N-hexacosanol reverses diabetic induced muscarinic hypercontractility of ileum in the rat

Shinbori, Chiko; Saito, Motoaki; Kinoshita, Yukako; Satoh, Itaru; Kono, Tomoharu; Hanada, Takuya; Nanba, Eiji; Adachi, Kaori; Suzuki, Hiroto; Yamada, Masashi; Satoh, Keisuke

doi:10.1016/j.ejphar.2006.06.043

Cited by 10 publications

(29 citation statements)

References 27 publications

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“…The C26-alcohol N-hexacosanol has been found to directly increase neurite extension as well as the biochemical differentiation of these neurons. Our previous reports indicated that N-hexacosanol has a beneficial effect not only on disorders of the central nervous system, but also on peripheral neuropathy (10,13,15,16). For example, we described the therapeutic effects of N-hexacosanol on streptozotocin induced-diabetic neuropathy in the trachea, urinary bladder, and ileum of the rat (13,15,16).…”

Section: Methodsmentioning

confidence: 99%

“…For example, we described the therapeutic effects of N-hexacosanol on streptozotocin induced-diabetic neuropathy in the trachea, urinary bladder, and ileum of the rat (13,15,16). Recently, we reported that N-hexacosanol ameliorates diabetes-induced hypercontractility of the rat ileum induced by carbachol, and we found that treatment with N-hexacosanol partially reverses the overexpression of muscarinic M 2 and M 3 receptor mRNAs (16). However, it remains important to investigate possible pathological changes in the pharmacological profiles of these muscarinic receptors and their mRNAs induced by diabetes in ileal smooth muscle tissue.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous reports indicated that N-hexacosanol has a beneficial effect not only on disorders of the central nervous system, but also on peripheral neuropathy (10,13,15,16). For example, we described the therapeutic effects of N-hexacosanol on streptozotocin induced-diabetic neuropathy in the trachea, urinary bladder, and ileum of the rat (13,15,16). Recently, we reported that N-hexacosanol ameliorates diabetes-induced hypercontractility of the rat ileum induced by carbachol, and we found that treatment with N-hexacosanol partially reverses the overexpression of muscarinic M 2 and M 3 receptor mRNAs (16).…”

Section: Methodsmentioning

confidence: 99%

“…All animal experiments were performed in accordance with the guidelines established by the Tottori University Committee for Animal Experimentation. Diabetes was induced in eight-week-old male Sprague-Dawley rats (SLC, Shizuoka, Japan) by an intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) dissolved in 0.1 M citrate-phosphate buffer (pH 4.2), according to a method described in our previous reports (10,13,15,16). Rats were divided randomly into four age-matched groups as follows: non-diabetic control rats (group A), untreated diabetic rats (group B), and diabetic rats treated with N-hexacosanol at a daily dose of 2 or 8 mg/kg (groups C and D, respectively) (n = 6-8).…”

Section: Methodsmentioning

confidence: 99%

“…Measurement of muscarinic receptor mRNAs was performed according to a method outlined in our previous reports (9,13,16). Muscarinic M 2 and M 3 receptor mRNAs in the experimental ileum were measured by real-time PCR.…”

Section: Real-time Polymerase Chain Reaction (Pcr) (Quantification Ofmentioning

confidence: 99%

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N-hexacosanol prevents diabetes-induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system

et al. 2007

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We evaluated the effects of N-hexacosanol, a cyclohexenonic long-chain fatty alcohol, on muscarinic receptors in diabetic rat ileal dysfunction. Eight-week-old male SD rats were divided into four groups. After induction of diabetes (streptozotocin 50 mg/kg, i.p.), three groups were maintained for eight weeks with treatment by N-hexacosanol (0, 2 or 8 mg/kg, s.c. every day). Ileum function was investigated by organ bath studies using carbachol and KCl, and the expression levels of muscarinic M 2 and M 3 receptors were investigated by real-time polymerase chain reaction. Various concentrations of subtype-selective muscarinic antagonists, i.e., atropine (non-selective), pirenzepine (M 1 selective), methoctramine (M 2 selective), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M 1 /M 3 selective), were used in this study. In the presence and absence of these antagonists, contractile response curves to increasing concentrations of carbachol were investigated. Treatment with N-hexacosanol did not alter the diabetic status of the rats, but did significantly prevent the carbachol-induced hypercontractility in diabetic rat ileum. Estimation of the pA 2 values for atropine, pirenzepine, methoctramine, and 4-DAMP indicated that the carbacholinduced contractile response in the ileum is mainly mediated through the muscarinic M 3 receptor subtype in all groups. Furthermore, N-hexacosanol significantly prevented the diabetes-induced up-regulation of intestinal muscarinic M 2 and M 3 receptor mRNAs in streptozotocin-diabetic rats. Our data indicated that N-hexacosanol exerts preventive effects with respect to carbachol-induced hypercontractility in the diabetic rat ileum without qualitative alteration of the muscarinic receptor system.Gastrointestinal smooth muscles receive a variety of excitatory and inhibitory inputs from the enteric nervous system. As cholinergic nerves are activated, the neurotransmitter acetylcholine (ACh) is released from their terminals. Subsequently, ACh acts on smooth muscle cells to activate cell-surface muscarinic receptors, thus activating various intracellular signaling pathways, and in turn inducing smooth muscle contraction (6, 7). To date, five muscarinic receptor subtypes (M 1 -M 5 ) have been identified (5,20). A recent reverse transcriptase-polymerase chain reaction (RT-PCR) study reported the possible expression of all five subtypes in gastrointestinal smooth muscle (5). The muscarinic M 2 and M 3 receptor subtypes are preferentially expressed, with a preponderance of the former subtype. In general, the muscarinic M 3 receptor subtype in smooth muscle is coupled to the G protein Gq/G11 and mediates the

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Real-time Polymerase Chain Reaction (Pcr) (Quantification Ofmentioning

confidence: 99%

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N-hexacosanol prevents diabetes-induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system

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Phytochemical Studies

Jain

Verma

2012

SpringerBriefs in Pharmacology and Toxicology

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Many chemical compounds have been isolated from different parts of B. ceiba worldwide. These belong mostly to phenolics, flavonoids, sesquiterpenoids, steroids, naphthoquinones and neolignans. Totally 16 compounds have been isolated from root, 8 from root bark, 3 from stem bark, 3 from heart wood, 2 from leaves, 78 from flowers, 19 from seeds and 11 from gum. Several of these compounds are novel and isolated for the first time. Compounds isolated from this plant possess very important biological activities including immunomodulatory, cytotoxic, antineoplastic, anti-inflammatory, hypotensive, hypolipidemic, antihyperglycemic and antioxidant.

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Effects of Cyclohexanonic Long-Chain Fatty Alcohol, tCFA15 on Amino Acids in Diabetic Rat Brain: A Preliminary Study

et al. 2008

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The aim of this study was to evaluate the effects of streptozotocin-induced type 1diabetes and a subchronic treatment with cyclohexanonic long-chain fatty alcohol, 3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (tCFA15) on contents of amino acids including aspartate, glutamate, glutamine, GABA, glycine, taurine, alanine, serine, threonine, and arginine in the prefrontal cortex, hippocampus and striatum. Levels of glutamate, threonine, taurine, alanine, arginine, and the ratio of glutamate/glutamine were altered region-differently in the brain of diabetic rats. However, tCFA15 region-specifically antagonized the changes in taurine and arginine levels and the ratio of glutamate/glutamine. The alteration in glutamate/glutamine ratio may indicate that experimental models of type 1 diabetes have abnormalities of neuron-gria interaction in brain.

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N-hexacosanol reverses diabetic induced muscarinic hypercontractility of ileum in the rat

Cited by 10 publications

References 27 publications

N-hexacosanol prevents diabetes-induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system

N-hexacosanol prevents diabetes-induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system

Phytochemical Studies

Effects of Cyclohexanonic Long-Chain Fatty Alcohol, tCFA15 on Amino Acids in Diabetic Rat Brain: A Preliminary Study

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