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Vitiligo repigmentation with Anapsos (Polypodium leucotomos)
... PL blocks some of the harmful effects of UV radiation on skin, such as LCs depletion, direct apoptosis, inflammation, inhibition of the expression of adhesive molecules needed for the migration of LCs towards skin [39,41]. PL not only prevents LCs depletion but also inhibits changes in their morphology, maintaining their functionality [35]. PL induces the expression of cellular mediators such as IL-10, IL-12 and TGF-b, which regulates other cellular responses such as macrophages. ...
... The first clinical study with PL tried to prove its potential antitumoral activity [23], although the mechanism of action was not deeply investigated. Later on, studies focused on anti-inflammatory activity, mainly related to skin diseases such as psoriasis [32], vitiligo [35] and atopic dermatitis [25]. The molecular basis of these effects is, at least in part, the immunomodulating ability of PL. ...
This article provides an overview of pharmacology, toxicity, pharmacokinetics and clinical data of Polypodium leucotomos L. (PL). PL aerial part has proven to exert antioxidant, photoprotective and immunomodulatory activities; its mechanism of action is complex and includes several activities: (1) PL diminishes the production of reactive oxygen and nitrogen species (ROS, RNS); (2) PL inhibits the photoisomerization of trans-urocanic acid (t-UCA); (3) PL inhibits apoptosis induced by ultraviolet radiation; (4) PL prevents damage to genetic material and (5) PL enhances DNA repair. PL is not mutagenic and does not induce acute or chronic toxicity. Its biological effects have been proved in cell cultures, animal models, murine models and in human beings. Photoprotective activity has been assessed in healthy volunteers as well as in patients suffering from several cutaneous diseases such as vitiligo, psoriasis, idiopathic photodermatosis or melasma. PL results to be an efficient treatment especially for sensitive cutaneous phototypes and adds extra protection when ultraviolet radiation (UVR) exposure cannot be avoided, such as wide or narrow band UVB phototherapy or treatment with psoralens plus UVA exposure radiation.
... The fern Polypodium leucotomos, grows in the rainforest of Central and South America. It has been the subject of research in the last years, in order to analyse its possible immunomodulating effect [1, 2] and its application in some autoimmune diseases345. In vitro and in vivo studies performed with a phytoextract called Anapsos, obtained from the rhizomes of this fern, have already shown changes in certain immune cell subsets and cytokines6789. ...
... The mechanism exerted by Anapsos on the adhesion molecules is still not known, but it could be related with its pleiotropic ability to down-regulate the secretion of proinflammatory cytokines such as IL-1 and to up-regulate anti-inflammatory cytokines such as IL-10 [8, 9]. The down-regulating effect that Anapsos exerts on the aforementioned adhesion molecules lets us justify why the product has shown to be efficient on several autoimmune diseases [3, 4, 23] and makes it interesting for being evaluated in other autoimmune pathologies. Different components of Anapsos justify its pleiotropic activity. ...
Anapsos is a medical prescription registered in the Health Ministry of Spain, that is obtained from the rhizomes of the fern Polypodium leucotomos. An immunomodulating effect of Anapsos on certain lymphocyte subsets and cytokines has already been described in the literature. The current study extends and supports part of the aforementioned results of the product on the immune system, showing the ability of Anapsos to stimulate proliferation and activation of T and natural killer lymphocytes, as well as an important down-regulating effect on CD11, CD18 and CD62-L adhesion molecules, both on peripheral blood mononuclear cells and on U-937 and HL-60 cell lines.
... Calagualine, which is derived from the fern of the genus Polypodium, commonly called calaguala, has had clinically documented use in South America and Spain in the treatment of malignant tumors [3], psoriasis, and atopic dermatitis [4 -7], all hyperproliferative disorders. Calagualine also prevents acute sunburn and psoralen-induced phototoxic reactions [8], and photoaging of the skin [9], and is used to induce vitiligo repigmentation [10]. Calagualine also exhibits antiproliferative effects against peripheral blood lymphocytes [11] and inhibits the production of inflammatory cytokines [12]. ...
... Third, the hypoxic tumor microenvironment can induce NF-kB activation [29]. Fourth, NF-kB activation induces resistance to chemotherapeutic agents [10,11]. Finally, several genes involved in tumor initiation, tumor promotion, and metastasis are regulated by NF-kB [30,31]. ...
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.
... A prevalência da doença varia expressivamente entre diferentes grupos étnicos, afetando em menor índice a Rússia (0,14% da população), seguida de Estados Unidos, representando 1% da população e Japão, com 2% da população. No Brasil, a prevalência do vitiligo é de 0,54%, com idade média para o início da doença entre os 13 e 22 anos (Dellatorre et al, 2020 (Mohammad, 1989 ...
O vitiligo é uma doença sistêmica crônica adquirida, com evolução clínica imprevisível, caracterizada pelo aparecimento de manchas acrômicas que afetam áreas da pele, mucosa e, eventualmente, os pelos. A doença resulta da ausência de melanina devido ao desaparecimento dos melanócitos nas regiões acometidas. Por muitos anos, diversas terapias foram administradas aos portadores da doença para seu controle, uma vez que, devido à sua complexidade, tratamentos específicos raramente eram realizados. Foram encontradas lacunas na literatura relacionadas ao consenso sobre o tratamento do vitiligo. Objetivo: compreender as terapias adotadas para o tratamento do vitiligo ao longo da história da patologia até os dias atuais, destacando os tratamentos atualmente utilizados. Metodologia: para a realização deste estudo, foi realizada uma revisão bibliográfica integrativa, de natureza qualitativa e exploratória, com artigos publicados na Biblioteca Virtual em Saúde (BVS), adotando critérios de elegibilidade para a seleção de artigos, respeitando o tema "vitiligo" e as abordagens de tratamento.
... More participants who got >50% re-pigmentation were within the group undergoing PUVA along with PL than the group undergoing PUVA with placebo. All subjects saw the successful treatment of their condition following Anopsos therapy for five months, which is a hydrosoluble lipid derivative of PL [34]. ...
Vitiligo is an acquired skin pigmentation disease with a global burden of 0.5 to 2 percent of the population. Vitiligo therapy frequently poses a difficulty, which has sparked interest in alternative treatment modalities, including multivitamins and herbal supplementation. It has previously been established that nutrition plays a crucial role in developing, amplifying, or rehabilitating an array of human disorders. However, the correlation between diet diversity and immune-mediated skin diseases is still up to interpretation. Several supplements have been studied, including vitamins, minerals, and herbal supplements. Most studies agree that combining vitamin B12, folic acid, and sun exposure is good for inducing repigmentation. Supplementation of zinc and phenylalanine when used in conjunction with topical steroids or UV-B (ultraviolet B) treatment shows therapeutic effects on vitiligo due to their role in the melanin synthesis pathway. Investigations conducted on herbal supplements have revealed that most of them contain antioxidants, which aid in repigmentation. This narrative review's purpose is to discuss nutrition's function in immune-mediated inflammatory skin diseases from the perspective of the most recent and reliable information available.
... It enhances the effect of both UVA and NB-UVB phototherapy and PUVA [118]. Another interesting study regarding a PL derivative, Anapso, over 5 months of treatment showed efficacy in disease control in all participants [119]. ...
Immune-mediated inflammatory skin diseases are characterized by a complex multifactorial etiology, in which genetic and environmental factors interact both in genesis and development of the disease. Nutrition is a complex and fascinating scenario, whose pivotal role in induction, exacerbation, or amelioration of several human diseases has already been well documented. However, owing to the complexity of immune-mediated skin disease clinical course and breadth and variability of human nutrition, their correlation still remains an open debate in literature. It is therefore important for dermatologists to be aware about the scientific basis linking nutrition to inflammatory skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, bullous diseases, vitiligo, and alopecia areata, and whether changes in diet can influence the clinical course of these diseases. The purpose of this narrative review is to address the role of nutrition in immune-mediated inflammatory skin diseases, in light of the most recent and validate knowledge on this topic. Moreover, whether specific dietary modifications could provide meaningful implementation in planning a therapeutic strategy for patients is evaluated, in accordance with regenerative medicine precepts, a healing-oriented medicine that considers the whole person, including all aspects of the lifestyle.
... Polypodium leucotomos é uma espécie vegetal nativa da América Central e está disponível como suplemento de saúde há 30 anos (Emanuel & Scheinfeld, 2007). Seu extrato foi estudado para o tratamento de várias condições, como psoríase, melasma, danos causados pela radiação ultravioleta e também para vitiligo (Mohammad, 1989 ...
O vitiligo é uma doença imunológica caracterizada pela despigmentação da pele, causando manchas acrômicas, sem predileção por sexo ou etnia. Ademais, pode provocar alterações emocionais, comprometimento da autoestima e nas relações sociais do indivíduo. Assim, esse trabalho propõe uma revisão sistemática da literatura objetivando evidenciar a eficiência de protocolos de terapias disponíveis para o vitiligo e sua correlação. Metodologia: Trata-se de um estudo de revisão sistemática, de caráter descritivo, retrospectivo realizado a partir de pesquisas nas principais bases de dados acadêmicas. Ex. PubMed, Lilacs e Periódicos Capes, etc. Assim, fez-se buscas livres de palavras relacionadas ao tema proposto: tratamento do vitiligo e associações, excluindo os trabalhos que mostraram ineficiência (baixo percentual de repigmentação) quando comparada aos tratamentos convencionais. Nesse sentido, foram encontrados 35 artigos científicos e 27 terapias distintas para o tratamento de vitiligo. Resultados e Discussão: Tais terapias foram divididas em 4 categorias: corticosteroides, fotobiomodulação, imunossupressores e antioxidantes. O uso de corticosteroides mostrou-se eficaz na estabilização da doença. Das fototerapias, a kelina agiu em 70% dos casos de repigmentação. Já os imunossupressores JAK demonstram repigmentação total ou acima de 75%. E os antioxidantes mostraram eficácia de 67% de repigmentação, com destaque para a espécie Polypodium leucotomos e Brosimum gaudichaudii com alto índice de repigmentação completa, principalmente quando associado a radiação UVB. Já o tratamento com Ginko biloba teve 80% de estabilização da doença. Conclusão: Os protocolos mostraram que a associação das fototerapias com terapias convencionais e inovadoras são mais frequentemente eficazes no tratamento do vitiligo, potencializando os resultados.
... 3,11 Studies have proved that oral PL has an important role in preventing erythema in UV-treated human skin, proving its capacity to restrict UV-mediated inflammation 14,15 and also in psoralen plus ultraviolet A based therapy, 15 which is often used in inflammatory skin diseases, such as vitiligo and psoriasis. 36,37 Apparently its molecular basis is due to its ability to suppress the expression of factors, such as (i) pro-inflammatory cytokines (TNF-α and inducible NOS (iNOS)); 38 (ii) redox-sensitive transcriptional factors AP-1 and NF-κB; 14,38,39 and (iii) COX-2 and PGE2. 40 A recent study regarding the effects of PL supplementation proved that administrated daily through oral supply, it reduces the inflammatory reaction caused by a single exposure to SSR, contributing to enhance erythematosus threshold. ...
... 63 Another interesting finding was that after 5 months of treatment with Anapsos, a lipid hydrosoluble extract derivative of P. leucotomos, all of the vitiligo participants had full improvement of their disease. 64 Capsaicin. Capsaicin is an ingredient found in hot chili pepper and is commonly used in spices, food additives, and drugs. ...
Background:
Vitiligo is an autoimmune skin condition that affects people globally anywhere, from <0.1% to more than 8% of individuals. The disease destroys skin melanocytes, resulting in a patchy depigmentation of the skin. About 50% of all patients develop the disease before their 20s.
Methods:
We systematically searched the literature and reviewed the evidence for the use of nutritional supplements and diet in the management of vitiligo. Embase and Medline were searched for diet, herbal, and nutrition-based clinical studies. Additional filters were applied that looked for controlled trial or randomized controlled trial and article or article in press or letter and English and clinical study. We selected clinical studies in humans that showed how diet or natural supplements can improve the symptoms of vitiligo in all of our searches.
Results:
There were 62 manuscripts that resulted from the PubMed search and 259 from the Embase search. A final of 26 studies were reviewed, and other supplemental case and case-control studies were used to introduce diet components that may influence either exacerbation or amelioration of vitiligo. Possible mechanisms of action are introduced for natural and supplemental interventions.
Conclusion:
Some of the supplements reviewed include Gingko biloba, oral Polypodium leucotomos, alpha lipoic acid, vitamins B12, D, and E, folic acid, phenylalanine, canthaxanthin, Nigella sativa oil, and other combined herbal bio-actives. Overall, the growing evidence is promising, but more studies are needed in this area to further explore the impact that supplements and diet can have on vitiligo management. The most promising therapies included oral phenylalanine as adjuvant therapy with UVA therapy, oral G. biloba as monotherapy, both of which can be used with other traditional therapies, and oral P. leucotomos with phototherapy or photochemotherapy.
... 63 Another interesting finding was that after 5 months of treatment with Anapsos, a lipid hydrosoluble extract derivative of P. leucotomos, all of the vitiligo participants had full improvement of their disease. 64 Capsaicin. Capsaicin is an ingredient found in hot chili pepper and is commonly used in spices, food additives, and drugs. ...
Background: Broad-spectrum antibiotics are the first-line treatment for small intestinal bacterial overgrowth (SIBO). However, many antibiotics have a considerable side-effect profile and SIBO commonly reoccurs after successful eradication with antibiotics. Alternative therapies such as probiotics, therapeutic diets, and herbal medicines have been used to individualize SIBO management, particularly in recalcitrant cases.
Objectives: The objective of this review is to evaluate the role of alternative therapies in SIBO treatment.
Data Sources: EMBASE, MEDLINE, and the Cochrane Central Register were systematically searched for clinical studies evaluating alternative therapies in the management of SIBO.
Study Eligibility Criteria: Human studies in which an alternative intervention was used to treat SIBO were included. Alternative interventions were defined as an intervention that included a probiotic supplement, herbal preparation, or a dietary change. Randomized controlled trials (RCTs), nonrandomized clinical trials with or without a control, and crossover studies were included.
Study Appraisal: The following information was extracted from the selected studies: study type, study participants, SIBO subtype, intervention, comparison, outcome measures, relevant results, relevant side effects, and Jadad score.
Results: Eight studies met inclusion criteria. The studies evaluated probiotics (n = 5), therapeutic diet (n = 1), and herbal medicines (n = 2). Among these studies, there were four RCTs, two open-label single-arm studies, one randomized, double-blind crossover study, and one two-arm open-label study with crossover. Main results are summarized.
Limitations: There may be studies not captured by the defined search criteria. Additionally, studies used different methodologies in both breath testing and measurement of clinical symptoms, making it difficult to draw conclusions on SIBO eradication and symptom improvement across studies.
Conclusions and Implications: Our findings suggest preliminary evidence for a role of alternative therapies in the treatment of SIBO. However, robust clinical trials are generally lacking. Existing studies tend to be small and lack standardized formulations of treatment. Breath testing protocols and clinical symptom measurement greatly varied between studies. Large-scale, randomized, placebo-controlled trials are needed to further evaluate the best way to utilize alternative therapies in the treatment of SIBO.
... Oral vitamins and supplements have also gained increased interest in the treatment of vitiligo owing to their antioxidant properties. L-phenylalanine, khellin, polypodium leucotomos, Ginkgo biloba, B12, folic acid, vitamins C and E, alpha lipoic acid, and zinc have all been studied either as monotherapies or in combination with other treatments with varying efficacy in improving vitiligo repigmentation 3, [77][78][79][80][81][82][83][84] . Though several of these treatments are promising, the majority of these studies have been done in a small number of patients and many without controls. ...
Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.
... Evidence of the role of PL in preventing UV-mediated inflammation stems from experiments that revealed that oral PL prevented erythema in UV-treated human skin [68,71,77] and also in PUVA-based therapy [67], which is often used in the treatment of vitiligo, psoriasis, and other inflammatory skin diseases [85,86]. The molecular basis of its anti-inflammatory properties could be due to its ability to suppress the expression of the following factors: (i) pro-inflammatory cytokines such as TNF-α and inducible NOS (iNOS) [35]; (ii) redox-sensitive transcriptional factors AP-1 and NF-κB [35,57,87]; and (iii) COX-2 and PGE2 [65]. ...
Healthier life styles include increased outdoors time practicing sports and walking. This means increased exposure to the sun, leading to higher risk of sunburn, photoaging and skin cancer. In addition to topical barrier products, oral supplementations of various botanicals endowed with antioxidant activity are emerging as novel method of photoprotection. Polypodium leucotomos extract (PL, commercial name Fernblock(®), IFC Group, Spain) is a powerful antioxidant due to its high content of phenolic compounds. PL is administered orally, with proven safety, and it can also be used topically. Its mechanisms include inhibition of the generation and release of reactive oxygen species (ROS) by ultraviolet (UV) light. It also prevents UV- and ROS-induced DNA damage with inhibition of AP1 and NF-κB and protection of natural antioxidant enzyme systems. At the cellular level, PL decreases cellular apoptosis and necrosis mediated UV and inhibits abnormal extracellular matrix remodeling. PL reduces inflammation, prevents immunosuppression, activates tumor suppressor p53 and inhibits UV-induced cyclooxygenase-2 (COX-2) enzyme expression. In agreement with increased p53 activity, PL decreased UV radiation-induced cell proliferation. PL also prevents common deletions mitochondrial DNA damage induced by UVA, and MMP-1 expression induced Visible Light and Infrared Radiation. These cellular and molecular effects are reflected in inhibitions of carcinogenesis and photoaging.
... To our knowledge, no formal toxicological studies on P. leucotomos extracts have been published, and because of the potential application of Fernblock ® as an ingredient in food and/or dietary supplements it is important that its safety for these applications has been investigated and confirmed. The small number of non-serious, and lack of serious, adverse events reported in fourteen clinical trials involving P. leucotomos extracts (Middelkamp-Hup et al., 2004a, 2004bAguilera et al., 2013;Ahmed et al., 2013;Caccialanza et al., 2007Caccialanza et al., , 2011Gonzalez et al., 1997;Middelkamp-Hup et al., 2007;Reyes et al., 2006;Jimenez et al., 1987;Mohammad, 1989;Padilla et al., 1974;Ramirez-Bosca et al., 2012;Solivellas and Martin, 2012) and its safe history of human use are encouraging indicators of probable safety when consumed as currently suggested. Of the published trials, nine (Middelkamp-Hup et al., 2004a, 2004bAguilera et al., 2013;Ahmed et al., 2013;Caccialanza et al., 2007Caccialanza et al., , 2011Gonzalez et al., 1997;Middelkamp-Hup et al., 2007;Reyes et al., 2006) used the specific PLE that is the topic of this manuscript. ...
A battery of toxicological studies was conducted in accordance with internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of Fernblock®, a commercial aqueous extraction of the leaves of the tropical fern Polypodium leucotomos used for its oral and topical photoprotective properties. No evidence of mutagenicity was observed in a bacterial reverse mutation test or in vitro mammalian chromosomal aberration test nor was any genotoxic activity observed in an in vivo mouse micronucleus test. Two repeated-dose oral toxicity studies were conducted in male and female Wistar rats. In the first study, no mortality or toxic effects were observed and no target organs were identified at doses administered for 14 days by gavage up to the maximum dose of 5000 mg/kg bw/day. Based on these results, a 90-day study was conducted at 0, 300, 600, and 1200 mg/kg bw/day. No mortality or treatment-related adverse effects were observed and no target organs were identified. The NOAEL from the 90-day study was determined to be 1200 mg/kg bw/day, the highest dose tested.
... Un pequeño grupo de 5 pacientes recibió Anapsos, un extracto derivado de Polypodium leucotomos, a dosis de 360 mg/día durante 5 meses, refiriéndose la curación en todos ellos. Sin embargo, no se describen las características clínicas de los pacientes ni se ofrecen datos acerca del grado de exposición solar o el seguimiento 43 . ...
... otros autores refieren un efecto del producto sobre células cDg+ en pacientes con otras patologías (297). ...
... Since remote times PLE has been empirically used in Central America to treat phlogistic disorders. More recently, a methanolic extract of PLE has been used to treat several inflammatory disorders such as psoriasis (Capella-Prrez & Castells Rodellas, 1981), atopic dermatitis (Jimrnez et al., 1986), vitiligo (Mohammad, 1989), where autoimmune mechanisms are probably involved. Rationale for its use was based on certain observations suggesting the ability of PLE to modify the distribution of some T lymphocyte subsets with an increase in the number of T suppressor lymphocytes (Jimrnez et al., 1986;Vargas et al., 1983). ...
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.
... Anapsos Ò , a hydroalcoholic extract obtained from the rhizome of the American fern Phlebodium pseudoaureum (synom.: Polypodium leucotomos P., Polypodiaceae), was included in the tests as reference standard. This drug, reported to be clinically useful against neoplasms 21 and autoimmune diseases such as atopic dermatitis, 22 psoriasis 23,24 and vitiligo, 25 might also have some utility in the treatment of allergic disorders 26 and as immunomodulator in vaccine formulation against parasites. 27 The results of the assays, shown in Table 1 ...
Lymphoproliferation inhibition and cytotoxicity of a number of lipidic aminoacids, aminoalcohols and diamines were evaluated as a preliminary screening to select potential immunomodulators. The four most potent/less toxic compounds were submitted to delayed hypersensibility (DTH) assays to define the best to be evaluated further Graft-vs-Host, NO production and other immunoevaluation (CD4(+), CD45, CD8, CD11b, I-Ek, and NK cells) assays, to establish their immunomodulation potential for being further considered as auxiliary agents for vaccination against some parasitic infections. Compounds 5d, 6d, 6f, 7a, and 9a, fairly inhibited the lymphoproliferation (71.6-79.5%, at 3.2-2.4 nM), while the aminoalcohol derivative 6f and the diamine 7a gave the most promising results in the DTH assays. Diamine derivative 8b induced nitrite production on normal macrophages, whereas compounds 6f and 7a induced nitrite production on LPS pre-stimulated macrophages. These two last compounds have been selected to follow in vivo vaccination assays.
Reactive oxygen species (ROS) generated during melanogenesis make melanocytes particularly vulnerable to oxidative stress, influencing their survival and melanin synthesis. Oxidative stress, significantly present in vitiligo and recently also detected in melasma, triggers inflammatory cascades and melanogenesis, making antioxidants a promising therapeutic avenue. A systematic search was conducted on Embase and Pubmed to study the efficacy of antioxidants for treating vitiligo and/or melasma. Meta-analysis was performed to assess the difference in Melasma Severity Index (MASI) scores between baseline and follow-up. Various antioxidants like polypodium leucotomos, ginkgo biloba, catalase/superoxide dismutase, and vitamin E have potential in vitiligo. For melasma, vitamin C, silymarin, and niacinamide were among those showing promise in reducing pigmentation, with vitamin C displaying significant effects in meta-analysis. Different antioxidants improve both vitiligo and melasma, with an increased minimal erythema dose (MED) following UV exposure being significant for vitiligo and tyrosinase inhibition being crucial for melasma. However, the efficacy of individual antioxidants varies, and their exact mechanisms, especially in stimulating melanocyte proliferation and anti-inflammatory pathways, require further investigation to understand better and optimize their use.
Background:
Vitiligo is a depigmenting illness that causes white areas on the skin. Vitiligo's pathogenetic genesis is based on the melanocyte's autoimmune destruction, in which oxidative stress causes melanocyte molecular, organelle, and exposure of antigen, as well as melanocyte cell death, and so plays a role in vitiligo progression. Natural compounds have recently shown a wide range of therapeutic bioactivities against a number of skin disorders.
Aim:
The aim of this work is drug delivery of natural products through nano-carriers for effective vitiligo therapy: A compendia review.
Methods & materials:
An online literature analysis was guided for vitiligo therapy, nanotechnology, phytochemical composition, and, types of vitiligo, types of nanomedicine. Appropriate information were taken from different electronic scientific databases such as Web of Science, Science Direct, Elsevier, Google Scholar, Springer, PubMed, and scripts.
Results:
Nano-carriers-based natural compounds provide a great relationship for the enhancement in the efficacy and safety of pharmacotherapeutic agents for the treatment of vitiligo.
Discussion:
In this study focuses on natural compounds' effects and processes on vitiligo models. Although topical therapy plays an important role in vitiligo treatment, its utility and patient compliance are hampered by adverse effects or inadequate efficacy. Novel drug delivery techniques can help improve topical medication delivery by improving epidermal localization, reducing side effects, and increasing effectiveness.
Conclusion:
This paper covers the significant potential of herbal-derived active compounds as anti-vitiligo drugs, as well as new drug delivery as a viable carrier and future possibilities to investigate.
Background:
Recurrent tonsillitis might reduce the immunological capability of fighting against the infection of tonsil tissue. Polypodium leucotomos (Anapsos) immunomodulating effect has been subject of research in the last years. The aim of this research is to test the in vitro immunomodulating capacity of Anapsos in a child palatine tonsil explants model.
Methods:
Palatine tonsils explants of children undergoing amigdalectomy were stimulated with mononuclear cells obtained from their own blood by density gradient centrifugation. Some were then treated with Anapsos while others rest untreated. Cytokines were measured by ELISA, immune cells activation was measured by flow cytometry and activation of immunoglobulins was appreciated by indirect immunofluorescence in tonsils tissue.
Results:
Anapsos activates Natural Killers cells. It increases IL-2 and IFN-γ levels by the activation of Th2 lymphocytes, and IL-10, by the Th1 lymphocytes. Anapsos also increases immunoglobulins IgM, IgD and IgG4 by B-lymphocyte activation in tonsils tissue.
Conclusion:
Anapsos has an immunomodulating effect, both in humoral and cellular responses, which might benefit children suffering of recurrent tonsillitis as it could enhance their immune system. This effect might reduce the number of episodes suffered and therefore the number of children undergoing surgery.
Vitiligo is an autoimmune disorder that involves the interplay between oxidative stress and the immune system. Preliminary observations suggest that the presence of gluten in the diet may play a role in vitiligo development in some patients, but to date vitiligo-specific diets have not been studied. The role of oral supplements, including vitamins, minerals, and botanicals, is increasingly being investigated as adjuncts to conventional medical treatment due to their antioxidant and immunomodulatory activity. Studies suggest that many of these agents may have some efficacy as monotherapy, but more often as adjuncts to topical agents and phototherapy.
Anapsos is a vegetal extract obtained from dried rhizhomes of the fern Polypodium leucotomos growing in Central America. This extract is devoid of toxic effects in animals and humans at therapeutic doses and is commercially available in Spain. An antitumoral effect of anapsos was found in early studies (Horwath et al., 1967), and this effect was confirmed by other authors suggesting an interaction of anapsos with cytoplasm receptors (Vargas et al., 1981). These studies show that anapsos has anabolic effects in normal tissues in vivo oppossite to the catabolic action exerted by cytostatics. Furthermore, Anapsos exerts immunoregulatory effects in control subjects (Sempere et al., 1997; Vargas et al., 1983) and in patients with atopic dermatitis (Jimenez et al., 1987), psoriasis (Padilla et al., 1974) or vitiligo (Mohamed, 1989), and increases the allograft survival in rats and mice with skin transplants (Pérez de las Casas et al., 1987; Tuominen et al., 1991). In healthy subjects anapsos increases the lymphoblast response to mitogens, serum immunoglobulin levels and the proportion of CD8+ cells in a dose-dependent manner (Vargas et al., 1983). Anapsos also stimulates cell proliferation, reduces LPS-stimulated IL-lβ levels and delays the peak response of IL-lβ to LPS+PHA in human PBMC cultures (Sempere et al., 1997). Recently, we have found that anapsos improves learning and reduces brain IL-lβ levels in normal rats; reverses learning impairment and brain IL-lβ overexpression in rats with lesions in the nucleus basalis of Meynert; improves motor functioning and influences the production of brain immune factors as histamine and IL-lβ in aged mice; and reduces behavioral deficits and neuronal degeneration induced by β-amyloid implants into the hippocampus, modulating IL-lβ and Superoxide dismutase (SOD) activity levels in the brain of βA-injected rats (Alvarez et al., 1992, 1995, 1996c, 1997; Fernández-Novoa et al., 1997).
Dieses Kapitel beschäftigt sich mit der Anwendung von Photochemotherapie und Phototherapie bei Vitiligo. Zunächst wird die Krankheit definiert und werden Differentialdiagnosen und assoziierte Phänomene beschrieben. Allgemeine therapeutische Maßnahmen und Alternativen zu phototherapeutischen Verfahren folgen. Den Hauptteil bildet die Beschreibung der praktischen Durchführung und Wirkung der Bestrahlungsbehandlung mit oder ohne Photosensibilisator sowie von kombinierten Therapieformen.
Rhizome and leaves, of three species, know as "calaguala", "calahuala", "polipodio", are used in folk medicine with analgesic, expectorant, febrifuge, tranquilizer, depurative, diuretic, anti-inflammatory, emmenagogue, and spasmolitic, properties. These species are: Phlebodium decumanum (Will.) J. Sm., Phlebodium pseudoaureum (Cav.) Lellinger and Phlebodium aureum (L.) J. Sm. The morphological and anatomical research performed on these species has revealed some common and non common characters (rhizome width, scales length and border, number of series and width, soris, tracheids length and width, meristele length); these allow us to recognize these species as pure drug. © 2008 Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas.
Vitiligo is an acquired cutaneous disorder of the pigmentation characterized by the appearance of sharply circumscribed, cosmetically disturbing, white spots, in which some or all of the melanocytes in the epidermis are selectively destroyed. The etiology remains unknown, though it is believed that there should be an important influence of the immune system in its development. Seemingly it represents a banal pathology nevertheless, supposes often a great aesthetic problem in the persons who endure it. Numerous therapeutic options exist but none of them definitive, being the basic steps the photochemotherapy, which aim is to stimulate the melanocytic proliferation and the melanin production; the immunomodulators, effective in the detention of the progression of the disease on having acted like suppressing of the autoimmunity and the different surgical techniques of the vitiligo, based on the transplant of melanocytes. Patients can use cosmetics that will help to camouflage the hipopigmented macules and always sunscreens should be given to minimize risk of sunburn, we must not forget that these patients are unprotected of their natural photoprotector: the melanin.
Many phytochemicals are endowed with photoprotective properties, that is, the capability to prevent the harmful effects of excessive exposure to ultraviolet (UV) light. These effects, most of them mediated by oxidative stress, include sunburn, immunosuppression photoaging, and skin cancer. A Polypodium leucotomos fern extract (Fernblock®) has shown cutaneous antioxidant properties after topical and/or oral administration. Fernblock inhibits the generation of reactive oxygen species (ROS), including superoxide anion and their release, which are both induced by UV light. It also prevents damage to the DNA, inhibits UV-induced AP1 and NF-κB, and protects the endogenous skin natural antioxidant enzymatic systems (i.e., CAT, GSH, and GSSR). At a cellular level, its photoprotective effects include a marked decrease of UV-mediated cellular apoptosis and necrosis and a profound inhibition of abnormal extracellular matrix remodeling. These molecular and cellular effects translate into long-term inhibition of photoaging and carcinogenesis.
› Vitiligo, an autoimmune disorder that targets melanocytes, is difficult to treat.
› At present, the best monotherapeutic option is narrowband ultraviolet B phototherapy.
› Most of the regimens that show reasonable efficacy in the treatment of vitiligo are either phototherapeutic regimens or combination therapies that include phototherapy.
Vitiligo is a common, acquired disorder of skin pigmentation that can significantly impact quality of life. It often represents a therapeutic challenge, which has resulted in interest in alternative treatments such as herbal and vitamin supplements. In this review, we provide an overview of the most commonly studied complementary agents, describe proposed mechanisms of action, identify potential adverse effects, and discuss the primary evidence supporting their use. Our discussion focuses on L-phenylalanine, Polypodium leucotomos, khellin, Ginkgo biloba, and vitamins and minerals, including vitamins B12, C, and E, folic acid, and zinc used as monotherapy or in combination with other treatments for the management of vitiligo.
Recently, several compounds including polyunsaturated fatty acids (linoleic, linolenic, arachidonic), the triflavonoid selligueain and a sulfonoglycolipid (SQDG) have been isolated from the South American fern, Polypodium decumanum using bioactivity directed fractionation. The present study describes the quantitative analysis using HPLC methods of these three classes of compounds in the leaves and rhizomes of the five Polypodium species. Furthermore, extracts of the five ferns are studied in three in vitro bioassays using platelet activating factor (PAF) and leukotriene B(4) (LTB(4)). The models are the same that previously have led to the isolation of the active principles in Polypodium decumanum. The objective of this study was to investigate if the identified active compounds could be used for standardization of the extracts. Since the SQDG was found to be present in pharmacologically detectable amounts in the crude extracts and since it presents a specific mode of action it is recommended that quantitative analysis of this constituent should be used for future standardization of the extracts.
The immunomodulant effects of Polypodium leucotomos extracts have been tested in BALB/c mice immunized with the third larval stage antigens of Anisakis simplex. A decrease in the specific antibodies was observed in animals treated either before or after immunization. This decrease was mainly in the IgG 1 isotype. In animals treated before immunization the reduction of the IgG 1 subclass was dramatic in relation to the untreated group while the IgG 2b subclass appeared earlier and at slightly higher levels than in the control group. In animals treated after immunization a reduction of the IgG 1 subclass was also observed although not as marked as in the preimmunization group. IgG 2a sub-class antibody levels were higher than those of the untreated group. As in the preimmunization group, the IgG 2b subclass antibodies appeared earlier but they remained at similar levels to those observed in the control group.
We have investigated the effects of Polypodium leucotomos extracts on nitric oxide (NO) production in bacterial lypopolysaccharide (LPS)-treated J774 macrophages. Co-administration of P. leucotomos extracts with LPS dose-dependently reduced the production of nitrite. At the concentrations tested, P. leucotomos extracts did not inhibit cellular respiration, so cytotoxicity and/or non-specific depression of cellular respiration did not account for the inhibition of nitrite accumulation seen with P. leucotomos extract. The results obtained provide a mechanism by which P. lecotomos extract exerts its anti-inflammatory activity.
Photoprotection is essential to prevent the deleterious effects of ultraviolet (UV) light, including skin cancer, photoaging and immunosuppression. Photoprotective agents can be classified according to their main mechanism of action. Some of them absorb or deflect UV photons (sunscreens), whereas others prevent or fix the deleterious effects of UV exposure. Here, we review recent evidence on the cellular and molecular mechanisms underlying the photoprotective effect of a Polypodium leucotomos fern extract (PL). PL is a natural mixture of phytochemicals endowed with powerful antioxidant properties. Its short-term effects include inhibition of reactive oxygen species production induced by UV radiation, DNA damage, isomerization and decomposition of trans-urocanic acid, prevention of UV-mediated apoptosis and necrosis, as well as degradative matrix remodeling, which is the main cause of photoaging. These short-term effects translate into long-term prevention of photoaging and photocarcinogenesis. A striking property is that PL can exert its effect when administered orally. Together, these effects postulate PL as a natural photoprotective agent and a potential adjuvant to phototherapy for various skin diseases.
The aim of the study was to test the immunomodulating capacity of Anapsos, Polypodium leucotomos extract, in vitro in an attempt to explore how this extract acts from an immunological 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 extract, Anapsos, obtained. Mononuclear cells were obtained by density gradient centrifugation from healthy donors, and stimulated with phytohemagglutinin or Pokeweed with and without Anapsos and with Anapsos alone. Cell proliferation was determined by thymidine incorporation. Cells were also stimulated and the following cytokines determined by ELISA at 0, 12, 24, 48, 72, and 96 h: IL-1 beta, TNF-alpha, IL-2, INF-8, IL-4 and IL-10.
Anapsos, Polypodium leucotomos extract, has a modulating effect on the in vitro production and release of cytokines by peripheral blood mononuclear cells of healthy subjects. At doses effective in vivo, Anapsos can stimulate PBMNc proliferation, delay IL-1 beta secretion and at the same time increase that of IL-2, IL-10, and INF-gamma.
Anapsos 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.
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-α-d-quinovopyranosyl)-glycerol 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 μm. It is suggested that the compound acts through PAF receptor antagonism in intact human neutrophils.
Sunburn, immune suppression, photoaging, and skin cancers result from uncontrolled overexposure of human skin to solar ultraviolet radiation (UVR). Preventive measures, including photoprotection, are helpful and can be achieved by topical sunscreening agents. Polypodium leucotomos (PL) has been used for the treatment of inflammatory diseases and has shown some in vitro and in vivo inmunomodulating properties. Its beneficial photoprotective effects in the treatment of vitiligo and its antioxidant properties encouraged us to evaluate in vivo the potentially useful photoprotective property of natural extract of PL after topical application or oral ingestion. Twenty-one healthy volunteers [either untreated or treated with oral psoralens (8-MOP or 5-MOP)] were enrolled in this study and exposed to solar radiation for evaluation of the following clinical parameters: immediate pigment darkening (IPD), minimal erythema dose (MED), minimal melanogenic dose (MMD), and minimal phototoxic dose (MPD) before and after topical or oral administration of PL. Immunohistochemical assessment of CD1a-expressing epidermal cells were also performed. PL was found to be photoprotective after topical application as well as oral administration. PL increased UV dose required for IPD (P < 0.01), MED (P < 0.001) and MPD (P < 0.001). After oral administration of PL, MED increased 2.8 +/- 0.59 times and MPD increased 2.75 +/- 0.5 and 6.8 +/- 1.3 times depending upon the type of psoralen used. Immunohistochemical study revealed photoprotection of Langherhans cells by oral as well as topical PL. The observed photoprotective activities of oral or topical PL reveal a new avenue in examining the potentially useful field of systemic photoprotection and suggests that PL can be used as adjunct treatment and can make photochemotherapy and phototherapy possibly safe and effective when the control of cutaneous phototoxicity to PUVA or UVB is a limiting factor in such phototherapies.
Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis.
After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group.
There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.
The immunomodulant effects of Anapsos, an extract of the naturally occurring fern Polypodium leucotomos was assessed in Balb/c mice immunized with a crude soluble extract (CSE) of Trichinella spiralis L1 larvae. Treatment from day 10 to 1 prior to immunization caused a significant reduction (p < 0.05) in total antibody levels (IgG + M) that was evident from week 2 onwards. Suppression of the IgG1 response was transient, as serum levels were significantly (p < 0. 01) decreased in treated animals during weeks 2 and 3 post-immunization, afterwards increasing to values similar to those in the control group. An opposite pattern was observed in the IgG2a and IgG 2b profiles where, following a brief increase in weeks 3 and 1, respectively, the values fell below those of the control and remained for the whole observation. Anapsos potentiates the IgG3 response against T. spiralis CSE. Deglycosylation of the CSE used in the ELISA assay significantly reduces the IgG3 recognition capacity in both control and treated mice. This treatment did not affect the time-course of an intestinal infection by T. spiralis.
We describe 6 patients with generalized vitiligo who responded to treatment with tacrolimus ointment. Moderate to excellent repigmentation was achieved in 5 patients. Although the number of cases in this noncontrolled, nonblinded series is small, tacrolimus ointment may be an efficacious and safe treatment option for vitiligo.
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.
We sought to assess oral Polypodium leucotomos (PL) extract in decreasing PUVA-induced phototoxicity of human skin on a clinical and histologic level.
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.
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.
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.
Immunomodulator effect of Anapsos (Polypodium leukotomas extract) in NMRI (US Naval Medical Research Institute) outbred mice infected by the intraperitoneal route with 10(7) Trichomonas vaginalis has been tested. Gross histopathologic changes in abdominal organs and mortality rate, as a consequence of the pathogenicity of the protozoa and the immune response of the host, were evaluated. Among the different treatment regimes assayed, Anapsos at doses of 20 mg/Kg/day administered for 10 days before infection decreases the parasite pathogenicity index (PI) in the treated animals when compared to those of the untreated control group. The immunosuppressor treatments with azathioprine (100 mg/Kg/day x 1), cyclophosphamide (100 mg/Kg/day x 1), and FK-506 (10 mg/Kg/day x 10) significantly decreased the PI, while an immunostimulant treatment with glycophosphopeptical (13 mg/Kg/day x 10) increased it. These assays have shown the usefulness of the murine model of experimental trichomoniasis for the study of immunomodulator activity of natural or synthetic drugs.
Previous studies have documented humoral and cell-mediated immunologic defects in patients with vitiligo.
This 24-week study assessed the efficacy and safety of tacrolimus 0.1% ointment in patients with generalized vitiligo as well as the pretreatment and post-treatment expression of cytokines in the depigmented and normal skin of patients compared with controls.
Twenty-three patients were enrolled in this investigation, and 19 patients completed the study; 8 were male and 11 were female. Fifteen age-, race-, and sex-matched control subjects were also included. Patients were treated with tacrolimus 0.1% ointment applied twice daily. Repeat evaluations were performed at 4, 8, 12, 16, 20, and 24 weeks. Three-millimeter punch biopsy specimens were taken from the depigmented, non-sun-exposed skin and adjacent normal skin of patients at baseline and 24 weeks, and from normal, non-sun-exposed skin of controls. Cellular messenger RNA expression for interleukin 2 (IL-2), IL-4, IL-10, tumor necrosis factor alfa (TFN-alpha), and interferon gamma (IFN-gamma) were determined by real-time quantitative polymerase chain reaction.
At 24 weeks, 17 of 19 patients (89%) achieved varying levels of repigmentation. There was a statistically significant decrease in overall disease severity scores at 24 weeks. Thirteen patients (68%) had greater than 75% repigmentation of face and/or neck lesions. Signs and symptoms of irritation were minimal. At baseline, compared with healthy controls, vitiligo patients demonstrated a statistically significant increase in the expression of IFN-gamma in involved and adjacent uninvolved skin (P=.05 and P=.02, respectively); significantly increased TNF-alpha expression in involved and uninvolved skin (P=.01 and P=0.02, respectively); and significantly increased IL-10 expression in involved and uninvolved skin (P=.01 and P=.04, respectively). Posttreatment, TNF-alpha expression decreased in the depigmented and adjacent uninvolved skin (P <.001). There was no statistically significant change in IL-10 or IFN-gamma posttreatment. These data suggest that tacrolimus 0.1% ointment is a safe and effective therapy for patients with vitiligo. It further suggests that an imbalance in local cytokine expression may play a role in the pathogenesis of vitiligo. Suppression of TNF-alpha after topical tacrolimus application may be associated with repigmentation of vitiligo.
UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL).
A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin.
A significant decrease in erythema was found in PL-treated skin (P < .01). Histologically, PL-treated biopsy specimens showed less sunburn cells (P < .05), cyclobutane pyrimidine dimers (P < .001), proliferating epidermal cells (P < .001), and dermal mast cell infiltration (P < .05). A trend toward Langerhans cell preservation was seen.
Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiation.
The immunomodulating effects of Anapsos, an aqueous hydrosoluble extract obtained from the rhizomes of the fern Polypodium leucotomos, on both pathogenicity and cytokine levels in serum (IFN-gamma/IL-4) were assayed in a Trichomonas vaginalis experimental model (BALB/c mice infected with 10(7) trichomonads and examined at day 15 after infection). Doses of 20 mg/kg/day administered for 10 days before the infection with the parasite induced a decrease of the experimental pathogenicity approximately 10-20% compared to controls. Gross histopathologic changes at abdominal organs and mortality rate, as a consequence of pathogenicity of the protozoa and the immune response of the host, were evaluated. IFN-gamma and IL-4 cytokines were determined on days -5, 0, 5, 10, and 15 postinfection by indirect ELISA. Treatment with PAL before infection modulates and downregulates the IFN-gamma concentration, while anticipates and upregulates the IL-4 level. The assays performed have showed the utility of the murine model of experimental trichomoniasis for the evaluation of immunomodulatory activity of synthetic or natural products.
Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos, used as raw material for topical and oral photoprotective formulations, was fractioned by HPLC and the main components with antioxidant capability were identified by means of UV spectra, electrochemical detection, and MSn. Phenolic compounds were identified as 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, vanillic acid, caffeic acid, 4-hydroxycinnamic acid, 4-hydroxycinnamoyl-quinic acid, ferulic acid, and five chlorogenic acid isomers. Total ferric antioxidant capacity (FRAP) of HPLC eluted fractions was measured. The results suggest that the herein identified compounds support, at least partially, the antioxidant and radical scavenging capacities of Fernblock.
Sequential displays of several treatment options for vitiligo have been scanned from the literature, and are presented here. A few of the medical modalities have been resigned to history, whereas others have become customary in clinical practice. There has also been a recent surge of interest in the surgical treatment of this disease. Accordingly, this has been appraised and summarized. Special attention has been given to prevalent medical modalities so that they may be effectively utilized by those currently in practice.
The first choice treatment for vitiligo vulgaris is narrow-band UVB (NB-UVB), but no satisfactory treatment exists.
To investigate if Polypodium leucotomos, an antioxidative and immunomodulatory plant extract, improves NB-UVB-induced repigmentation.
Fifty patients with vitiligo vulgaris randomly received 250 mg oral P. leucotomos or placebo three times daily, combined with NB-UVB twice weekly for 25-26 weeks.
Repigmentation was higher in the P. leucotomos group vs. placebo in the head and neck area (44% vs. 27%, P = 0.06). Small repigmentation increases (P = n.s.) were observed for the trunk (6% increased repigmentation), extremities (4%), and hands and feet (5%) in the P. leucotomos group vs. placebo. Patients attending more than 80% of required NB-UVB sessions showed increased repigmentation in the head and neck area in the P. leucotomos group vs. placebo (50% vs. 19%, P < 0.002); no significant differences were seen in the other body areas. Patients with skin types 2 and 3 showed more repigmentation in the head and neck area in the P. leucotomos group vs. placebo (47% vs. 21%, P = 0.01), and no significant differences were seen in the other body areas. No conclusions could be drawn on skin types 4 and 5 due to low patient numbers.
There is a clear trend towards an increase in repigmentation of vitiligo vulgaris affecting the head and neck area when NB-UVB phototherapy is combined with oral P. leucotomos. This effect may be more pronounced in light skin types.
Ultraviolet (UV) irradiation causes multifaceted damage to the skin and adjacent tissue layers, and is one of the leading causes of premature skin aging, immunosuppression and carcinogenesis. Photoprotection can be achieved by the use of sunscreens and also by systemically administered compounds that fight the deleterious biological effects of UV exposure, or preferably both. In this review, we summarize the current knowledge on the tissue, cellular and molecular mechanisms underlying the photoprotective effect of Polypodium leucotomos fern extract. P. leucotomos blocked the deleterious effect of UV irradiation both in vivo and in vitro. The molecular basis of photoprotection relies on its ability to inhibit free radical generation, prevent photodecomposition of both endogenous photoprotective molecules and DNA, and prevent UV-induced cell death. Its complete loss of toxicity combined with its multifactor protection makes it a valuable tool not only for direct photoprotection, but also as an efficacious adjuvant to phototherapy of various skin diseases.
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