Sphingolipids are a class of lipids that include sphingomyelins and glycolipids, which play crucial roles in cellular functions, including the structure of cell membranes and cell signaling. They are particularly abundant in the central nervous system and are essential for protecting the structure of nerve cells and facilitating nerve signal transmission. 

The name describes the structure of the molecule:

• Sphingo- comes from the Greek myth of the Sphinx, a symbol of mystery and enigma. This prefix was chosen to reflect the complexity and initial lack of understanding of these compounds when they were first discovered.
• lipids are fatty molecules or fat-like substances that are important components of cell membranes and are involved in many essential biological functions.

Industrial Production Process

• Biological source selection. The process begins with the selection of sources rich in sphingolipids, such as animal tissues, plants, or microorganisms.
• Lipid extraction. The selected biological materials are treated with organic solvents, such as chloroform and methanol, to extract total lipids, including sphingolipids.
• Separation. The lipid mixture is then subjected to separation techniques like column chromatography or high-performance liquid chromatography (HPLC) to isolate sphingolipids from unwanted lipids.
• Hydrolysis. Sphingolipids can be hydrolyzed, if necessary, to break down complex bonds and facilitate further purification of specific components like ceramides or sphingosines.
• Further purification. After hydrolysis, components are further purified using more specific techniques, such as ion exchange chromatography or size exclusion chromatography, to achieve a high degree of purity.
• Concentration. The purified fractions are concentrated under vacuum or using rotary evaporators to remove residual solvents and concentrate the sphingolipids.
• Quality control. Each batch of sphingolipids is analyzed to ensure purity and compound identity using mass spectrometry and NMR spectroscopy.

What they are used for and where they are used

In cosmetics, sphingolipids are used for their moisturizing and restructuring properties on the skin. They help restore the skin barrier, improve skin elasticity, and can contribute to reducing the appearance of wrinkles and dryness.

What it is used for and where

Cosmetics - INCI Functions

Skin conditioning agent - Emollient. Emollients have the characteristic of enhancing the skin barrier through a source of exogenous lipids that adhere to the skin, improving barrier properties by filling gaps in intercorneocyte clusters to improve hydration while protecting against inflammation. In practice, they have the ability to create a barrier that prevents transepidermal water loss.  Emollients are described as degreasing or refreshing additives that improve the lipid content of the upper layers of the skin by preventing degreasing and drying of the skin. The problem with emollients is that many have a strong lipophilic character and are identified as occlusive ingredients; they are oily and fatty materials that remain on the skin surface and reduce transepidermal water loss. In cosmetics, emollients and moisturisers are often considered synonymous with humectants and occlusives.

Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Skin protectant. It creates a protective barrier on the skin to defend it from harmful substances, irritants, allergens, pathogens that can cause various inflammatory conditions. These products can also improve the natural skin barrier and in most cases more than one is needed to achieve an effective result.

CAS   85116-74-1

EC number   285-526-0

Main uses and benefits of sphingolipids.

Skin Barrier. They strengthen the skin barrier, improving skin hydration and protecting it from external irritants and allergens.

Anti-Aging Properties. They help reduce the appearance of wrinkles and fine lines by stimulating natural collagen production and improving skin elasticity.

Cell Regeneration. Sphingolipids are involved in regulating cell growth and death, contributing to healthy skin maintenance and promoting the repair of damaged tissue.

Hydration. They help maintain the skin's natural moisture, preventing dryness and improving softness and radiance.

Antioxidant Protection. They provide protection against oxidative stress caused by free radicals, helping to prevent cellular damage and premature aging.

Versatile Application. Sphingolipids can be incorporated into a variety of skincare products, including moisturizers, serums, lip balms, and anti-aging treatments.

References_____________________________________________________________________

(1) Hannun YA, Obeid LM. Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol. 2018 Mar;19(3):175-191. doi: 10.1038/nrm.2017.107. Epub 2017 Nov 22. Erratum in: Nat Rev Mol Cell Biol. 2018 Oct;19(10):673. 

Abstract. Studies of bioactive lipids in general and sphingolipids in particular have intensified over the past several years, revealing an unprecedented and unanticipated complexity of the lipidome and its many functions, which rivals, if not exceeds, that of the genome or proteome. These results highlight critical roles for bioactive sphingolipids in most, if not all, major cell biological responses, including all major cell signalling pathways, and they link sphingolipid metabolism to key human diseases. Nevertheless, the fairly nascent field of bioactive sphingolipids still faces challenges in its biochemical and molecular underpinnings, including defining the molecular mechanisms of pathway and enzyme regulation, the study of lipid-protein interactions and the development of cellular probes, suitable biomarkers and therapeutic approaches.

(2) Farwick M, Watson RE, Rawlings AV, Wollenweber U, Lersch P, Bowden JJ, Bastrilles JY, Griffiths CE. Salicyloyl-phytosphingosine: a novel agent for the repair of photoaged skin. Int J Cosmet Sci. 2007 Aug;29(4):319-29. doi: 10.1111/j.1467-2494.2007.00394.x. 

Abstract. In recent years the importance of sphingolipids (cerebrosides, sphingomyelin, ceramides, sphingosine-1-phospate, etc.) in skin biology is receiving an increasing interest. Not only are ceramides essential for the barrier function of the skin, especially through their phytosphingosine, sphingosine and 6-hydroxysphingosine derivatives, they are now also known to be cell-signalling mediators which can improve epidermal differentiation. However, their effects on dermal anti-ageing markers and reduction of wrinkles have not been established. In this study, we were interested in the effects of a sphingolipid derivative, salicyloyl-phytosphingosine (SP), because of the known independent beneficial effects of salicylic acid and phytosphingosine on skin. Both of these agents are known to reduce the activities of the activator protein-1 transcription factor, in a manner similar to that observed with retinoic acid (RA) treatment. Through this mechanism, RA was shown to reduce the levels of matrix metalloproteases (MMPs) and the increase levels of extracellular matrix proteins. Therefore, we examined the effects of SP on procollagen-I synthesis in fibroblasts in vitro, its effects in vivo on the expression of dermal markers such as fibrillin-1, procollagen-I and MMP-1 immunochemically in biopsies taken from a short-term occluded patch test protocol and, its effects on periorbital wrinkle reduction over 4 weeks using Fast Optical In Vivo Topometry of Human Skin. In vitro we observed a significant increase in the production of procollagen-I by adult human fibroblasts (two fold increase, P < 0.01) which encouraged us to test the effects of SP in vivo. Initially, test products (SP at 0.05% and 0.2%, all-trans RA (0.025%) and vehicle were applied under occlusion for 8 days prior to biopsy and histological assessment in photoaged volunteers (n = 5). Increased deposition of fibrillin-1 and procollagen-I, together with reductions in the levels of MMP-1, were observed for the SP treatments (P < 0.05). Similar effects were observed for RA, except for the increases in procollagen-I. With these beneficial effects on the basement membrane and papillary dermal markers, we evaluated the effects of SP in an oil-in-water (O/W) cream for its effects in reducing the appearance of periorbital wrinkles in a 4-week, half-face clinical study compared to placebo cream (moderately photoaged female subjects aged 41-69 years; n = 30). Clear reductions in wrinkle depth and Rz (skin smoothness) together with Ra (skin roughness) parameters were observed (P < 0.05), indicating an anti-wrinkle benefit. In conclusion, this series of studies demonstrated for the first time that a ceramide derivative, such as that SP, was a novel agent for the repair of photoaged skin and highlight its effects at the cellular, tissue and organ levels.

(3) Nojima H, Freeman CM, Gulbins E, Lentsch AB. Sphingolipids in liver injury, repair and regeneration. Biol Chem. 2015 Jun;396(6-7):633-43. doi: 10.1515/hsz-2014-0296. 

Abstract. Sphingolipids are not only essential components of cellular membranes but also function as intracellular and extracellular mediators that regulate important physiological cellular processes including cell survival, proliferation, apoptosis, differentiation, migration and immune responses. The liver possesses the unique ability to regenerate after injury in a complex manner that involves numerous mediators, including sphingolipids such as ceramide and sphingosine 1-phosphate. Here we present the current understanding of the involvement of the sphingolipid pathway and the role this pathway plays in regulating liver injury, repair and regeneration. The regulation of sphingolipids and their enzymes may have a great impact in the development of novel therapeutic modalities for a variety of liver injuries and diseases.

(4) Gaggini M, Fenizia S, Vassalle C. Sphingolipid Levels and Signaling via Resveratrol and Antioxidant Actions in Cardiometabolic Risk and Disease. Antioxidants (Basel). 2023 May 16;12(5):1102. doi: 10.3390/antiox12051102. 

Abstract. Resveratrol (RSV) is a phenolic compound with strong antioxidant activity, which is generally associated with the beneficial effects of wine on human health. All resveratrol-mediated benefits exerted on different systems and pathophysiological conditions are possible through resveratrol's interactions with different biological targets, along with its involvement in several key cellular pathways affecting cardiometabolic (CM) health. With regard to its role in oxidative stress, RSV exerts its antioxidant activity not only as a free radical scavenger but also by increasing the activity of antioxidant enzymes and regulating redox genes, nitric oxide bioavailability and mitochondrial function. Moreover, several studies have demonstrated that some RSV effects are mediated by changes in sphingolipids, a class of biolipids involved in a number of cellular functions (e.g., apoptosis, cell proliferation, oxidative stress and inflammation) that have attracted interest as emerging critical determinants of CM risk and disease. Accordingly, this review aimed to discuss the available data regarding the effects of RSV on sphingolipid metabolism and signaling in CM risk and disease, focusing on oxidative stress/inflammatory-related aspects, and the clinical implications of this relationship.