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26 reviewsgreater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell,
particularly mitochondria, the endolysosomal–autophagy system, and is accompanied by senescence-associated
secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala
Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation.
Purpose: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in
vivo and in vitro, offering a potential medicine for clinical treatment for HLAP.
Study design and methods: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER,
then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with
RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were
obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition,
western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial
function, autophagy flux, and SASP.
Results: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers
in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of
NLRP3 and IL-1β in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxida
…