Muscarinic and Nitric oxide Pathway Involvement in the Intestinal Transit and Gastric Emptying delay of Salvia barrelieri Methanol Extract in Mice
Abstract
This study investigated the influence of Salvia barrelieri (SBA) methanol and decocted extracts (ME and DE) on intestinal transit (IT) and gastric emptying (GE) in mice. Only the doses of ME SBA induced a strong inhibition of GE at 46.82 ± 4.34, 54.71 ± 3.29 and 48.45 ± 1.33% (P≤0.0001) for the dosages 100, 200 or 400 mg·kg-1 respectively. The extracts by themselves had no effects on intestinal movement (only a slight, non–significant increase at 400 mg·kg-1). However, blocking muscarinic receptors resulted in a decrease in IT by 10.34 and 17.53% with ME and DE extracts, respectively, compared to control. Conversely, co–administration with L–arginine (Nitric Oxide donor) significantly decreased transit (47.31 and 50.80% for ME and DE, respectively), while inhibiting Nitric Oxide Synthase (NOS) with L–Nω–Nitro–Arginine (L–NNA) had a smaller effect (12.24 and 17.24% for ME and ED, respectively). Only ME SBA extracts significantly inhibited GE (46.82–54.71% decrease across doses), mimicking atropine’s effect. DE extracts and combining ME with atropine showed no significant impact. Interestingly, L–arginine only affected emptying with DE SBA (27.8% decrease), not ME SBA. Inhibiting NOS partially blocked the effect of ME SBA. These findings suggest that ME SBA extracts primarily target GE through mechanisms involving both muscarinic and NO pathways, while DE extracts have minimal effects. This study highlights the intricate interplay of pathways in gut function and the potential influence of extract type and formulation on their effectiveness.
Downloads
References
Codutti A, Cremer J, Alim K. Changing flows balance nutrient absorption and bacterial growth along the gut. Phys. Rev. Lett. [Internet]. 2022; 129(13):138101. doi: https://doi.org/gqv67h
Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA. [Internet]. 2015; 313(9):949–958. doi: https://doi.org/ghj28x
Jedidi S, Rtibi K, Selmi S, Aloui F, Selmi H, Wannes D, Sammari H, Dhawefi N, Chaâbane A, Sebai H. Phytochemical/Antioxidant Properties and Individual/Synergistic Actions of Salvia officinalis L. Aqueous Extract and Loperamide on Gastrointestinal Altering Motor Function. J. Med. Food. [Internet]. 2019; 22(12):1235–1245. doi: https://doi.org/m6gj
Mamache W, Amira S, Ben Souici C, Laouer H, Benchikh F. In vitro antioxidant, anticholinesterases, anti‐α‐amylase, and anti‐α‐glucosidase effects of Algerian Salvia aegyptiaca and Salvia verbenaca. J. Food Biochem. [Internet]. 2020; 44(11):e13472. doi: https://doi.org/mbkp
Dolatabadi F, Abdolghaffari AH, Farzaei MH, Baeeri M, Ziarani FS, Eslami M, Abdollahi M, Rahimi R. The protective effect of Melissa officinalis L. in visceral hypersensitivity in rat using 2 models of acid–induced colitis and stress–induced irritable bowel syndrome: a possible role of nitric oxide pathway. J. Neurogastroenterol. Motil. [Internet]. 2018; 24(3):490–501. doi: https://doi.org/gdp4jx
Papathanasopoulos A, Rotondo A, Janssen P, Boesmans W, Farré R, Vanden Berghe P, Tack J. Effect of acute peppermint oil administration on gastric sensorimotor function and nutrient tolerance in health. Neurogastroenterol. Motil. [Internet]. 2013; 25(4):e263–e271. doi: https://doi.org/m6gm
Napoli E, Ruberto G, Carrubba A, Sarno M, Muscarà C, Speciale A, Cristani M, Cimino F, Saija A. Phenolic Profiles, Antioxidant and Anti–Inflammatory Activities of Hydrodistillation Wastewaters from Five Lamiaceae Species. Molecules. [Internet]. 2022; 27(21):7427. doi: https://doi.org/m6gk
Kaoudone C, Benchikh F, Abdennour C, Benabdallah H, Mamache W, Amira S. Free Radical Scavenging and Antinociceptive Activities of the Aqueous Extract from Matricaria chamomilla L. Flowers. TURJAF. [Internet]. 2022; 10(10):2076–2080. doi: https://doi.org/m6gn
Yacob T, Shibeshi W, Nedi T. Antidiarrheal activity of 80% methanol extract of the aerial part of Ajuga remota Benth (Lamiaceae) in mice. BMC Complement. Altern. Med. [Internet]. 2016; 16(303):1–8. doi: https://doi.org/gkq5vn
Mehmood MH, Munir S, Khalid UA, Asrar M, Gilani AH. Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K+–channels activation. BMC Complement. Altern. Med. [Internet]. 2015; 15(75):1–9. doi: https://doi.org/f69j2p
Amira S, Soufane S, Gharzouli K. Effect of sodium fluoride on gastric emptying and intestinal transit in mice. Exp. Toxicol. Pathol. [Internet]. 2005; 57(1):59–64. doi: https://doi.org/b9zqdn
Demireezer LÖ, Gürbüz P, Uğur EPK, Bodur M, Özenver N, Uz A, Güvenalp Z. Molecular docking and ex vivo and in vitro anticholinesterase activity studies of Salvia sp. and highlighted rosmarinic acid. Turkish J. Med. Sci. [Internet]. 2015; 45(5):1141–1148. doi: https://doi.org/m6gp
de Souza ILI, Oliveira GA, Travassos RA, Vasconcelos LHC, Correia AC, Martins IRR, dos Santos Júnior MSM, Costa VC, Tavares JF, da Silva MS, da Silva BA. Spasmolytic activity of Hyptis macrostachys Benth.(Lamiaceae). J. Med. Plants Res. [Internet]. 2013 [cited 20 Dec 2023]; 7(33):2436–2443. Available in: https://goo.su/p6lFa
Makrane H, Aziz M, Mekhfi H, Ziyyat A, Bnouham M, Legssyer A, Gressier B, Eto B. Antispasmodic and Myorelaxant Activity of Organic Fractions from Origanum majorana L. on Intestinal Smooth Muscle of Rodents. Euro. J. Med. Plants. [Internet]. 2018; 23(2):1–11. doi: https://doi.org/m6gr
Capasso R, Borrelli F, Zjawiony J, Kutrzeba L, Aviello G, Sarnelli G, Capasso F, Izzo AA. The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A reduce inflammation–induced hypermotility in mice. Neurogastroenterol. Motil. [Internet]. 2008; 20(2):142–148. doi: https://doi.org/bnqgt5
Tack J. Gastric motor disorders. Best Pract. Res. Clin. Gastroenterol. [Internet]. 2007; 21(4):633–644. doi: https://doi.org/bx6s4m
Goyal RK, Guo Y, Mashimo H. Advances in the physiology of gastric emptying. Neurogastroenterol. Motil. [Internet]. 2019; 31(4):e13546. doi: https://doi.org/gg6px4
Ishiguchi T, Nakajima M, Sone H, Tada H, Kumagai AK, Takahashi T. Gastric distension–induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat. J. Physiol. [Internet]. 2001; 533(3):801–813. doi: https://doi.org/ddg8s4
Yuan SY, Costa M, Brookes SJ. Neuronal control of the pyloric sphincter of the guinea–pig. Neurogastroenterol. Motil. [Internet]. 2001; 13(3):187–198. doi: https://doi.org/dfs4zr
Carnevali TR, Waller SB, Ferrasso MM, Rosa Júnior AS, Carapeto LP, Freitag RA, Schuch LFD, Cleff MB. Radiological determination of gastric motility in experimental model treated with Rosmarinus officinalis Linn. (Lamiaceae) extracts. Indian J. Exp. Biol. [Internet]. 2019 [cited 18 Jan 2024]; 57(9):708–714. Available in: https://goo.su/ib1n
Aydin S, Seker E. Effect of an aqueous distillate of Origanum onites L. on isolated rat fundus, duodenum and ileum: evidence for the role of oxygenated monoterpenes. Pharmazie. [Internet]. 2005 [cited 08 Jan 2024]; 60(2):147–150. Available in: https://goo.su/zlqM
Ghayur MN, Khan AH, Gilani AH. Ginger facilitates cholinergic activity possibly due to blockade of muscarinic autoreceptors in rat stomach fundus. Pak. J. Pharm. Sci. [Internet]. 2007 [cited 10 Jan 2024]; 20(3):231–235. Available in: https://goo.su/t4bVs
Badary OA, Awad AS, Sherief MA, Hamada FMA. In vitro and in vivo effects of ferulic acid on gastrointestinal motility: inhibition of cisplatin–induced delay in gastric emptying in rats. World J. Gastroenterol. [Internet]. 2006; 12(33):5363–5367. doi: https://doi.org/m6gx
Wang X, Zhang C, Zheng M, Gao F, Zhang J, Liu F. Metabolomics Analysis of L–Arginine Induced Gastrointestinal Motility Disorder in Rats Using UPLC–MS After Magnolol Treatment. Front. Pharmacol. [Internet]. 2019; 10(183):1–14. doi: https://doi.org/gnpdcd
Wu Z, Zhang S, Li P, Lu X, Wang J, Zhao L, Wang Y. Effect of Aurantii fructus immaturus flavonoid on the contraction of isolated gastric smooth muscle strips in rats. Evid. Based Complement. Alternat. Med. [Internet]. 2016; 2016(5616905):1–7. doi: https://doi.org/f8vs3z
Baggio CH, Freitas CS, Mayer B, dos Santos AC, Twardowschy A, Potrich FB, Cipriani TR, de Souza LM, Sassaki GL, Iacomini M, Marques MCA, Mesia–Vela S. Muscarinic–dependent inhibition of gastric emptying and intestinal motility by fractions of Maytenus ilicifolia Mart ex. Reissek. J. Ethnopharmacol. [Internet]. 2009; 123(3):385–391. doi: https://doi.org/b7k4m5
Dufour C, Loonis M, Delosière M, Buffière C, Hafnaoui N, Santé–Lhoutellier V, Rémond D. The matrix of fruit & vegetables modulates the gastrointestinal bioaccessibility of polyphenols and their impact on dietary protein digestibility. Food Chem. [Internet]. 2018; 240:314–222. doi: https://doi.org/m6hx
Copyright (c) 2024 Fatima Benchikh, Hind Amira, Walid Mamache, Hassiba Benabdallah, Smain Amira
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.