Frontiers in Pharmacology (Jan 2023)

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

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

DOI
https://doi.org/10.3389/fphar.2022.1104705
Journal volume & issue
Vol. 13

Abstract

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Bryophyllumpinnatum (Crassulaceae) is used in traditional medicine for treating skin wounds. In our previous study, a topical gel containing B. pinnatum aqueous leaf extract showed a preclinical anti-inflammatory effect in in vivo acute edema models. In continuation, the present study aims to evaluate the phytochemical content and the stability of a formulation in gel containing B. pinnatum aqueous leaf extract and its healing properties and mechanism of action through an experimental model of induction of skin wounds in rats and in vitro 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® 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.

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