title: Anti-hyperalgesic and anti-inflammatory effects of the modified Chinese herbal formula Huo Luo Xiao Ling Dan (HLXL) in rats.
abstract: Chinese herbal medicine has been used for thousands of years in China and other Asian countries to treat a variety of inflammatory diseases. The classic Chinese herbal formula, Huo Luo Xiao Ling Dan (HLXL) is commonly used in traditional Chinese herbal medicine for the treatment of joint pain and other symptoms of arthritis. The present study is an investigation of the effects of a modified HLXL extract on persistent hyperalgesia and edema in rats with peripheral inflammation. Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hind paw. Four dosages of the extract were compared to a vehicle control. Each was administered intragastrally (i.g.) daily for seven days beginning one day before CFA. Hyperalgesia was assessed using a paw withdrawal latency (PWL) test and edema was determined by measuring paw thickness at pre-CFA and 2 hours, 24 hours, and 5 days post-CFA. Immunohistochemistry was performed 2 hours post-CFA to determine spinal Fos protein expression. Adverse effects of the extract were monitored by observing the animals closely for unusual behavioral changes. Compared to the control, HLXL at the two lower dosages (0.575 g/kg and 1.15 g/kg) were effective in the later stage (day 5) of inflammatory hyperalgesia and edema, while the two higher dosages (2.3 g/kg and 4.6 g/kg) alleviated early stage hind paw inflammation and hyperalgesia and facilitated recovery from paw edema and hyperalgesia during the late stage. HLXL at 2.30 g/kg significantly suppressed Fos expression in laminae I-II, III-IV and V-VI ipsilaterally and in III-IV contralaterally. No significant signs of toxicity or adverse effects were observed. The data suggest that HLXL dosage-dependently attenuates CFA-induced inflammation and hyperalgesia, at least in part by inhibiting noxious transmission at the dorsal horn of the spinal cord.
authors.affiliation: Center for Integrative Medicine, School of Medicine, Department of Family Medicine, University of Maryland School of Medicine, 2200 Kernan Drive, 3rd Floor, Baltimore, MD 21207, USA. LLao@compmed.umm.edu
authors.forename: Lixing
authors.initials: L
authors.lastname: Lao
authors.forename: Arthur Yin
authors.initials: AY
authors.lastname: Fan
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Zhang
authors.forename: Annan
authors.initials: A
authors.lastname: Zhou
authors.forename: Zhong-Ze
authors.initials: ZZ
authors.lastname: Ma
authors.forename: David Yue-Wei
authors.initials: DY
authors.lastname: Lee
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Brian
authors.initials: B
authors.lastname: Berman
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005620:Freund's Adjuvant; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D016760:Proto-Oncogene Proteins c-fos; C547651:huo luo xiao ling dan; D005620:Freund's Adjuvant