Effect of Gelsemium elegans and Mussaenda pubescens, the Components of a Detoxification Herbal Formula, on Disturbance of the Intestinal Absorptions of Indole Alkaloids in Caco-2 Cells

Abstract

Gelsemium elegans (GE) is a kind of well-known toxic plant. It can be detoxified by Mussaenda pubescens (MP), but the detoxification mechanism is still unclear. Thus, a detoxification herbal formula (GM) comprising GE and MP was derived. The Caco-2 cells monolayer model was used to evaluate GM effects on transporting six kinds of indole alkaloids of GE. The bidirectional transport studies demonstrated that absorbance percentage of indole alkaloids in GE increased linearly over time. But in GM, Papp (AP→BL) values of the most toxic members, gelsenicine, humantenidine, and gelsevirine, were lower than that of Papp (BL→AP) (P < 0.05). The prominent analgesic effect members, gelsemine and koumine, were approximately 1.00 in γ values. Nowhere was this increasing efflux more pronounced than in the case of indole alkaloids with N-O structure. In the presence of verapamil, the γ values of humantenidine, gelsenicine, gelsevirine, and humantenine were decreased by 43.69, 41.42, 36.00, and 8.90 percent, respectively. The γ values in presence of ciclosporin were homologous with a decrease of 42.32, 40.59, 34.00, and 15.07 percent. It suggested that the efflux transport was affected by transporters. Taken together, due to the efflux transporters participation, the increasing efflux of indole alkaloids from GM was found in Caco-2 cells.

Clinical manifestations and causes of gelsemium poisoning in Hong Kong from 2005 to 2017: Review of 33 cases

“…Interestingly, a recent study showed a protective effect of M. pubescentis when used together with G. elegans in a 40:1 extract ratio in mice without affecting the therapeutic effect as analgesia. 13 The protective effect of M. pubescentis was not observed in our case likely because of the inadequate dosage of M. pubescentis used. There are two reasons for the misidentification.…”

CYP3A4/5 mediates the metabolic detoxification of humantenmine, a highly toxic alkaloid from Gelsemium elegans Benth.

“…Conversely, CYP3A4/5 inducers, such as hexadecadrol (Hellmann et al, ), are suggested as therapeutic agents for detoxifying HMT. Gelsemium can be detoxified by Mussaenda pubescens (Wang, Wang, Wu, Li, & Chen, ), and the detoxification mechanism decreases the absorption of toxic compounds. Nevertheless, whether M. pubescens also stimulates the CYP3A4/5 activity should be further investigated.…”

Characterization of the Intestinal Absorption of Morroniside from Cornus officinalis Sieb. et Zucc via a Caco-2 Cell Monolayer Model

“…The conditions for Caco-2 cell culture have been described previously(21). In brief, Cells were cultured in a humidified atmosphere of 5% CO 2 and 95% air at 37 °C.…”