Spanish Society of Neurology, XLVI Annual Symposium
Kalawalla in Multiple Sclerosis (MS) Patients
Immunological Phenotype and Treatment with Polypodium leucotomos (Kalawalla) in Multiple Sclerosis (MS) Patients
Spanish Society of Neurology, XLVI Annual Symposium
MM Carreño, P Castro, Dept. of Neurology, Navarra University, Pamplona, Spain
Introduction and Obejectives
Several studies have shown the existence of abnormal immunological phenotypes in MS, and more specifically a imbalance in the suppressor function.
Objectives: To determine quantitavive abnormalities in the lymphocyte subpopulation of MS patients, to establish the relationship with the different clinical pictures and to study the response to the treatment with an extract of Polypodium leucotomos.
Patients and Methods: 12 patients, 10 women and 2 men, with well established MS; mean age of 43.7 years; evolution time 6.5 years; treated for one yeat only with an extract of Polypodium leucotomos (360 – 720 mg / day). The immunological phenotype was studied counting the lymphocyte sub population.
Statistical analysis were carried out by non parametric techniques.
Results: More frequent basal immunological alterations were increased CD4 in d LB (62.5%), decreased CD8 suppressors (50%). There was no correlation between the increase in ICD4 in LB – progressive form and decrease ICD8 – relapsing / remitting form. The treatment brought the lymphocyte count to normal in 100% of the patients with increased CD4 in B. the clinical evolution, according to the EDSS scale was: Normal development of course of disease 3 patients (37.5%), stabilization and improvement 5 patients (62.5%) Increased in ICD8 suppressor figures were normalized in 3 patients (50%); worsening was recorder in only 1 patient.
Med Cutan Ibero Lat Am. 1983;11(1):65-72. Related Articles, Links
2 years personal experience in Anapsos (Polypodium leucotomos extract) treatment of psoriasis in various clinical forms
[Article in Spanish]
Pineiro Alvarez B.
A personal experience on 495 patients affected by several forms of psoriasis and its answer to the treatment with Anapsos (Polypodium leucotomos extract) is presented. The whitenings between 80% and 100% of the affected skin were achieved on 304 patients (61.41%); 46 patients whitened between 30% and 80% of their lesions, 15 obtained null results and only 11 had relapses. It is remarkable the high number of abandonments to treatment which came at 119 patients (24.04%) due to slowness of process and other reasons probably. The association with PUVA which shortens the treatment and gives other advantages is pointed out as positive. The average time of treatment was 6 months, and daily doses were from 80 mg. and 720 mg. depending on age, weight and treatment phase. Side effects appeared in two patients only: one with intense pruritus and the other one with gastric disturbances. In both cases, these side effects disappeared when the treatment was interrupted.PMID: 6348443 [PubMed – indexed for MEDLINE]Comments: Out of 495 patients 93% of those who completed the 6 months treatment with Polypodium leucotomos extract showed good results.
University of Texas
Cancer Lett. 2003 Feb 20;190(2):171-82. Related Articles, Links
Calagualine inhibits nuclear transcription factors-kappaB activated by various inflammatory and tumor promoting agents.
Manna SK, Bueso-Ramos C, Alvarado F, Aggarwal BB.
Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 143, Houston, TX 77030, USA
Calagualine derived from the fern of the genus Polypodium, commonly called calaguala, has had clinically documented medicinal uses in South America and Spain and been shown to block tumor metastasis, proliferation, and inflammation, all known to require the activation of nuclear transcription factor-kappaB (NF-kappaB). Therefore, we investigated the effect of calagualine on NF-kappaB activation induced by various inflammatory and tumor promoting agents. Calagualine blocked tumor necrosis factor (TNF)-induced activation of NF-kappaB through inhibition of phosphorylation and degradation of IkappaBalpha, an inhibitor of NF-kappaB. The effects of calagualine were not cell type-specific, as it blocked TNF-induced NF-kappaB activation in a variety of cells. NF-kappaB-dependent reporter gene transcription activated by TNF was also suppressed by calagualine. The TNF-induced NF-kappaB activation cascade involving TNFR1-TNF receptor-associated death domain-TNF receptor-associated factor 2 (TRAF2)-NF-kappaB-inducing kinase (NIK)-IkappaBalpha kinase was interrupted at the TRAF2 and NIK sites by calagualine, which would account for its suppression of NF-kappaB reporter gene expression. Calagualine blocked NF-kappaB activation induced by phorbol ester and lipopolysaccharide. Overall our results indicate that calagualine inhibits activation of NF-kappaB and this may provide a molecular basis for calagualine’s ability to suppress inflammation and tumorigenesis.
PMID: 12565172 [PubMed – indexed for MEDLINE]
Preliminary communication on the treatment of psoriasis with Anapsos (Polypodium leucotomos extract). Mercadal Peyri O; Maesci Cappitanio F Actas dermo-sifilograficas (1981 Jan-Feb), 72(1-2), 65-8. Journal code: 0373062. ISSN:0001-7310. Journal; Article; (JOURNAL ARTICLE) written in Spanish. PubMed ID 7257904 AN 81252352 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))
Comments: Most patients showed significant improvement within the period of treatment.
Effects of calaguala and an active principle, adenosine, on platelet activating factor. Tuominen, M.; Bohlin, L.; Rolfsen, W. Dep. Pharmacogn., Uppsala Univ., Uppsala, Swed. Planta Medica (1992), 58(4), 306-10. CODEN: PLMEAA ISSN: 0032-0943. Journal written in English. CAN 117:245226 AN 1992:645226 CAPLUS (Copyright 2004 ACS on SciFinder (R))
Calaguala, an ext. from the fern Polypodium decumanum, is used to treat psoriasis and related immunol. disorders. The inhibitory activity of the ext. was studied in 2 blood platelet-activating factor (PAF)-related models. PAF was used to release the proteolytic enzyme elastase from human neutrophils. Calaguala inhibited this effect with an IC50 = 0.1 mg/mL. The PAF antagonist ginkgolide (BN 52021) was used as a pos. control with an IC50 = 0.034 mg/mL. In the second model the inhibition of PAF biosynthesis in neutrophils was studied using lyso-PAF and labeled acetyl-CoA. Calaguala showed a concn.-dependent activity with the IC50 = 0.2 mg/mL. Since PAF may be involved in the pathogenesis of psoriasis, the activity of calaguala seen in these PAF assays may contribute to the clin. efficacy of the ext.
The flavonoid constituents of two Polypodium species (Calaguala) and their effect on the elastase release in human neutrophils. Vasaenge, Mervi; Liu, Boling; Welch, Christopher J.; Rolfsen, Wenche; Bohlin, Lars. Division Pharmacognosy, Department Pharmacy, Biomedical Center, Uppsala University, Uppsala, Swed. Planta Medica (1997), 63(6), 511-517. CODEN: PLMEAA ISSN: 0032-0943. Journal written in English. CAN 128:119490 AN 1998:2481 CAPLUS (Copyright 2004 ACS on SciFinder (R))
Five flavonoid compds. were isolated from 2 Polypodium species (P. decumanum and P. triseriale) with the common name Calaguala. Structure elucidation was carried out using different NMR techniques and revealed the presence of 1 new glycoside (kaempferol 3-O-?-D-xylopyranosyl-(1-2)-?-D-arabinopyranoside) (I), 2 known flavonoid glycosides, rutin and kaempferol 3-O-?-D-arabinopyranoside, the trimeric proanthocyanidin, selligueain, and the coumarinic acid deriv., melilotoside. The compds. were tested for their activity in platelet activating factor (PAF) induced exocytosis in human neutrophils but none of the compds. showed PAF specific activity. Instead, they showed more general effects on the neutrophil including inhibition of the spontaneous elastase release (melilotoside) and potentiation of the release induced by PAF I. Selligueain inhibited the proteolytic enzyme, elastase in vitro.
International journal of dermatology
Vitiligo repigmentation with Anapsos (Polypodium leucotomos extract). Mohammad A International journal of dermatology (1989 Sep), 28(7), 479. Journal code: 0243704. ISSN:0011-9059. Letter written in English. PubMed ID 2777452 AN 89379534 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))
Anapsos (Polypodium leucotomos extract): neuroimmunotrophic treatment in Alzheimer disease and neurodegenerative disorders. Alvarez, Anton; Miguel-Hidalgo, Jose J.; Fernandez-Novoa, Lucia; Diaz, Joaquin; Sempere, Jose M.; Cacabelos, Ramon. EuroEspes Biomedical Research Center, Basic and Clinical Neurosciences Research Center, A Coruna, Spain. CNS Drug Reviews (1997), 3(2), 181-206. CODEN: CDREFB ISSN: 1080-563X. Journal; General Review written in English. CAN 128:83971 AN 1997:791966 CAPLUS (Copyright 2004 ACS on SciFinder (R))
Biomedical Research Center
Double-blind, randomized, placebo-controlled pilot study with Anapsos (Polypodium leucotomos extract) in senile dementia: effects on cognition, brain bioelectrical activity and cerebral hemodynamics. Alvarez X A; Pichel V; Perez P; Laredo M; Corzo D; Zas R; Fernandez-Novoa L; Sempere J M; Diaz J; Cacabelos R EuroEspes Biomedical Research Center, A Coruna, Spain. firstname.lastname@example.org Methods and findings in experimental and clinical pharmacology (2000 Sep), 22(7), 585-94. Journal code: 7909595. ISSN:0379-0355. (CLINICAL TRIAL); Journal; Article; (JOURNAL ARTICLE); (RANDOMIZED CONTROLLED TRIAL) written in English. PubMed ID 11196347 AN 2001177090 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))
The aim of this study was to evaluate the effects of two doses of Anapsos (Polypodium leucotomos extract) in comparison with placebo on cognitive performance, brain bioelectrical activity pattern and cerebral hemodynamic parameters in patients with mild to moderate senile dementia of vascular type and Alzheimer type. Forty-five patients (age 73.8 +/- 7.6 years; range 56-89 years) with mild to moderate senile dementia (Global Deterioration Scale: stages 3-5) of the vascular (VD; n = 22) or the Alzheimer type (AD; n = 23) were included in a double-blind randomized placebo-controlled clinical trial. After a 2-week period of drug washout, patients were treated with placebo (n = 15; age 72.7 +/- 7.5 years), 360 mg/day of Anapsos (Polypodium leucotomos extract) (n = 15; age 75.5 +/- 7.2 years), or 720 mg/day of Anapsos (Polypodium leucotomos extract) (n = 15; age 73 +/- 7.7 years) for 4 weeks (28 days). At baseline and after the 4-week period of double-blind treatment, cognitive performance, brain bioelectrical activity power and blood flow hemodynamics in the middle cerebral arteries were evaluated with ADAScog, brain mapping and transcranial Doppler ultrasonography, respectively. Patients receiving 360 mg/day of Anapsos (Polypodium leucotomos extract) showed a significant improvement in cognitive performance after treatment (ADAScog scores: p < 0.05) that was not observed in patients treated with placebo or 720 mg/day of Anapsos (Polypodium leucotomos extract). As compared to placebo, Anapsos (Polypodium leucotomos extract) (360 mg/day) induced a significant improvement in ADAScog scores in mild senile dementia patients (p < 0.01) and in the subset of patients with AD (p < 0.05). Anapsos (Polypodium leucotomos extract) (360 mg/day) also increased cerebral blood flow velocities in left and right middle cerebral arteries in the subgroup of AD patients, whereas with the dose of 720 mg/kg this increase was only observed in the left side. Patients treated with Anapsos (Polypodium leucotomos extract) (360 mg/day) showed a decrease in relative delta power and an increase in relative theta and alpha brain bioelectrical activity frequencies, indicating an acceleration of the EEG pattern.
The present results show that Anapsos (Polypodium leucotomos extract) (360 mg/day) improves cognitive performance, cerebral blood perfusion and brain bioelectrical activity in patients with senile dementia. These effects of Anapsos (Polypodium leucotomos extract) were more marked in demented patients with mild mental deterioration and/or with dementia of the Alzheimer type.
In vitro studies on the immunomodulating effects of Polypodium leucotomos extract on human leukocyte fractions. Brend, A.; Ramirez-Bosca, A.; Huber, H.; Diaz, Alperi, J.; Thaci, D.; Sewell, A.; Quintanilla, Almagro, E. Zentrum der Dermatologie und Venerologie, Wolfgang Goethe-Universitaet, Frankfurt/Main, Germany. Arzneimittel-Forschung (1995), 45(8), 901-4. CODEN: ARZNAD ISSN: 0004-4172. Journal written in English. CAN 123:275468 AN 1995:862800 CAPLUS (Copyright 2004 ACS on SciFinder (R))
The in vitro effect of Anapsos (Polypodium leucotomos extract), a water based ext. of the naturally occurring fern Polypodium leucotomos (Calagualine), on human leukocyte fractions was investigated. Calagualine inhibited interleukin-2 secretion and Con A (Con A) stimulated proliferation of T-lymphocytes in a concn.-dependent manner. In contrast, a greatly enhanced secretion of IL-1a, IL-1? and tumor necrosis factor a was induced suggesting a stimulation of monocytes and dendritic cells also present in this system. Endotoxin induced stimulation was excluded. Also in the absence of Con A, calagualine stimulated cytokine prodn. The presented data show for the first time that calagualine exerts an immunomodulating effect on leukocyte fractions, paving the way for further detailed studies related to possible clin. efficacy.
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Sweden Journal of pharmacy and pharmacology
Skin disorders, including Psoriasis
A sulphonoglycolipid from the fern Polypodium decumanum and its effect on the platelet activating-factor receptor in human neutrophils. Vasange M; Rolfsen W; Bohlin L Department of Pharmacy, Uppsala University, Sweden Journal of pharmacy and pharmacology (1997 May), 49(5), 562-6. Journal code: 0376363. ISSN:0022-3573. Journal; Article; (JOURNAL ARTICLE) written in English. PubMed ID 9178195 AN 97321474 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))
The South American fern Polypodium decumanum, traditional name calaguala, has documented clinical use in oral treatment of skin disorders, including psoriasis. The inflammatory mediator platelet-activating factor (PAF), has been implicated in the pathogenesis of psoriasis. A constituent of a calaguala extract has been shown to have inhibitory activity in a PAF-induced exocytosis model in human neutrophils. The compound was identified as the sulphoquinovosyl diacylglycerol 1,2-di-O-palmitoyl-3-O-(6-sulpho-alpha-D-quinovopyranosyl)-glycero l by spectroscopic means. When subsequently studied in an in-vitro model for [3H]PAF binding in neutrophils from man the compound caused dose-dependent displacement of [3H]PAF from its receptor with an IC50 value of 2 microM. It is suggested that the compound acts through PAF receptor antagonism in intact human neutrophils.
The fern Polypodium decumanum, used in the treatment of psoriasis, and its fatty acid constituents as inhibitors of leukotriene B4 formation. Vasange-Tuominen, M.; Perera-Ivarsson, P.; Shen, J.; Bohlin, L.; Rolfsen, W. Dep. Pharm., Uppsala, Swed. Prostaglandins, Leukotrienes and Essential Fatty Acids (1994), 50(5), 279-84. CODEN: PLEAEU ISSN: 0952-3278. Journal written in English. CAN 120:315432 AN 1994:315432 CAPLUS (Copyright 2004 ACS on SciFinder (R))
The fern P. decumanum, commonly called Calaguala, has a clin. documented use in South America and Spain in the treatment of psoriasis. One of the inflammatory mediators isolated in abnormally high quantities in the psoriatic skin is leukotriene B4 (LTB4). Calaguala was tested in an in vitro model using human leukocytes for its ability to inhibit the LTB4 formation. The inhibition was found to be caused by the polyunsatd. fatty acids (PUFAs) linoleic, linolenic and arachidonic acid. IC50 values were detd. for the isolated acids and compared to a group of closely related acids also commonly found in nature. IC50 values for most acids tested were of the same magnitude (20-60 ?M) except for arachidonic acid which showed stimulatory activity and 8-(R)-hydroxylinoleic acid which gave 30% inhibition with the highest dose tested (120 ?M). The amts. of PUFAs in different Calaguala ext. were quant. analyzed and it is concluded that the fatty acid constituents of Calaguala may contribute to the clin. effects of the ext.