Table 5 Autophagy-modulating therapies
From: Pharmacological and cell-based treatments to increase local skin flap viability in animal models
Pharmacologic therapy | MoA | RoA | Animal model | Treatment protocol | References |
|---|---|---|---|---|---|
Calcitriol | Activation of vitamin D receptor (VDR) and autophagy-related genes | Intraperitoneal injection | Rat random pattern skin flap | Daily post-operative injection for 7Â days | Chen et al. [53] |
Gastrodin | Stimulation of the Nrf2/HO1 cascade, suppression of nuclear factor-κB cascade and inflammatory mediators IL-6α and IL-1β | Intraperitoneal injection | Rat random pattern skin flap | Daily post-operative injection for 7 days | Chen et al. [55] |
Nobiletin | Activation of AMPK, anti-adipogenic effects, reduction of GPDH, PPARγ) and C/EBPα activity | Intraperitoneal injection | Rat random pattern skin flap | Daily post-operative injection for 7 days | Jiang et al. [56] |
Andrographolide | Downregulation of Bax, CYC, and CASP3, stimulation of the PI3K/Akt-eNOS, PI3K/Akt pathway and levels of VEGF, Cadherin5, MMP9, HO1, eNOS, and SOD1 | Intraperitoneal injection | Mice random pattern skin flap | Daily post-operative injection for 7Â days | Jiang et al. [57] |
Catalpol | Activation of SIRT1, a NAD + -dependent class III histone deacetylase | Intraperitoneal injection | Rat McFarlane flap | Daily post-operative injection for 7 days | Jiang et al. [58] |
Baicalin | AMPK-regulated TFEB nuclear transcription | Oral | Rat random pattern skin flap | Daily oral administration (dissolved in DMSO and further diluted in saline) for 7Â days | Zhang et al. [59] |
Exenatide | Regulation of AMPK–SKP2–CARM1 and AMPK–mTOR signaling | Subcutaneous injection | Mice random pattern skin flap | Daily post-operative injection for 7 days | Li et al. [60] |
Trehalose | Regulation of AMPK-regulated TFEB nuclear transcription | Intraperitoneal injection | Mice random pattern skin flap | Administration starting 12Â days before operation and continued until the animals were euthanized | Wu et al. [61] |
Metformin | Activation of autophagy by AMPk-mTOR-TFEB signaling pathway | Intraperitoneal injection | Rat caudally-based dorsal random pattern flap | Pre-operative and post-operative injection once daily for 7Â days | Wu et al. [62] |