title: Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models.
abstract: BACKGROUND
  Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed.
  
  
  METHODS
  The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification.
  
  
  RESULTS
  Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities.
  
  
  CONCLUSIONS
  Plants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA.
authors.affiliation: Thailand Center of Excellence for Drug Discovery and Development (TCEDDD), Thammasat University, Pathumthani, Thailand.
authors.forename: Tullayakorn
authors.initials: T
authors.lastname: Plengsuriyakarn
authors.forename: Vithoon
authors.initials: V
authors.lastname: Viyanant
authors.forename: Veerachai
authors.initials: V
authors.lastname: Eursitthichai
authors.forename: Porntipa
authors.initials: P
authors.lastname: Picha
authors.forename: Piengchai
authors.initials: P
authors.lastname: Kupradinun
authors.forename: Arunporn
authors.initials: A
authors.lastname: Itharat
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013785:Thailand; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D003474:Curcumin