Healing effect of Dillenia indica fruit extracts standardized to betulinic acid on ultraviolet radiation-induced psoriasis-like wounds in rats

Pharm Biol. 2017 Dec;55(1):641-648. doi: 10.1080/13880209.2016.1266672.

Abstract

Context: Dillenia indica Linn. (Dilleniaceae) is traditionally used to treat skin inflammation.

Objective: This study evaluated the healing effect of Dillenia indica fruit extracts on induced psoriasis-like wounds in Wistar rats.

Materials and methods: Extracts were standardized to betulinic acid, including an aqueous ethanolic extract (AEE), ethyl acetate extract (EAE) and petroleum ether extract. Effects against lipid peroxidation were assessed in vitro. Wounds were created at rat tails (n = 12). Topical treatments were applied once daily for 7 days (1 mL of AEE or EAE at 5 or 50 mg/mL). Maximal dose was defined by the extract solubility. A 10-fold lower dose was also tested. Positive and negative controls were treated with clobetasol (0.5 mg/mL) or excipient. Half of each group was euthanized for histology. The remaining animals were observed for 20 days for wound measurements.

Results: Yields of AEE and EAE were 4.3 and 0.7%, respectively. Betulinic acid concentrations in AEE and EAE were 4.6 and 107.6 mg/g. Extracts neutralized lipid peroxidation in vitro at 0.02 μg/mL, accelerating healing at 50 mg/mL. Complete healing in mice treated with AEE occurred 16 days after wound induction. This time was 14 and 12 days in mice treated with EAE and clobetasol. Compared to orthokeratosis, parakeratosis was reduced by AEE (25%), EAE (45%) and clobetasol (55%). EAE caused superior protection against biomolecules oxidation of skin compared to AEE.

Discussion and conclusion: EAE exhibited activity closer to that of clobetasol. Betulinic acid may be an active constituent, which should be assessed in future studies.

Keywords: Plant; anti-inflammatory; antioxidant; skin; topical treatment.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / standards
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Antioxidants / standards
  • Betulinic Acid
  • Biomarkers / metabolism
  • Clobetasol / pharmacology
  • Dermatologic Agents / isolation & purification
  • Dermatologic Agents / pharmacology*
  • Dermatologic Agents / standards
  • Dilleniaceae / chemistry*
  • Disease Models, Animal
  • Fruit / chemistry*
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Pentacyclic Triterpenes
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / standards
  • Plants, Medicinal
  • Protein Carbonylation / drug effects
  • Psoriasis / drug therapy*
  • Psoriasis / etiology
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Rats, Wistar
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Solvents / chemistry
  • Time Factors
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*
  • Triterpenes / standards
  • Ultraviolet Rays*
  • Wound Healing / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Biomarkers
  • Dermatologic Agents
  • Pentacyclic Triterpenes
  • Plant Extracts
  • Solvents
  • Triterpenes
  • Malondialdehyde
  • Clobetasol
  • Betulinic Acid

Grants and funding

Marina dos Reis Correa and Morgana Miranda Clarinda had scholarships from Art. 170 from the Government of Santa Catarina state, Brazil. Amanda Fernandes Freitas had a scholarship from the Programa Institucional de Bolsas de Iniciação Científica (PIBIC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. Fabrícia Petronilho and Rozangela Curi Pedrosa are recipients of research grants from CNPq (Proc. 309048/2014-1 and 300353/2012-0, respectively).