Pien-tze-huang promotes wound healing in streptozotocin-induced diabetes models associated with improving oxidative stress via the Nrf2/ARE pathway

Abstract

Diabetic foot ulcers are a serious complication of diabetes, with high mortality and a lack of effective clinical treatment, which leads to a considerable financial burden. Pien-Tze-Huang (PZH) is a Chinese traditional medicine with a long history that has been found to be an effective and convenient treatment for inflammatory diseases such as skin abscesses and ulcers. In this study, we assessed the effects of PZH on diabetic wounds and the underlying mechanisms. The wounds were established on the backs of streptozotocin-induced type 1 diabetic rats and type 2 diabetic mouse models. We found that PZH treatment used locally or by gavage significantly promoted wound healing, accelerated re-epithelialization and vasculature in the wound tissue, upregulated the expression of the growth factors VEGF-A, PDGF, and EGF, and activated the Nrf2/ARE pathway in the wound tissue. In vitro assays showed that PZH improved the proliferation, migration and angiogenic function of human umbilical vein endothelial cells (HUVECs) cultured in palmitic acid, reduced the expression of the apoptotic proteins p53, Bax, and cleaved-caspase3, and activated Nrf2/ARE signaling; however, these protective effects were abrogated after Nrf2 was knocked down by specific siRNA. In addition, the levels of the serum inflammatory cytokines IL-1β, TNF-α, and IL-6 were reduced after PZH gavage treatment. In conclusion, the positive role of PZH in diabetic wound healing might be related to the activation of the Nrf2/ARE pathway to regulate the level of oxidative stress in vivo and increase the expression of growth factors to improve angiogenesis.

Curcumin-Loaded Macrophage-Derived Exosomes Effectively Improve Wound Healing

“…All of these results indicate that Exos-cur can promote the migration ability of HUVECs. The proliferation and migration capabilities of endothelial cells have laid a good foundation for the formation of blood vessels . The formation of blood vessels in skin defects is the key to improving blood flow in the wound and promoting skin regeneration .…”

“…The proliferation and migration capabilities of endothelial cells have laid a good foundation for the formation of blood vessels. 32 The formation of blood vessels in skin defects is the key to improving blood flow in the wound and promoting skin regeneration. 33 In order to explore whether Exos-cur can promote angiogenesis, we conducted tube formation experiments with HUVECs (Figure 2C,E).…”

The Role of p53 in Regulating Chronic Inflammation and PANoptosis in Diabetic Wounds

“…Makes wound healing faster. [12] Asiaticoside Asiaticoside works by inhibiting the ROS-dependent p53-Bcl-2caspase 3 pathway.…”

“…Pien-tze-huang (PZH), a traditional Chinese medicine with a long history, has been identified as an effective and convenient treatment for inflammatory diseases such as skin abscesses and ulcers. It has also demonstrated antioxidant effects in DW and reduced the expression of apoptotic proteins such as p53 and Bax, resulting in faster wound healing [12].…”

“…Progressive upregulation of senescence and apoptosis markers such as p53-Cdkn1a (p21) -p16, β-galactosidase (SA-β-gal), and B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), accompanied by diminished bcl-2expression, has been documented in these wounds [7][8][9][10]. Inhibition of p53 activity has been shown to expedite wound repair processes [11][12][13].…”