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Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant activity of berberine chloride.
Eur J Pharmacol 2007; 569(1-2):77-83EJ

Abstract

Berberine is an isoquinoline alkaloid isolated from Berberis aristata, a major herb widely used in Indian and Chinese systems of medicine. Berberine possessed a wide range of biological activity including antidiarrheal, antimicrobial, anti-inflammatory effects and some central nervous system activity as well. The present study was designed to explore the antidepressant activity and its possible mechanism of action. Further, the involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant action of berberine chloride was investigated. The antidepressant activity was assessed in forced-swim and tail-suspension tests. Total immobility period was recorded during a six-min test. Berberine (5-20 mg/kg, i.p.) produced a reduction in immobility period in both the tests. When berberine (5 mg/kg, i.p.) was co-administered with other antidepressant drugs, it enhanced the anti-immobility effect of subeffective doses of imipramine (2 mg/kg, i.p.), desipramine (5 mg/kg, i.p.), tranylcypromine (4 mg/kg, i.p.), fluoxetine (5 mg/kg, i.p.), venlafaxine (2 mg/kg, i.p.) or bupropion (10 mg/kg, i.p.) in forced-swim test. However, berberine did not modify the effects of mianserine (32 mg/kg, i.p.) or trazodone (2 mg/kg, i.p.), the two atypical antidepressant drugs. The neurochemical analysis revealed that berberine (5 mg/kg, i.p.) increased the levels of norepinephrine, serotonin or dopamine in the mouse whole brain. The antidepressant-like effect of berberine (5 mg/kg, i.p.) in forced-swim test was prevented by pretreatment with L-arginine (750 mg/kg, i.p.) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (25 mg/kg, i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor] produced potentiation of the action of subeffective dose of berberine (2 mg/kg, i.p.). In addition, treatment of mice with methylene blue (10 mg/kg, i.p.) [direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC)] potentiated the effect of berberine (2 mg/kg, i.p.) in the forced-swim test. Furthermore, the reduction in the immobility period elicited by berberine (5 mg/kg, i.p.) was also inhibited by pretreatment with sildenafil (5 mg/kg, i.p.) [phosphodiesterase 5 inhibitor]. The various modulators and their combination with berberine did not produce any changes in locomotor activity. Our findings demonstrated that berberine exerted antidepressant-like effect in various behavioural paradigms of despair possibly by modulating brain biogenic amines (norepinephrine, serotonin or dopamine) and further, the antidepressant-like effect of berberine in the forced-swim test involved an interaction with the L-arginine-NO-cGMP pathway.

Authors+Show Affiliations

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India. skpu@yahoo.comNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17585901

Citation

Kulkarni, Shrinivas K., and Ashish Dhir. "Possible Involvement of L-arginine-nitric Oxide (NO)-cyclic Guanosine Monophosphate (cGMP) Signaling Pathway in the Antidepressant Activity of Berberine Chloride." European Journal of Pharmacology, vol. 569, no. 1-2, 2007, pp. 77-83.
Kulkarni SK, Dhir A. Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant activity of berberine chloride. Eur J Pharmacol. 2007;569(1-2):77-83.
Kulkarni, S. K., & Dhir, A. (2007). Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant activity of berberine chloride. European Journal of Pharmacology, 569(1-2), pp. 77-83.
Kulkarni SK, Dhir A. Possible Involvement of L-arginine-nitric Oxide (NO)-cyclic Guanosine Monophosphate (cGMP) Signaling Pathway in the Antidepressant Activity of Berberine Chloride. Eur J Pharmacol. 2007 Aug 13;569(1-2):77-83. PubMed PMID: 17585901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant activity of berberine chloride. AU - Kulkarni,Shrinivas K, AU - Dhir,Ashish, Y1 - 2007/05/22/ PY - 2007/02/21/received PY - 2007/04/16/revised PY - 2007/05/01/accepted PY - 2007/6/26/pubmed PY - 2007/10/27/medline PY - 2007/6/26/entrez SP - 77 EP - 83 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 569 IS - 1-2 N2 - Berberine is an isoquinoline alkaloid isolated from Berberis aristata, a major herb widely used in Indian and Chinese systems of medicine. Berberine possessed a wide range of biological activity including antidiarrheal, antimicrobial, anti-inflammatory effects and some central nervous system activity as well. The present study was designed to explore the antidepressant activity and its possible mechanism of action. Further, the involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant action of berberine chloride was investigated. The antidepressant activity was assessed in forced-swim and tail-suspension tests. Total immobility period was recorded during a six-min test. Berberine (5-20 mg/kg, i.p.) produced a reduction in immobility period in both the tests. When berberine (5 mg/kg, i.p.) was co-administered with other antidepressant drugs, it enhanced the anti-immobility effect of subeffective doses of imipramine (2 mg/kg, i.p.), desipramine (5 mg/kg, i.p.), tranylcypromine (4 mg/kg, i.p.), fluoxetine (5 mg/kg, i.p.), venlafaxine (2 mg/kg, i.p.) or bupropion (10 mg/kg, i.p.) in forced-swim test. However, berberine did not modify the effects of mianserine (32 mg/kg, i.p.) or trazodone (2 mg/kg, i.p.), the two atypical antidepressant drugs. The neurochemical analysis revealed that berberine (5 mg/kg, i.p.) increased the levels of norepinephrine, serotonin or dopamine in the mouse whole brain. The antidepressant-like effect of berberine (5 mg/kg, i.p.) in forced-swim test was prevented by pretreatment with L-arginine (750 mg/kg, i.p.) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (25 mg/kg, i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor] produced potentiation of the action of subeffective dose of berberine (2 mg/kg, i.p.). In addition, treatment of mice with methylene blue (10 mg/kg, i.p.) [direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC)] potentiated the effect of berberine (2 mg/kg, i.p.) in the forced-swim test. Furthermore, the reduction in the immobility period elicited by berberine (5 mg/kg, i.p.) was also inhibited by pretreatment with sildenafil (5 mg/kg, i.p.) [phosphodiesterase 5 inhibitor]. The various modulators and their combination with berberine did not produce any changes in locomotor activity. Our findings demonstrated that berberine exerted antidepressant-like effect in various behavioural paradigms of despair possibly by modulating brain biogenic amines (norepinephrine, serotonin or dopamine) and further, the antidepressant-like effect of berberine in the forced-swim test involved an interaction with the L-arginine-NO-cGMP pathway. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17585901/Possible_involvement_of_L_arginine_nitric_oxide__NO__cyclic_guanosine_monophosphate__cGMP__signaling_pathway_in_the_antidepressant_activity_of_berberine_chloride_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00540-7 DB - PRIME DP - Unbound Medicine ER -