title: Piper betel leaves induces wound healing activity via proliferation of fibroblasts and reducing 11β hydroxysteriod dehydrogenase-1 expression in diabetic rat.
abstract: BACKGROUND
  Increased oxidative stress and stress enzyme 11β hydroxysteriod dehydrogenase-1 (11β HSD-1) served as the major contributing factors for delayed wound healing in diabetes mellitus (DM). Piper betel (PB) leaves are reported to possess anti-diabetic, anti-oxidant and anti-microbial properties.
  
  
  OBJECTIVE
  The objective was to investigate the effectiveness of topical application of PB leaves extract on oxidative stress and 11β hydroxysteriod dehydrogenase-1 (11β HSD-1) expression in diabetic wounds.
  
  
  METHODS
  A total 64 male Sprague-Dawley rats were randomly chosen. The experimental rats received a single intramuscular injection of streptozotocin (45 mg/kg). Four full thickness (6 mm) wounds were created on the dorsum of each rat. The animals were equally divided (n = 8) into four groups based on the days of treatment (i.e. days 3 and 7): Control (Ctrl), diabetic untreated (DM-Ctrl), diabetic treated with 1% silver nitrate cream (DM-SN) and diabetic treated with 50 mg/kg of P. betel leaves extract (DM-PB). The rats were sacrificed on day 3 and 7 of post wound creations.
  
  
  RESULTS
  Following day 7 wound creation, topical application of PB extract showed significant increase in hydroxyproline content, superoxide dismutase (SOD) level and decreased malondialdehyde (MDA) level, 11β-HSD-1 enzyme expression in the diabetic wounds compared to untreated diabetic wounds. The results were supported by the observations based on histological and ultrastructural features of the wound tissue applied with PB extract.
  
  
  CONCLUSIONS
  PB leaves extract improved the delayed wound healing in diabetes mellitus by decreasing the oxidative stress markers and 11β HSD-1 expression.
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Nur Amalina
authors.initials: NA
authors.lastname: Ghazali
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Azree
authors.initials: A
authors.lastname: Elmy
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Lee Chee
authors.initials: LC
authors.lastname: Yuen
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Nurul Zaidah
authors.initials: NZ
authors.lastname: Sani
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Srijit
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Farihah
authors.initials: F
authors.lastname: Suhaimi
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Rafizul
authors.initials: R
authors.lastname: Yusof
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Nurul Huda
authors.initials: NH
authors.lastname: Yusoff
authors.affiliation: Department of Anatomy, Pre-clinical Building, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000, Cheras, Kuala Lumpur, Malaysia; Anatomy Disciplines, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000, Sungi Buloh, Selangor, Malaysia. Electronic address: zarrchii@gmail.com.
authors.forename: Zar Chi
authors.initials: ZC
authors.lastname: Thent
keywords: 11β-HSD-1 enzyme; Diabetes mellitus; Oxidative stress; Piper betel; Wound