title: Protective effect of AVS073, a polyherbal formula, against UVA-induced melanogenesis through a redox mechanism involving glutathione-related antioxidant defense.
abstract: BACKGROUND
  Ayurved Siriraj Brand Wattana formula (AVS073), a Thai herbal formula, has traditionally been used for health promotion and prevention of age-related problems. Ultraviolet A (UVA) is recognized to play a vital role in stimulation of melanin synthesis responsible for abnormal skin pigmentation possibly mediated by photooxidative stress. We thus aimed to study the inhibitory effect of AVS073 extracts on UVA-induced melanogenesis via a redox mechanism involving glutathione (GSH) synthesis and glutathione S-transferase (GST) using human melanoma (G361) cell culture.
  
  
  METHODS
  The standardization of AVS073 extracts was carried out by TLC and UHPLC to obtain fingerprinting profiles of the formula, which identified several phenolic compounds including gallic acid (GA) in the formula. Antimelanogenic actions of AVS073 (up to 60 μg/ml) and GA (up to 10 μg/ml) were investigated by measuring tyrosinase activity and mRNA as well as melanin level in G361 cells irradiated with UVA. Moreover, antioxidant actions of the herbal formula and GA were determined by evaluating oxidant formation and modulation of GSH-related antioxidant defenses including GSH content, GST activity and mRNA level of γ-glutamate cysteine ligase catalytic (γ-GCLC) and modifier (γ-GCLM) subunit and GST.
  
  
  RESULTS
  AVS073 extracts and GA, used as a reference compound, suppressed UVA-augmented tyrosinase activity and mRNA and melanin formation. In addition, pretreatment with AVS073 and GA was able to inhibit cellular oxidative stress, GSH depletion, GST inactivation and downregulation of γ-GCLC, γ-GCLM and GST mRNA in G361 cells exposed to UVA radiation.
  
  
  CONCLUSIONS
  AVS073 formula exerted antimelanogenic effects possibly through improving the redox state by upregulation of GSH and GST. Moreover, pharmacological activity of the polyherbal formula would be attributed to combined action of different phenolic compounds present in the formula.
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. uraiwan.pan@mahidol.ac.th
authors.forename: Uraiwan
authors.initials: U
authors.lastname: Panich
authors.forename: Thanyawan
authors.initials: T
authors.lastname: Pluemsamran
authors.forename: Vanida
authors.initials: V
authors.lastname: Tangsupa-a-nan
authors.forename: Jantanee
authors.initials: J
authors.lastname: Wattanarangsan
authors.forename: Rattana
authors.initials: R
authors.lastname: Phadungrakwittaya
authors.forename: Pravit
authors.initials: P
authors.lastname: Akarasereenont
authors.forename: Tawee
authors.initials: T
authors.lastname: Laohapand
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012880:Skin Pigmentation / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D008543:Melanins; D010636:Phenols; D010936:Plant Extracts; D020011:Protective Agents; D014442:Monophenol Monooxygenase; D005978:Glutathione