title: Magnolol and honokiol regulate the calcium-activated potassium channels signaling pathway in Enterotoxigenic Escherichia coli-induced diarrhea mice.
abstract: To explore the regulatory mechanisms of magnolol and honokiol on calcium-activated potassium channels signaling pathway in Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea mice, the concentrations of serum chloride ion (Cl(-)), sodium ion (Na(+)), potassium ion (K(+)) and calcium ion (Ca(2+)) were measured. Additionally, the mRNA expressions of calmodulin 1 (CaM), calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα) and beta subunit (CaMKIIβ), ryanodine receptor 1, inositol 1,4,5-trisphosphate receptors (IP3 receptors), protein kinases C (PKC), potassium intermediate/small conductance calcium-activated channels (SK) and potassium large conductance calcium-activated channels(BK)were determined. A diarrhea mouse model was established using ETEC suspensions (3.29×10(9)CFU/ml) at a dosage of 0.02ml/g live body weight (BW). Magnolol or honokiol was intragastrically administered at dosages of 100 (M100 or H100), 300 (M300 or H300) and 500 (M500 or H500) mg/kg BW according to a 3×3 factorial arrangement. Magnolol and honokiol increased the Cl(-) and K(+) concentrations, further, upregulated the CaM, BKα1 and BKβ3 mRNA levels but downregulated the IP3 receptors 1, PKC, SK1, SK2, SK3, SK4 and BKβ4 mRNA expressions. Magnolol and honokiol did not alter the CaMKIIα, CaMKIIβ, ryanodine receptor 1, IP3 receptor 2, IP3 receptor 3, BKβ1 and BKβ2 mRNA expressions. These results clarify that magnolol and honokiol, acting through Ca(2+) channel blockade, inhibit the activation of IP3 receptor 1 to regulate the IP3-Ca(2+) store release, activate CaM to inhibit SK channels, and effectively suppress PKC kinases to promote BKα1 and BKβ3 channels opening and BKβ4 channel closing, which modulates the intestinal ion secretion.
authors.affiliation: National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, Hunan 410128, PR China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Key Laboratory for Agro-Ecological Processes in Subtropical Region, and South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, PR China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory for Agro-Ecological Processes in Subtropical Region, and South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, PR China.
authors.forename: Shaoxun
authors.initials: S
authors.lastname: Tang
authors.affiliation: National Research Center of Engineering & Technology for Utilization of Botanical Functional Ingredients, Hunan Agricultural University, Changsha, Hunan 410128, PR China. Electronic address: xiaowenjunggong@163.com.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Key Laboratory for Agro-Ecological Processes in Subtropical Region, and South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, PR China. Electronic address: zltan@isa.ac.cn.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Key Laboratory for Agro-Ecological Processes in Subtropical Region, and South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, PR China.
authors.forename: Chuanshe
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Agro-Ecological Processes in Subtropical Region, and South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory for Agro-Ecological Processes in Subtropical Region, and South-Central Experimental Station of Animal Nutrition and Feed Science in Ministry of Agriculture, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, PR China.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Kang
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002147:Calmodulin / Q000235:genetics; D002712:Chlorides / Q000097:blood; D003967:Diarrhea / Q000097:blood / Q000378:metabolism*; D054307:Enterotoxigenic Escherichia coli; D004927:Escherichia coli Infections / Q000097:blood / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011188:Potassium / Q000097:blood; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000097:blood; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D002118:Calcium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002147:Calmodulin; D002712:Chlorides; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017705:Lignans; D011188:Potassium; D024681:Potassium Channels, Calcium-Activated; D011493:Protein Kinase C; D019837:Ryanodine Receptor Calcium Release Channel; D012964:Sodium; C000595843:Calm1 protein, mouse; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Calcium-activated potassium channel; Diarrhea; Enterotoxigenic Escherichia coli; Honokiol; Honokiol ( PubChem CID: 72303); Inositol 1,4,5-trisphosphate receptor; Loperamide hydrochloride ( PubChem CID: 71420); Magnolol; Magnolol (PubChem CID: 72300)