Accelerative action of topical piperonylic acid on mice full thickness wound by modulating inflammation and collagen deposition

Abstract

Epidermal growth factor (EGF) promotes cell growth, proliferation, and survival in numerous tissues. Piperonylic acid, a metabolite present in peppers (Piper nigrum L. and Piper longum L.), can bind to the epidermal growth factor receptor (EGFR) and induce an intracellular signaling cascade leading to the transcription of genes responsible for these actions, especially in keratinocytes. These cells are fundamental in maintaining cutaneous homeostasis and are the first to be damaged in the case of a wound. Thus, we hypothesized that piperonylic acid improves wound healing. C57BL6/J male mice were submitted to dorsal skin wounds caused by a 6 mm punch and treated topically with piperonylic acid or vehicle. The wounds were evaluated macro- and microscopically, and tissue samples were collected for immunofluorescence and real-time PCR analyses on days 6, 9 and 19 post-injury. Topical piperonylic acid improved wound healing from day 6 post-injury until closure. This phenomenon apparently occurred through EGFR activation. In addition, piperonylic acid modulated the gene expression of interleukin (Il)-6, il-1β, tumor necrosis factor (Tnf)-α, il-10, monocyte chemoattractant protein (Mcp)-1 and insulin-like growth factor (Igf)-1, which are important for the healing process. By day 19 post-injury, the new tissue showed greater deposition of type I collagen and a morphology closer to intact skin, with more dermal papillae and hair follicles. We conclude that piperonylic acid may be a viable option for the treatment of skin wounds.

Iridium Nanoparticles on NiO as Heterogeneous Catalysts for Acceptorless Dehydrogenation of Primary Alcohols with Tunable Product Selectivity

“…For instance, 2-furancarboxylic acid obtained by dehydrogenation of furfuryl alcohol is a very important chemical generally used as a food preservative and flavoring agent in the food industry, as a fungicide and a bactericide, and as an intermediate in the pharmaceutical industry . Similarly, piperonylic acid, obtained by dehydrogenation of piperonyl alcohol, showed several pharmacological applications such as anticancer, anti-inflammatory, antidiarrheal, antioxidant, etc. , Likewise, 1-adamantane ethanol on dehydrogenation gives 1-adamantane acetic acid, which shows antiviral properties . We were delighted to see that our catalyst could convert furfuryl alcohol, piperonyl alcohol, and 1-adamantane ethanol to their corresponding acid in 36 (Table , Entry 2m ), 53 (Table , Entry 2n ), and 32% (Table , Entry 2p ) yields, respectively, with the liberation of hydrogen gas.…”

“…62 Similarly, piperonylic acid, obtained by dehydrogenation of piperonyl alcohol, showed several pharmacological applications such as anticancer, anti-inflam-matory, antidiarrheal, antioxidant, etc. 63,64 Likewise, 1adamantane ethanol on dehydrogenation gives 1-adamantane acetic acid, which shows antiviral properties. 65 We were delighted to see that our catalyst could convert furfuryl alcohol, piperonyl alcohol, and 1-adamantane ethanol to their corresponding acid in 36 (Table 1, Entry 2m), 53 (Table 1, Entry 2n), and 32% (Table 1, Entry 2p) yields, respectively, with the liberation of hydrogen gas.…”

Synthesis and Bioactivities of Novel Piperonylic Acid Derivatives Containing a Sulfonic Acid Ester Moiety

“…Due to its characteristics of unique mechanism of action, novel scaffolds, and easy derivation, the natural products have always been a valuable source for lead compounds discovery in agricultural chemistry. Piperonylic acid is an aromatic acid mainly found in black pepper ( Moreira et al, 2021 ). Lots of research results revealed members of the piperonylic acid family had a range of biological activities and were further developed into a commercial drug and widely used in the field of medicine, such as oxolinic acid ( Yamazawa et al, 2021 ; Boycov et al, 2022 ; Quan et al, 2022 ), kakuol ( Jang et al, 2020 ; Matsumoto et al, 2020 ; Sui et al, 2020 ), and miloxacin ( Horie and Nakazawa, 1992 ; Ueno and Aoki, 1996 ; Ueno et al, 2001 ).…”