Skin Rejuvenation: Synthetic Snake Venom to the Rescue?

Synthetic snake venom is one of an increasingly wide range of bioactive ingredients that have been undergoing validation and incorporation into Korean cosmeceutical formulations.¹ This column discusses some of the emerging data in this novel area of medical and dermatologic research. For more detailed information, a review on the therapeutic potential of peptides in animal venom was published in 2003 (Nat Rev Drug Discov. 2003 Oct;2[10]:790-802).

The Potential of Peptides Found in Snake Venom

Snake venom is known to contain carbohydrates, nucleosides, amino acids, and lipids, as well as enzymatic and nonenzymatic proteins and peptides, with proteins and peptides comprising the primary components.²

Dr Leslie Baumann

There are many different types of peptides in snake venom. The peptides and the small proteins found in snake venoms are known to confer a wide range of biologic activities, including antimicrobial, antihypertensive, analgesic, antitumor, and analgesic, in addition to several others. These peptides have been included in antiaging skin care products.³ Pennington et al. have observed that venom-derived peptides appear to have potential as effective therapeutic agents in cosmetic formulations.⁴ In particular, Waglerin peptides appear to act with a Botox-like paralyzing effect and purportedly diminish skin wrinkles.⁵

Issues With Efficacy of Snake Venom in Skin Care Products

As with many skin care ingredients, what is seen in cell cultures or a laboratory setting may not translate to real life use. Shelf life, issues during manufacturing, interaction with other ingredients in the product, interactions with other products in the regimen, exposure to air and light, and difficulty of penetration can all affect efficacy. With snake venom in particular, stability and penetration make the efficacy in skin care products questionable.

The problem with many peptides in skin care products is that they are usually larger than 500 Dalton and, therefore, cannot penetrate into the skin. Bos et al. described the "500 Dalton rule" in 2000.6 Regardless of these issues, there are several publications looking at snake venom that will be discussed here.

Antimicrobial and Wound Healing Activity

In 2011, Samy et al. found that phospholipase A2 purified from crotalid snake venom expressed antibacterial activity in vitro against various clinical human pathogens. The investigators synthesized peptides based on the sequence homology and ascertained that the synthetic peptides exhibited potent microbicidal properties against Gram-negative and Gram-positive (Staphylococcus aureus) bacteria with diminished toxicity against normal human cells. Subsequently, the investigators used a BALB/c mouse model to show that peptide-treated animals displayed accelerated healing of full-thickness skin wounds, with increased re-epithelialization, collagen production, and angiogenesis. They concluded that the protein/peptide complex developed from snake venoms was effective at fostering wound healing.⁷

In that same year, Samy et al. showed in vivo that the snake venom phospholipase A₂ (svPLA₂) proteins from Viperidae and Elapidae snakes activated innate immunity in the animals tested, providing protection against skin infection caused by S. aureus. In vitro experiments also revealed that svPLA₂ proteins dose dependently exerted bacteriostatic and bactericidal effects on S. aureus.⁸ In 2015, Al-Asmari et al. comparatively assessed the venoms of two cobras,four vipers, a standard antibiotic, and an antimycotic as antimicrobial agents. The methicillin resistant Staphylococcus aureus bacterium was the most susceptible, followed by Gram-positive S. aureus, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa. While the antibiotic vancomycin was more effective against P. aeruginosa, the venoms more efficiently suppressed the resistant bacteria. The snake venoms had minimal effect on the fungus Candida albicans. The investigators concluded that the snake venoms exhibited antibacterial activity comparable to antibiotics and were more efficient in tackling resistant bacteria.⁹ In a review of animal venoms in 2017, Samy et al. reported that snake venom–derived synthetic peptide/snake cathelicidin exhibits robust antimicrobial and wound healing capacity, despite its instability and risk, and presents as a possible new treatment for S. aureus infections. They indicated that antimicrobial peptides derived from various animal venoms, including snakes, spiders, and scorpions, are in early experimental and preclinical development stages, and these cysteine-rich substances share hydrophobic alpha-helices or beta-sheets that yield lethal pores and membrane-impairing results on bacteria.¹⁰

New Drugs and Emerging Indications

An ingredient that is said to mimic waglerin-1, a snake venom–derived peptide, is the main active ingredient in the Hanskin Syn-Ake Peptide Renewal Mask, a Korean product, which reportedly promotes facial muscle relaxation and wrinkle reduction, as the waglerin-1 provokes neuromuscular blockade via reversible antagonism of nicotinic acetylcholine receptors.^2,4,5

Waheed et al. reported in 2017 that recent innovations in molecular research have led to scientific harnessing of the various proteins and peptides found in snake venoms to render them salutary, rather than toxic. Most of the drug development focuses on coagulopathy, hemostasis, and anticancer functions, but research continues in other areas.¹¹ According to An et al., several studies have also been performed on the use of snake venom to treat atopic dermatitis.¹²

Conclusion

Snake venom is a substance known primarily for its extreme toxicity, but it seems to offer promise for having beneficial effects in medicine. Due to its size and instability, it is doubtful that snake venom will have utility as a topical application in the dermatologic arsenal. In spite of the lack of convincing evidence, a search on Amazon.com brings up dozens of various skin care products containing snake venom. Much more research is necessary, of course, to see if there are methods to facilitate entry of snake venom into the dermis and if this is even desirable.

Snake venom is, in fact, my favorite example of a skin care ingredient that is a waste of money in skin care products. Do you have any favorite "charlatan skincare ingredients"? If so, feel free to contact me, and I will write a column. As dermatologists, we have a responsibility to debunk skin care marketing claims not supported by scientific evidence. I am here to help.

Leslie S. Baumann, MD, is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. She has written two textbooks and a New York Times Best Sellers book for consumers. She has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt's Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at dermnews@mdedge.com.

References

1. Nguyen JK et al. J Cosmet Dermatol. 2020 Jul;19(7):1555-69.

2. Munawar A et al. Snake venom peptides: tools of biodiscovery. Toxins (Basel). 2018 Nov 14;10(11):474.

3. Almeida JR et al. Curr Med Chem. 2017;24(30):3254-82.

4. Pennington MW et al. Bioorg Med Chem. 2018 Jun 1;26(10):2738-58.

5. Debono J et al. J Mol Evol. 2017 Jan;84(1):8-11.

6. Bos JD, Meinardi MM. Exp Dermatol. 2000 Jun;9(3):165-9.

7. Samy RP et al. Methods Mol Biol. 2011;716:245-65.

8. Samy RP et al. Curr Med Chem. 2011;18(33):5104-13.

9. Al-Asmari AK et al. Open Microbiol J. 2015 Jul;9:18-25.

10. Perumal Samy R et al. Biochem Pharmacol. 2017 Jun 15;134:127-38.

11. Waheed H et al. Curr Med Chem. 2017;24(17):1874-91.

12. An HJ et al. Br J Pharmacol. 2018 Dec;175(23):4310-24.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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