AUTHOR=Araújo Edilane Rodrigues Dantas , Xavier-Santos Jacinthia Beatriz , da Silva Valéria Costa , de Lima Juliana Bessa Figueiredo , Schlamb Jade , Fernandes-Pedrosa Matheus de Freitas , da Silva Júnior Arnóbio Antônio , de Araújo Júnior Raimundo Fernandes , Rathinasabapathy Thirumurugan , Moncada Marvin , Esposito Debora , Guerra Gerlane Coelho Bernardo , Zucolotto Silvana Maria 

TITLE=Gel formulated with Bryophyllum pinnatum leaf extract promotes skin wound healing in vivo by increasing VEGF expression: A novel potential active ingredient for pharmaceuticals

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1104705

DOI=10.3389/fphar.2022.1104705

ISSN=1663-9812

ABSTRACT=<p><italic>Bryophyllum</italic><italic>pinnatum</italic> (Crassulaceae) is used in traditional medicine for treating skin wounds. In our previous study, a topical gel containing <italic>B. pinnatum</italic> aqueous leaf extract showed a preclinical anti-inflammatory effect in <italic>in vivo</italic> acute edema models. In continuation, the present study aims to evaluate the phytochemical content and the stability of a formulation in gel containing <italic>B. pinnatum</italic> aqueous leaf extract and its healing properties and mechanism of action through an experimental model of induction of skin wounds in rats and <italic>in vitro</italic> assays. The animals were treated topically for 7 or 14 days with a formulation in gel containing extract at 5% or a placebo or Fibrinase<sup>®</sup> in cream. In addition, to establish some quality control parameters, the total phenolic content (TPC), total flavonoid content (TFC), and a study focusing on the phytochemical and biological stability of a gel for 30 days at two different conditions (room temperature and 40°C/75% RH) were performed. Gel formulation containing extract showed a TPC and TFC of 2.77 ± 0.06 mg of gallic acid/g and 1.58 ± 0.03 mg of quercetin/g, respectively. Regarding the stability study, the formulation in gel showed no significant change in the following parameters: pH, water activity, chromatographic profile, and the content of the major compound identified in the extract. The gel formulation containing extract stimulated skin wound healing while reducing the wound area, as well as decreasing the inflammatory infiltrate, reducing the levels of IL-1β and TNF-α, and stimulating angiogenesis with increased expression of VEGF, an effect similar to Fibrinase. In conclusion, the gel formulation containing extract exhibited relevant skin wound healing properties and, therefore, has the potential to be applied as a novel active ingredient for developing wound healing pharmaceuticals.</p>