Polypodium leucotomos

Polypodium leucotomos of Phlebodium aureum (Golden polypody, Golden serpent fern or Cabbage palm fern; syns Polypodium aureum, Polypodium leucatomos - commonly, but incorrectly, cited as Polypodium leucotomos) is an epiphytic fern native to tropical and subtropical regions of the Americas. It is confined to the eastern side of the continents, extending north into the United States to Florida and the extreme southeast of Georgia, and south through the Caribbean (the Bahamas, Puerto Rico, and Lesser Antilles), and northern and eastern South America to Paraguay. It is the only species of Phlebodium found in North America, the other species all confined to South America. Other common names include Calaguala (among Spanish speaking peoples), Kalawalla, Samambia,[1] and Anapsos.

It has been shown to be effective when administered orally as an immunomodulator (selectively modulates overactive immune cells), antipsoriatic, neuroprotective (protects brain cells), cough suppressant, anti-inflammatory, and ultraviolet light protectant.[2] [3] [4] [5] It has been commercially available since 1982 in Europe, and as yet has had no toxicity reports, although it may enhance the effects of digoxin and/or other digoxin-type prescription heart drugs.
Its uses include:
for psoriasis and other skin conditions
for Alzheimer's disease, dementia, and memory problems
for coughs, bronchitis, chest colds, and other upper respiratory problems
for autoimmune disorders
It is also reported to have been an aid for those with Multiple Sclerosis and Vitiligo.

^ Gonzalez S, Alonso-Lebrero JL, Del Rio R, Jaen P (July 2007). "Polypodium leucotomos extract: a nutraceutical with photoprotective properties". Drugs Today 43 (7): 475–85.doi:10.1358/dot.2007.43.7.1062667. PMID 17728848.
^ Middelkamp-Hup MA, Pathak MA, Parrado C, et al. (December 2004). "Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin". J. Am. Acad. Dermatol. 51 (6): 910–8. doi:10.1016/j.jaad.2004.06.027. PMID 15583582.
^ Siscovick JR, Zapolanski T, Magro C, et al. (June 2008). "Polypodium leucotomos inhibits ultraviolet B radiation-induced immunosuppression". Photodermatol Photoimmunol Photomed 24 (3): 134–41. doi:10.1111/j.1600-0781.2008.00352.x. PMID 18477132.
^ Mulero M, Rodríguez-Yanes E, Nogués MR, et al. (August 2008). "Polypodium leucotomos extract inhibits glutathione oxidation and prevents Langerhans cell depletion induced by UVB/UVA radiation in a hairless rat model". Exp. Dermatol. 17 (8): 653–8. doi:10.1111/j.1600-0625.2007.00684.x. PMID 18312382.


Edit1. Sources and Composition

1.1. Sources
Polypodium Leucotomos is the more common and taxonomically incorrect name for the herb known as Phlebodium aureum, in the Polypodiaceae family but the Phlebodium genus; this herb is commonly referred to as Calaguala or Golden serpent fern and is commonly grown in Central America.[1] This herb is sometimes referred to by its brandname of Heliocare.

1.2. Composition
Polypodium Leucotomos tends to contain:
Calagualine,[2] common to the genus Polypodium[3]
Phenolic compounds such as ferulic acid, vanillic acid, caffeic acid, and Chlorogenic Acid[4][5]
3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid[5]

Edit2. Pharmacology

2.1. Absorption
In vitro testing using Caco-2 cells suggest that some of the anti-oxidative molecules, the benzoic and hydroxycinnamic acids, exhibited great permeability and the authors suggested a possible bioavailability of 70-100%.[4]

Edit3. Immunology and Inflammation

3.1. Mechanisms
One study using 0.25mg/kg Polypodium Leukotomos (PL) hydrosoluble extract (intramuscular injections) for 7 days leading up to sugery noted that PL was able to normalize a trauma-induced shift in T-cell morphology and attenuate changes in select cytokines (IL-6 and IL-12, but not IL-1, 2, or 4) that are seen as indicative of this shift of T-cell morphology.[6] Inhibitory effects have also been noted in response to Fasciola hepatica antigen, which triggers a similar Th2 immune response.[7]

3.2. Bacterial Infections
One study in which twice daily supplementation of 240mg Polypodium Leucotomos extract for 3 months (480mg daily) was used in athletes noted lower rates of infection.[8] This study had athletes who trained for over 20 hours a week of mixed gender (n=116) and noted that a 56% infection rate in control over 8 months was reduced to 14%, and cases of pharyngoamygdalitis were reduced from 24% of the control group to 6% of the Polypodium Leucotomos groups with no differences noted based on age or gender.[8]

Edit4. Interactions with Aesthetics

4.1. Mechanisms
Multiple studies note an enhancement of p53 expression in skin cells following the combination of UV radiation and PL ingestion (300mg/kg) relative to UV radiation alone,[9][10] the degree of induction being 2-4 fold higher than irradiated control.[10] p53 is a well known tumor suppressor gene,[11] and its activation may be the mechanism underlying genomic protection and anti-inflammatory effects.[12][13] It may also underlie suppression of radiation-induced proliferation of skin cells in mice exposed to UV radiation.[9]

A protective trend has also been noted in regards to MMP proteins in vitro, where MMP1-3 were all inhibited in a concentration dependent manner in the range of 0.001-1% Polypodium Leucotomos (PL) and MMP9 between 0.1-1%.[14] The IC50 values of PL on MMP1, 2, 3, and 9 were 0.5, 0.05, 0.1, and 0.5% respectively.[14] A stimulation of TIMP-1 and TIMP-2 was noted to 145-166% and 230-260% of contorl at 0.3% and 1% respectively in normal fibroblasts; thought to be protective.[14]

 Leucostomos appears to make p53 be activated to a greater degree in response to UV radiation, which may underlie a variety of protective effects
Anti-oxidant properties have been noted in vitro with Polypodum Leucotomos (PL) including Superoxide, Hydroxy, Lipid peroxides, and ROS[15] and it has been hypothesized that these properties reduce UV-induced production of Cyclobutane Pyrimidine Dimers secondary to DNA repair enzymes in skin, leading to less UV-induced DNA mutations.[16]

Increases in antioxidant enzymes SOD (29%), GST (32%) and GPX (15%) in erythrocytes and a higher general ORAC rating in plasma (23%) have been noted in mice following oral ingestion of 300mg/kg bodyweight PL,[9] and the theorized suppression of DNA mutations has been noted in mice at 300mg/kg bodyweight via drinking water, where oxidation-induced DNA Damage was reduced 37%, 67%, and 78% relative to irradiated control when measured at 0, 6, and 24 hours.[10] This resulted in 25% less mutations existing in DNA when measured 2 weeks later.[10]

 Oral ingestion of Leucostomos appears to increase anti-oxidant capacity of the blood, and reduces genomic damage to the skin secondary to this
One study using 300mg/kg oral ingestion of Leucostomos has noted a suppression of COX2 induction in response to radiation (70%), which was normalized within 48 hours (and may be downstream to induction of p53,[17] also noted in this study).[10] A reduction in inflammation (neutrophil infiltration) was noted with Leucostomos, although no difference existed immediately but a 60% reduction 6 hours after UV irradiation and 68% after 24 hours.[10] Similar reductions in infiltration have been noted with macrophages, but these reductions persist at 24 hours (48%), 48 hours, (51%) and even 72 hours after UV irradiation (41%).[10] Interestingly, oral ingestion of Polypodium may also protect against UV(B) induced immunosuppression during prolonged irradiation.[18]

These may also be downstream of p53 activation, known to suppress inflammatory responses,[12] and other studies have noted similar antiinflammatory actions when measuring serum TNF-α and iNOS expression.[19]

 Some anti-inflammatory properties occur in response to oral ingestion of Leucostomos, where significantly less immune cell infiltration occurs over 24 hours after UV exposure

4.2. Skin Quality
One study has noted that Polypodium Leucotomos was able to stimulate collagen expression (type I, II, and V) at 1% concentrations, as well as the Type I collagen promoter.[14] These effects occurred in control cells, and persisted during UV irradiation.[14]

4.3. Skin Conditions
A hydrophilic extract of Polypodium Leucotomos was first described in 1974.[2] This study isolated a triterpenoid glycoside from the mashed and dried rhizomes and was named Calagualine in honor of the common name of Polypodium Leucotomos, Calaguala. 36 psoriatic patients aged 6-63 with psoriasis for at least 1 month to 24 years of duration were then recruited and given 20 capsules of Polypodium Leucotomos extract (dose of plant not specified) or placebo in a cross-over manner resulted in significant improvements in clinical signs of psoriasis.[2]

 May help Psoriasis when consumed orally
One multicenter phase IV trial in youth using corticosteroids/histamines to suppress symptoms of atopic dermatisis noted that 240-480mg Polypodium daily for a period of noted that usage of corticosteroids (to be used when inflammation was deemed excessive) was not significantly changed in treatment relative to placebo but that histamine usage (used in response to itching) was reduced from 13.6% of days to 4.5%.[20]

 At least one study suggesting reduced itching associated with atopic dermatitis
A Cochrane systemic review on possible herbal compounds to benefit Vitilgo, which assessed Polypodium Leucostomos, failed to find sufficient evidence for a meta-analysis to support any benefit to Vitilgo.[21] In regrads to the trials themselves, 250mg of Leucostomos taken thrice a day (750mg total) for 26 weeks was unsuccessful in promoting significant benefits to repigmentation, although it appeared to trend towards benefits.[22]

 May hold promise for Vitilgo (loss of skin pigmentation), but evidnece is currently not convincing of its efficacy

4.4. Sunlight (Photodermatitis)
One study assessing the interaction of Polypodium Leucotomos and Polymorphic Light Eruptions (PLEs, itchy rashes from sun exposure; not burns) noted via an open-label study that 30 persons who suffered from these eruptions and took 720-1200mg daily (depending on weight) for 2 weeks had a subset of the group not get the eruptions at all during testing (30%) while the average time to induce eruptions in the rest of the group was extended 34.3%,[23] and a lower dose in 25 persons given 480mg daily noted slight improvement (10-50%) in 36% of the sample and resolution (100% improvement) in 31% of the sample, with 5 persons (20%) not experiencing any benefit.[24] Both studies are limited by no placebo group or blinding, but suggest that Polypodium Leucotomos may protect from PLEs.[23] Another study using Polypodium at 480mg daily (based off 7.5mg/kg bodyweight) with a 15 day 'loading' period before sun exposure noted that 73.68% of the 57 subjects (53 of whom experienced PLEs) reported benefit, with 43.86% reporting benefit relative to their baseline status (subjective rating) while 29.82% reported no change relative to before exposure.[25]

Another study in persons with Phototype II or III skin (non-pale white persons) exposed to UV rays who did not otherwise have skin conditions noted that 7.5mg/kg Polypodium Leucotomos taken the night previous to testing was able to delay the rate of which the skin reddens (erythema) alongside a reduction in mast cell infiltration.[26] Although a preservation of Langerhans cells (related to the immune system) has been noted previously associated with Polypodium Leucotomos in animals[27] and humans,[28] this study merely noted a trend.[26]

One of the few controlled trials on the matter note reduced DNA damage secondary to UV(A) radiation, where in measuring levels of the common deletion (CD) of a 4977 base-pair mitochondiral DNA (used as a biomarker for UV(A)-induced damage[29]) where the amount of CD induction at twice the level of UVA required to induce reddening (217% in control relative to baseline) was reduced by 86%, and the induction at thrice the level (760% of baseline) was reduced 61%.[30] Unfortunately, these results were not statistically significant (P values of 0.06 and 0.07; respectively),[30] and beyond this controlled trial mostly case studies exist.[31]

 Appears to be somewhat effective in protecting the skin against the damage induced by ultraviolet radiation, although larger and more well controlled trials are needed. The trends suggest that it can reduce reddening and reduce the rate of which skin burns in the sunlight
Scientific Support & Reference Citations

References
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  • Padilla HC, Laínez H, Pacheco JA. A new agent (hydrophilic fraction of polypodium leucotomos) for management of psoriasis. Int J Dermatol. (1974)
  • Manna SK, et al. Calagualine inhibits nuclear transcription factors-kappaB activated by various inflammatory and tumor promoting agents. Cancer Lett. (2003)
  • Gombau L, et al. Polypodium leucotomos extract: antioxidant activity and disposition. Toxicol In Vitro. (2006)
  • Garcia F, et al. Phenolic components and antioxidant activity of Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos. Methods Find Exp Clin Pharmacol. (2006)
  • Navarro-Zorraquino M, et al. Pharmacological immunomodulation of surgical trauma. J Invest Surg. (2007)
  • López-Abán J, et al. Immunomodulation of the response to excretory/secretory antigens of Fasciola hepatica by Anapsos in Balb/C mice and rat alveolar macrophages. J Parasitol. (2007)
  • Polypodium leucotomos Extract use to prevent and reduce the risk of infectious diseases in high performance athletes
  • Rodríguez-Yanes E, et al. Polypodium leucotomos decreases UV-induced epidermal cell proliferation and enhances p53 expression and plasma antioxidant capacity in hairless mice. Exp Dermatol. (2012)
  • Zattra E, et al. Polypodium leucotomos extract decreases UV-induced Cox-2 expression and inflammation, enhances DNA repair, and decreases mutagenesis in hairless mice. Am J Pathol. (2009)
  • Kastan MB. Wild-type p53: tumors can't stand it. Cell. (2007)
  • Komarova EA, et al. p53 is a suppressor of inflammatory response in mice. FASEB J. (2005)
  • Smith ML, Fornace AJ Jr. p53-mediated protective responses to UV irradiation. Proc Natl Acad Sci U S A. (1997)
  • Philips N, et al. Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells. Arch Dermatol Res. (2009)
  • González S, Pathak MA. Inhibition of ultraviolet-induced formation of reactive oxygen species, lipid peroxidation, erythema and skin photosensitization by polypodium leucotomos. Photodermatol Photoimmunol Photomed. (1996)
  • Emanuel P, Scheinfeld N. A review of DNA repair and possible DNA-repair adjuvants and selected natural anti-oxidants. Dermatol Online J. (2007)
  • Fosslien E. Review: molecular pathology of cyclooxygenase-2 in cancer-induced angiogenesis. Ann Clin Lab Sci. (2001)
  • Siscovick JR, et al. Polypodium leucotomos inhibits ultraviolet B radiation-induced immunosuppression. Photodermatol Photoimmunol Photomed. (2008)
  • Jańczyk A, et al. A Polypodium leucotomos extract inhibits solar-simulated radiation-induced TNF-alpha and iNOS expression, transcriptional activation and apoptosis. Exp Dermatol. (2007)
  • Ramírez-Bosca A, et al. Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial. Actas Dermosifiliogr. (2012)
  • Whitton ME, et al. Interventions for vitiligo. Cochrane Database Syst Rev. (2010)
  • Middelkamp-Hup MA, et al. Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: a randomized double-blind placebo-controlled study. J Eur Acad Dermatol Venereol. (2007)
  • Tanew A, et al. Oral administration of a hydrophilic extract of Polypodium leucotomos for the prevention of polymorphic light eruption. J Am Acad Dermatol. (2012)
  • Caccialanza M, et al. Photoprotective activity of oral polypodium leucotomos extract in 25 patients with idiopathic photodermatoses. Photodermatol Photoimmunol Photomed. (2007)
  • Caccialanza M, Recalcati S, Piccinno R. Oral polypodium leucotomos extract photoprotective activity in 57 patients with idiopathic photodermatoses. G Ital Dermatol Venereol. (2011)
  • Middelkamp-Hup MA, et al. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin. J Am Acad Dermatol. (2004)
  • Mulero M, et al. Polypodium leucotomos extract inhibits glutathione oxidation and prevents Langerhans cell depletion induced by UVB/UVA radiation in a hairless rat model. Exp Dermatol. (2008)
  • González S, et al. Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoralen-induced phototoxic reactions as well as depletion of Langerhans cells in human skin. Photodermatol Photoimmunol Photomed. (1997)
  • Berneburg M, et al. Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion. J Biol Chem. (1999)
  • Villa A, et al. Decrease of ultraviolet A light-induced "common deletion" in healthy volunteers after oral Polypodium leucotomos extract supplement in a randomized clinical trial. J Am Acad Dermatol. (2010)
  • Breithaupt AD, Jacob SE. Subacute cutaneous lupus erythematosus: a case report of Polypodium leucotomos as an adjuvant therapy. Cutis. (2012)
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