Angelica Dahurica Regulated the Polarization of Macrophages and Accelerated Wound Healing in Diabetes: A Network Pharmacology Study and In Vivo Experimental Validation

Abstract

Diabetic wounds exhibit retarded and partial healing processes. Therefore, patients are exposed to an elevated risk of infection. It has been verified that Angelica dahurica (Hoffm.) Benth. and Hook. f. ex Franch. and Sav (A. dahurica) is conducive for wound healing. However, the pharmacological mechanisms of A. dahurica are yet to be established. The present study uses network pharmacology and in vivo experimental validation to investigate the underlying process that makes A. dahurica conducive for faster wound healing in diabetes patients. 54 potential targets in A. dahurica that act on wound healing were identified through network pharmacology assays, such as signal transducer and activator of transcription 3 (STAT3), JUN, interleukin-1β (IL-1β), tumor necrosis factor (TNF), and prostaglandin G/H synthase 2 (PTGS2). Furthermore, in vivo validation showed that A. dahurica accelerated wound healing through anti-inflammatory effects. More specifically, it regulates the polarization of M1 and M2 subtypes of macrophages. A. dahurica exerted a curative effect on diabetic wound healing by regulating the inflammation. Hence, pharmacologic network analysis combined with in vivo validation elucidated the probable effects and underlying mechanisms of A. dahurica’s therapeutic effect on diabetic wound healing.

Kampo herbal ointments for skin wound healing

“…Angiogenesis is a pivotal process in wound repair, and this therapeutic property of A. dahurica root makes its use relevant for wound healing. The oral intake of A. dahurica also regulates the polarization of M1 and M2 subtypes of macrophages and thus inflammation ( Hu et al, 2021 ). On the diabetic mice model, oral intake of the A. dahurica root extract activated the phosphoinositide 3-kinase/protein kinase B signaling pathway (PI3K/AKT).…”

The Angelica dahurica: A Review of Traditional Uses, Phytochemistry and Pharmacology

“…dahurica was extensively used as a traditional Chinese medicine in treating skin-associated diseases. In recent years, several studies revealed that A. dahurica has excellent activity on diabetes-induced skin ulcer (Guo et al, 2020;Chao et al, 2021;Hu et al, 2021). Guo et al (2020) indicated that 10 days treatment with A. dahurica at 1.8 g/kg b. w. significantly promoted would healing and angiogenesis by activating phosphatidylinositide 3kinase/protein kinase B (PI3K/AKT) and HIF-1α/plateletderived growth factor-β (PDGF-β) pathways in db/db mice.…”

“…Some of these bioactivities are consistent with the traditional uses of A. dahurica root, such as analgesic activity and effects on skin diseases. In addition, A. dahurica also exerts specific effects, related to anti-diabetic (Han et al, 2018), lowering blood lipids (Lu et al, 2016), improving immunity (Wang et al, 2021), anti-ulcer (Hu et al, 2021) and cosmetic effects (Cho et al, 2006).…”

Corylin accelerated wound healing through SIRT1 and PI3K/AKT signaling: a candidate remedy for chronic non-healing wounds

“…Fibroblasts are critical in the proliferation phase of wound healing and play a dominant role in collagen deposition, granulation tissue formation, and epithelialization ( Liu et al, 2022 ). Currently, various therapeutic approaches have been used in the treatment of chronic non-healing wounds, including surgical debridement, antimicrobial agents, bioengineered skin equivalents, and growth factors ( Han and Ceilley, 2017 ; Dubey et al, 2021 ; Hu et al, 2021 ; Sarojini et al, 2021 ; Wang et al, 2021 ). However, limited therapeutic effects and numerous side effects restrict their application ( Han and Ceilley, 2017 ).…”