Shiitake Complex
History and Origin
Shiitake mushrooms (Lentinus edodes) were first cultivated in Asia over 1000 years ago and were used to increase energy, extend longevity and promote overall vitality. Shiitake mushrooms contain the polysaccharide, lentinan. The mannentake or reishi mushroom (Ganoderma lucidum) has been used for thousands of years in Traditional Chinese Medicine for the treatment of wounds and inflammation. It is one of the most studied botanical treatments studied in Asia.
Johnson & Johnson Consumer Companies, Inc.
The majority of anti-aging skin care products aim to improve fine lines and wrinkles. However, these are not the only visible signs of cutaneous aging. Uneven pigmentation (particularly in individuals of color), skin surface roughness, and dullness are frequent concerns of women as they age.
Recently, AVEENO® researchers have developed a unique combination of mushroom extracts for formulation into products designed to stimulate surface cell renewal and improve the visible signs of photoaging. This mushroom extract combination, Natural Shiitake Complex, combines shiitake and mannentake (reishi) mushrooms.
Activity, Properties, Chemical Structure
Recent research has revealed that both shiitake and reishi mushrooms are rich in vitamins and amino acids. They contain a variety of polysaccharides with immunostimulatory properties. Other bioactive substances contained in these mushroom extracts include triterpenes, proteins, lipids, phenols and cerebrosides. (Sliva). A recent Chinese clinical study also revealed that the phenols in reishi mushrooms have free radical scavenging and antioxidant activity. (Mau).
Pre-Clinical Studies of Natural Shiitake Complex
A number of preclinical studies were performed to assess the effects of the Natural Shiitake Complex (composed of Shiitake and Reishi mushroom extracts) on mediators of photoaging including dermal matrix degradation, inflammation, oxidative stress as well as on its ability to stimulate skin cell growth and renewal. Figure 1 depicts the interplay of these factors in the development of photoaging. Figure 2 shows how oxidative stress due to free radical generation can lead to the stimulation of matrix-degrading enzymes and inflammation-producing cytokines. Natural Shiitake Complex was found to protect skin from numerous pathways which can accelerate the skin aging process.
Figure 1: Exogenous Influences Leading to Photoaging
Figure 2: Free Radical Damage to the Skin
Collagen
Activator Protein-1 (AP-1) is a transcription factor that can regulate the downstream production of enzymes such as the matrix metalloproteinases (MMPs) collagenase, gelatinase and stromelysins that can degrade collagen and lead to the wrinkled, sagging genotype associated with photoaging. Solar ultraviolet irradiation activates the transcription factor AP-1, inducing production of MMPs which can lead to skin aging. Doses of the Natural Shiitake Complex ranging from 10/μg/mL to 100 μg/mL concentrations were tested for their ability to inhibit AP-1 activation. At these concentrations, the Natural Shiitake Complex demonstrated moderate activity with significant reductions in the AP-1 gene reporter. (Fig.3). In laboratory studies, Natural Shiitake Complex was shown to inhibit the production of MMPs.
Figure 3: Results from AP-1 Activation Model
Elastin
As skin ages, it generally loses elasticity. This is attributed to skin thinning and loss of elastin fibers in the dermal matrix which are expressed as sagging of the skin. Skin is continuously exposed to numerous external aggressions (UV, pollution) that can trigger activation of enzymes such as elastase, which degrades elastin fibers and can lead to decrease in skin elasticity. Natural Shiitake Complex was tested in vitro for its ability to inhibit the activity of elastase. Fig. 4 shows the effect of varying concentrations of Natural Shiitake Complex on human elastase activity, inhibiting elastase with a half maximal inhibitory concentration (IC50) of 50.7 μg/ml.
Figure 4: Results from Elastase Enzyme Activity Model
Inflammation
Chronic, sub-clinical inflammation may lead to an acceleration in the signs of skin aging. Therefore, reducing the persistant irritation or skin may reduce extrinsic factors that can lead to skin aging. Natural Shiitake Complex was found to inhibit the release of pro-inflammatory mediators, such as interleukin-8 (IL-8), from human keratinocytes was tested in vitro. Natural Shiitake Complex showed good inhibition of IL-8 release with an IC50 of 61.2 μg/ml. (Fig. 5) By reducing the the persistent irritation of skin Natural Shiitake Complex may reduce extrinsic factors that can led to premature skin aging.
Figure 5: Anti-Inflammatory Activity
Oxidative Stress
Skin is under continual assault from a variety of damaging environmental factors such as ultraviolet irradiation and atmospheric pollutants. With progressing age the cumulative damage exceeds the skin's capacity of endogenous antioxidant defenses resulting in chronic inflammation and premature aging. Botanical extracts such as Natural Shiitake Complex containing naturally occurring antioxidants could replenish the depleted cutaneous stores and perhaps forestall these degenerative changes. Natural Shiitake Complex was tested in vitro for its ability to reduce free oxygen radicals into a less reactive form. Natural Shiitake Complex showed a moderate anti-oxidant capacity (IC50= 35.3μg/ml) in dismuting the highly reactive superoxide radical. Out of 8 mushroom extracts tested, Natural Shiitake Complex was the only one that exhibited this activity. (Fig. 6) Through the ability to scavenge free radicals, Natural Shiitake Complex has the potential to protect skin from the numerous external aggressions encountered daily by skin and reduce the damage to oxidatively challenged skin.
Figure 6: Superoxide Dismutase Activity
Cell Renewal
A 5% Natural Shiitake Complex formulation was compared to a placebo formulation without Natural Shiitake Complex were tested in a preclinical model of epidermal proliferation. As shown in Fig. 7, Natural Shiitake Complex was shown to significantly stimulate epidermal proliferation after 4 weeks of application. A 22% increase was shown with the Natural Shiitake Complex compared with placebo.
Figure 7: Murine Model of Epidermal Thickness
Safety and Toxocological Studies
- The AVEENO® Positively Ageless™ products were tested utilizing standard clinical safety methodologies. These included HRIPT (200 subject panels), cumulative irritation, phototoxicity and photoallergy. All products in the line have been shown to be well-tolerated when used as directed.
- The mushroom extracts included in the products have undergone a rigorous extraction process which leaves only a purified fraction intended for cosmetic use. There is no pathogenic component associated with this material.
References
Sliva D. Cellular and physiological effects of Ganoderma lucidum (reishi). Mini Rev Med Chem. 2004;4:873-879.
Mau JL, Lin HC, Chen CC. Antioxidant properties of several medicinal mushrooms J Agric Food Chem. 2002;50:6072-6077.
Nebus J, Costes F, Wallo W, Miller D. Clinical improvements in facial photoaging with topical treatments containing mushroom extracts. Poster presented at:American Academy of Dermatology 65th Annual Meeting. Washington, D.C. Feb. 2-6, 2007.
Further Reading
Chang HM, But P. Pharmacology and Applications of Chinese Materia Medica, Vol. 1. 1986; Singapore: World Scientific.
Fig. 1: Exogenous Influences Leading to Photoaging (Slide 3 in Pdf Preclinical Review of Bimini)
Fig. 2: Free Radical Damage to the Skin: (slide 4 in ibid)
Fig. 3: Results From AP-1 Activation Model (Appendix 1 From Bimini Scientific Dossier)
Fig. 4.: Results From Elastase Enzyme Activity Model (Appendix 2 ibid)
Fig. 5: Anti-Inflammatory Activity (Appendix 3: ibid)
Fig. 6: Superoxide Dismutase Activity (Appendix 4 ibid)
Fig. 7: Murine Model of Epidermal Thickness (Appendix 5 ibid).