Bamethan Sulfate

Stimulant laxatives are widely used to treat constipation. We investigated in human small and large intestinal preparations the effects of bis‐(p‐hydroxyphenyl)‐pyridyl‐2‐methane (BHPM), the active metabolite of the laxatives bisacodyl and sodium picosulfate on smooth muscle tone and epithelial secretion.

Circular and longitudinal muscle tone of small or large intestinal preparations were recorded with isometric force transducers. Epithelial ion flux (ISC) and tissue resistance was measured with Ussing chamber technique after apical and basolateral BHPM application to large intestinal mucosa/submucosa preparations. Studies were performed in macroscopically normal specimens from 79 patients.

BHPM concentration‐dependently (0.5‐5 μM) increased the tone of circular and longitudinal muscle from small to large intestine. The effect was strongest in large intestinal longitudinal muscle and smallest in small intestinal circular muscle. Increase in muscle tone was prevented by the L‐type Ca++ channel blocker nifedipine but insensitive to the nerve blocker tetrodotoxin. Apical or basolateral BHPM concentration‐dependently decreased or increased ISC, respectively. The KCa1.1 (BK) channel blocker iberiotoxin reversed apical ISC decrease whereas tetrodotoxin reversed basolateral ISC increase. BHPM had no effect on tissue resistance or nerve‐mediated secretory or muscle response with one exception: at the highest concentration basolateral BHPM reduced nerve‐mediated secretion.

BHPM enhanced mucosal secretion and muscle contractility. Results suggested that the laxative effect of BHPM was a consequence of the increase in muscle tone as well as an increased K+ secretion when acting luminally and a nerve‐driven Cl− and HCO3− secretion once acting basolaterally after absorption.

Hippocampus is a traditional medicine in China, which can be used for treating tumors, aging, fatigue, thrombosis, inflammation, hypertension, prostatic hyperplasia, and other diseases. 1‐(5‐Bromo‐2‐hydroxy‐4‐methoxyphenyl)ethanone [SE1] from seahorse (Hippocampus kuda Bleeler) has been shown to suppress proinflammatory responses. In the present study, SE1 potently inhibited gelatin digestion by MMP‐9 induced by phorbol 12‐myristate 13‐acetate (PMA) and migration of human fibrosarcoma HT1080 cells in dose‐dependent manner. Moreover, western blot analysis and immunofluorescence analysis have been studied on MAPKs (ERK1/2, p38 kinase and JNK) and NF‐κB (p65 and IκB), which refer to the clear molecular mechanism. The results indicated that SE1 significantly suppressed the phosphorylation of mitogen‐activated protein kinases (MAPK: p38 kinase and JNK) and NF‐κB. Finally, molecular docking result showed SE1 interacts with TYR245 and HIS226 of MMP‐9 by hydrogen bond and Pi‐Pi bond to suppress MMP‐9 activity. This data suggested that the SE1 may possess therapeutic and preventive potential for the treatment of MMP‐9 related disorders.