Polypodium Leucotomos – An Overview of Basic Investigative Findings

February 2016 | Volume 15 | Issue 2 | Original Article | 224 | Copyright © February 2016


Brian Berman MD PhD,a,b Charles Ellis MD,c and Craig Elmets MDd,*

aCenter for Clinical and Cosmetic Research, Aventura, FL
bEmeritus Professor of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine,Miami, FL
cUniversity of Michigan Medical School, Ann Arbor, MI
dUniversity of Alabama at Birmingham, Birmingham, AL
*Supported by NIH Grant AR050948

capsules or placebo for 6 months. Although the use of P. leucotomos did not significantly reduce the mean percentage of days on which topical corticosteroids were used, there was a significant reduction in median percentage of days of oral antihistamine use (4.5% for P. leucotomos vs 13.6% for placebo; P=0.038).
A recent study was undertaken to determine the safety of capsules containing a carefully controlled extract of P. leucotomos (Heliocare, IFC, Spain) extract (240 mg) taken orally twice daily based on clinical history, physical findings and clinical laboratory parameters and to determine its ability to increase the minimal erythema dose or to reduce ultraviolet-associated erythema. In the randomized, double-blind, placebo-controlled study healthy subjects with Fitzpatrick skin types I-IV were randomized to receive oral PL extract (240 mg) twice daily at 8 AM and 2 PM for 2 months (N=20) and the other group received a placebo capsule twice daily for 2 months (N=20). Overall safety was assessed in both groups on day 0 and days 14, 28, and 56. Safety assessments included vital signs, complete blood count (CBC), a comprehensive metabolic panel, PT-PTT and any adverse events. The MED and UVB-associated erythema were assessed in 12 subjects from each group on days 0, 14, and 28. These measures included MED, sunburn history and the number of hours of sun exposure.
All 40 subjects completed the study. No treatment-related serious adverse events were reported during 2 months of treatment and there were no significant changes in physical examinations, clinical laboratory parameters or vital signs. Four subjects treated with P. leucotomos extract reported mild episodic fatigue, bloating, and headaches while one placebo-treated subject reported fatigue. There were no significant between-group differences in sun exposure before or during the study, however, subjects in the placebo group showed a six-fold greater chance of experiencing at least one sunburn during the study than did subjects taking the P. leucotomos extract (P=0.04). Subjects in the PLE group had a 22-fold greater incidence (odds ratio) of an increase in UVB MED compared to the Placebo group after 28 days of treatment (P=0.01).32

CONCLUSION

In vitro and in vivo animal and human studies have demonstrated the beneficial effects of Polypodium leucotomos. Together, these data indicate that extracts of this unique plant utilize multiple mechanisms for providing photoprotection and therapeutic activity that include reducing UV-induced cell damage, reducing oxidative stress and DNA damage, blocking UV radiation-induced immune suppression, and inhibiting the release of UV-induced levels of cyclooxygenase-2 and inflammatory cytokines. The in vivo studies show that the effects of P. leucotomos extract are not just theoretical; indeed, benefit has been demonstrated in animals and in humans. Thus, this natural plant extract has the potential to complement sunscreens and other methods of photoprotection. This agent which can be taken orally and has not been noted to have serious adverse reactions, offers unique advantages in that it can be given orally, thus avoiding patient resistance to topically applied sunscreens.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the assistance of Dr. Carl Hornfeldt during the preparation of this manuscript.

DISCLOSURES

Dr. Berman is and has served on Advisory Boards and as investigator for Ferndale. Dr. Ellis serves as a consultant to Ferndale Healthcare, Inc. and to companies that market products for the treatment or prevention of photoaging, psoriasis, and atopic dermatitis. Dr. Elmets is a consultant for Ferndale Healthcare, Inc.

REFERENCES

  1. Padilla HC, Laínez H, Pacheco JA. A new agent (hydrophilic fraction of Polypodium leucotomos) for management of psoriasis. Int J Dermatol.1974;13:276-82.
  2. Ramírez-Bosca A, Zapater P, Betlloch I, et al. Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial. Actas Dermosifiliogr. 2012;103:599-607.
  3. Middelkamp-Hup MA, Bos JD, Rius-Diaz F, et al. Treatment of vitiligo vulgaris with narrow-band UVB and oral Polypodium leucotomos extract: a randomized double-blind placebo-controlled study. J Eur Acad Dermatol Venereol. 2007;21:942-50.
  4. Tanew A, Radakovic S, Gonzalez S, et al. Oral administration of a hydrophilic extract of Polypodium leucotomos for the prevention of polymorphic light eruption. J Am Acad Dermatol. 2012;66:58-62.
  5. Horvath A, Alvarado F, Szöcs J, et al. Metabolic effects of calagualine, an antitumoral saponine of Polypodium leucotomos. Nature. 1967;214:1256-8.
  6. Garcia F, Pivel JP, Guerrero A, et al. Phenolic components and antioxidant activity of Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos. Methods Find Exp Clin Pharmacol. 2006;28:157-60.
  7. Gombau L, García F, Lahoz A, et al. Polypodium leucotomos extract: antioxidant activity and disposition. Toxicol In Vitro. 2006;20:464-71.
  8. van Kranen HJ, de Gruijl FR. Mutations in cancer genes of UV-induced skin tumors of hairless mice. J Epidemiol. 1999;9:S58-65.
  9. Perez C, Parker-Thornburg J, Mikulec C, et al. SKHIN/Sprd, a new genetically defined inbred hairless mouse strain for UV-induced skin carcinogenesis studies. Exp Dermatol. 2012;21:217-20.
  10. Alcaraz MV, Pathak MA, Rius F, et al. An extract of Polypodium leucotomos appears to minimize certain photoaging changes in a hairless albino mouse animal model. A pilot study. Photodermatol Photoimmunol Photomed. 1999;15:120-6.
  11. Zattra E, Coleman C, Arad S, et al. Polypodium leucotomos extract decreases UV-induced Cox-2 expression and inflammation, enhances DNA repair, and decreases mutagenesis in hairless mice. Am J Pathol. 2009;175:1952-61.
  12. Elmets CA, Viner JL, Pentland AP, et al. Chemoprevention of nonmelanoma skin cancer with celecoxib: A randomized, double-blind, placebo-controlled trial. J Natl Cancer. I 2010;102:1835-44.
  13. An KP, Athar M, Tang X, et al. Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches. Photochem Photobiol. 2002;76:73-80.
  14. Rodríguez-Yanes E, Juarranz Á, Cuevas J, et al. Polypodium leucotomos decreases UV-induced epidermal cell proliferation and enhances p53 expression and plasma antioxidant capacity in hairless mice. Exp Dermatol. 2012;21:638-40.
  15. Elmets CA, Cala CM, Xu H. Photoimmunology. Dermatol Clin. 2014;32(3):277-90, vii. doi: 10.1016/j.det.2014.03.005. PubMed PMID: 24891051.
  16. Siscovick JR, Zapolanski T, Magro C, et al. Polypodium leucotomos inhibits ultraviolet B radiation-induced immunosuppression. Photodermatol Photoimmunol Photomed. 2008;24:134-41.
  17. Mulero M, Rodriguez-Yanes E, Nogues MR, Giralt M, Romeu M, Gonzalez S, Mallol J. Polypodium leucotomos extract inhibits glutathione oxidation and prevents Langerhans cell depletion induced by UVB/UVA radiation in a hairless rat model. Exp Dermatol. 2008;17(8):653-8. doi: 10.1111/j.1600-0625.2007.00684.x. PubMed PMID: 18312382.
Close Menu