Leczenie depresji ziołową terapią biologiczną (układ immunologiczny) cz.1


Depresja jest chorobą psychoneuroimmunologiczną bezpośrednio powiązaną z układem immunologicznym oraz psychoneuroendokrynalną powiązaną z układem hormonalnym. Mamy coraz więcej dowodów na to iż przewlekłe stany zapalne regulowany przez nasz układ immunologiczny odgrywają istotną rolę w patologii depresji . Cytokiny prozapalne (  IL-6 , IL  -1B , TNF  , IFN ,IL-17)  wraz   z dysfunkcjonalnym systemem dokrewnym oraz wadliwym funkcjonowaniem neuroprzekaźników ,powodują patologiczne zmiany które leżą u podstaw depresji. Leki przeciwdepresyjne nowej generacji powinny  angażować układ odpornościowy oraz hormonalny nie zaś opierać się wyłącznie na oddziaływaniu na neuroprzekaźniki np. inhibitory monoaminooksydazy  [1],[2] . Warte rozważenia w terapii depresji są tzw psychobiotyki , bakterie probiotyczne takie jak bifidobacterium infantis które spełniają funkcje immunomodulatora hamującego stany zapalne.

1) Rośliny  oddziaływujące na układ immunologiczny dezaktywujące cytokiny prozapalne (IL-6 , IL  -1B , TNF , IFN, IL-17 ) [1] :

a) Bluszczyk  (Glechoma hederacea) – hamuje odpowiedz komórkową Th1 poprzez hamowanie cytokin IL-12, TNF-alpha, IFN-gamma [5] . Nalewka na etanolu 40% 1:3 . Trzy razy dziennie 3 ml . Bluszczyk

b) Łubin biały (Lupinus albus)  –  hamuje cytokiny IL-1  , IL-6, TGF-beta,  TNF-alpha ,silnie aktywuje IL-4 [8]. Nalewka z nasion na etanolu 40% 1:5 . Trzy razy dziennie 3 ml .

Łubin biały

c) Wiciokrzew japoński (Lonicera Japonica) –  hamuje cytokiny IL-1ß, TNF-alpha, INF-gamma, IL-6, IL-12 i IL-17. Wpływa hamująca na odpowiedz komórkową Th1 oraz silnie prozapalną Th17.  Nalewka z kwiatów na etanolu 50%-60% 1:5 . Trzy razy dziennie 3 ml  [3].

Lonicera Japonica

d) Magnolia (Magnolia officinalis) – hamuje  interleukiny IL-6 oraz IL-8 [4]. Nalewka lub intrakt z kory na etanolu 70% 1:5 . Trzy razy dziennie 5 ml .


e) Rdestowiec japoński (Polygonum cuspidatum) – hamuje interleukiny IL-17,IL-1B,IL-6 [6],[7]. Intrakt z kłącza na etanolu 50% 1:5 . Trzy razy dziennie 5 ml .




[1] Int Rev Psychiatry. 2013 Oct;25(5):592-603. doi: 10.3109/09540261.2013.813442.
Cytokines as biomarkers in depressive disorder: Current standing and prospects.
Lichtblau N, Schmidt FM, Schumann R, Kirkby KC, Himmerich H.
SourceDepartment of Psychiatry and Psychotherapy, University Hospital Leipzig , Leipzig Germany.
Abstract The frequently observed co-occurrence of depressive disorders and inflammatory diseases suggests a close connection between the nervous and the immune systems. Increased pro-inflammatory and type 1 cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF) and interferon (IFN), appear to be an important link. Cytokines are synthesized by immune cells in the blood and peripheral tissues and by glial cells in the central nervous system (CNS). Evidence suggests that the blood-brain barrier (BBB) is permeable to cytokines and immune cells, and that afferent nerves, e.g. the vagus nerve, mediate the communication between peripheral inflammatory processes and CNS. Cytokines such as IL-1ß, TNF and IFN seem to contribute to the pathophysiology of depression by activating monoamine reuptake, stimulating the hypothalamic-pituitary-adrenocortical (HPA) axis and decreasing production of serotonin due to increased activity of indolamine-2,3-dioxygenase (IDO). However, critical appraisal of these hypotheses is required, because cytokine elevation is not specific to depression. Moreover, several effective antidepressants such as amitriptyline and mirtazapine have been shown to increase cytokine production. When applying immunomodulatory therapies, these drugs may increase the risk of specific side effects such as infections or interact with antidepressant drugs on important functions of the body such as the coagulation system.

[2] Immune Cells Outside Brain May Regulate Vulnerability to Depression
Dec. 12, 2013 — A new study shows that immune cells outside the brain may regulate propensity to develop depression. The data were presented at the American College of Neuropsychopharmacology (ACNP) Annual Meeting.
Depression is a chronic disorder with a devastating impact on the quality of life, health and life expectancy of those who suffer from the disorder. The underlying causes of the disorder remain something of a mystery.
In a study, led by Georgia Hodes at the Icahn School of Medicine at Mount Sinai, the effects of the circulating pro-inflammatory immune chemical called interleukin-6 on depression-like behaviors was investigated in rodents.
The investigators found that rodents with increased propensity to show depression-like behaviors had elevated levels of circulating interleukin-6, suggesting that individual differences in the peripheral immune system contributes to vulnerability to developing depression.
To more directly investigate the role for immune responses in depression-like behaviors, the investigators used irradiation to lesion the immune system of mice. They then carried out bone marrow transplants to replace the immune system with one from mice that showed either high or low levels of interleukin-6 levels in response to stress. It was found that mice that received transplants from high-responding donors had increased expression of depression-like behaviors compared to those who received transplants from low-responding donors.
The findings suggest that circulating immune chemicals that can act in the brain may influence vulnerability to depression. As noted by Dr. Hodes, „These studies represent a new way of thinking about diagnosing and treating depression as an inflammatory illness in the body rather than the brain.”
Future studies will be required in humans to determine if a similar role for the peripheral immune system in depression can be established. If so, this may lead to novel treatment approaches for the disorder.

[3]  Prophylactic effects of Lonicera japonica extract on dextran sulphate sodium-induced colitis in a mouse model by the inhibition of the Th1/Th17 response.
Park JW, Bae H, Lee G, Hong BG, Yoo HH, Lim SJ, Lee K, Kim J, Ryu B, Lee BJ, Bae J, Lee H, Bu Y.
College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Inflammatory bowel diseases (IBD) are chronically relapsing inflammatory disorders of the intestine. Although some therapeutic agents, including steroids, are available for the treatment of IBD, these agents have limited use. Therefore, dietary supplements have emerged as possible interventions for IBD. Japanese honeysuckle flower, the flower of Lonicera japonica, is a well-known dietary supplement and has been used to prevent or treat various inflammatory diseases. In the present study, we investigated the effects of L. japonica on experimental murine colitis. Colitis was induced by 5 % dextran sulphate sodium (DSS) in Balb/c mice. The water extract of L. japonica (LJE) at doses of 20, 100 or 500 mg/kg was orally administered to mice twice per day for 7 d. Body weight, colon length and a histological damage score were assessed to determine the effects on colitis. Cytokine profiles were assessed to examine the effects on helper T (Th) cell-related immunological responses. In addition, CD4?CD25?Foxp3?T cells were analysed in vivo and in vitro for investigating the effects on regulatory T (Treg) cells. LJE showed dose-dependent inhibitory effects against colon shortening, weight loss and histological damage. LJE down-regulated IL-1ß, TNF-?, interferon-?, IL-6, IL-12 and IL-17. However, LJE did not show any significant effects on IL-10, IL-23, transforming growth factor-ß1 and Treg cell populations. In conclusion, LJE showed protective effects against DSS-induced colitis via the Th1/Th17 pathway and not via Treg cell-related mechanisms.

 [4]   Am J Chin Med. 2013;41(3):531-44. doi: 10.1142/S0192415X13500389.
Identification of Magnolia officinalis L. bark extract as the most potent anti-inflammatory of four plant extracts.
Walker JM, Maitra A, Walker J, Ehrnhoefer-Ressler MM, Inui T, Somoza V.
Department of Nutritional and Physiological Chemistry, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria.
This study was designed to compare the anti-inflammatory potential of a Magnolia officinalis L. bark extract solely or in combination with extracts prepared from either Polygonum aviculare L., Sambucus nigra L., or Isodon japonicus L. in bacterial lipopolysaccharide (LPS) stimulated human gingival fibroblasts (HGF-1) and human U-937 monocytes, as cell models of periodontal disease. HGF-1 and U-937 cells were incubated with LPS from either Porphyromonas gingivalis or Escherichia coli together with the four plant extracts alone or in combination. Secretion of anti-inflammatory cytokines from HGF-1 and U-937 cells was measured by means of a multiplexed bead assay system. Magnolia officinalis L. bark extract, at concentrations of 1 µg/mL and 10 µg/mL, reduced interleukin 6 (IL-6) and interleukin-8 (IL-8) secretion from HGF-1 cells to 72.5 ± 28.6% and reduced matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) secretion from U-937 cells to 8.87 ± 7.97% compared to LPS-treated cells (100%). The other three extracts also reduced secretion of these inflammatory markers but were not as effective. Combination of 9 µg/mL Magnolia officinalis L. extract with 1 µg/mL of each of the other extracts maintained the anti-inflammatory effect of Magnolia officinalis L. extract. Combination of 5 µg/mL Magnolia officinalis L. extract with 5 µg/mL Isodon japonicus L. extract also maintained the anti-inflammatory potential of the Magnolia officinalis L. extract, whereas increasing concentrations of any of the other plant extracts in the combination experiments reduced the Magnolia officinalis L. extract efficacy in U-937 cells.

[5]  J Ethnopharmacol. 2006 Jul 19;106(3):418-24. Epub 2006 Mar 10.
Glechoma hederacea inhibits inflammatory mediator release in IFN-gamma and LPS-stimulated mouse peritoneal macrophages. An HJ, Jeong HJ, Um JY, Kim HM, Hong SH.
Glechoma hederacea (GH) is an herb widely used herb medicine for the treatment of a variety of pathologies. In this study, the effect of GH on interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS)-induced production of nitric oxide (NO), interleukin (IL)-12p70, IL-12p40, tumor necrosis factor-alpha (TNF-alpha), and IL-6 were examined using mouse peritoneal macrophages. GH inhibits IFN-gamma/LPS-induced NO in a dose-dependent manner. The decrease in NO synthesis was reflected as a decreased amount of inducible NO synthase protein. We also found that GH inhibits pro-inflammatory cytokine, IL-12p70, and TNF-alpha production. However, GH increased IFN-gamma/LPS-induced IL-12p40 production. GH doesn’t affect the IL-6 production. These findings mean that GH can be used in controlling macrophages mediated inflammation related disease.

[6]  J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):509-18.Resveratrol in Chlamydia pneumoniae-induced foam cell formation and interleukin-17A synthesis.Di Pietro M, De Santis F, Schiavoni G, Filardo S, Sessa R.
Author informationAbstractThe involvement of Chlamydia pneumoniae in the pathogenesis of atherosclerosis has been suggested by numerous seroepidemiological, in vivo and in vitro studies. In particular, it has been shown that C. pneumoniae is able to promote the accumulation of low-density lipoproteins into macrophages, thus facilitating foam cell formation. The aim of our study was to investigate the effects of resveratrol on macrophage derived foam cell formation induced by C. pneumoniae, examining its underlying biochemical mechanisms. Our results showed a relevant decrease in the number of foam cells, in the production of thiobarbituric acid reactive substances, superoxide anion and IL 17A while treating C. pneumoniae infected macrophages with resveratrol. Furthermore, the inhibition of Peroxisome Proliferator-Activated Receptors gamma by a specific antagonist (GW 9662), in presence of resveratrol and C. pneumoniae, enhanced intracellular lipid and cholesterol accumulation and the subsequent foam cell formation. In conclusion, the main result of our study is the evidence of an antiatherogenic effect of resveratrol on macrophage-derived foam cell formation and IL-17A production induced by C. pneumoniae.
[7]  Zhonghua Xin Xue Guan Bing Za Zhi. 2013 Oct;41(10):866-9.[Resveratrol reduces inflammatory cytokines via inhibiting nuclear factor-κB and mitogen-activated protein kinase signal pathway in a rabbit atherosclerosis model].
Song R1, Li WQ, Dou JL, Li L, Hu YJ, Guo JZ, Lu D, Zhang G, Sun L2.
Inflammation serves as the initial pathologic step of cardiovascular diseases including atherosclerosis. Resveratrol possesses many pharmacological properties including antioxidant, cardioprotective and anti-cancer effects. In this study, we investigate the anti-inflammatory effect and mechanisms of resveratrol in an atherosclerotic rabbit model.METHODS:
Rabbit were assigned to six groups (n = 10 each): control, high fat diet group, resveratrol low, medium and high dose groups, resveratrol pretreatment group. The serum tumor necrosis factor-α (TNF- α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were analyzed by Enzyme-linked immuno sorbent assay(ELISA). Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades and NF-κB were determined by Western blot.RESULTS:
Compared with the control group, the expression of serum inflammatory factors IL-1β, IL-6, TNF-α were increased in high-fat group (all P < 0.05). Compared with high-fat group, the expressions of IL-6, IL-1β, TNF-α were significantly reduced in resveratrol low, medium, high dose groups and resveratrol pretreatment group (all P < 0.01), and this effect is dose-dependent. In addition, the NF-κB, p38MAPK, JNK, ERK1/2 protein phosphorylation in high-fat group were significantly upregulated compared with control group (P < 0.05), which (except ERK1/2 phosphorylation level) were significantly downregulated in resveratrol treatment group and resveratrol pretreatment group.CONCLUSION:
This study indicates that resveratrol reduces serum inflammatory cytokines in this atherosclerotic rabbit model via down-regulation phosphorylation of NF-κB, and MAPKs signaling, which might serve as the anti-inflammatory molecular basis of resveratrol.
[8]   J Periodontol. 2005 Aug;76(8):1329-38.
Lupinus albus, a novel vegetable extract with metalloproteinase inhibitory properties: a potential periodontal therapy.
Gaultier F, Ejeil AL, Dridi SM, Piccardi N, Piccirilli A, Msika P, Pellat B, Godeau G, Gogly B.
Author information AbstractBACKGROUND:In this study we examine the properties of a vegetable extract from seeds of Lupinus albus (LU 105). In previous works we demonstrated that LU 105 reduced the expression, by gingival fibroblasts, of both matrix metalloproteinase (MMP)-2 and MMP-9. We decided to study the impact of LU 105 on cell proliferation and morphology. Using organ culture media we also studied the MMP and tissue inhibitors of metalloproteinases (timp) expression AND THE cytokines secretion.

METHODS:Healthy and inflamed gingival biopsies were placed in appendage culture with or without LU 105. The organ culture media were analyzed using Western blottings (MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, TIMP-1, and TIMP-2) and gelatine zymography. A reverse transcription polymerase chain reaction (RT-PCR) was also performed on healthy and inflamed gingival biopsies, which were maintained in culture with or without LU 105 0.1%. Then, we decided to determine the amount of cytokines present in the organ culture media such as interleukin (IL)-1 beta, IL-4, IL-6, transforming growth factor (TGF)-beta, and tumor necrosis factor (TNF)-alpha.

RESULTS:When gingival biopsies derived from inflamed tissues were cultured with LU 105 0.1% in the culture media, the MMP and TIMP expression and activity decreased significantly when compared to cultures without LU 105. Moreover, we did not note any statistical difference in the cell proliferation compared with human gingival fibroblast cultures without LU 105. Furthermore, IL-1 beta, IL-6, TGF-beta, and TNF-alpha amounts in the culture media decreased significantly, whereas IL-4 increased significantly when LU 105 0.1% was added to the culture media.

CONCLUSION:LU 105, a novel metalloproteinase inhibitor with few consequences on cell proliferation and morphology, is a vegetable extract with potential clinical capacity.



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