title: The safety of Homnawakod herbal formula containing Aristolochia tagala Cham. in Wistar rats.
abstract: BACKGROUND
  A dried root of Aristolochia tagala Cham. (ATC) is often used in Thai traditional medicine as an antipyretic, anti-inflammatory agent, muscle relaxant, appetite-enhancing agent, and analeptic. Homnawakod, an important herbal recipe, originally contains ATC in its formula, however, some Aristolochia species have been reported to cause nephrotoxicity due to aristolochic acid (AA) and its derivatives, resulting in ATC removal from all formulae. Therefore, this study investigates the chemical profiles of ATC, the original (HNK+ATC) and the present Homnawakod Ayurved Siriraj Herbal Formulary™ (HNK), and investigates whether they could cause nephrotoxicity or aggravate LPS-induced organ injuries in vivo.
  
  
  METHODS
  HPLC and LC/MS were used for chemical profile study. Male Wistar rats were randomly divided into groups in which the rats were intragastrically administered distilled water (2 groups), ATC (10 or 30 mg/kg), HNK+ATC (540 or 1,620 mg/kg), or HNK (1,590 mg/kg) for 21 days. A positive control group was administered with single dose 100 mg/kg standard AA-I intragastrically at day 1. Serum creatinine and urea were measured at baseline and at 7, 14 and 21 days of the treatment. On day 22, a model of lipopolysaccharide (LPS)-induced endotoxemia was used. One-way and two-way analyses of variance were performed and a P value of less than 0.05 was considered to be significant.
  
  
  RESULTS
  The similarity of the HPLC chromatograms of HNK+ATC and HNK could suggest that the qualities of both formulae are nearly the same in terms of chemical profile. The amount of AA-I found in ATC is 0.24%w/w. All experimental groups exhibited similar levels of serum urea at baseline and 7 and 14 days of the treatment. At 21 days, rats received AA exhibited a significant increase in serum urea, whereas the others did not exhibit such toxicity. On day 22, there were no significant changes in LPS-induced renal and liver dysfunction, or LPS-induced mean arterial pressure (MAP) reduction upon administration of ATC, HNK+ATC, HNK or AA-I.
  
  
  CONCLUSIONS
  These results suggest that ATC, HNK+ATC or HNK, at the animal dose equivalent to that used in human, do not cause the acute nephrotoxicity in rats and do not aggravate LPS-induced organ injuries even further.
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. pinpat.tri@mahidol.ac.th
authors.forename: Pinpat
authors.initials: P
authors.lastname: Tripatara
authors.forename: Winita
authors.initials: W
authors.lastname: Onlamul
authors.forename: Suksalin
authors.initials: S
authors.lastname: Booranasubkajorn
authors.forename: Jantanee
authors.initials: J
authors.lastname: Wattanarangsan
authors.forename: Sukit
authors.initials: S
authors.lastname: Huabprasert
authors.forename: Natchagorn
authors.initials: N
authors.lastname: Lumlerdkij
authors.forename: Pravit
authors.initials: P
authors.lastname: Akarasereenont
authors.forename: Tawee
authors.initials: T
authors.lastname: Laohapand
mesh_terms: D000818:Animals; D030022:Aristolochia / Q000009:adverse effects* / Q000737:chemistry; D034341:Aristolochic Acids / Q000009:adverse effects* / Q000032:analysis / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D007022:Hypotension / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008515:Medicine, Ayurvedic; D008518:Medicine, East Asian Traditional; D010936:Plant Extracts / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D014508:Urea / Q000097:blood
chemical_list: D034341:Aristolochic Acids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014508:Urea; C000228:aristolochic acid I