Dihydrocapsaicin suppresses the STING-mediated accumulation of ROS and NLRP3 inflammasome and alleviates apoptosis after ischemia-reperfusion injury of perforator skin flap.

Avascular necrosis frequently occurs as a complication following surgery involving the distal perforator flap. Dihydrocapsaicin (DHC) can protect tissue from ischemia-reperfusion (I/R) injury, but its specific role in multizone perforator flaps remains unclear. In this study, the prospective target of DHC in the context of I/R injury was predicted using network pharmacology analysis. Flap viability was determined through survival area analysis, laser Doppler blood flow, angiograms, and histological examination. The expressions of angiogenesis, apoptosis, NLR family pyrin domain containing 3 (NLRP3) inflammasome, oxidative stress, and molecules related to cyclic guanosine monophosphate (GMP)-adenosine monophosphate synthase (cGAS)-interferon gene stimulant (STING) pathway were assessed using western blotting, immunofluorescence, TUNEL staining, and dihydroethidium (DHE) staining. Our finding revealed that DHC promoted the perforator flap survival, which involves the cGAS-STING pathway, oxidative stress, NLRP3 inflammasome, apoptosis, and angiogenesis. DHC induced oxidative stress resistance and suppressed the NLRP3 inflammasome, preventing apoptosis in vascular endothelial cells. Through regulation of STING pathway, DHC controlled oxidative stress in endothelial cells and NLRP3 levels in ischemic flaps. However, activation of the cGAS-STING pathway led to the accumulation of reactive oxygen species (ROS) and NLRP3 inflammasome, thereby diminishing the protective role of DHC. DHC enhanced the survival of multidomain perforator flaps by suppressing the cGAS-STING pathway, oxidative stress, and the formation of NLRP3 inflammasome. These findings unveil a potentially novel mechanism with clinical significance for promoting the survival of multidomain perforator flaps.

Baicalin promotes random-pattern skin flap survival by inducing autophagy via AMPK-regulated TFEB nuclear transcription.

The random-pattern skin flap is a generally used technique to cover the soft tissue defect, while its application is often constrained by complications after the flap transplant. Necrosis of the flap remains a principal obstacle. The purpose of this study was to investigate the effect of Baicalin on skin flap survival and its mechanism. First of all, we discovered that administering Baicalin stimulated cell migration and boosted the formation of capillary tubes in human umbilical vein endothelial cells. Then, we detected that Baicalin reduced apoptosis-induced oxidative stress by using western blot and oxidative stress test kit. After that, we observed that Baicalin increased autophagy and utilized 3MA to block autophagy augmentation substantially reversing the effects of Baicalin therapy. Furthermore, we uncovered the underlying mechanisms of Baicalin-induced autophagy via AMPK-regulated TFEB nuclear transcription. Finally, our in vivo experiment findings showed that Baicalin reduces oxidative stress, inhibits apoptosis, promotes angiogenesis, and boosts the levels of autophagy. After autophagy was blocked, substantially reversing the effects of Baicalin therapy. Our study indicated that Baicalin-induced autophagy via AMPK regulated TFEB nuclear transcription and then promotes angiogenesis and against oxidative stress and apoptotic promotes skin flap survival. These findings highlight the therapeutic potential for the clinical application of Baicalin in the future.