Hydro-alcoholic extract of Matricaria recutita exhibited dual anti-spasmodic effect via modulation of Ca2+ channels, NO and PKA2-kinase pathway in rabbit jejunum

Document Type: Original Research Article


1 Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran

2 Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

3 Department of Botany, Islamic Azad University, Gorgan, Iran


Objective: Several studies have shown the antispasmodic activity of Matricariarecutita without detailing the underlying mechanism(s). The present study was designed to determine whether the antispasmodic mechanisms of M. recutita extract mediated via histaminergic/cholinergic receptors, Ca2+channels, activation of PKA2 and NO release in isolated rabbit jejunum.
Methods and Materials: The concentration- dependent (3 × 10-3–1.3 × 10-2 mg/ml) antispasmodic effect of the hydro-alcoholic extract of M. recutita flowers was studied in isolated rabbit jejunum. The isolated jejunum preparations were divided into seven groups, including the pharmacological probes that modulate cholinergic, histaminergic, and nitrergic receptors, as well as PKA2.
Results: M. recutita inhibited spontaneous smooth muscle contractility of the jejunum in a concentration-dependent manner (3 × 10-3–1.3 × 10-2 mg/ml) and reduced both K+- and Ca2+-induced contractions, which is similar to the effect of verapamil. The antispasmodic effect of M. recutita wasinhibited by H89 (a PKA2 inhibitor). The myorelaxant effect of M. recutita increased in the presence of ACh/His and H89.
Conclusion: M. recutita evoked antispasmodic and spasmolytic effects mediated through different signaling pathways. Our results have shown this dual inhibitory effect is mediated by blocking Ca2+ channels, activating His and ACh receptors, releasing NO, and activating PKA2.


Main Subjects

Abad A, Nouri M, Gharjanie A,Tavakoli F. 2011. Effect of Matricaria chamomilla Hydroalcoholic Extract on Cisplatin-induced Neuropathy in Mice. Chin J Nat Meds, 9: 126-131.

Achterrath-Tuckermann U, Kunde R, Flaskamp E, Isaac O,Thiemer K. 1980. Pharmacological investigations with compounds of chamomile. V. Investigations on the spasmolytic effect of compounds of chamomile and Kamillosan on the isolated guinea pig ileum. Planta Med, 39: 38-50.

Amira S, Rotondo A,Mule F. 2008. Relaxant effects of flavonoids on the mouse isolated stomach: structure-activity relationships. Eur J Pharmacol, 599: 126-130.

Ammon HP, Kelber O, Okpanyi SN. 2006. Spasmolytic and tonic effect of Iberogast (STW 5) in intestinal smooth muscle. Phytomedicine, 13 Suppl 5: 67-74.

Chen CC, Ke WH, Ceng LH, Hsieh CW,Wung BS. 2010. Calcium- and phosphatidylinositol 3-kinase/Akt-dependent activation of endothelial nitric oxide synthase by apigenin. Life Sci, 87: 743-749.

Cortes AR, Delgadillo AJ, Hurtado M, Dominguez-Ramirez AM, Medina JR,Aoki K. 2006. The antispasmodic activity of Buddleja scordioides and Buddleja perfoliata on isolated intestinal preparations. Biol Pharm Bull, 29: 1186-1190.

Di Carlo G, Mascolo N, Izzo AA,Capasso F. 1999. Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sci, 65: 337-353.

Eto M, Kitazawa T, Yazawa M, Mukai H, Ono Y,Brautigan DL. 2001. Histamine-induced vasoconstriction involves phosphorylation of a specific inhibitor protein for myosin phosphatase by protein kinase C alpha and delta isoforms. J Biol Chem, 276: 29072-29078.

Farre AJ, Colombo M, Fort M,Gutierrez B. 1991. Differential effects of various Ca2+ antagonists. Gen Pharmacol, 22: 177-181.

Forster HB, Niklas H, Lutz S. 1980. Antispasmodic effects of some medicinal plants. Planta Med, 40: 309-319.

Gharzouli K, Holzer P. 2004. Inhibition of guinea pig intestinal peristalsis by the flavonoids quercetin, naringenin, apigenin and genistein. Pharmacology, 70: 5-14.

Grifoni SC, Bendhack LM. 2000. Relaxation induced by histamine is not endothelium dependent in tail arteries of L-NAME-treated rats. Gen Pharmacol, 34: 435-441.

Guenwaldr J, Brendler T, Jaenicke C. 1998. Matricaria Chamomilla (Chamomile) In: M. N.J (Ed.), PDR for Herbal Medicines, pp. 961, Medical Economics Company.

Hagelauer D, Kelber O, Weiser D, Heinle H. 2006. Effects of STW 5 (Iberogast®) on prostaglandinF2α –induced contractions of ileum of mice in vitro. Planta Med, 72: 280.

Heinle H, Hagelauer D, Pascht U, Kelber O, Weiser D. 2006. Intestinal spasmolytic effects of STW 5 (Iberogast) and its components. Phytomedicine, 13 Suppl 5: 75-79.

Hobbs AJ, Ignarro LJ. 1996. Nitric oxide-cyclic GMP signal transduction system. Methods Enzymol, 269: 134-148.

Kochar NI, Chandewal AV, Bakal RL, Kochar PN. 2011. Nitric oxide and the gastrointestinal tract. Int. J. Pharmacol, 7: 31-39.

Maschi O, Cero ED, Galli GV, Caruso D, Bosisio E, Dell'Agli M. 2008. Inhibition of human cAMP-phosphodiesterase as a mechanism of the spasmolytic effect of Matricaria recutita L. J Agric Food Chem, 56: 5015-5020.

Mazandarani M, hoseini F, Seifi A, Bayat H, Pourabouk M, Badaghabadi F, Rajaei M, Moheimani H, Khori V. 2011. Role of Histaminegic and calcium channels in the inhibitory effects of hydroalcoholic extract of Matricaria recutita L. on isolated rabbit jejunum. Physiology and Pharmacology, 15: 361-370.

McKay DL, Blumberg JB. 2006. A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res, 20: 519-530.

Michel T, Hoffman B. 2011. Treatment of myocardial ischemia and hypertension In: L. Brunton, B. Chabner, & B. Knollman (Eds.), Goodman and Gilman's The Pharmacological Basis of Therapeutics, pp. 763, McGraw-Hill Education.

Mohammedi Z, Atik F. 2011. Impact of solvent extraction type on total polyphenols content and biological activity from Tamarix aphylla (L.) karst. IJPBS: 609-615.

Murthy KS. 2006. Signaling for contraction and relaxation in smooth muscle of the gut. Annu Rev Physiol, 68: 345-374.

Murti K, Panchal M, Gajera V, Solanki I. 2012. Pharmacological Properties of Matricaria recutita: A Review. Pharmacologia, 3: 348-351.

Peng ZF, Strack D, Baumert A, Subramaniam R, Goh N K, Chia T F, Tan S N,Chia L S. 2003. Antioxidant flavonoids from leaves of Polygonum hydropiper L. Phytochemistry, 62: 219-228.

Rotondo A, Serio R, Mule F. 2009. Gastric relaxation induced by apigenin and quercetin: analysis of the mechanism of action. Life Sci, 85: 85-90.

Van Rossum JM. 1963. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther, 143: 299-330.

Westfall TC, Westfall DP. 2011. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems In: L. Brunton, B. chabner, & B. knollman (Eds.), Goodman & Gilman's The Pharmacological Basis of Therapeutics, pp. 181, McGraw-Hill Education.