title: Safety of essential bee venom pharmacopuncture as assessed in a randomized controlled double-blind trial.
abstract: BACKGROUND
  While bee venom (BV) pharmacopuncture use is common in Asia, frequent occurrence of allergic reactions during the treatment process is burdensome for both practitioner and patient.
  
  
  OBJECTIVE
  This study compared efficacy and safety in isolated and purified essential BV (eBV) pharmacopuncture filtered for phospholipase A2 (PLA2) and histamine sections, and original BV to the aim of promoting safe BV pharmacopuncture use.
  
  
  METHODS
  In in vitro, we examined the effect of BV and eBV on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and clinically, 20 healthy adults aged 20-40 years were randomly allocated and administered eBV 0.2mL and BV pharmacopuncture 0.2mL on left and right forearm, respectively, and physician, participant, and outcome assessor were blinded to treatment allocation. Local pain, swelling, itching, redness, wheals, and adverse reactions were recorded by timepoint.
  
  
  RESULTS
  eBV and BV exhibited similar inhibitory effects on NO production. Also, in comparison between eBV and BV pharmacopuncture administration areas on each forearm, eBV displayed significantly lower local pain at 24h post-administration (P=0.0062), and less swelling at 30min (P=0.0198), 2 (P=0.0028), 24 (P=0.0068), and 48h post-administration (P=0.0253). eBV also showed significantly less itching at 24 (P=0.0119), 48 (P=0.0082), and 96h (P=0.0141), while redness was significantly less at 30min (P=0.0090), 6 (P=0.0005), and 24h (P<0.0001). Time-by-treatment interactions were statistically significant for itching and redness (P<0.001, and P<0.001, respectively), and all original BV pharmacopuncture administered regions showed a tendency toward more severe itching and redness in later measurements.
  
  
  CONCLUSIONS
  eBV and BV displayed comparable anti-inflammatory effects, and eBV pharmacopuncture presented less local allergic reactions.
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Ahn
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Joon-Shik
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Yoon Jae
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Me-Riong
authors.initials: MR
authors.lastname: Kim
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Ye-Sle
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Ki Byung
authors.initials: KB
authors.lastname: Park
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Eun Jee
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Lee
authors.affiliation: National Development Institute of Korean Medicine, Gyeongsan-si, Gyeongbuk, Republic of Korea.
authors.forename: Hwa Dong
authors.initials: HD
authors.lastname: Lee
authors.affiliation: National Development Institute of Korean Medicine, Gyeongsan-si, Gyeongbuk, Republic of Korea.
authors.forename: Yoonmi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: National Development Institute of Korean Medicine, Gyeongsan-si, Gyeongbuk, Republic of Korea.
authors.forename: SungGeun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea.
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 858 Eonju-ro, Gangnam-gu, Seoul, Republic of Korea. Electronic address: hanihata@gmail.com.
authors.forename: In-Hyuk
authors.initials: IH
authors.lastname: Ha
mesh_terms: D026881:Acupuncture / Q000379:methods; D000328:Adult; D000818:Animals; D001514:Bee Venoms / Q000008:administration & dosage* / Q000276:immunology*; D002460:Cell Line; D004311:Double-Blind Method; D005260:Female; D005542:Forearm; D006801:Humans; D006967:Hypersensitivity / Q000178:diet therapy* / Q000276:immunology; D007299:Insect Bites and Stings / Q000188:drug therapy* / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000276:immunology; D054467:Phospholipases A2 / Q000276:immunology
chemical_list: D001514:Bee Venoms; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D054467:Phospholipases A2
keywords: Anti-inflammatory agents; Bee venoms; Drug hypersensitivity; Drug-related side effects and adverse reactions; Safety; Toxicity