This article is, in essence, an unconventional encounter between Yul and Pro‑Xylane.
A little over two years ago, while reading papers about Pro‑Xylane, I discovered that Pro‑Xylane is a xyloside—an inhibitor of proteoglycans, which are crucial components within the skin. So why was the media describing it as something that “promotes collagen production”?
With that question in mind, I followed the trail and looked up a lot of the original research on Pro‑Xylane, and more or less pieced the story together. The ingredient itself was likely the “by‑product” of an academic project that synthesized a series of xylosides with different scaffolds. After being acquired by a multinational group, it was repackaged at multiple levels and embedded in various types of experiments—ultimately presented as a distinctive, research‑driven innovative ingredient.
So, in 2023 I wrote the article below and submitted it to the Journal of Clinical Dermatology, because that journal had once published an experimental paper on Pro‑Xylane. Work and life made me forget about it, but roughly five months later I received a response asking for revisions. I had originally thought I was just summarizing my own “research” process, and didn’t expect it to meet the bar. After two rounds of revision, it actually got slated for publication in July 2025.
As July approached, however, I hesitated. Over more than two years, my views on efficacy claims for cosmetic ingredients and on cosmetic advertising had evolved. Even though Pro‑Xylane is still being promoted in the marketplace, the earlier claims about “promoting proteoglycans” have long since disappeared. As for the safety concerns I previously raised about Pro‑Xylane—can years of market circulation be treated as a kind of “Phase III clinical trial”?
After careful consideration, I felt this piece had missed its best window for publication, but it could still be read as a kind of “essay of its time.”
Hello, nice to meet you, Pro‑Xylane. I’m Yul, and I used to question you a lot! Even though you’re a glycoside that’s hardly absorbed—your effect is pretty much equivalent to moisturization—I really did split hairs about you back then!
“Reply: Advances in the Study of Topical C‑Xyloside in Promoting Skin Rejuvenation”
In 2011, Pineau N et al. reported a possible mechanism by which a novel C‑xyloside could increase glycosaminoglycans (GAGs) in skin, and proposed that this C‑xyloside was a potential ingredient for treating skin aging and GAG deficiency. Notably, their results showed that while the C‑xyloside stimulated fibroblasts to produce short‑chain, free GAGs, it inhibited the formation of proteoglycans (PGs). [1][2]
Glycosaminoglycans (GAGs) are long, linear, negatively charged polysaccharides composed of repeating disaccharide units containing amino sugars. GAGs are widely present in skin tissue—inside cells, on cell surfaces, and within the extracellular matrix—and occur mainly as chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, heparin, and hyaluronic acid. On one hand, GAGs possess strong water‑binding capacity and viscosity, helping to maintain the spatial architecture of the dermal extracellular matrix. On the other hand, GAG–proteoglycan (GAG–PG) complexes play important roles in many biological processes, influencing cell migration, proliferation, and differentiation, as well as the biological functions of various cytokines and proteins. [3]
Proteoglycans (PGs) consist of a core protein (CP) covalently attached to one or more GAG chains. Xylose is the linkage sugar that connects the GAG chain to the serine residue of the core protein. [4]
Figure 1. GAGs attach to the core protein (CP) via xylose to form proteoglycans (PGs). Shown schematically as (GAGs–GlcA–Gal–Gal–Xyl–O–Serine–Core Protein) (GAGs–GlcA–Gal–Gal–Xyl–O–CP).
The first step of PG biosynthesis is catalyzed by O‑xylosyltransferase (XT, EC 2.4.2.26), which transfers xylose to a serine residue, thereby establishing the attachment site through which GAGs are linked to the core protein to form PGs. [4]
Xylosides are chemical moieties that compete with xylose at the xylosyltransferase active site, preventing GAG chains from attaching to proteins. [5] Thus, xylosides can be used as inhibitors of endogenous cellular GAG and PG biosynthesis. In 2017, Jie Shi Chua reported that hundreds of synthesized xylosides tested exhibited inhibitory effects on PG synthesis. [6]
The C‑xyloside reported by Pineau N et al. in 2011 has been registered and marketed by a multinational cosmetics company as Pro‑Xylane™ (INCI: Hydroxypropyl Tetrahydropyrantriol). [2] However, there are still insufficient human data on long‑term topical application of C‑xyloside for skin rejuvenation; results from in vitro reconstructed skin models should not be regarded as equivalent to human efficacy trials. [1][6][7] Importantly, based on the principle that xylosides inhibit PG synthesis and on Pineau’s 2011 data—namely, that short‑chain GAGs increased in fibroblast culture eluates while PGs decreased—we can outline the likely sequence of how this C‑xyloside acts within cells. [1]
Figure 2.
A: Endogenous GAGs are attached to cell‑surface proteoglycans (PGs).
B: C‑xyloside inhibits assembly of GAGs onto endogenous PGs; xyloside‑initiated GAGs compete with endogenous GAGs for binding to proteins.
Therefore, given that the 2011 cellular data for this C‑xyloside show inhibition of PGs, continuing to pursue it as a potential cosmetic raw material is rather bewildering. The potential toxicity to healthy cells and skin tissue from long‑term topical use of this C‑xyloside warrants attention. This is especially pertinent because, since 2020, the Chinese market has seen a surge of cosmetics promoting high concentrations of C‑xyloside, and even claims that invert the logic—asserting that C‑xyloside can promote the production of skin PGs. I believe it is necessary to review the mechanisms and discovery history of xylosides as inhibitors of PG synthesis. Whether marketing for a novel cosmetic ingredient ought to be based on adequate human data, or whether it is acceptable to transpose concepts across experimental systems to exaggerate claims, is a long‑term topic worthy of discussion. For the sake of consumer safety, I recommend that cosmetics manufacturers pay closer attention to the PG‑inhibitory potency of C‑xyloside and to its potential cytotoxicity and reproductive toxicity, so as to ensure safe inclusion levels in cosmetic formulations.
References
(1) Pineau N, Carrino D A, Caplan A I, et al. Biological evaluation of a new C‑xylopyranoside derivative (C‑Xyloside) and its role in glycosaminoglycan biosynthesis. European Journal of Dermatology (EJD). 2011;21(3):359. DOI:10.1684/ejd.2011.1340.
(2) Richard John BETTS, 苏士纹, 孔佩慧, et al. 局部外用C‑木糖苷促进皮肤年轻化的研究进展. 临床皮肤科杂志. 2021;50(7):5.
(3) Esko JD, Kimata K, Lindahl U. Proteoglycans and sulfated glycosaminoglycans. In: Varki A, Cummings RD, Esko JD, et al., eds. Essentials of Glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2009. Chapter 16.
(4) Briggs D C, Hohenester E. Structural Basis for the Initiation of Glycosaminoglycan Biosynthesis by Human Xylosyltransferase 1. Structure. 2018:801. DOI:10.1016/j.str.2018.03.014.
(5) Chua J S, Kuberan B. Synthetic Xylosides: Probing the Glycosaminoglycan Biosynthetic Machinery for Biomedical Applications. Accounts of Chemical Research. 2017. DOI:10.1021/acs.accounts.7b00289.
(6) Mencio C P, Tilve S M, Suzuki M, et al. Correction: A novel cytoskeletal action of xylosides. PLoS ONE. 2024;19(6). DOI:10.1371/journal.pone.0305286. (Original: PLoS ONE. 2022;17(6):e0269972. DOI:10.1371/journal.pone.0269972.)
(7) 李潇, 张晓娥, 卢永波, 等. 化妆品功效评价(Ⅷ)——3D皮肤模型在化妆品功效评价中的应用. 日用化学工业. 2018;48(9):7. DOI:10.13218/j.cnki.csdc.2018.09.002.