title: Rhodomyrtone as a potential anti-proliferative and apoptosis inducing agent in HaCaT keratinocyte cells.
abstract: Psoriasis is a skin disease associated with hyperproliferation and abnormal differentiation of keratinocytes. Available approaches using synthetic drugs for the treatment of severe psoriasis may cause side effects. Alternatively, plant-derived compounds are now receiving much attention as alternative candidates for the treatment of psoriasis. In this study, the effects of rhodomyrtone, a bioactive plant extract isolated from Rhodomyrtus tomentosa leaves on the proliferation, growth arrest, and apoptosis of HaCaT keratinocytes were investigated. Percentage anti-proliferative activity of rhodomyrtone on HaCaT cells at concentrations of 2-32µg/ml after 24, 48, and 72h ranged from 13.62-61.61%, 50.59-80.16%, and 61.82-85.34%, respectively. In a scratch assay, rhodomyrtone at 2 and 4µg/ml significantly delayed closure of a wound by up to 61.78%, and 71.65%, respectively, after 24h incubation. HaCaT keratinocytes treated with rhodomyrtone showed chromatin condensation and fragmentation of nuclei when stained with Hoechst 33342. This indicated that rhodomyrtone induced apoptosis in the keratinocytes. In addition, flow cytometric analysis demonstrated an increase in the percentage of apoptosis of keratinocytes after treatment with rhodomyrtone at 2-32µg/ml from 1.2-10%, 8.2-35.4%, and 21.0-77.8% after 24, 48, and 72h, respectively, compared with the control. To further develop the compound as a potential anti-psoriasis agent, a rhodomyrtone formulation was prepared and subjected to skin irritation tests in rabbits. The formulation caused no skin irritation including such as erythema and edema. The results indicated that rhodomyrtone had the potential as a promising candidate for further development as a natural anti-psoriasis agent.
authors.affiliation: Excellent Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand; Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Julalak
authors.initials: J
authors.lastname: Chorachoo
authors.affiliation: Excellent Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand; Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Dennapa
authors.initials: D
authors.lastname: Saeloh
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Teerapol
authors.initials: T
authors.lastname: Srichana
authors.affiliation: Excellent Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand; Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Thanaporn
authors.initials: T
authors.lastname: Amnuaikit
authors.affiliation: Excellent Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Khadar Syed
authors.initials: KS
authors.lastname: Musthafa
authors.affiliation: Immunology and Virology Unit, Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Somporn
authors.initials: S
authors.lastname: Sretrirutchai
authors.affiliation: Excellent Research Laboratory on Natural Products, Faculty of Science and Natural Product Research Center of Excellence, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand; Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand. Electronic address: supayang.v@psu.ac.th.
authors.forename: Supayang P
authors.initials: SP
authors.lastname: Voravuthikunchai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects*; D019684:Magnoliopsida / Q000737:chemistry; D011565:Psoriasis / Q000188:drug therapy; D011817:Rabbits; D044004:Xanthones / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D044004:Xanthones; C541823:rhodomyrtone
keywords: Anti-proliferative; Anti-psoriasis agent; Apoptosis; HaCaT cells; Psoriasis; Rhodomyrtone