Identification of key transporters mediating uptake of aconitum alkaloids into the liver and kidneys and the potential mechanism of detoxification by active ingredients of liquorice

Abstract

Aconite as a commonly used herb has been extensively applied in the treatment of rheumatoid arthritis, as pain relief, as well as for its cardiotonic actions. Aconitum alkaloids have been shown to be the most potent ingredients in aconite, in terms of efficacy against disease, but they are also highly toxic. Apart from neurological and cardiovascular toxicity exposed, the damage to hepatocytes and nephrocytes with long-term use of aconitum alkaloids should also be carefully considered. This study attempted to investigate the critical role of uptake transporters mediating the transport of aconitum alkaloids into the liver and the kidneys. The resulting data revealed that hOATP1B1, 1B3, hOCT1 and hOAT3 were mainly involved in the uptake of aconitum alkaloids. Additionally, the inhibitory effects of bioactive ingredients of liquorice on uptake transporters were screened and further confirmed by determining the IC 50 values.The in vitro study suggested that liquorice might lower the toxicity of aconite by reducing its exposure in the liver and/or kidneys through inhibition of uptake transporters. Eventually, the in vivo study was indicative of detoxification of liquorice by decreasing the exposure of aconitine as representative compound in liver after co-administration, even though the exposure in kidney altered was less significant. In summary, hOATP1B1, 1B3, hOCT1 and hOCT3 were determined as the key uptake transporters mediating the transport process of aconitum alkaloids into the liver and/or kidneys, and liquorice may alleviate the toxicity caused by reduction of exposure through inhibition of those key uptake transporters.

Evaluate the effect of licorice on anti-liver fibrosis: a systematic review and meta-analysis

“…Fourth, inhibiting enzymes of glycolysis; HK-2, LDH-A and PK-M2. He et al (2019) investigate the critical role of uptake transporters mediating the transport of aconitum alkaloids into the liver, the result showed liquorice might lower the toxicity of aconite by reducing its exposure in the liver through inhibition of uptake transporters. Also Salawu et al (2019) showed that the composite blends Moringa leaf + Licorice root at a regulated dose, could be explored as functional food in the provision of nutritionally important minerals, and the management of stress-related diseases.…”

FEK self‐assembled peptide hydrogels facilitate primary hepatocytes culture and pharmacokinetics screening

“…3,4 The cells can be rescued from these adverse effects by sandwich culture (SC), in which the hepatocytes can rebuild hepatic polarity and differentiation-related functions between collagen and Matrigel layers. [5][6][7] Currently, SC in vitro models are used widely to study hepatocyte transporters, 8,9 drug metabolism, 10 and drug screening using short-term cultures to detect hepatotoxicity. [11][12][13] However, the complexity, variability, ambiguity, and lack of reproducibility of ECM undermine the reliability of experimental results obtained using SC, limiting the SC usage in drug research and development.…”