Comparative study on detoxification and efficacy-preserving mechanisms of two Tiebangchui processing methods from...

Tiebangchui (TBC) is a traditional Tibetan medicinal herb with narrow therapeutic window due to inherent toxicity, requiring processing before clinical use. However, the mechanism of processing-mediated detoxification with retained efficacy remains unclear. Therefore, this study employed an integrated UPLC-Q-Orbitrap and UPLC-TQ-MS strategy to comparatively analyze the chemical changes induced by two representative processing methods: highland barley wine soaking (non-heating) and boiling (heating). Furthermore, the blood-absorbed components, cardiac/joint distributions, and urinary/fecal excretions were comparatively analyzed between the two processing methods. The results demonstrate that highland barley wine processing achieves detoxification-efficacy preservation through a coordinated mechanism involving facilitated leaching of toxic diester-diterpenoid alkaloids (DDAs), their biotransformation into less toxic alkaloids, enhanced absorption of less toxic alkaloids, and accelerated excretion of specific DDAs. The boiling process mediates detoxification through the thermal hydrolysis of DDAs, resulting in limited systemic exposure (blood absorption) and cardiac distribution, with no detectable components in the joint tissues. These findings provide a crucial chemical foundation for elucidating the mechanism underlying toxicity reduction and efficacy retention during TBC processing.