Leczenie depresji ziołową terapią biologiczną (Inhibitory MAO,Agoniści receptora 5-HT1A) cz.3
Inhibitory ( MAO ) są to substancje chemiczne które hamują czynność enzymów oksydazy monoaminowej . Są one szczególnie skuteczne w leczeniu tzw. depresji atypowej charakteryzującej się obecnością w obrazie chorobowym nadmiernej senności, zwiększonego apetytu i pogarszania się nastroju w godzinach wieczornych.
1) Inhibitory monoaminooksydazy MAO-A i MAO-B
a) Krzyżownica (Polygala tenuifolia) – inhibitor MAO-A oraz MAO-B ,blokuje podwyższony poziom kortyzolu w osoczu który jest wskaźnikiem aktywności osi podwzgórze-przysadka-nadnercza (HPA) . Ekstrakt z nadziemnych części na etanolu 50% 1:5 . Dawkowanie 5ml 3 razy dziennie co 8 godzin.
b) Kozieradka pospolita (Trigonella foenum-graecum L.) – inhibitor MAO-A . Ekstrakt etanolowy 50% 1:5 z nasion. Dawkowanie 5 ml trzy razy dziennie.
c) Seler (Apium L.) – inhibitor MAO-A . Ekstrakt etanolowy 40% 1:5 z liści . Dawkowanie 5ml trzy razy dziennie.
d) Wrzos pospolity (Calluna vulgaris) – inhibitor MAO-A . Wodny ekstrakt z nadziemnych części rośliny . Jedną kopiastą łyżeczkę zalać 250 ml wrzącej wody . Pić trzy razy dziennie po jednej szklance.
Dysfunkcja receptora 5-HT1A może być przyczyną zaburzeń depresyjnych . Receptory 5-HT mogą odgrywać rolę w łagodzeniu depresji przez tzw. odczulanie autoreceptorów 5-HT1A. Leki przeciwdepresyjne, takie jak inhibitory MAO i TLPD, SSRI, lit, wszystkie zwiększają postsynaptyczną sygnalizacji 5-HT 1A. Zioła stanowią skuteczną oraz bezpieczną alternatywę dla tego typu leków syntetycznych.
2) Agoniści receptora 5-HT1A:
a) Nelumbinis – agonista receptora 5-HT1A . Wodny ekstrakt z nasion. Jedną łyżeczkę nasion zalać 250 ml wrzącej wody . Pić trzy razy dziennie po jednej szklance.
b) Kurkumina (Curcuma longa) – agonista receptorów 5-HT (1a/1b) i 5-HT (2C) . Rozdrobnione kłącze zażywamy w ilości 3 gramy trzy razy dziennie popijając wodą .
c) Lawenda (Lavandula angustifolia) – agonista receptora 5-HT1A . Stosujemy w formie inhalacji olejkiem 3 razy dziennie po 10-15 minut.
d) Mięta meksykańska (Agastache mexicana) – agonista receptora 5-HT1A . Nadziemnie części rośliny zalewamy etanolem 40% 1:5 . Dawkowanie 5 ml trzy razy dziennie.
J Pharm Pharmacol. 2011 Jun;63(6):869-74. doi: 10.1111/j.2042-7158.2011.01281.x. Epub 2011 May 3.
Possible mechanism of the antidepressant effect of 3,6′-disinapoyl sucrose from Polygala tenuifolia Willd.
Hu Y, Liu M, Liu P, Guo DH, Wei RB, Rahman K.
SourceDepartment of Clinical Pharmacology and Pharmacy, Center of Pharmacy, Chinese PLA General Hospital, Beijing, China.
OBJECTIVE: The present study was designed to observe the effects of 3,6′-disinapoyl sucrose (DISS), an active oligosaccharide ester component obtained from the roots of Polygala tenuifolia Willd., on behavioral and biochemical aspects of depression induced by chronic mild stress (CMS) in rats. It is the first exploration of the possible association between DISS’s antidepressant-like effects and biochemical markers of depression, and involved measuring monoamine oxidase (MAO) activity, cortisol levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels.
METHODS: Rats were exposed to stressor once daily for consecutive 5 weeks. DISS and a positive control drug, fluoxetine, were administered via gastric intubation to once daily for consecutive 3 weeks from the third week.
KEY FINDINGS: The results showed that rats subjected to CMS exhibit a reduction in sucrose intake. Conversely, brain MAO-A and MAO-B activity, plasma cortisol levels, and MDA levels were increased, while SOD activity was decreased following CMS exposures. DISS significantly inhibited MAO-A and MAO-B activity and blocked plasma elevated cortisol level, an indicator of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, DISS increases SOD activity, inhibits lipid peroxidation, and lessens production of MDA.
CONCLUSION: These results suggest that DISS may possess potent and rapid antidepressant properties, which are mediated via MAO, the HPA axis and oxidative systems. These antidepressant actions make DISS a potentially valuable drug for the treatment of depression.
J Ethnopharmacol. 2013 Feb 13;145(3):822-5. doi: 10.1016/j.jep.2012.12.021. Epub 2012 Dec 21.
Screening of plants used in Danish folk medicine to treat depression and anxiety for affinity to the serotonin transporter and inhibition of MAO-A.
Jäger AK, Gauguin B, Andersen J, Adsersen A, Gudiksen L.
SourceDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, 2100 Copenhagen O, Denmark. Electronic address: firstname.lastname@example.org
ETHNOPHARMACOLOGICAL RELEVANCE: A number of plant species are used in Danish folk medicine for treatment of depression and anxiety.
MATERIALS AND METHODS: Aqueous and ethanolic extracts of 17 plant species were tested for affinity to the serotonin transporter and for inhibition of MAO-A-both targets for antidepressive treatment.
RESULTS: An ethanolic extract of aerial parts of Borago officinalis had affinity to the serotonin transporter. Ten extracts, from eight plants, had IC(50) values below 25µg/ml extract in the MAO-A assay. The most active extracts in the MAO-A assay were the ethanol extract of seeds of Trigonella foenum-graecum (IC(50) 4µg/ml); ethanol extract of leaves of Apium graveolens (IC(50) 5µg/ml) and the water extract of aerial parts of Calluna vulgaris (IC(50) 8µg/ml).
CONCLUSIONS: Besides Borago officinalis, which toxicity profile excludes it from further development as an herbal drug, none of the plants had potential as serotonin reuptake inhibitors. Several plants had MAO-A inhibitory activity.
Arch Pharm Res. 2004 Oct;27(10):1065-72.
Nelumbinis Semen reverses a decrease in 5-HT1A receptor binding induced by chronic mild stress, a depression-like symptom.
Jang CG, Kang M, Cho JH, Lee SB, Kim H, Park S, Lee J, Park SK, Hong M, Shin MK, Shim IS, Bae H.
SourceDepartment of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of 5-HT1A receptors. The present study assessed if Nelumbinis Semen (N.s.) had an anti-depression effect through reversing a decrease in 5-HT1A receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a 5-HT1A receptor binding assay, with a specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N.s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N.s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H.p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N.s. The N.s. treatment significantly reversed the decreased sucrose intake under CMS (P < 0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N.s. and H.p. reversed the CMS-induced decrease in 5-HT1A receptor binding. In the I to II regions of the frontal cortex, N.s. and H.p. also reversed the CMS-induced decrease in 5-HT1A receptor binding, and even showed a significant increase in 5-HT1A receptor binding compared to the F treatment group (N.s. vs. P, p < 0.05, H.p. vs. P, p < 0.05). However, in the hypothalamus, all treatments reversed the CMS-induced decrease in 5-HT1A receptor binding. This reversal effect of N.s. on the decrease in 5-HT1A receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H.p, but different from that of F. It is concluded that N.s. presents an anti-depression effect through enhancing 5-HT1A receptor binding.
Eur J Pharmacol. 2008 Jan 6;578(1):43-50. Epub 2007 Sep 19.
The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors.
Wang R, Xu Y, Wu HL, Li YB, Li YH, Guo JB, Li XJ.
SourceDepartment of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, China.
Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test. The purpose of this study was to explore the possible contribution of serotonin (5-HT) receptors in the behavioral effects induced by curcumin in this animal model of depression. 5-HT was depleted by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) prior to the administration of curcumin, and the consequent results showed that PCPA blocked the anti-immobility effect of curcumin in forced swimming test, suggesting the involvement of the serotonergic system. Moreover, pre-treatment of pindolol (10 mg/kg, i.p., a beta-adrenoceptors blocker/5-HT(1A/1B) receptor antagonist), 4-(2′-methoxy-phenyl)-1-[2′-(n-2”-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI, 1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane, 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist) was found to prevent the effect of curcumin (10 mg/kg) in forced swimming test. On the other hand, a sub-effective dose of curcumin (2.5 mg/kg, p.o.) produced a synergistic effect when given jointly with (+)-8-hydroxy-2-(di-n-propylamino)tetralin, (8-OH-DPAT, 1 mg/kg, i.p., a 5-HT(1A) receptor agonist), anpirtoline (0.25 mg/kg, i.p., a 5-HT(1B) receptor agonist) or ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist with higher affinity to 5-HT(2A) receptor) or R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg, i.p., a 5-HT(2A) receptor agonist). Taken together, these results indicate that the antidepressant-like effect of curcumin in the forced swimming test is related to serotonergic system and may be mediated by, at least in part, an interaction with 5-HT(1A/1B) and 5-HT(2C) receptors.
J Ethnopharmacol. 2013 May 20;147(2):412-8. doi: 10.1016/j.jep.2013.03.028. Epub 2013 Mar 22.
Anxiolytic-like effect of lavender essential oil inhalation in mice: participation of serotonergic but not GABAA/benzodiazepine neurotransmission.
Chioca LR, Ferro MM, Baretta IP, Oliveira SM, Silva CR, Ferreira J, Losso EM, Andreatini R.
SourceDepartamento de Farmacologia, Setor de Ciencias Biológicas, Universidade Federal do Paraná, Centro Politécnico, PO Box 19031, Curitiba, PR 81540-990, Brazil. email@example.com
ETHNOPHARMACOLOGICAL RELEVANCE: Lavandula angustifolia (lavender) inhalation has been used in folk medicine for the treatment of anxiety, and clinical and animal studies have corroborated its anxiolytic effect, although its mechanism of action is still not fully understood.
AIMS OF THE STUDY: The objective of the present study was to determine whether the GABAA/benzodiazepine complex or serotonin neurotransmission mediates the anxiolytic-like effect of lavender essential oil.
MATERIALS AND METHODS: Male Swiss mice were subjected to the marble-burying test after being exposed to the aroma of lavender essential oil (1-5%), amyl acetate (5%; used as a behaviorally neutral odor), or distilled water for 15 min via inhalation. Additionally, the effect of 5% lavender essential oil was also evaluated in mice subjected to the elevated plus maze. GABAA/benzodiazepine mediation was evaluated by pretreating the mice with the GABAA receptor antagonist picrotoxin before the marble burying test and [(3)H]flunitrazepam binding to the benzodiazepine site on the GABAA receptor. Serotonergic mediation was studied by pretreating the mice with O-methyl-[3H]-N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635), a serotonin 5-HT1A receptor antagonist before the marble burying test. We also evaluated changes in the pharmacologically induced serotonin syndrome and the effects of combined administration of subeffective doses of lavender essential oil and the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).
RESULTS: Lavender essential oil (1-5%) decreased the number of marbles buried compared with the control and amyl acetate groups. In the elevated plus maze, 5% lavender essential oil inhalation increased the percentage of time spent on and number of entries into the open arms compared with controls. No effect was seen in the number of closed arm entries or number of beam interruptions in the automated activity chamber. Pretreatment with the GABAA receptor antagonist picrotoxin (0.5mg/kg) did not modify the behavioral effect of 5% lavender essential oil in the marble-burying test. Lavender essential oil also did not alter [(3)H]flunitrazepam binding to the benzodiazepine site on the GABAA receptor. Pretreatment with the serotonin 5-HT1A receptor antagonist WAY100635 (3mg/kg) blocked the anxiolytic-like effect of lavender essential oil and the 5-HT1A receptor agonist 8-OH-DPAT (3mg/kg). A combination of ineffective doses of 8-OH-DPAT (0.5mg/kg) and lavender essential oil (0.1%) reduced the number of marbles buried. Finally, 5% lavender essential oil attenuated the serotonin syndrome induced by 40 mg/kg fluoxetine plus 80 mg/kg 5-hydroxytryptophan.
CONCLUSIONS: These results indicate an important role for the serotonergic system in the anxiolytic-like effect of lavender essential oil.
Pharmacol Biochem Behav. 2013 Sep;110:255-64. doi: 10.1016/j.pbb.2013.07.020. Epub 2013 Aug 7.
Ursolic acid from Agastache mexicana aerial parts produces antinociceptive activity involving TRPV1 receptors, cGMP and a serotonergic synergism.
Verano J, González-Trujano ME, Déciga-Campos M, Ventura-Martínez R, Pellicer F.
SourceLaboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias del Instituto Nacional de Psiquiatría Ramón de la Fuente Muniz, Calz. México-Xochimilco 101, Col. Sn Lorenzo Huipulco, 14370 México, D.F., Mexico; Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Col. Santo Tomás, 11340 México, D.F., Mexico.
Agastache mexicana is a plant that has long been used in large demands in Mexican folk medicine to treat anxiety, insomnia and pain, among others affections. Chromatographic technique was used to identify ursolic acid (UA), 130.7mg/g and 20.3mg/g, as an antinociceptive active compound identified in ethyl acetate and methanol extracts of A. mexicana aerial parts, respectively. Temporal course curves of the antinociceptive response demonstrated a dose-dependent and significant activity of UA (1 to 100mg/kg, i.p.) with an ED50=2mg/kg in comparison to the efficacy of diclofenac (1 or 30 to 100mg/kg, i.p.), a non-steroidal anti-inflammatory drug, with an ED50=11.56mg/kg. The antinociceptive response consisted in the reduction of abdominal constrictions induced with 1% acetic acid in mice. Similarly, UA at 2mg/kg produced significant antinociception in the intracolonic administration of 0.3% capsaicin (a TRPV1 agonist) in mice. It has been reported the inhibition produced by UA on the calcium-flux induced by capsaicin on TRPV1 receptor suggesting the antagonistic activity of this receptor. Finally, an ED50=44mg/kg was calculated in the neurogenic and inflammatory nociception induced in the formalin test in rats. The antinociceptive response of UA in the formalin test was not modified in presence of naloxone, flumazenil or l-arginine. Nevertheless, it was reverted in presence of 1-H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, an inhibitor of soluble guanylyl cyclase) and increased in presence of N(G)-l-nitro-arginine methyl ester (l-NAME, inhibitor of nitric oxide synthase), theophylline (inhibitor of phosphodiesterase) and WAY100635 (an antagonist of 5-HT1A receptors). Current results provide evidence that the antinociceptive response of A. mexicana depends in part on the presence of UA. Moreover, this triterpene may exerts its antinociceptive effect mediated by the presence of cGMP and an additive synergism with 5HT1A receptors, but also an antagonistic activity towards TRPV1 receptors may be involved.