Germacrone improved markers by activating - signaling, promoting , and reducing NLRP3 inflammation.
Evidence
Preclinical in vitro and in vivo experiments screened sesquiterpenoids and tested germacrone effects on TFEB activation, renal function, renal pathology, autophagy, and NLRP3 inflammasome clearance.
Caveat
The abstract does not describe human clinical testing, so germacrone remains a mechanistic preclinical intervention rather than an established DKD treatment.
Simplified
(DKD) is widely recognized as the primary cause of end-stage renal disease (ESRD). Activating is considered a key strategy to improve DKD. Here, through luciferase reporter gene screening of several sesquiterpenoids, it was found that germacrone (GER) significantly activated the (TFEB), and its effect on DKD and the underlying molecular mechanism was investigated. GER significantly improved renal function impairment and alleviated renal pathological damage. GER inhibited NLR family pyrin domain containing 3 (NLRP3)-mediated inflammatory responses bothand. Mechanistically, GER activated TFEB to promote autophagy and clear NLRP3 inflammasomes, and the GER-mediated degradation of NLRP3 was reversed by the autophagy inhibitor chloroquine (CQ). Additionally, GER did not affect the expression of TFEB protein but increased its expression in the nucleus. This effect was attributed to the dephosphorylation of p-TFEB (S122) protein caused by the activation of (PP2A) by GER. This result was further confirmed by supplementing with the PP2A inhibitor okadaic acid (OA). Docking results indicated a stable binding between GER and PP2A. These findings highlighted GER as a potential intervention for treating DKD and clarified the underlying mechanism through which it functions by regulating the PP2A-TFEB pathway. in vitro in vivo
Key numbers
significant
Decrease in Serum Creatinine
Measured levels of serum creatinine in mice.
significant
Decrease in Blood Urea Nitrogen
Blood urea nitrogen levels assessed in mice.
significant
Decrease in Expression
protein levels measured in renal tissues.
Full Text
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