• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.1-9
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• 2017

Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.47-53
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• 2014

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline ($20{\mu}M$) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a $Ca^{2+}$ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is $Ca^{2+}$ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of $Ca^{2+}$, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.

• Korean Journal of Veterinary Research
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• v.34 no.1
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• pp.63-67
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• 1994

Berberine $(10^{-7}-10^5M)$ increased the contractility dose-dependently in isolated rabbit ileal and jejunal segments. Atropine and hemicholinium abolished this response but not mecamylamine. Berberine$(10^{-8}-10^5M)$ enhanced the transmurally-stimulated(80 V, 0.5 ms, 0.05 Hz) twitch response in the isolated guinea-pig ileal segments. Atropine and hemicholinium also abolished this response but not mecamylamine. Effect of KCI, carbachol and histamine were not affected by pretreatment with berberine$(10^{-5}M)$. The results of our study suggest that berberine increases the intestinal contractility by increasing a small amount of acetylcholine release from the postganglionic parasympathetic nerve terminal but not by a direct activation of muscarinic receptors.

• Journal of Ginseng Research
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• v.22 no.3
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• pp.200-205
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• 1998

Isolated rabbit jejunal segments were used to study the effects of ginseng total saponins (GTS) , protopanaxatriol saponins (PT) and protopanaxadiol saponins (PD) on intestinal contractility. GTS, PT and PD caused a dose-dependent decrease in intestinal spontaneous movements, and PT was the most efficacious of them. The effect of GTS, PT and PD were not blocked by pretreatment with phentolamine (10-6 M), yohimbine (10-6 M), d1-propranolol (10-6 M), naloxone(10-6∼10-5M), Nu-nitro-L-arginine methyl ester (10-4 M), methylene blue (10-5M), and N-ethylmaleimide (10-4 M). However, pretreatment with tetraethylammonium chloride (3-10 mM) antagonized the effect of GTS, PT and PD. Furthermore, 4-amlnopyridine (1 mM) also inhibited the effect of GTS, PT and PD. The results suggest that GTS, PT and PD inhibited the spontaneous movements in isolated rebait jejunum by causing hyperpolarization through an activation of K+ channels directly.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.609-616
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• 2017

Ardipusilloside-I is a natural triterpenoid saponin, which was isolated from Ardisia pusilla A. DC. The aim of the study was to evaluate the stimulation of ardipusilloside-I on gastrointestinal motility in vitro and in vivo. The experiment of smooth muscle contraction directly monitored the contractions of the isolated jejunal segment (IJS) in different contractile states, and the effects of ardipusilloside-I on myosin were measured in the presence of $Ca^{2+}$-calmodulin using the activities of 20 kDa myosin light chain ($MLC_{20}$) phosphorylation and myosin $Mg^{2+}$-ATPase. The effects of ardipusilloside-I on gastro emptying and intestinal transit in constipation-predominant rats were observed, and the MLCK expression in jejuna of constipated rats was determined by western blot. The results showed that, ardipusilloside-I increased the contractility of IJS in a dose-dependent manner and reversed the low contractile state (LCS) of IJS induced by low $Ca^{2+}$, adrenaline, and atropine respectively. There were synergistic effects on contractivity of IJS between ardipusilloside-I and ACh, high $Ca^{2+}$, and histamine, respectively. Ardipusilloside-I could stimulate the phosphorylation of $MLC_{20}$ and $Mg^{2+}$-ATPase activities of $Ca^{2+}$- dependent phosphorylated myosin. Ardipusilloside-I also stimulated the gastric emptying and intestinal transit in normal and constipated rats in vivo, respectively, and increased the MLCK expression in the jejuna of constipation-predominant rats. Briefly, the findings demonstrated that ardipusilloside-I could effectively excite gastrointestinal motility in vitro and in vivo.