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Scientifically speaking ...

Although the literature on Kalawalla (Polypodium leucotomos extract) is not limited to all of the trials summarized below, you can find a compendium of some of the most important trials that have been carried out with Polypodium leucotomos extract under its different registered brands

Clinical trials by Harvard Medical School details how Kalawalla modulates the T cells and its usefulness in auto aggressive / inflammatory conditions.
Anticancer Res. 2000 May-Jun;20(3A):1567-75. Related Articles, Links

An extract of the fern Polypodium leucotomos (Difur) modulates Th1/Th2 cytokines balance in vitro and appears to exhibit anti-angiogenic activities in vivo: pathogenic relationships and therapeutic implications.

Gonzalez S, Alcaraz MV, Cuevas J, Perez M, Jaen P, Alvarez-Mon M, Villarrubia VG.

Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA, USA.

In the present study we show the capacity of an extract of the fern Polypodium leucotomos (PLE) to partially inhibit the production of cytokines showing a Th1 pattern (IL-2, IFN-gamma and TNF-alpha) in human PHA-stimulated peripheral blood mononuclear cells. The percentage of inhibition was 24% for IL-2, 72% for INF-gamma and 53% for TNF-alpha. With regard to Th2 cytokines, the addition of PLE resulted in a significant increase (33%) in IL-10 production. Surprisingly, the production of the inflammatory cytokine IL-6 was completely abolished (100% inhibition) by PLE at all doses tested. In a second experiment in vivo we show that, the topical application of PLE to the skin of hairless albino mice (Skh-1) significantly diminished the mast cell infiltrate as well as the number of blood vessels triggered by chronic ultraviolet B (UVB) irradiation. These data show that PLE moderately inhibits the immunological Th1 responses, thus explaining the immunosuppressive as well as the anti-inflammatory and antioxidant activities reported in other studies carried out with PLE. The clear inhibitory effect on TFN-alpha and IL-6 production strongly suggest that this may be the mechanism by which PLE: (a) inhibits angiogenesis in vivo in the mouse model described here, and (b) prevents Langerhans' cells depletion caused by solar irradiation in humans. Taken together, these data suggest that PLE works through the induction of suppressive/anti-inflammatory cytokines such as IL-10 and/or TGF-beta which in turn appear to allow the partial deactivation of macrophages or other accessory cells. These features suggest that PLE could be useful in the treatment of autoaggressive/inflammatory conditions due to an exacerbation of Th1 responses.

PMID: 10928072 [PubMed - indexed for MEDLINE]

Authors: Pablo Cambar+, MD, MSc Pharmacology, University of Pennsylvania, Danilo Alvarado+, MD, MSc Pathology, University of Illinois
- Toxicology performed on rats type Wistar, Albino mice type C3H and rabbits type New Zealand White*.
Lethal Dose 50 (LD50) of PLE intraperithoneal in rats: LD50 = 2,800 mg / kg, Lethal Dose 50 (LD50) of PLE intraperithoneal in mice: LD50=3,900 mg / kg
Lethal Dose 50 (LD50) of PLE intraperithoneal in rabbits: LD50=3,700 mg / kg
Lethal Dose 50 (LD50) of PLE orally in rats: LD50=7000 mg / kg **
Lethal Dose 50 (LD50) of PLE orally in mice: LD50=20,000 mg / kg **
Lethal Dose 50 (LD50) of PLE orally in rabbits: LD50=35,000 mg / kg **
1. Hemathological Parameters Measured (at initial time, 4 weeks and 12 weeks):
Estrocytes, Leucocytes, Hematocrites, Hemoglobin
2. Biochemical (at initial time, 4 weeks and 12 weeks):
Glucose, Cholesterol, Urea, Creatinine, Total lipids, TGO, TGP, Total protein, Triglicerids
3. Physical (measured daily):
Water intake, Food intake, Excreted urine, Body weight
- Length of study: 12 weeks
Additional parameters: Blood analyzed taken from the heart. Once the toxicology was completed, the animals were sacrificed and the following organs were extracted, weighed and preserved in formalin for a histopathological analysis: heart, lungs, liver, kidneys, stomach, suprarhenal, pancreas, testicles, ovaries, large intestine, small intestine, bladder.

Results: No abnormalities or alterations attributed to the administering of PLE were found.
* Complete toxicology data is fully available for rats, mice and rabbits.
** This dose is over 1200 times the recommended dose for a 70 kg adult in a single serving or approximately 1.4 kilos of pure PLE extract (2.8 kilos of PLE powder). This dose did not provoke the death in any of the rats, mice or rabbits in the study, rendering the product completely non toxic when used at suggested dose.

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.

The most frequent immunological alterations of the phenotype in MS are increase L ind B and decreased L supp. They are not related to classical forms. The treatment of Multiple Sclerosis with an extract of Polypodium leucotomos is useful to correct these phenotype imbalance and can contribute to a clinical stabilization.

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.

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))

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. me-direccion@lcg.servicom.es 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.

1. Capella Perez MC, Castells RA. [Double-blind study using "Polypodium leucotomos" 120 mg. in the treatment of psoriasis]. Actas Dermosifiliogr 1981;72(9-10):487-494.
Comments: 61 psoriatic patients were treated for a period of 6 months with Polypodium leucotomos extract. 90% of the patients showed significant improvement within this period.

Comparative study between 120 mg. of Anapsos (Polypodium leucotomos extract) and a placebo in 37 psoriasis patients. Del Pino Gamboa J; De Sambricio Guiu F; Colomo Gomez C Medicina cutanea ibero-latino-americana (1982), 10(3), 203-8. Journal code: 7601805. ISSN:0210-5187. (CLINICAL TRIAL); (CONTROLLED CLINICAL TRIAL); Journal; Article; (JOURNAL ARTICLE) written in Spanish. PubMed ID 6759814 AN 83113784 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))


It is presented a comparative and clinical study on 37 patients affected by psoriasis, 13 of them took placebo and 22 finished treatment with Anapsos (Polypodium leucotomos extract) in capsules of 120 mg. One patient abandoned treatment by intolerance and another one with possible laryngeal neoplasm, the drug showed a discordant result. 9 out of 22 who used Anapsos (Polypodium leucotomos extract), obtained full whitening, 5 got whitenings between 40% and 80% of the affected surface, 5 got a maximum of 40% and 3 had null result. The absence of side effects, minimum intolerance of product and the amount of obtained successes make the authors to consider the future of Anapsos (Polypodium leucotomos extract) optimistically for the treatment of psoriasis.

Comments: Most patients treated with Polypodium leucotomos extract showed significant improvement while placebo patients did not.

J Am Acad Dermatol. 2004 Jan;50(1):41-9. Related Articles, Links
Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin.

Middelkamp-Hup MA, Pathak MA, Parrado C, Garcia-Caballero T, Rius-Diaz F, Fitzpatrick TB, Gonzalez S.

Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.

BACKGROUND: The use of psoralen-UVA (PUVA) in patients of skin phototype I to II is limited by side effects of acute phototoxicity and possible long-term carcinogenesis. OBJECTIVE: We sought to assess oral Polypodium leucotomos (PL) extract in decreasing PUVA-induced phototoxicity of human skin on a clinical and histologic level. METHODS: A total of 10 healthy patients with skin phototypes II to III were exposed to PUVA alone (using 0.6 mg/kg oral 8-methoxypsoralen) and to PUVA with 7.5 mg/kg of oral PL. RESULTS: Clinically, phototoxicity was always lower in PL-treated skin after 48 to 72 hours (P<.005), and pigmentation was also reduced 4 months later. Histologically, PL-treated skin showed a significant numeric reduction of sunburn cells (P=.05), preservation of Langerhans cells (P< or =.01), decrease of tryptase-positive mast cell infiltration (P<.05), and decrease of vasodilation (P< or =.01). No differences were found in Ki-67+ proliferating cells. CONCLUSIONS: PL is an effective chemophotoprotector against PUVA-induced skin phototoxicity and leads to substantial benefits of skin protection against damaging effects of PUVA as evidenced by histology.

PMID: 14699363 [PubMed - indexed for MEDLINE]

Metabolic effects of calagualine, an antitumoral saponine of Polypodium leucotomos. Horvath A; Alvarado F; Szocs J; de Alvardo Z N; Padilla G Nature (1967 Jun 17), 214(94), 1256-8. Journal code: 0410462. ISSN:0028-0836. Journal; Article; (JOURNAL ARTICLE) written in English. PubMed ID 6066125 AN 68089646 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))

Anapsos (Polypodium leucotomos extract) modifies immunological parameters and improves the clinical course in atopic dermatitis. Jimenez D; Doblare E; Naranjo R; Munoz C; Vargas J F Dermatologica (1986), 173(3), 154-5. Journal code: 0211607. ISSN:0011-9075. (CLINICAL TRIAL); Letter written in English. PubMed ID 3533665 AN 87031144 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))

Anapsos (Polypodium leucotomos extract), an antipsoriatic drug, in atopic dermatitis. Jimenez D; Naranjo R; Doblare E; Munoz C; Vargas J F Departamento de Dermatologia y Venereologia, Universidad de Granada, Spain Allergologia et immunopathologia (1987 Jul-Aug), 15(4), 185-9. Journal code: 0370073. ISSN:0301-0546. Journal; Article; (JOURNAL ARTICLE) written in English. PubMed ID 2891287 AN 88073810 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R))


An open, controlled study was carried out in young patients with atopic dermatitis, who during one month received oral anti-psoriatic drug, Anapsos (Polypodium leucotomos extract) (n = 46), or antihistamines (n = 30), simultaneously with topic applications. The activity and extension of the cutaneous lesions improved under both treatments, but more markedly with Anapsos (Polypodium leucotomos extract) in spite of the fact that topical applications did not contain steroids in the group treated with Anapsos (Polypodium leucotomos extract), and the effect was still appreciable several months after interruption of medication. Anapsos (Polypodium leucotomos extract), which was well tolerated, considerably relieved the respiratory symptoms of all patients with asthma. Studies performed on patients with atopic dermatitis have shown high IgE levels, eosinophils and T4 counts, and a marked decrease in T8 suppressor cells in peripheral blood. Our data also show a slight decrease in T8 cells (%), a significant increase in T4 sub-sets (%) and a high T4/T8 ratio as a previously reported by several authors. Such an imbalance between helper and suppresor cells may cause alterations in the response to extrinsic and intrinsic antigens, as shown in particular by the abnormally high IgE levels observed in atopic dermatitis. Anapsos (Polypodium leucotomos extract) was associated with a correction in T lymphocytes imbalances, specifically through the increase of the initially low T8 cells levels and subsequent normalization of the mean T4/T8 index. The tolerance and promising therapeutic activity of this antipsoriatic drug deserve further research in other conditions characterized by a deficit of suppressor cells.

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.

Br J Rheumatol. 1998 Aug;37(8):912. Related Articles, Links
Modification of the inflammatory activity of psoriatic arthritis in patients treated with extract of Polipodium leucotomos (Anapsos (Polypodium leucotomos extract)) Navarro-Blasco FJ, Sempere JM.

Comments: The use of Polypodium leucotomos proved beneficial to most patients in the study.

A new agent (hydrophilic fraction of polypodium leucotomos) for management of psoriasis. Padilla H C; Lainez H; Pacheco J A International journal of dermatology (1974 Sep-Oct), 13(5), 276-82. Journal code: 0243704. ISSN:0011-9059. (CLINICAL TRIAL); (CONTROLLED CLINICAL TRIAL); Journal; Article; (JOURNAL ARTICLE) written in English. PubMed ID 4609374 AN 75035388 MEDLINE (Copyright 2004 U.S. National Library of Medicine on SciFinder (R)

Int J Immunopharmacol. 1997 Jan;19(1):9-14. Related Articles, Links
An extract of the fern Polypodium leucotomos inhibits human peripheral blood mononuclear cells proliferation in vitro.

Rayward J, Villarrubia VG, Guillen C, Prieto A, Rodriguez-Zapata M, Sada G, Alvarez-Mon M.

Departamento De Medicina, Hospital Principe De Asturias, Universidad De Alcala De Henares, Madrid, Spain.

An alcoholic extract of the fern polypodium leucotomos (PLE) has been empirically used as an immunosuppressor for the treatment of several autoimmune diseases. In this paper, we investigated the effects of PLE on activation and proliferative responses of peripheral blood mononuclear cells (PBMNC) from healthy donors to T lymphocyte polyclonal mitogens. PLE shows a significant inhibitory effect on the proliferative response of PBMNC to stimulation with phytohaemagglutinin (PHA) or anti CD3 monoclonal antibodies (p < 0.05). In contrast, PLE did not modify the proliferative response of PBMNC to phorbol esters (p > 0.05). The inhibitory effect of PLE upon mitogen induced PBMNC proliferation is time dependent and can be overcome by the exogenous addition of interleukin-2 to the culture medium (p < 0.05). The decreased proliferative response of PBMNC to PHA stimulation in the presence of PLE is not associated with a significant modification of expression of the alpha chain (CD25) of the IL-2 receptor (p > 0.05). In conclusion, PLE shows an inhibitory effect on the polyclonal proliferative response of PBMNC to T lymphocyte mitogens that interact with cytoplasmic membrane molecules.

PMID: 9226474 [PubMed - indexed for MEDLINE]

F. Alvarado, JA Pacheco, PR Portillo, Z Alvarado, Polypodium leucotomos extract, an effective treatment against psoriasis. Internal company document.
Comments: Out of 42 patients treated with Polypodium leucotomos during a 4 month period, all of them showed a 75 – 100% clearing of the lesions within this period.

Effect of Anapsos (Polypodium leucotomos extract) on in vitro production of cytokines. Sempere, J. M.; Rodrigo, C.; Campos, A.; Villalba, J. F.; Diaz, J. Scientific Dept., ASAC Pharmaceutical International, Alicante, Spain. British Journal of Clinical Pharmacology (1997), 43(1), 85-89. CODEN: BCPHBM ISSN: 0306-5251. Journal written in English. CAN 126:198476 AN 1997:146151 CAPLUS (Copyright 2004 ACS on SciFinder (R))


The aim of the study was to test the immunomodulating capacity of Anapsos (Polypodium leucotomos extract), in vitro to explore how this ext. acts from an immunol. point of view and thus to identify a common link capable of explaining most of its effects. Polypodium leucotomos rhizomes were harvested in Guatemala and the ext., Anapsos (Polypodium leucotomos extract), obtained. Mononuclear cells were obtained by d. gradient centrifugation from healthy donors, and stimulated with phytohemagglutinin or pokeweed with and without Anapsos (Polypodium leucotomos extract) and with Anapsos (Polypodium leucotomos extract) alone. Cell proliferation was detd. by thymidine incorporation. Cells were also stimulated and the following cytokines detd. by ELISA at 0, 12, 24, 48, 72, and 96 h: IL-1?, TNF-?, IL-2, IFN-?, IL-4 and IL-10. Anapsos (Polypodium leucotomos extract), has a modulating effect on the in vitro prodn. and release of cytokines by peripheral blood mononuclear cells of healthy subjects. At doses effective in vivo, Anapsos (Polypodium leucotomos extract) can stimulate PBMC proliferation, delay IL-1? secretion and at the same time increase that of IL-2, IL-10, and IFN-?. Anapsos (Polypodium leucotomos extract) may have an antagonistic effect on some of the cytokines released on cell stimulation with LPS and/or PHA, which suggests that this product has a pleiotropic effect on different populations in the immune system.

Anapsos (Polypodium leucotomos extract), an antipsoriatic drug which increases the proportion of suppressor cells in human peripheral blood. Vargas, J.; Munoz, C.; Osorio, C.; Garcia-Olivares, E. Dep. Fisiol. Bioquim., Fac. Med., Granada, Spain. Annales d'Immunologie (Paris) (1983), 134C(3), 393-400. CODEN: ANIMCZ ISSN: 0300-4910. Journal written in English. CAN 99:151816 AN 1983:551816 CAPLUS (Copyright 2004 ACS on SciFinder (R))


Anapsos (Polypodium leucotomos extract), an antipsoriatic drug, was administered to normal volunteers. After 3 days of treatment, the drug decreased the lymphoblastic response to pokeweed mitogen (PWM) and very slightly reduced the serum levels of Igs. After 5 days of treatment, however, both values were normal. The response to ConA decreased, and there was an increase in the suppressor index and in the proportion of T-cells of the OKT 8+ subpopulation. The drug did not vary the proportion of OKT 4+ and OKT 3+ cells. These results suggest that Anapsos (Polypodium leucotomos extract) acts by increasing the no. of suppressor cells. Such Anapsos (Polypodium leucotomos extract)-induced suppressor cells are probably responsible for the diminished response to ConA, but did not seem to affect the response to PWM and serum levels of Ig after 5 days 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.

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.

Quantitative determination of antiinflammatory principles in some Polypodium species as a basis for standardization. Liu, B.; Diaz, F.; Bohlin, L.; Vasaenge, M. Div. Pharmacognosy, Dep. Pharmacy, Biomedical Center, Uppsala Univ., Uppsala, Swed. Phytomedicine (1998), 5(3), 187-194. CODEN: PYTOEY ISSN: 0944-7113. Journal written in English. CAN 129:140525 AN 1998:371470 CAPLUS (Copyright 2004 ACS on SciFinder (R))


Polyunsatd. fatty acids (linoleic, linolenic, arachidonic acid), the triflavonoid selligueain, and a sulfonoglycolipid (SQDG) were detd. quant. by high-performance liq. chromatog. in the leaves and rhizomes of 5 Polypodium species (Calaguala). Exts. of the 5 ferns were studied in 3 in vitro bioassays using platelet activating factor and leukotriene B4. SQDG was present in pharmacol. detectable amts. in the crude exts. The anal. method for quant. detn. of SQDG was recommended to be used for standardization of Calaguala ext. in herbal drug prepns.

Therapeutic properties of Polypodium angustifolium (Calahuala). Pareja, Bertha; et al. Fac. Farm. Bioquim., Univ. Nac. Mayor San Marcos, Lima, Peru. Boletin de la Sociedad Quimica del Peru (1988), 54(2), 89-95. CODEN: BSQPAQ ISSN: 0037-8623. Journal written in Spanish. CAN 111:219163 AN 1989:619163 CAPLUS (Copyright 2004 ACS on SciFinder (R))


Calahuala is a folk medicine, derived from the fern P. angustifolium, which is used in South America as an anti-inflammatory prepn. and for other purposes. Anal. of an EtOH ext. of the leaves of this plant indicates that the active component of Calahuala is an anthraquinone which may be suitable for use as a starting material for synthesis of corticosteroid hormones.

J Photochem Photobiol B. 2003 Apr;70(1):31-7. Related Articles, Links
Photoprotective properties of a hydrophilic extract of the fern Polypodium leucotomos on human skin cells.

Alonso-Lebrero JL, Dominguez-Jimenez C, Tejedor R, Brieva A, Pivel JP.

R&D Department, Industrial Farmaceutica Cantabria S.A., Madrid, Spain.

The effect of a hydrophilic extract of the fern Polypodium leucotomos (PLE) has been investigated in terms of photoprotection against UV-induced cell damage. PLE efficiently preserved human fibroblast survival and restored their proliferative capability when the cells were exposed to UVA light. This effect was specific and dose-dependent. Photoprotection was not restricted to fibroblasts, as demonstrated by its effect on survival and proliferation of the human keratinocyte cell line HaCat. Finally, treatment of the cells with PLE prevented UV-induced morphological changes in human fibroblasts, namely disorganisation of F-actin-based cytoskeletal structures, coalescence of the tubulin cytoskeleton and mislocalization of adhesion molecules such as cadherins and integrins. Our in vitro results demonstrate the photoprotective effect of PLE on human cells and support its use in the preventive treatment of sunburning and skin pathologies associated with UV-mediated damage.

PMID: 12745244 [PubMed - indexed for MEDLINE]

T. Hornedo, Inigo, JM Belmar, Clinical assay on 44 psoriatic patients using Polypodium leucotomos extract. Antol. Dermat. No. 1 (52 – 55), Jan 1983
Comments: 80% of the patients treated obtained good results within 2 – 5 months of use.

Internal Company Statistics. Out of a 3 year study on Organic Hope patients and their satisfaction with Polypodium leucotomos for the treatment of different types of psoriasis, 95% of all patients showed complete satisfaction within 6 months of use of Kalawalla.

Internal Company Research: There is no toxicity associated with the short or long term use of Polypodium leucotomos extract. Side effects reported: upset stomach (less than 5 in 1,000 patients). Interactions: HBP lowering medications. Polypodium leucotomos theoretical reduces HBP, hence producing an unsafe decrease in BP when combined with HBP medications. Other supplements with simihttps://www.advancedalternativescenter.com/Kalawalla_p/ohk.htmlar BP lowering effects.

Kalawalla is a 100% natural product with no known toxic side effects.

This product contains (per capsule):

Polypodium leucotomos Extract …….……120 mg
Polypodium leucotomos Rhizome ………..180 mg

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