Hange-shashin-to (Variation Ban Xia Xie Xin Tang)

Pharmacological Properties of Traditional Medicine (XXIX): Effect of Hange-shashin-to and the Combinations of Its Herbal Constituents on Rat Experimental Colitis

Kawashima K, Nomura A, Makino T, Saito K-I, Kano Y. Biological and Pharmaceutical Bulletin. Vol. 27 (2004) No. 10 P 1599-1603

Hange-shashin-to (HST) has been used as an herbal formula to treat inflammatory ulcerative gut diseases complicated with psychoneurosis in Japanese traditional Kampo medicine. The aim of the present study is to clarify anti-colitic effect of HST using a model of colitis induced by intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats, and to evaluate the pharmaceutical properties of its herbal components. The colonic damage was elucidated by macroscopic damage scores, colon wet weight and area of mucosal necrosis. Orally administered HST significantly reduced the colonic damage. Other rats were orally treated with single-component berberine (BE), baicalin (BA), glycyrrhizin (GL) or saponin fraction of ginsenosides (GS), or with the mixture (TL) of BA, BE, GL and GS, or with the combinations of BA plus BE (BA-BE), or that of GL plus GS (GL-GS). Oral treatment of TL ameliorated colitis observations. However, no effects were found in the treatment of single-component BA, BE, GL or GS, whereas the GL-GS combination ameliorated the colitis. These results suggest that HST might suppress inflammatory bowel disease (IBD) and imply that there will be a potential benefit in the traditionally derived herbal combination.

Hange-shashin-to raises levels of somatostatin, motilin, and gastrin in the plasma of healthy subjects.

Naito T, Itoh H, Yasunaga F, Takeyama M. Biol Pharm Bull. 2002 Mar; 25(3): 327-31.

Hange-shashin-to has been used for chronic hypofunction of the gastrointestinal tract and to improve functional abnormalities of the upper and lower gastrointestinal system. To determine whether the pharmacological effects of Hange-shashin-to are due to gut-regulatory peptide levels, we developed a sensitive and specific double-antibody enzyme immunoassay (EIA) for detecting motilin and also examined the levels of somatostatin-, motilin-, gastrin-, and vasoactive intestinal peptide (VIP)-immunoreactive substances (IS) in plasma from healthy subjects. We developed a sensitive (3.5 pg, 1.4 pg/well) and specific (carboxy-terminal region) EIA for motilin. A single oral administration of Hange-shashin-to 6.0 g caused significant increases somatostatin-IS (20-60 min), motilin-IS (40 min), and gastrin-IS (40-90 min) levels in plasma compared with levels in a placebo group. Hange-shashin-to had no significant effect on VIP-IS levels after single administration. These changes in hormone levels (somatostatin, motilin, and gastrin) might relate to normalization of the upper and lower gastrointestinal system by Hange-shashin-to.

Si-Ni-San, a traditional Chinese prescription, and its active ingredient glycyrrhizin ameliorate experimental colitis through regulating cytokine balance.

Sun Y, Cai TT, Shen Y, Zhou XB, Chen T, Xu Q. Int Immunopharmacol. 2009 Nov;9(12):1437-43. Epub 2009 Sep 4.

The therapeutic potential of Si-Ni-San and its ingredient glycyrrhizin in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice, a well-characterized murine model for Crohn's disease. Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis with reduced mortality and recovery of body weights. In addition, Si-Ni-San and glycyrrhizin dose-dependently decreased macroscopic inflammation scores, microscopic histological scores, and myeloperoxidase activity. Furthermore, Si-Ni-San and glycyrrhizin caused a decrease in pro-inflammatory cytokines including IFN-gamma, IL-12, TNF-alpha and IL-17 and an increase in regulatory cytokine IL-10 in colon of the mice. It should be noticed the therapeutic effect of Si-Ni-San at 450 mg/kg was much better than that of its contained content of glycyrrhizin at 10 mg/kg. In conclusion, Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis in mice through regulating pro- and anti-inflammatory cytokine production.

Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice.

Yan F, Wang L, Shi Y, Cao H, Liu L, Washington MK, Chaturvedi R, Israel DA, Cao H, Wang B, Peek RM Jr, Wilson KT, Polk DB. Am J Physiol Gastrointest Liver Physiol. 2012 Mar 1;302(5):G504-14. Epub 2011 Dec 15.

Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immune responses to microflora in genetically susceptible hosts. A major challenge for IBD research is to develop new strategies for treating this disease. Berberine, an alkaloid derived from plants, is an alternative medicine for treating bacterial diarrhea and intestinal parasite infections. Recent studies suggest that berberine exerts several other beneficial effects, including inducing anti-inflammatory responses. This study determined the effect of berberine on treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. Berberine was administered through gavage to mice with established DSS-induced intestinal injury and colitis. Clinical parameters, intestinal integrity, proinflammatory cytokine production, and signaling pathways in colonic macrophages and epithelial cells were determined. Berberine ameliorated DSS-induced body weight loss, myeloperoxidase activity, shortening of the colon, injury, and inflammation scores. DSS-upregulated proinflammatory cytokine levels in the colon, including TNF, IFN-γ, KC, and IL-17 were reduced by berberine. Berberine decreased DSS-induced disruption of barrier function and apoptosis in the colon epithelium. Furthermore, berberine inhibited proinflammatory cytokine production in colonic macrophages and epithelial cells in DSS-treated mice and promoted apoptosis of colonic macrophages. Activation of signaling pathways involved in stimulation of proinflammatory cytokine production, including MAPK and NF-κB, in colonic macrophages and epithelial cells from DSS-treated mice was decreased by berberine. In summary, berberine promotes recovery of DSS-induced colitis and exerts inhibitory effects on proinflammatory responses in colonic macrophages and epithelial cells. Thus berberine may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders.