A paradoxical stimulatory effect of berberine on guinea-pig ileum contractility: Possible involvement of acetylcholine release from the postganglionic parasympathetic nerve and cholinesterase inhibition

doi:10.1016/0024-3205(93)90623-B

Life Sciences

Volume 53, Issue 19, 1993, Pages 1495-1500

https://doi.org/10.1016/0024-3205(93)90623-B Get rights and content

Abstract

The effects of berberine on guinea-pig ileum contractility were studied in both transmurally-stimulated and unstimulated preparations. Transmural stimulation (80 V, 0.5 ms, 0.05 Hz) of the guinea-pig ileal segments produced a twitch response. Berberine (10⁻⁸–10⁻⁵ M) enhanced this response dose-dependently. Atropine (10⁻⁷ M), but not mecamylamine (10⁻⁵ M), abolished this response. Acetylcholine (3 × 10⁻⁹ and 10⁻⁸ M) also enhanced the response to transmural stimulation. Pretreatment with hemicholinium (3 × 10⁻⁵ M) antagonized the effect of berberine but failed to change that of acetylcholine. Berberine (10⁻⁵ M) also antagonized the α₂-adrenoceptor agonist xylazine (10⁻⁸ and 10⁻⁷ M)-induced inhibition of the twitch response to transmural stimulation. In unstimulated ileal preparations, berberine (10⁻⁵ M) produced contractile responses. In these preparations, atropine (10⁻⁶ M), but not mecamylamine (10⁻⁴ M), abolished the response to berberine. Furthermore, berberine (10⁻⁶ – 10⁻⁴ M) inhibited dose-dependently the cholinesterase activity of the guinea-pig blood. The results suggest that berberine increase ileal contractility by: 1) increasing acetylcholine release from the postganglionic parasympathetic nerve terminal, 2) increasing acetylcholine retention through an inhibition of cholinesterase activity, and 3) blocking α₂-adrenoceptors, possibly in the postganglionic parasympathetic nerve.

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Cited by (21)

The effects of jatrorrhizine on contractile responses of rat ileum
2011, European Journal of Pharmacology
Citation Excerpt :
Berberine is the most medically important ingredient among the protoberberine alkaloids. It has been reported that berberine increased the contraction of rat antral smooth muscle cells (Liu Xiaoni et al., 2004) and guinea pig ileum longitudinal muscle and these actions were mostly mediated by increasing acetylcholine release from the postganglionic nerve terminal and acetylcholine retention via an inhibition of acetylcholinesterase activity (Shin et al., 1993), suggesting that the protoberberine alkaloids may be a kind of natural components for treatment of patients with functional dyspepsia. However, it is unknown whether other protoberberine alkaloids possessed similar effects as berberine to mediate smooth muscle motility until now.
This study was designed to evaluate the effect of jatrorrhizine on smooth muscle contractions isolated from rat ileum longitudinal muscles. Jatrorrhizine increased the amplitude of spontaneous contractions of ileum longitudinal muscles in concentration-dependent manner with an EC₅₀ of 30.0 ± 8.4 μM. Preincubation of ileum strips with atropine (1 μM), 4-diphenyllacetoxy-N (2-chloriethyl)-piperidine (4-DAMP, 1 μM) or darifenacin (1 μM) significantly inhibited acetylcholine (0.1 μM)- and jatrorrhizine (100 μM)-induced ileum longitudinal muscle contractions, whereas they were not affected by AF-DX116 (1 μM) or hexamethonium (100 μM). Pretreatment with SB204070 (1 μM) rather than 3-tropanyl-indole-3-carboxyleat (tropisetron, 1 μM) significantly inhibited 5-HT (10 μM)-induced ileum longitudinal muscle contractions. In contrast, jatrorrhizine-induced ileum longitudinal muscle contractions were not inhibited by tropisetron or SB204070. Furthermore, jatrorrhizine-induced ileum longitudinal muscle contractions were strongly inhibited by nifedipine (1 μM), and also attenuated by removal of extracellular Ca²⁺, U73122 (1 μM), ruthenium red (50 μM) or 2-aminoethoxydiphenylborate (2-APB, 10 μM). Taken together, jatrorrhizine-elicited spontaneous contractions in rat ileum longitudinal muscles are mediated by activation of acetylcholine receptors, mostly the M₃ receptor. Ca²⁺ influx through L-type Ca²⁺ channel is significantly contributed to jatrorrhizine-elicited spontaneous contractions, and Ca²⁺ release via IP₃ and ryanodine pathways are also involved.
Berberine possesses muscarinic agonist-like properties in cultured rodent cardiomyocytes
2011, Pharmacological Research
Citation Excerpt :
One group finds that the anti-amnesic effect of berberine might be related to an increase in peripheral and central cholinergic neuronal system activity [21], an effect also associated with the classic cholinergic receptor agonist, carbachol. Another researcher reports that berberine enhances contractility of guinea pig ileum by inhibiting cholinesterase activity [22], an activity sometimes associated with muscarinic agonists. These studies suggest that berberine may interact with muscarinic cholinergic receptors, but berberine's efficacy has not been reported for any muscarinic receptor subtype.
Berberine, a natural product alkaloid, has been shown to display a wide array of pharmacological effects. Generally, the mechanism of action of each of these effects has not been well described. The aim of the present study is to test the hypothesis that some of berberine's cardiovascular effects are mediated through activation of cardiac M2 muscarinic cholinergic receptors. In our studies, we tested the ability of berberine to alter the contraction rate of cultured neonatal rodent cardiomyocytes. In these spontaneously contracting primary cultured cells, berberine reduced the contraction rate in a manner independent of β-adrenergic receptor blockade but sensitive to pertussis toxin, a Gi/o G protein inhibitor. Muscarinic antagonists completely blocked the effect of berberine on contraction rate of cardiomyocytes, whereas the effect of berberine was not opposed by antagonists to opioid, adenosine or α-adrenergic receptors. Further, berberine bound to muscarinic receptors of adult mouse heart membranes with relatively high affinity (K_i = 5.4 × 10⁻⁶ M) comparable to that of the classic muscarinic agonist, carbachol, and to muscarinic M2 receptors exogenously expressed in HEK 293 cells (K_i = 4.9 × 10⁻⁶ M). Therefore, the findings of the present study suggest that berberine is a muscarinic agonist at M2 receptors, potentially explaining some of its reported cardiovascular effects.
Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells
2010, European Journal of Pharmaceutical Sciences
Maintenance of the mucosal barrier is a critical function of intestinal epithelial tight junction. Berberine is one of the main constituents of Coptidis rhizoma, which has been used for patients with gastrointestinal disorders for a long time. This study aimed to determine whether berberine could alleviate pro-inflammatory cytokine-induced intestinal epithelial tight junction damage. Caco-2 monolayers were treated with tumor necrosis factor-α and interferon-γ to induce barrier dysfunction. The protective effect of berberine on tight junctions was analyzed by measuring the trans-epithelial electrical resistance (TEER). Transmission electron microscopy was used to observe the morphology of tight junction, and subcellular localization of tight junction proteins was investigated by immunofluorescence microscopy and Western blot. Berberine significantly prevented pro-inflammatory cytokines induced decrease in TEER. The distortion of tight junction morphology and redistribution of tight junction protein occludin was also prevented by berberine treatment. Western blot analysis demonstrated that berberine inhibit the dislocation of occludin from raft fractions to non-raft fractions in membrane microdomains of tight junctions. We concluded that berberine can ameliorate pro-inflammatory cytokines induced intestinal epithelia tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states.
The effect of berberine in vitro on tight junctions in human Caco-2 intestinal epithelial cells
2009, Fitoterapia
Berberine is one of the main alkaloids of Rhizoma coptidis which has been used for patients with gastrointestinal disorders. The major aim of this study was to investigate the effect of berberine on tight junction. Caco-2 cells were treated with various concentration of berberine. We observed the integrity of tight junction by measuring the transepithelial electrical resistance (TEER), and also studied the effect of berberine on morphology of tight junction and tight junction protein. These findings showed the first time that berberine could reduce epithelial gut permeability, and might help explain the possible mechanisms of anti-diarrhea activity of berberine.
Materia Medica
2007, Veterinary Herbal Medicine
Materia Medica
2006, Veterinary Herbal Medicine

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¹: On sabbatical leave from the Department of Veterinary Pharmacology, Chonnam National University, Kwangju, Republic of Korea.

²: On sabbatical leave from the Department of Veterinary Medicine, Beijing Agricultural College, Beijing, People's Republic of China.

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A paradoxical stimulatory effect of berberine on guinea-pig ileum contractility: Possible involvement of acetylcholine release from the postganglionic parasympathetic nerve and cholinesterase inhibition

Abstract

Eur. J. Pharmacol.

Jpn. J. Pharmacol.

Gen. Pharmacol.

J. Ind. Med. Assoc.

J. Ind. Med. Assoc.

Chin. J. Vet. Med.

Ind. J. Med. Res.

J. Pediatr. Gastroenterol. Nutr.

Ind. J. Pathol. Bacteriol.

Nature

Can. J. Microbiol.

J. Pharmacol. Exp. Ther.