Phlebodium aureum

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] and extracts from this plant are called Anapsos.^[2]

Polypodium Leucotomos tends to contain:

• Calagualine^[3] which common to the genus Polypodium^[4]
• Wallichiene (neohop-13(18)-ene)^[2]
• Fern-9(11)-ene^[2]
• The phenolic acids Ferulic, fumaric, vanillic, quinic, caffeic, and chlorogenic acid^[5][6][2]
• 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid^[6]

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%.^[5]

Supplementation of 360-720mg of anapsos for a period of 28 days in adults with senile dementia, supplementation of the lower dose only was able to improve cognition (assessed via ADAS-Cog) and improve cerebral blood flow.^[7]

The expression of adhesion factors on immune cells appears to be reduced following 11 days of supplementation with 720mg anapsos in otherwise healthy persons, with reductions of CD11b on monocytes and reductions in CD11a, CD11b, and CD18 on lymphocytes.^[2]

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.^[8] Inhibitory effects have also been noted in response to Fasciola hepatica antigen, which triggers a similar Th2 immune response.^[9]

Supplementation of 720mg anapsos daily for 11 days in otherwise healthy adults appears to cause a trend to increase CD4+ T cells that failed to reach statistical significance.^[2]

Anapsos appeared to stimulate NK cells in vitro at a concentration of 150µg/mL, yet oral supplementation at 720mg for 11 days has failed to significantly increase NK cell count in otherwise healthy adults (instead showing a positive trend).^[2]

240mg polypodium Leucotomos twice daily for 3 months (480mg daily) has been noted to be associated with less risk of bacterial infections, as athletes with over 20 hours of exercise a week using supplementation had the infection rate in placebo (56% overall, 24% getting pharyngoamygdalitis) reduced (14% and 6%, respectively) over the next eight months of observation.^[10]

May improve resistance to bacterial sickness in high intensity athletes

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,^[11][12] the degree of induction being 2-4 fold higher than irradiated control.^[12] p53 is a well known tumor suppressor gene,^[13] and its activation may be the mechanism underlying genomic protection and anti-inflammatory effects.^[14][15] It may also underlie suppression of radiation-induced proliferation of skin cells in mice exposed to UV radiation.^[11]

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%.^[16] The IC₅₀ values of PL on MMP1, 2, 3, and 9 were 0.5, 0.05, 0.1, and 0.5% respectively.^[16] 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.^[16]

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^[17] 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.^[18]

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,^[11] 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.^[12] This resulted in 25% less mutations existing in DNA when measured 2 weeks later.^[12]

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,^[19] also noted in this study).^[12] 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.^[12] 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%).^[12] Interestingly, oral ingestion of Polypodium may also protect against UV(B) induced immunosuppression during prolonged irradiation.^[20]

These may also be downstream of p53 activation, known to suppress inflammatory responses,^[14] and other studies have noted similar antiinflammatory actions when measuring serum TNF-α and iNOS expression.^[21]

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

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.^[16] These effects occurred in control cells, and persisted during UV irradiation.^[16]

A hydrophilic extract of Polypodium Leucotomos was first described in 1974.^[3] 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.^[3]

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%.^[22]

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.^[23] 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.^[24]

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

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%,^[25] 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.^[26] Both studies are limited by no placebo group or blinding, but suggest that Polypodium Leucotomos may protect from PLEs.^[25] 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.^[27]

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.^[28] Although a preservation of Langerhans cells (related to the immune system) has been noted previously associated with Polypodium Leucotomos in animals^[29] and humans,^[30] this study merely noted a trend.^[28]

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^[31]) 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%.^[32] Unfortunately, these results were not statistically significant (P values of 0.06 and 0.07; respectively),^[32] and beyond this controlled trial mostly case studies exist.^[33]

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