased protein levels of the esterases hCE1 and hCE2 in Caco-2 cells were observed. Aspirin is mainly hydrolyzed by hCE2, and decreased expression of hCE2 might account for the PNS-mediated decrease in aspirin hydrolysis (Sun, Wu, Liu, et al, 2018a;Sun, Wu, Yang, et al, 2018b). This is supported by a study showing that red ginseng extract improves the absorption of salicylic acid and slows down its metabolism.…”