Samambaia

Patients in Europe taking the herbal extract “Anapsos” for psoriasis, who also had Alzheimer’s noted a noticeable improvement in this condition, which led researchers to begin studying Samambaia’s beneficial effects against this debilitating disease.

Since then Samambaia has been shown to be effective in protecting brain cells from degeneration and promotes the repair of damaged brain cells. Samambaia has been found to improve the blood supply to the brain, improve cognitive performance, and increase electrical impulses in the brain in patients with senile dementia and Alzheimer’s at just 360 mg per day. The results were noted to be much more significant in patients with early, or mild dementia than in those with severe dementia. Anapsos is now also used to treat Alzheimer’s and dementia in various European countries ^{3Reference 3Taylor · 2005The healing power of rainforest herbs: A guide to understanding and using herbal medicinals}.

Some of the same actions that are useful in treating and preventing psoriasis are also found to be useful in cancer prevention. This includes samambaia’s effects on inhibiting NF-kappaB and TNF alpha. ^{3Reference 3Taylor · 2005The healing power of rainforest herbs: A guide to understanding and using herbal medicinals}. This is a normal part of the inflammatory response but can lead to cell damage if chronic, long term stress is present. This factor (NF-kB) is suggested to be an ideal target for anticancer treatment because of a few key factors:

1. Its activation blocks apoptosis and promotes proliferation ^{10,11Reference 10D.K et al. · 1998D.K. Giri, B.B. Aggarwal, Constitutive activation of NF- kappaB causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates, J. Biol Chem. 273 (1998) 14008 – 14014.Reference 11H et al. · 1997H. Nakshatri, P. Bhat-Nakshatri, D.A. Martin, R.J. Goulet Jr, G.W. Sledge Jr, Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth, Mol. Cell. Biol. 17 (1997) 3629 – 3639.} which are both negative influences on the treatment of cancer.
2. In the presence in tumor cells, NF-kB induces further proliferation ^{12,13Reference 12G et al. · 1999AnimalG. Dong, Z. Chen, T. Kato, C. Van Waes, The host environment promotes the constitutive activation of nuclear factor-kappaB and proinflammatory cytokine expression during metastatic tumor progression of murine squamous cell carcinoma, Cancer Res. 59 (1999) 3495–3504.Reference 13C.Y et al. · 1999C.Y. Wang, J.C. Cusack Jr, R. Liu, A.S. Baldwin Jr, Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB, Nat. Med. 5 (1999) 412 – 417.}
3. The hypoxic conditions present in the tumor can signal NF-kB activation ^{14Reference 14C.Y et al. · 1999C.Y. Wang, D.C. Guttridge, M.W. Mayo, A.S. Baldwin Jr, NF-kappaB induces expression of the Bcl-2 homologue A1/ Bfl-1 to preferentially suppress chemotherapy-induced apop- tosis, Mol. Cell. Biol. 19 (1999) 5923 – 5929.}.
4. NF-kB can induce resistance to chemotherapeutic agents ^{15,16Reference 15A et al. · 1989A. Mohammad, Vitiligo repigmentation with Anapsos (Poly- podium leucotomos ), Int. J. Dermatol. 28 (1989) 479 – 482.Reference 16J et al. · 1997In vitroJ. Rayward, V.G. Villarrubia, C. Guillen, A. Prieto, M. Rodriguez-Zapata, G. Sada, M. Alvarez-Mon, An extract of the fern Polypodium leucotomos inhibits human peripheral blood mononuclear cells proliferation in vitro, Int. J. Immunopharmacol. 19 (1997) 9 – 14.}.
5. NF-kB regulates several genes involved in tumor initiation ^{17,18Reference 17H.W et al. · 1996H.W. Sharma, R. Narayanan, The NF-kB transcription factor in oncogenesis, Anticancer Res. 16 (1996) 589 – 596.Reference 18K.G et al. · 1999K.G. Waddick, F.M. Uckun, Innovative treatment programs against cancer: II. Nuclear factor-kappaB (NF-kappaB) as a molecular target, Biochem. Pharmacol. 57 (1999) 9 – 17.}.

It’s because of all of these factors that NF-kB has become a key concept of research for future cancer therapies. Samambaia leaf extract (calagualine) has been found in several studies to possess potent NF-kB inhibiting properties in multiple cell lines ^{19Reference 19Manna et al. · 2003Calagualine inhibits nuclear transcription factors-κB activated by various inflammatory and tumor promoting agentsView study →}. A leaf extract of samambaia which included calagualine was reported to protect against peripheral blood lymphocyte proliferation ^{5Reference 5J et al. · 1997In vitroJ. Rayward, V.G. Villarrubia, C. Guillen, A. Prieto, M. Rodriguez-Zapata, G. Sada, M. Alvarez-Mon, An extract of the fern Polypodium leucotomos inhibits human peripheral blood mononuclear cells proliferation in vitro, Int. J. Immunopharmacol. 19 (1997) 9 – 14.}.

NF-kB is a normal part of the stress response. This response will return to normal after the damage has been repaired, but in chronic long term inflammation and stress, significant adverse side effects can persist.

The samambaia extract was also shown to block tumor formation in the skin of albino mice after exposure to UVB ^{43Reference 43Zattra et al. · 2009AnimalOral Polypodium leucotomos decreases UV-induced Cox-2 expression, inflammation, and enhances DNA repair in Xpc +/− mice}. This action has been suggested to be due to Samambaia’s ability to reduce reactive oxygen species formation such as inhibiting the formation of COX-2 induced by ultraviolet radiation, which is involved in carcinogenesis ^{44,45,46,47Reference 44Alcaraz et al. · 1999AnimalAn extract of Polypodium leucotomos appears to minimize certain photoaging changes in a hairless albino mouse animal modelReference 45Fischer et al. · 1999Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesisReference 46Pentland et al. · 1999AnimalReduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibitionReference 47Rundhaug et al. · 2007The effect of cyclooxygenase-2 overexpression on skin carcinogenesis is context dependent}. Samambaia has also been shown to induce the activation of tumor suppressor p53 ^{43Reference 43Zattra et al. · 2009AnimalOral Polypodium leucotomos decreases UV-induced Cox-2 expression, inflammation, and enhances DNA repair in Xpc +/− mice}.

Leaf extracts from Samambaia have been found to inhibit inflammatory cytokines ^{6Reference 6J.M et al. · 1997In vitroJ.M. Sempere, C. Rodrigo, A. Campos, J.F. Villalba, J. Diaz, Effect of Anapsos (Polypodium leucotomos extract) on in vitro production of cytokines, Br. J. Clin. Pharmacol. 43 (1997) 85–89.}, and NF-kB ^{19Reference 19Manna et al. · 2003Calagualine inhibits nuclear transcription factors-κB activated by various inflammatory and tumor promoting agentsView study →}.

Samambaia leaf also inhibits the formation of reactive oxygen intermediates, blocks lipid peroxidation, and regulates superoxide dismutase ^{7,8Reference 7L et al. · 1997AnimalL. Fernandez-Novoa, X.A. Alvarez, J.M. Sempere, J.J. Miguel-Hidalgo, J. Diaz, A. Franco-Maside, R. Cacabelos, Effects of anapsos on the activity of the enzyme Cu-Zn- superoxide dismutase in an animal model of neuronal degeneration, Methods Find. Exp. Clin. Pharmacol. 19 (1997) 99–106.Reference 8S et al. · 1996S. Gonzalez, M.A. Pathak, Inhibition of ultraviolet-induced formation of reactive oxygen species, lipid peroxidation, erythema and skin photosensitization by Polypodium leuco- tomos, Photodermatol. Photoimmunol. Photomed. 12 (1996) 45–56.}, which leads to an inhibition of the inflammatory response.

Psoriasis is a type of inflammatory dermatosis characterized by red, itchy, scaly patches of skin. This condition is regulated mainly by NF-kB which is a protein transcription factor that causes cell proliferation and differentiation. Psoriasis is marked by an increase in phosphorylated NF-kB ^{48Reference 48Goldminz et al. · 2013NF-κB: An essential transcription factor in psoriasisView study →}.

Samambaia leaf extracts have been found to inhibit NF-kB ^{19Reference 19Manna et al. · 2003Calagualine inhibits nuclear transcription factors-κB activated by various inflammatory and tumor promoting agentsView study →}.

Some of the actions of Samambaia against psoriasis are suggested to be due to the ability of samambaia to decrease skin overgrowth and thickening. Through this action, samambaia can reduce the severity of skin lesions ^{3Reference 3Taylor · 2005The healing power of rainforest herbs: A guide to understanding and using herbal medicinals}.

Samambaia has known benefits on other skin pigmentation dysfunctions such as vitiligo and melasma, through various other protective effects on skin cells ^{38,39,40,41Reference 38Kishan Kumar YH et al. · 2009Evaluation of narrow-band uvB phototherapy in 150 patients with vitiligoReference 39Reyes E et al. · 2006Systemic immunomodulatory effects of Polypodium leucotomos as an 42Reference 40Middelkamp-Hup MA et al. · 2007RCTTreatment of vitiligo vulgaris with narrow-band uvB and oral Polypodium 44Reference 41Martin lK et al. · 2012RCTA randomized double-blind placebo controlled study evaluating the effectiveness and tolerability of oral Polypodium leucotomos in patients with melasma}.

Its use as an alterative may prove a separate mechanism of action in a similar way to sarsaparilla (Smilax spp.), more research is needed, however.

A prescription drug from Spain made from the water extract of Samambaia rhizome is commonly used to treat psoriasis. It’s named “Anapsos” ^{3Reference 3Taylor · 2005The healing power of rainforest herbs: A guide to understanding and using herbal medicinals}. It’s useful for both psoriasis and vitiligo.

Extracts from samambaia have been shown to possess antiviral effects against herpesvirus type 1 in an earlier study ^{9Reference 9A.R et al. · 1995A.R. McCutcheon, T.E. Roberts, E. Gibbons, S.M. Ellis, L.A. Babiuk, R.E. Hancock, G.H. Towers, Antiviral screening of British Columbian medicinal plants, J. Ethnopharmacol. 49 (1995) 101 – 110.}.

In a study investigating the effects of Samambaia extract on high-intensity exercise-induced immunosuppression, found that samambaia (Amaya fuerte) extract was able to decrease the incidence of infectious disease contraction and duration in athletes.

Previous studies have shown that samambaia extract can increase both T lymphocyte, and natural killer cell populations ^{20Reference 20Sempere JM et al. · 1999Induction of T lymphocytes and NK cells by anapsos}. It offers modulation in various adhesion model expressions which indicates its possible use as an immunomodulator for both immunocompromised and autoimmune conditions ^{21,22,23,24Reference 21Sempere JM et al. · 1997In vitroEffects of anapsos (Polypodium leucotomos extract) on in vitro production of cytokinesReference 22Carreno MM · 1994Clinical trialImmune Phenotype and Polypodium leuco- tomos treatment in patients with MSReference 23De Castro P et al. · 1999Effects of anapsos in the treatment of multiple sclerosis patientsReference 24Ramirez A et al. · 2008Clinical trialReduced consumption of topical steroids in patients with atopic dermatitis treated with anapsos}.

Some of samambaia’s effects on immune function are suggested to be through protection of the skin against UV damage. UV radiation induces skin immunosuppression through the loss of skin dendritic cells (Langerhans cells), which are crucial mediators of the immune response in the skin ^{42Reference 42Kurimoto et al. · 1992Deleterious effects of cis-urocanic acid and UVB radiation on Langerhans cells and on induction of contact hypersensitivity are mediated by tumor necrosis factor-alpha}.

Samambaia has been shown to produce a protective effect on the skin from sunburn and other skin damage when taken internally or applied topically to the skin ^{27,28Reference 27Middelkamp-Hup MA et al. · 2004Orally administered Polypodium leucotomos extract decreases psoralen-uvA-induced phototoxicity, pigmentation, and damage of human skinReference 28Middelkamp-Hup MA et al. · 2004Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin}. Some of this protective action from UV radiation is understandably from antioxidant compounds found in the plant ^{3Reference 3Taylor · 2005The healing power of rainforest herbs: A guide to understanding and using herbal medicinals}, while other chemicals have been discovered to offer photoprotective effects through other mechanisms as well. One mechanism of action is through the improved structural integrity of the extracellular matrix that is typically affected by UV damage. This improvement occurs due to an increased matrix metalloproteinase expression, as well as inhibition of collagen synthesis. ^{29,30Reference 29Philips N et al. · 2003Predominant effects of Polypodium leucotomos on membrane integrity, lipid peroxidation, and expression of elastin and matrixmetalloproteinase-1 in ultraviolet radiation exposed fibroblasts, and keratinocytesReference 30Philips N et al. · 2009Cancer cell growth and extracellular matrix remodeling mechanism of ascorbate; beneficial modulation by P}. These effects on photoprotection are noted to be more significant in photosensitive individuals ^{31,32,33Reference 31Caccialanza M et al. · 2007Photoprotective activity of oral Polypodium leucotomos extract in 25 patients with idiopathic photodermatosesReference 32Caccialanza M et al. · 2011Oral Polypodium leucotomos extract photoprotective activity in 57 patients with idiopathic photodermatosisReference 33Tanew A et al. · 2012Oral administration of a hydrophilic extract of Polypodium leucotomos for the prevention of polymorphic light eruption}.

Another compound, calagualine has been shown to prevent acute sunburn and psoralen induced phototoxic reactions ^{1Reference 1S et al. · 1997S. Gonzalez, M.A. Pathak, J. Cuevas, V.G. Villarrubia, T.B. Fitzpatrick, 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. Photoimmu- nol. Photomed. 13 (1997) 50–60.}, and photoaging of the skin ^{2Reference 2M.V et al. · 1999AnimalM.V. Alcaraz, M.A. Pathak, F. Rius, N. Kollias, S. Gonzalez, An extract of Polypodium leucotomos appears to minimize certain photoaging changes in a hairless albino mouse animal model. A pilot study, Photodermatol. Photoimmunol. Photo- med. 15 (1999) 120 – 126.}.

The main chemicals contained in Samambaia that have been found to possess antioxidant and photoprotective effects include p-coumaric, ferulic, caffeic, vanillic, 3,4-dihydroxybenzoic, 4-hydroxybenzoic, 4-hydroxycinnamic, 4-hydroxycinnamoyl-quinic, and chlorogenic acids ^{25,26Reference 25Gombau l et al. · 2006In vitroPolypodium leucotomos extract: antioxidant activity and dispositionReference 26Garcia F et al. · 2006Phenolic components and antioxidant activity of Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos}.

Vitiligo is an acquired and chronic loss of pigmentation of the skin. There are two main types of vitiligo, generalized and segmental. Generalized vitiligo is a form of vitiligo is characterized by white, and often symmetrical patches that generally increase over time. This form of vitiligo generally occurs with an increasing and substantial loss of functioning epidermal melanocytes ^{34Reference 34Taïeb A et al. · 2007The definition and assessment of vitiligo: a consensus report of the vitiligo European Task Force}. Segmental vitiligo is characterized by unilateral white patches in the skin associated with a dermatome.

The cause of vitiligo remains unknown, but genetic factors, autoimmune disorders, cytotoxic effects, and neural injury are considered causative factors ^{35,36Reference 35Borderé AC et al. · 2009Current and emerging therapy for the management of vitiligoReference 36Spritz rA · 2011The genetics of vitiligo}. Because of the appearance of vitiligo, especially on darker skinned individuals, psychological factors are also associated with this disorder and may lead to depression, and anxiety ^{37Reference 37levy ll · 2012ReviewEmotional benefit of cosmetic camouflage in the treatment of facial skin conditions: personal experience and review}. Therefore it’s crucial that we find effective treatments to reduce the occurrence and severity of this non-life threatening disease.

The conventional treatment for vitiligo involves the use of psoralens, and ultraviolet A light which causes the skin to redden, and results in a darker pigmentation.

Side effects of this treatment include severe sunburns, blistering, and abnormally dark pigmentations. A more modern treatment using narrowband UVB therapy is now available which doesn’t require the use of psoralens and has been suggested to be successful in up to 75% of patients with this condition but required multiple sessions a week for a year or more ^{38Reference 38Kishan Kumar YH et al. · 2009Evaluation of narrow-band uvB phototherapy in 150 patients with vitiligo}. Polypodium leucotomos was found to be effective as an adjunct therapy alongside both of these modern treatments, significantly improving the effectiveness of these current treatments ^{39,40Reference 39Reyes E et al. · 2006Systemic immunomodulatory effects of Polypodium leucotomos as an 42Reference 40Middelkamp-Hup MA et al. · 2007RCTTreatment of vitiligo vulgaris with narrow-band uvB and oral Polypodium 44}.

Melasma, another pigment related disorder found most commonly in pregnant females, and women on hormone replacement therapy is characterized by dark patches of skin around the forehead, cheeks, and upper lip. It’s often referred to as the “mask of pregnancy” due to its association with pregnancy. A study investigating the effects of an oral samambaia extract taken twice per day for 12 weeks found it was able to decrease the appearance and severity of this condition. 70% of the patients in the placebo control group reported worsened melasma severity compared to 0% in the Samambaia extract group. The species used in this study was Polypodium leucotomos ^{41Reference 41Martin lK et al. · 2012RCTA randomized double-blind placebo controlled study evaluating the effectiveness and tolerability of oral Polypodium leucotomos in patients with melasma}.

Calagualine extract from samambaia has been used to induce vitiligo repigmentation by itself as well ^{4Reference 4A et al. · 1989A. Mohammad, Vitiligo repigmentation with Anapsos (Poly- podium leucotomos ), Int. J. Dermatol. 28 (1989) 479 – 482.}.