title: Xiaotan Tongfu granules contribute to the prevention of stress ulcers.
abstract: OBJECTIVE
  To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules (XTTF) in stress ulcers.
  
  
  METHODS
  One hundred sixty rats were randomly divided into 4 groups (n = 10) as follows: the model group (MP group), the control group (CP group), the ranitidine group (RP group) and the XTTF granule group (XP group). Rats in the MP group received no drugs, rats in the CP group received 0.2 mL of a 0.9% sodium chloride solution via oral gavage, and rats in the RP and XP groups received the same volume of ranitidine (50 mg/kg) or XTTF granule (4.9 g/kg). The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration. Afterwards, rats were sacrificed at 0, 3, 6 and 24 h. Gastric pH was measured by a precise pH meter; gastric emptying rate (GER) was measured by using a methylcellulose test meal; myeloperoxidase activity (MPO), macrophage migration inhibitory factor (MIF), proliferating cell nuclear antigen (PCNA), and heat shock protein 70 (HSP70) were measured by immunohistochemical staining; and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.
  
  
  RESULTS
  In the cold-restraint stress model, the development of stress ulcers peaked at 3 h and basically regressed after 24 h. Gastric lesions were significantly different in the RP and XP groups at each time point. Interestingly, although this index was much lower in the RP group than in the XP group immediately following stress induction (7.00 ± 1.10 vs 10.00 ± 1.79, P < 0.05. Concerning gastric pH, between the RP and XP groups, we detected a statistically significant difference immediately after stress induction (0 h: 4.56 ± 0.47 vs 3.34 ± 0.28, P < 0.05) but not at any of the subsequent time points. For GER, compared to the RP group, GER was remarkably elevated in the XP group because a statistically significant difference was detected (3 h: 46.84 ± 2.70 vs 61.16 ± 5.12, P < 0.05; 6 h: 60.96 ± 6.71 vs 73.41 ± 6.16, P < 0.05; 24 h: 77.47 ± 3.17 vs 91.31 ± 4.34, P < 0.05). With respect to MPO and MIF, comparisons between the RP and XP groups revealed statistically significant differences at 3 h (MPO: 18.94 ± 1.20 vs 13.51 ± 0.89, P < 0.05; MIF: 150.67 ± 9.85 vs 122.17 ± 5.67, P < 0.05) and 6 h (MPO: 13.22 ± 1.54 vs 8.83 ± 0.65, P < 0.05; MIF: 135.50 ± 9.46 vs 109.83 ± 6.40, P < 0.05). With regard to HSP70, HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups. In addition, comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h. The expression of PCNA was higher in the RP and XP groups 3 h after stress induction. Between these two groups, small but statistically significant differences were observed at all of the time points (3 h: 69.50 ± 21.52 vs 79.33 ± 15.68, P < 0.05; 6 h: 107.83 ± 4.40 vs 121.33 ± 5.71, P < 0.05; 24 h: 125.33 ± 5.65 vs 128.50 ± 14.49, P < 0.05) except 0 h. With regard to apoptosis, the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups. The XP group exhibited a higher inhibition of cell apoptosis than the RP group at 3 h (232.58 ± 24.51 vs 174.46 ± 10.35, P < 0.05) and 6 h (164.74 ± 18.31 vs 117.71 ± 12.08, P < 0.05).
  
  
  CONCLUSIONS
  The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers. It exhibited multiple underlying mechanisms and deserves further study.
authors.affiliation: Bing Yan, Jun Shi, Li-Juan Xiu, Xuan Liu, Yu-Qi Zhou, Shou-Han Feng, Can Lv, Xiu-Xia Yuan, Yin-Cheng Zhang, Yong-Jin Li, Pin-Kang Wei, Zhi-Feng Qin, Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Xiu
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Zhou
authors.forename: Shou-Han
authors.initials: SH
authors.lastname: Feng
authors.forename: Can
authors.initials: C
authors.lastname: Lv
authors.forename: Xiu-Xia
authors.initials: XX
authors.lastname: Yuan
authors.forename: Yin-Cheng
authors.initials: YC
authors.lastname: Zhang
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Li
authors.forename: Pin-Kang
authors.initials: PK
authors.lastname: Wei
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Qin
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D008516:Medicine, Chinese Traditional; D010437:Peptic Ulcer / Q000209:etiology / Q000517:prevention & control*; D011897:Random Allocation; D011899:Ranitidine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D013315:Stress, Psychological
chemical_list: D000897:Anti-Ulcer Agents; D004365:Drugs, Chinese Herbal; D018840:HSP70 Heat-Shock Proteins; C000589577:xiaotan tongfu; D011899:Ranitidine
keywords: Gastric emptying rate; Heat shock protein 70; Inflammation; Proliferation and apoptosis; Stress ulcer; Xiaotan Tongfu granule
references.citation: Crit Care Med. 2010 Apr;38(4):1197-205
references.pmid: 20173630
references.citation: Dig Dis Sci. 1999 Jun;44(6):1177-83
references.pmid: 10389693
references.citation: FEBS Lett. 2007 Jul 31;581(19):3716-22
references.pmid: 17507013
references.citation: Proc Soc Exp Biol Med. 1967 Apr;124(4):1221-3
references.pmid: 6024838
references.citation: Jpn J Pharmacol. 1994 Sep;66(1):139-47
references.pmid: 7861659
references.citation: Am J Gastroenterol. 2006 Oct;101(10):2206-8
references.pmid: 17032184
references.citation: Gastroenterology. 1996 Aug;111(2):345-57
references.pmid: 8690199
references.citation: Ann Intern Med. 1987 Apr;106(4):562-7
references.pmid: 3548524
references.citation: Dig Dis Sci. 1987 Nov;32(11):1261-7
references.pmid: 3665681
references.citation: Eur J Pharmacol. 2000 Jul 7;399(2-3):205-14
references.pmid: 10884521
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Evid Based Complement Alternat Med. 2012;2012:457370
references.pmid: 23093981
references.citation: Pharmacology. 1994 Sep;49(3):144-50
references.pmid: 7972328
references.citation: Compr Ther. 1999 Jan;25(1):30-8
references.pmid: 9987590
references.citation: J Invest Dermatol. 1982 Mar;78(3):206-9
references.pmid: 6276474
references.citation: World J Gastroenterol. 2005 Sep 21;11(35):5480-4
references.pmid: 16222740
references.citation: J Cell Biol. 1992 Nov;119(3):493-501
references.pmid: 1400587
references.citation: Br J Pharmacol. 1982 Nov;77(3):443-8
references.pmid: 6128042
references.citation: Helicobacter. 2004 Oct;9(5):470
references.pmid: 15361089
references.citation: Gastroenterology. 1977 Oct;73(4 Pt 1):777-80
references.pmid: 892382
references.citation: Pharm Res. 1995 Sep;12(9):1316-22
references.pmid: 8570528
references.citation: Eur J Pharmacol. 2002 Jan 2;434(1-2):81-6
references.pmid: 11755169
references.citation: Experientia. 1982 Mar 15;38(3):385-6
references.pmid: 6122592
references.citation: World J Gastroenterol. 2005 Jul 21;11(27):4154-60
references.pmid: 16015682
references.citation: Crit Care Med. 2002 May;30(5):1175-6
references.pmid: 12006831
references.citation: Arch Surg. 1993 Feb;128(2):185-91; discussion 191-2
references.pmid: 8431119
references.citation: Gut. 2006 Jun;55(6):797-802
references.pmid: 16488898
references.citation: Neurotoxicology. 2009 Nov;30(6):1114-9
references.pmid: 19723537
references.citation: Evid Based Complement Alternat Med. 2011;2011:642027
references.pmid: 20981317
references.citation: Neurosci Lett. 2009 Jan 16;449(3):215-9
references.pmid: 19007859
references.citation: J Crit Care. 2010 Jun;25(2):214-20
references.pmid: 19683892
references.citation: Am J Physiol. 1987 Aug;253(2 Pt 1):G241-5
references.pmid: 3497585
references.citation: J Chromatogr Sci. 2013 Mar;51(3):273-85
references.pmid: 22977122
references.citation: Curr Opin Crit Care. 2009 Apr;15(2):139-43
references.pmid: 19578324
references.citation: J Biol Chem. 2009 Jul 17;284(29):19705-15
references.pmid: 19439408
references.citation: Gut. 1967 Feb;8(1):32-5
references.pmid: 6019987
references.citation: Pharm Res. 1995 Sep;12(9):1311-5
references.pmid: 8570527
references.citation: Nat Rev Immunol. 2003 Oct;3(10):791-800
references.pmid: 14502271
references.citation: Ann Pharmacother. 2002 Dec;36(12):1929-37
references.pmid: 12452757
references.citation: Cancer. 2000 Dec 15;89(12):2637-45
references.pmid: 11135226
references.citation: Gut. 1983 Apr;24(4):277-83
references.pmid: 6832623
references.citation: Evid Based Complement Alternat Med. 2013;2013:518094
references.pmid: 23476694
references.citation: Digestion. 1999 Sep-Oct;60(5):461-8
references.pmid: 10473971
references.citation: Crit Care. 1999;3(6):145-149
references.pmid: 11056739
references.citation: Gastroenterology. 1997 Oct;113(4):1188-97
references.pmid: 9322514
references.citation: Gut. 1994 Sep;35(9):1189-96
references.pmid: 7525421
references.citation: Am J Physiol. 1998 Sep;275(3):G467-72
references.pmid: 9724257
references.citation: Br J Pharmacol. 1975 Nov;55(3):387-92
references.pmid: 1203624
references.citation: J Gastroenterol Hepatol. 2000 Mar;15 Suppl:D12-9
references.pmid: 10759215
references.citation: Gastroenterology. 1986 Jan;90(1):20-6
references.pmid: 3940246
references.citation: Gastroenterology. 1982 Dec;83(6):1200-6
references.pmid: 7129028
references.citation: World J Gastroenterol. 2006 Aug 28;12(32):5205-10
references.pmid: 16937534
references.citation: Am J Chin Med. 2002;30(2-3):207-14
references.pmid: 12230009
references.citation: Nat Clin Pract Gastroenterol Hepatol. 2008 Nov;5(11):624-36
references.pmid: 18825145
references.citation: JAMA. 1998 Nov 11;280(18):1585-9
references.pmid: 9820260
references.citation: Dig Dis Sci. 2003 Feb;48(2):340-8
references.pmid: 12643613
references.citation: Gastroenterology. 2001 Sep;121(3):619-30
references.pmid: 11522746
references.citation: World J Gastroenterol. 2005 Feb 28;11(8):1204-9
references.pmid: 15754406
references.citation: Digestion. 2002;66(3):160-72
references.pmid: 12481162
references.citation: Dig Dis Sci. 2001 May;46(5):997-1003
references.pmid: 11341671