title: Heme oxygenase 1-mediated novel anti-inflammatory activities of Salvia plebeia and its active components.
abstract: BACKGROUND
  Salvia plebeia R. Br. (SP) has been widely used as a traditional folk medicine for the treatment of infectious diseases and pain. An anti-inflammatory potential of SP has remains largely unknown.
  
  
  OBJECTIVE
  We tried to elucidate the principle mechanism and the active ingredients underlying the anti-inflammatory activities of SP.
  
  
  METHODS
  We investigated the protective activities of SP methanolic extract (SPME) and seven representative ingredients against inflammation. Quantitative analysis using HPLC-DAD-ESI/MS was conducted to determine the relative amounts of these seven active ingredients in SPME. Both in vitro murine macrophages and in vivo mouse models were employed to elucidate SP- and active ingredient-mediated anti-inflammatory effects.
  
  
  RESULTS
  SPME significantly reduced inflammatory processes both in vivo in a TPA-induced ear edema model and in vitro in lipopolysaccharide (LPS)-activated macrophages. SPME decreased the release of nitric oxide (NO) and prostaglandin E2 (PGE2) and expression of inducible nitric oxide synthase (iNOS). Seven active components (luteoloside (C1), nepitrin (C2), homoplantagenin (C3), luteolin (C4), nepetin (C5), hispidulin (C6), and eupatorin (C7)) of SPME were analyzed and their relative concentrations were determined, demonstrating that C2, C3, C5 and C6 were present in higher amounts than were C1, C4, and C7. These major compounds inhibited NO and PGE2 production, and iNOS and COX-II protein expression through heme oxygenase-1 (HO-1) induction via activation of nuclear factor erythroid 2-related factor2 (Nrf2).
  
  
  CONCLUSIONS
  Our data demonstrate that SPME possesses potent in vitro and in vivo anti-inflammatory activities. Nepetin and hispidulin, and their glycosides are the major active compounds in SPME, and their effects are mediated by Nrf2/HO-1 signaling. Taken together, we propose that SPME and its active ingredients may serve as novel therapeutic candidates for diseases associated with excessive inflammation.
authors: College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea.
authors: Muhammad
authors: M
authors: Akram
authors: College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea.
authors: Ahmed Shah
authors: AS
authors: Syed
authors: College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea.
authors: Kyeong-A
authors: KA
authors: Kim
authors: CL Institute Korea (CLIK), Ansan, Republic of Korea; Department of Chemistry, Ajou University, Suwon, Republic of Korea.
authors: Jong Soo
authors: JS
authors: Lee
authors: College of Pharmacy, Ajou University, Suwon, Republic of Korea.
authors: Sun-Young
authors: SY
authors: Chang
authors: College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea. Electronic address: chulykim@hanyang.ac.kr.
authors: Chul Young
authors: CY
authors: Kim
authors: College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Republic of Korea. Electronic address: onbae@hanyang.ac.kr.
authors: Ok-Nam
authors: ON
authors: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D027544:Salvia
chemical_list: D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D051547:Heme Oxygenase-1
keywords: Anti-inflammatory activity; Heme oxygenase-1 (HO-1); Hispidulin; Nepetin; Nuclear factor erythroid 2–related factor2 (Nrf2); Salvia plebeia R. Br