Sandeepa S Bhoir1, Vinod Vishwapathi2, Kamalinder K Singh3. 1. C. U. Shah College of Pharmacy, S.N. D. T. Women's University, Santacruz (W), Mumbai 400049, India. 2. School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom. 3. School of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom. Electronic address: ksingh1@uclan.ac.uk.
Abstract
BACKGROUND: Corticosteroids remains compound of choice for topical treatment of psoriasis. Several side effects associated with chronic application of corticosteroids limit its uses. Hence, there is a need to find a safe and effective alternative agent for psoriasis treatment. PURPOSE: The study aimed to investigate the in vitro and in vivo efficacy of petroleum ether extract of Annona squamosa seeds (ASO) as an antipsoriatic agent. The toxicity profile of ASO and its effect on psoriasis-induced inflammation has also been determined. METHODS: Physicochemical characterization was performed to determine constituents of ASO. Anti-proliferative activity of ASO was studied by Sulforhodamine B (SRB) assay using HaCaT cell lines. Oxazolone-induced psoriasis in female Balb/C mice was used as an animal model for investigating in vivoefficacy of ASO. Inflammatory markers were analyzed by immunohistochemical staining of mice ears. Safety profile of ASO was confirmed by performing acute dose dermal toxicity and repeated dose dermal toxicity testing. RESULTS: Predominant presence of polyunsaturated fatty acids viz. linoleic acid and oleic acid in ASO was confirmed by 1H NMR, 13C NMR and GC-MS analysis. The petroleum ether extract of Annona squamosa seeds showed inhibition of cell proliferation of keratinocytes (HaCaT cells). The growth inhibitory property of ASO was significantly higher than that was observed in presence of corticosteroid, clobetasol propionaste (CP). Application of ASO to the ears of Balb/C mice with oxazolone induced psoriasis showed marked reduction in erythema and edema, which was comparable to treatment with 0.05% CP cream. The increased levels of cytokines IL6, IL17, TNF-α, INF-γ, GMCSF, and infiltration of CD4 T cells observed in psoriasis lesions were decreased upon application of ASO. Acute and repeated dermal toxicity studies of ASO did not reveal any adverse events affirming the safety of ASO. CONCLUSION: The present data has demonstrated that ASO is a safe and effective anti-psoriatic agent when tested in animal models. The efficacy of ASO in preclinical studies could further be exploited for the development of potential novel topical antipsoriatic agent for therapy in humans.
BACKGROUND: Corticosteroids remains compound of choice for topical treatment of psoriasis. Several side effects associated with chronic application of corticosteroids limit its uses. Hence, there is a need to find a safe and effective alternative agent for psoriasis treatment. PURPOSE: The study aimed to investigate the in vitro and in vivo efficacy of petroleum ether extract of Annona squamosa seeds (ASO) as an antipsoriatic agent. The toxicity profile of ASO and its effect on psoriasis-induced inflammation has also been determined. METHODS: Physicochemical characterization was performed to determine constituents of ASO. Anti-proliferative activity of ASO was studied by Sulforhodamine B (SRB) assay using HaCaT cell lines. Oxazolone-induced psoriasis in female Balb/C mice was used as an animal model for investigating in vivoefficacy of ASO. Inflammatory markers were analyzed by immunohistochemical staining of mice ears. Safety profile of ASO was confirmed by performing acute dose dermal toxicity and repeated dose dermal toxicity testing. RESULTS: Predominant presence of polyunsaturated fatty acids viz. linoleic acid and oleic acid in ASO was confirmed by 1H NMR, 13C NMR and GC-MS analysis. The petroleum ether extract of Annona squamosa seeds showed inhibition of cell proliferation of keratinocytes (HaCaT cells). The growth inhibitory property of ASO was significantly higher than that was observed in presence of corticosteroid, clobetasol propionaste (CP). Application of ASO to the ears of Balb/C mice with oxazolone induced psoriasis showed marked reduction in erythema and edema, which was comparable to treatment with 0.05% CP cream. The increased levels of cytokines IL6, IL17, TNF-α, INF-γ, GMCSF, and infiltration of CD4 T cells observed in psoriasis lesions were decreased upon application of ASO. Acute and repeated dermal toxicity studies of ASO did not reveal any adverse events affirming the safety of ASO. CONCLUSION: The present data has demonstrated that ASO is a safe and effective anti-psoriatic agent when tested in animal models. The efficacy of ASO in preclinical studies could further be exploited for the development of potential novel topical antipsoriatic agent for therapy in humans.