Positive Effect of Andrographolide Induced Autophagy on Random-Pattern Skin Flaps Survival

Abstract

Random-pattern skin flap replantation is generally used in the reconstruction of surgical tissues and covering a series of skin flap defects. However, ischemia often occurs at the flap distal parts, which lead to flap necrosis. Previous studies have shown that andrographolide (Andro) protects against ischemic cardiovascular diseases, but little is known about the effect of Andro on flap viability. Thus, our study aimed to building a model of random-pattern skin flap to understand the mechanism of Andro-induced effects on flap survival. In this study, fifty-four mice were randomly categorized into the control, Andro group, and the Andro+3-methyladenine group. The skin flap samples were obtained on postoperative day 7. Subsequently, the tissue samples were underwent a series of evaluations such as changes in the appearance of flap tissue, the intensity of blood flow, and neovascularization density of skin flap. In our study, the results revealed that Andro enhanced the viability of random skin flaps by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Furthermore, our results have also demonstrated that the administration of Andro caused an elevation in the autophagy, and these remarkable impact of Andro were reversed by 3-methyladenine (3-MA), the most common autophagy inhibitor. Together, our data proves novel evidence that Andro is a potent modulator of autophagy capable of significantly increasing random-pattern skin flap survival.

Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective

“…This is similar to recent studies which found A. paniculata and its bioactive diterpenoids protected dermalfibroblasts and deratinocytes against inflammation and oxidative stress 194 . A recent study reported andrographolide increased random‐pattern skin flap survival by inducing autophagy 195 . These findings indicate that andrographolide may be available to treat skin diseases.…”

“…194 A recent study reported andrographolide increased random-pattern skin flap survival by inducing autophagy. 195 These findings indicate that andrographolide may be available to treat skin diseases. For most skin diseases, topical administration of andrographolide may be more acceptable to patients.…”

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches

“…Unfortunately, however, ischemia frequently occurs at the flap distal parts, which bring about flap necrosis. A recent work exhibited that, as a significant modulator of autophagy capable, andrographolide may prove fruitful for the increasing random‐pattern skin flap survival through enhancing angiogenesis, suppressing apoptosis and lessening oxidative stress (Jiang et al, 2021). Treatment of H9c2 cardiomyocytes and diabetic cardiomyopathy C57/BL6J mice with various concentrations of andrographolide resulted in a dose‐dependent inhibition of cardiac inflammation and oxidative stress, accompanied by reducing cardiac apoptosis, which the mechanism involve the modulation of NOX/Nrf2‐mediated oxidative stress and NF‐κ B‐mediated inflammation (Liang, Liu, Du, Yang, & Zhao, 2018).…”

Pharmacological and cell-based treatments to increase local skin flap viability in animal models

“…Other compounds capable of stimulating autophagy have also been shown to be effective at promoting skin flap survival in various mouse and rat studies. These include catapol, a biologically active compound found in the flowering plant Rehmannia glutinosa , andorgrapholide, a diterpenoid isolated from the stem and leaves of Andrographis paniculata , and nobiletin, a flavonoid found in citrus fruits [ 56 , 58 – 57 ]. Each of these have been shown to positively regulate autophagy, through sirtuin 1, phophosoinositide 3-kinase/Akt, and 5′ adenosine monophosphate-activated protein kinase (AMPK) activation, respectively.…”