SKIN-AGING AND INFLAMMAGING TREATMENT 333 antiaging effect of the encapsulated serum of vitamin C, vitamin E, and cell culture ex- tract of raspberry leaves based on different skin parameters. Results showed the serum had synergistic antiaging effects, such as improvements in elasticity, wrinkles, radiance, smoothness, and skin darkening (117). Centella asiatica is widely used in Indian herbal medicine and known for its benefi cial skin effects. Maramaldi et al. (118) evaluated antiglycation and anti-infl ammaging of Centella asiatica in oil-in-water emulsion formulation (Supplementary Table 1). Triterpenes con- tained in the extract promote collagen synthesis moreover, both triterpenes and polyphe- nolics have shown a synergistic action for normalization of keratinocyte hyperproliferation, infl ammation, and generation of the natural epidermal homeostasis. This study showed C. asiatica extract promoted collagen synthesis, reduced DNA damage by UV, decreased photodimerization of thymine and expression of interleukin-1α, inhibited carboxymethyl lysine synthesis, and densifi ed epidermal collagen network in the papillary dermis (118). TOPICAL COLLAGEN FORMULATIONS For a substance to be delivered via the skin, many physicochemical properties need to be considered, including molecular weight, solubility, and partition coeffi cient (119). Im- portantly, topically applied collagen seems ineffective as it cannot be absorbed through the skin because of its high molecular weight, and only naturally produced collagen can be effective (120). Commercial products such as Collagen Hydrating Serum produced by Wilma Schumann (121) and Matricol Caviar Deluxe Collagen produced by Matricol (Medskin Solutions Dr. Suwelack AG, Billerbec, Germany) (122) whose unit price ex- ceeds $200 and $300, respectively, contain collagen (Table 1). Thus, their claims of de- livering pure natural collagen in high concentration through the skin and promoting new collagen are highly doubtful. Other commercial products are listed in Table 1. On the other hand, palmitoyl pentapeptide-4, with the trade name of Matrixyl (DECIEM Company, Toronto, Canada) is an active peptide of small size that is based on collagen type I propeptide (132). It was reported that Matrixyl promotes collagen type I synthesis in both in vitro cell culture and clinical studies (132). For example, controlled two double-blind clinical studies conducted in females revealed that the product improved wrinkle depth (133). Recently, hydrolyzed collagen has gained a lot of fame in the cosmetic industry because of its low molecular weight, it can penetrate the skin and produce antiaging properties. Zhang et al. (134) conducted an ex vivo study to investigate collagen hydrolysate penetra- tion and found that only 8% penetrated mouse skin. Moreover, in vitro and ex vivo studies cannot refl ect the in vivo bioavailability of these products, and there are limited studies that evaluate the in vivo permeation and effi cacy of such peptides (135). Unfortunately, numerous drawbacks, concerns, and challenges are associated with nutra- ceutical products. In addition, both topical and oral antiaging formulations have not been compared with Food and Drug Administration approved injected collagen or hyaluronic acid products, such as Evolence and others (136). Consequently, the market is currently fl ooded with expensive antiaging products that suffer from questionable safety and effi cacy profi les. Hence, valid, well-established, and common regulations for antiaging nutraceuticals along with in-depth clinical, in vivo, and in vitro studies are required to monitor emerging trends and demands of antiaging nutraceuticals in the global market ( 137).

Table I Commercial coll a gen-based nutraceutical formulations sold online Brand Ingredients Formulation type Claims Company Refs. BioCell Hydrolyzed collagen type II Capsules Reduces fi ne lines and wrinkles Health Logics (135) Hyaluronic acid Reduces 76% of skin dryness Reduces joint discomfort and stiffness Japanese Beauty Suppliment Meiji Amino collagen Premium collagen Amino collagen Powder – Meiji (132) 3 Bio-Mask 24k Gold Collection Peel Off + Serum 24 K – Kit Hydrolyzed collagen Mask and serum Prevents and treats premature aging Bioage Skincare Solutions (134) Hyaluronic acid Antioxidant Saponaria pumila callus culture extract Slows the glycation Khaya Senegalensis bark extract and others Collagen Hydrating Serum Native collagen fl uid Serum Antiaging, provides hydration, and decreases wrinkles and fi ne line appearance Wilma Schumann (130) Glycerin Promotes new collagen in skin Panthenol Lactic acid Matricol Caviar Deluxe Pure natural collagen Mask sheets Active prevention against skin aging Matricol (131) Caviar extract Provides optimum skin moisture Collagen Moisture Filler/ Combleur Hydrant Natural collagen Cream Provides intense hydration L’Oreal (133,138) Helps fi ll in lines and wrinkles JOURNAL OF COSMETIC SCIENCE 334