title: Chemical profiles and pharmacological activities of Chang-Kang-Fang, a multi-herb Chinese medicinal formula, for treating irritable bowel syndrome.
abstract: BACKGROUND
  Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown.
  
  
  OBJECTIVE
  To investigate the chemical profiles and effects of CKF on IBS model.
  
  
  METHODS
  The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated.
  
  
  RESULTS
  80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0g/kg/d.
  
  
  CONCLUSIONS
  CKF could alleviate the symptoms of IBS by modulating the brain-gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF.
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address: nancymq2008@hotmail.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China. Electronic address: shileid@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China. Electronic address: wzgjsmg@xinhuanet.com.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China. Electronic address: yhlnj@163.com.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China. Electronic address: wyy9260@126.com.
authors.forename: Yin-Yu
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China. Electronic address: xueli@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China. Electronic address: minlud@126.com.
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address: jjm405@sina.com.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Ju
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address: xujindi1985@163.com.
authors.forename: Jin-Di
authors.initials: JD
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address: kongming1027@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address: 787106148@qq.com.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China. Electronic address: mqshen@163.com.
authors.forename: Min-Qin
authors.initials: MQ
authors.lastname: Shen
authors.affiliation: Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Department of Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address: songlinli64@126.com.
authors.forename: Song-Lin
authors.initials: SL
authors.lastname: Li
mesh_terms: D019342:Acetic Acid; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D043183:Irritable Bowel Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D064209:Phytochemicals / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013373:Substance P / Q000097:blood / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D059265:Visceral Pain / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D004365:Drugs, Chinese Herbal; D064209:Phytochemicals; C000619811:chang-kang-fang; D012701:Serotonin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D015740:Calcitonin Gene-Related Peptide; D019342:Acetic Acid
keywords: Bioactivities; Chang-Kang-Fang formula; Chemical profile; Irritable bowel syndrome