Search Results (44)

Stress-induced sebaceous hyperactivity is a key driver of acne and seborrheic dermatitis; however, research investigating the pathway-specific mechanisms through which stress exerts its effects and the suppression of sebum production via targeting stress signaling remains relatively limited. In this study, we investigated whether Camellia nitidissima flower extract (CNF) could counteract stress-induced sebaceous dysfunction and its underlying mechanisms. Using a cortisone-stimulated SZ95 human sebocyte model, we evaluated lipid accumulation, cortisol production, signaling pathway activation, and apoptotic markers. CNF treatment dose-dependently suppressed cortisone-induced lipid production, reducing triglyceride, cholesterol, and free fatty acid levels by up to 35.44%, 38.02%, and 46.39%. Mechanistically, CNF inhibited 11β-HSD1 expression (17.17% reduction) and cortisol secretion (32.84% decrease), thereby blocking local cortisol reactivation. This upstream interception subsequently attenuated PI3K/Akt/mTOR hyperphosphorylation, downregulated lipogenic transcription factors (SREBP-1, PPARγ, LXRα, C/EBP-α) and their target enzymes (FAS, ACC, DGAT). Beyond lipid synthesis inhibition, CNF reversed cortisone-induced apoptosis resistance by reducing the Bcl-2/Bax ratio and suppressing PCNA-mediated hyperproliferation, thereby decreasing sebocyte number. These findings demonstrate that CNF exerts dual oil-control effects: reducing lipid production per cell and reducing lipid-producing cell abundance. Collectively, CNF represents a promising multi-target botanical agent for managing stress-related sebaceous disorders and cosmetic sebum regulation. Full article

The sebaceous gland (SG) is a highly dynamic skin appendage that plays a central role in maintaining skin homeostasis through lipid production, immune modulation, and interactions with the skin microbiome. Dysregulation of SG function is implicated in several dermatological disorders, including acne and other inflammatory skin diseases. Over the past decades, a wide range of experimental models has been developed to investigate SG biology and pathology. These include in vivo animal models, ex vivo human skin explants, primary sebocyte cultures, and immortalized sebocyte cell lines, each offering distinct advantages and limitations. More recently, significant progress has been made in the development of advanced three-dimensional (3D) models of sebaceous gland biology, including sebocyte spheroids, SG organoids, human skin equivalents containing sebaceous components, and organotypic co-culture models, which better recapitulate the structural and functional complexity of SGs. In particular, the emergence of SG organoids derived from adult or pluripotent stem cells represents a breakthrough, enabling the study of sebocyte differentiation, lipid metabolism, and cell–cell interactions in a physiologically relevant context. Despite these advances, current models still face important challenges, including incomplete cellular maturation, limited representation of the immune and vascular components, and insufficient modeling of the native skin microenvironment. Future developments integrating bioengineering approaches, microfluidic platforms, and multi-cellular systems are expected to further enhance model complexity and translational relevance. This review summarizes current knowledge on experimental models developed to study SG and sebocyte physiology and pathology. Full article

Pathological aggregation of α-synuclein (αSyn) is a hallmark of Parkinson’s disease (PD), but increasing evidence indicates that αSyn deposits extend beyond the central nervous system to peripheral tissues, including the skin. In PD patients, cutaneous αSyn accumulation has been associated with seborrheic dermatitis (SD), a chronic inflammatory condition linked to sebocyte dysfunction and altered sebum production. Marked differences in sebum composition between PD patients and healthy controls have been described. We aimed to investigate whether pathological αSyn could contribute to dysregulated sebum production and composition by assessing key markers of sebocyte differentiation and lipogenesis in human sebaceous gland cells and skin biopsies from PD patients (n = 5) and matched controls (n = 5) without clinically recorded SD. O-αSyn exposure of immortalized sebaceous gland cells (SZ95) altered the transcriptional programs related to sebocyte differentiation, inflammation, metabolism, and lipogenesis. Consistently, protein markers of mid-to-late sebocyte differentiation were increased. Upregulation of PLIN2, together with elevated PPARγ, SREBP1, SCD1, and FADS2, indicated progression toward a mature and lipid-producing phenotype characterized by enhanced accumulation of neutral lipids within lipid droplets. Lipidomic profiling revealed remodeling of multiple lipid classes, with increases in triglycerides, ceramides, and selected phospholipids. Increased expression of PLIN2 and PPARγ was also observed in sebaceous glands from PD skin biopsies compared to controls. Collectively, our findings indicate that O-αSyn exposure is associated with molecular changes consistent with altered sebocyte differentiation and lipid remodeling. These results support a potential association between αSyn and lipid dysregulation in sebocytes and suggest that these cells may represent unrecognized peripheral targets of αSyn. Full article

Sebaceous glands consist of epithelial cells, known as sebocytes, that undergo differentiation to deliver the components of sebum into the sebaceous duct and eventually to the hair and skin surface. The final step of the terminal differentiation program is called holocrine secretion because the entire cell content is converted into sebum. Holocrine secretion is a mode of programmed cell death, which involves the degradation of the nucleus and other organelles and the rupture of the cell membrane. Here, we review the current knowledge of differentiation-associated death of sebocytes and discuss open questions regarding its mechanism and functions. In vivo studies have provided evidence for degradation of nuclear and mitochondrial DNA by lysosomal deoxribonuclease 2 (DNase 2), indicating a key role of lysosomes in holocrine secretion. We discuss the influence of tight junctions on the spatial localization of holocrine secretion within glands, the regulation of holocrine cell death by autophagy and potential mediators of membrane lysis. Further studies of holocrine secretion are needed to fully uncover its molecular control and to determine potential clinical implications. Full article

Industrial hemp (Cannabis sativa L.) has emerged as a sustainable source of bioactive compounds, with increasing interest in cosmeceutical applications for acne management. This systematic review synthesises evidence on cannabinoid-containing hemp extracts, particularly cannabidiol (CBD), with emphasis on anti-inflammatory and sebostatic mechanisms, alongside formulation considerations and supply-chain sustainability. Reporting followed PRISMA 2020 guidelines and encompassed preclinical and clinical evidence relevant to acne-associated outcomes. The review protocol was registered prospectively with PROSPERO (CRD420251272093). Across cell-based, ex vivo and early clinical studies, CBD modulated key inflammatory mediators, including TNF-α, IL-1β, IL-6 and IL-8; normalised sebocyte activity and attenuated Cutibacterium acnes (Propionibacterium acnes)-induced inflammatory signalling. Preliminary clinical observations indicate reductions in lesion counts and erythema, with generally favourable short-term tolerability; however, interpretation is limited by small sample sizes, predominantly non-randomised designs, heterogeneous formulations and frequent co-formulation with additional active ingredients. Evidence supporting direct antimicrobial efficacy and durable clinical benefit remains limited. Lipid-rich hemp seed-derived products were considered only in a contextual capacity for barrier-supportive and nutritional properties and were excluded from efficacy synthesis unless cannabinoid content was verified. Sustainability analyses highlight hemp’s low water requirements, carbon sequestration potential and relevance to Sustainable Development Goal 3 (SDG 3: Good Health and Well-Being) and Sustainable Development Goal 12 (SDG 12: Responsible Consumption and Production), supporting its role in environmentally responsible cosmeceutical development. Overall, CBD-containing hemp extracts show biologically plausible and clinically promising adjunctive potential for mild-to-moderate inflammatory acne, but current evidence remains preliminary. This review highlights the need for methodologically rigorous and transparent clinical studies, standardised formulations, validated outcome measures and the integration of sustainability metrics to strengthen evidence synthesis, clarify clinical relevance and guide responsible cosmeceutical development. Full article

This study evaluated olive leaf extract (OLE) as a multifunctional dermocosmetic candidate for sebum-related and inflammatory responses relevant to oily and acne-prone skin using an axis-aligned in vitro panel: (i) sebocyte lipogenesis, (ii) inflammatory mediator production in keratinocytes, and (iii) fibroblast-mediated collagen gel contraction. In addition, supportive mechanistic evidence for the sebum-related effects of OLE was obtained by examining signaling proteins associated with sebocyte lipogenesis, including PPAR-γ and SREBP-1. As a result, OLE significantly inhibited linoleic acid-induced lipid accumulation in SEB-1 sebocytes without cytotoxicity. In HaCaT keratinocytes, OLE significantly reduced the production of pro-inflammatory cytokines, including IL-8, TNF-α, and PGE₂, induced by Cutibacterium acnes or UVB. In dermal fibroblast-containing collagen gels, OLE enhanced fibroblast-mediated gel contraction. Additionally, analysis of the main mechanisms of lipid inhibition using SEB-1 sebocytes revealed that OLE exerts a dual regulatory role in lipid synthesis and inflammation by downregulating AKT and ERK phosphorylation and inhibiting PPAR-γ and SREBP-1 expression. Furthermore, among the tested extracts, the 70% ethanol extract (OLE70) exhibited the strongest antioxidant activity, the greatest gel contraction response, and the highest content of oleuropein, a major bioactive phenolic compound derived from olive. Like OLE, oleuropein also showed sebum-regulatory activity by reducing lipid accumulation in SEB-1 sebocytes, an inhibitory effect on IL-8 expression in HaCaT keratinocytes, and an inhibitory effect on the expression of PPAR-γ and SREBP-1, which are involved in sebum secretion. Taken together, these findings suggest that OLE and its major phenolic constituent, oleuropein, may modulate sebum-related, inflammatory, oxidative, and dermal remodeling-associated responses in skin cell models. These results should be interpreted as exploratory and provide a basis for further mechanistic and translational investigation. Full article

Background/Objectives: Sebocytes, the primary cell type in sebaceous glands (SGs), produce a lipid mixture called sebum that is released onto the skin surface and is required for skin homeostasis. The lipid receptor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) regulates sebocyte proliferation and lipid synthesis and is involved in acne development. As inhibition of PPARγ has been shown to reduce insulin-induced lipogenesis and Akt/mTOR signalling in SZ95 sebocytes, we here investigated the effects of PPARγ deletion on lipid homeostasis and autophagic stress responses and how the secretomes affect dermal fibroblasts. Methods: SZ95 sebocytes wildtype (WT) and PPARγ knockout (KO) were shifted to low serum and EGF-deficient conditions permissive for autophagy. Untargeted and targeted HPLC-MS/MS analyses were used to analyze native and oxidized lipids, respectively. Protein levels of LC3I/II and p62 were assessed using immunoblots and immunofluorescence microscopy to investigate the autophagic flux. Dermal fibroblasts were exposed to conditioned media. Results: In low serum culture media, KO SZ95 sebocytes displayed significantly altered levels of 23 lipid classes. We observed a significant increase in ether-linked fatty acids as components of complex lipids and detected elevated levels of phospholipid hydroperoxides and aldehydolipids in the KO sebocytes. KO SZ95 sebocytes failed to show the typical responses to lipoxidative stress, such as elevated p62 crosslinking or inclusion body formation, and had reduced LC3II/I ratios as compared to WT cells. PPARγ KO conditioned media promoted a trend towards an inflammatory fibroblast phenotype. Conclusions: These findings suggest that PPARγ in sebocytes may alter the lipidome, elevate redox stress, and affect the autophagic machinery, which could cause accumulation of oxidized lipids and other potentially harmful compounds in sebocytes. Full article

Cannabinoids (CBs) derived from Cannabis sativa have attracted growing interest for dermatological applications due to their anti-inflammatory, antiproliferative, antimicrobial, antifibrotic, and antipruritic properties. However, their clinical translation is significantly limited by physicochemical and pharmacokinetic challenges, including poor aqueous solubility, lipophilicity, instability, variable skin penetration, and inconsistent bioavailability. At the molecular level, CBs modulate keratinocyte proliferation, sebocyte activity, fibroblast function, melanocyte balance, and immune signalling through CB1/CB2 receptors, TRP channels, and PPARγ pathways. Evidence supports their potential in the treatment of psoriasis, atopic dermatitis, acne, allergic contact dermatitis, pruritus, scleroderma, and skin cancers. Clinical evidence remains preliminary: topical and oral formulations have demonstrated anti-inflammatory, antiproliferative, antibacterial, and antifibrotic effects, with improvements in pruritus, lesion severity, and quality of life in early-phase studies. However, most trials are small, uncontrolled, and lack placebo comparators, limiting generalisability. To overcome formulation barriers and enhance dermal delivery, advanced pharmaceutical strategies such as liposomes, nanoemulsions, polymeric nanoparticles, micelles, and transdermal systems have been investigated to improve stability, controlled release, and targeted skin deposition while minimising systemic exposure. This review integrates mechanistic insights, clinical evidence, and emerging nanotechnology-enabled delivery approaches, emphasising rational formulation design and translational considerations necessary for advancing CBs toward standardised and clinically reliable dermatological therapeutics. Full article

Leucine-rich repeats and immunoglobulin-like domains protein 1 (Lrig1) is a functional inhibitor of the epidermal growth factor receptor. Lrig1-positive stem cells are located in the isthmus region of the mouse hair follicle (HF) and are known contributors to sebaceous gland (SG) formation and homeostasis. In this study, we performed a topical tamoxifen inducible diphtheria toxin-mediated ablation of Lrig1-expressing cells in transgenic mice to investigate their function in vivo. Selective depletion of Lrig1-positive cells resulted in a complete but reversible loss of SGs, with atrophy beginning at day 14 and full recovery occurring after six months. In the absence of the Lrig1 niche, junctional-zone keratinocytes adopted an interfollicular epidermis-like phenotype (K1-positive), and repopulating cells from other epidermal compartments failed to differentiate into the sebocyte lineage. These findings demonstrate that Lrig1-positive progenitors are crucial for proper sebaceous gland morphogenesis and maintenance. Our results highlight the importance of Lrig1-positive cells in SG-related skin physiology. Full article

Reticulated acanthoma with sebaceous differentiation (RASD) is a rare, benign cutaneous neoplasm. Its variable clinical presentation frequently mimics both benign and malignant entities, posing a significant diagnostic challenge. We report a case of pigmented RASD in a 78-year-old Malay male of Fitzpatrick skin type IV who presented with a 5-year history of an 8 × 5 mm deeply pigmented, asymmetrical nodule on the left upper back, with a 2 mm central raised area showing less pigmentation. The lesion was clinically suspicious for malignant melanoma. Histopathological examination revealed characteristic features of RASD: a broad, plate-like, reticulated and pigmented epidermal proliferation with clusters of mature sebocytes at the bases of anastomosing rete ridges. Following biopsy confirmation, the residual lesion is being managed conservatively with observation. This case demonstrates an unusual heavily pigmented clinical presentation that completely obscured the typical yellowish hue associated with sebaceous differentiation, highlighting pigmented RASD as an important diagnostic pitfall in patients with skin of color. In conclusion, RASD should be included in the differential diagnosis of pigmented cutaneous lesions, especially in patients with skin of color. Recognition of this benign entity can prevent unnecessary aggressive surgical intervention. Full article

Chronic dermatological conditions such as acne vulgaris, androgenetic alopecia (AGA), and alopecia areata (AA) affect hundreds of millions worldwide and contribute substantially to quality-of-life impairment. Despite the availability of systemic retinoids, anti-androgens, and JAK inhibitors, therapeutic responses remain heterogeneous and relapse is common, underscoring the need for biologically grounded stratification. Over the past decade, large genome-wide association studies and functional analyses have clarified disease-specific and cross-cutting mechanisms. In AA, multiple independent HLA class II signals and immune-regulatory loci such as BCL2L11 and LRRC32 establish antigen presentation and interferon-γ/JAK–STAT signalling as central drivers, consistent with clinical responses to JAK inhibition. AGA is driven by variation at the androgen receptor and 5-α-reductase genes alongside WNT/TGF-β regulators (WNT10A, LGR4, RSPO2, DKK2), explaining follicular miniaturisation and enabling polygenic risk prediction. Acne genetics highlight an immune–morphogenesis–lipid triad, with loci in TGFB2, WNT10A, LGR6, FASN, and FADS2 linking follicle repair, innate sensing, and sebocyte lipid metabolism. Barrier modulators such as FLG and OVOL1, first described in atopic dermatitis, further shape inflammatory thresholds across acne and related phenotypes. Together, these findings position genetics not as an abstract catalogue of risk alleles but as a map of tractable biological pathways. They provide the substrate for patient-stratified interventions ranging from JAK inhibitors in AA, to endocrine versus morphogenesis-targeted strategies in AGA, to lipid- and barrier-directed therapies in acne, while also informing cosmetic practices focused on barrier repair, sebaceous balance, and follicle health. Full article

A fast-paced lifestyle contributes to heightened emotional stress, driving the demand for milder and safer cosmetic ingredients that can counteract stress-induced skin damage—a focus of cutting-edge research in the field. Aim: The aim was to elucidate the role and mechanistic basis of tea (Camellia sinensis) seed meal saponin (Sap) in regulating stress-induced sebum overproduction and inflammatory responses. Methods: The composition and chemical structure of Sap were analyzed using UV-vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). In vitro models of cortisone-induced excessive lipid accumulation and the tumor necrosis factor-alpha (TNF-α)-stimulated inflammatory models were established on sebaceous gland cells (SZ95) and normal human epidermal keratinocytes (NHEKs), respectively. Cortisol and inflammatory cytokine secretion levels in cells were detected using ELISA. Additionally, the signaling pathways were revealed by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-PCR). Results: Five saponins were identified in the Sap extract, all belonging to the oleanolic-acid-type pentacyclic triterpenes. Sap treatment significantly attenuated cortisone-induced cortisol secretion and lipid accumulation in SZ95 sebocytes. Mechanistically, Sap inhibited the 11β-HSD1/SREBP-1 pathway, which mediates its sebosuppressive effects, while concurrently down-regulating the mRNA expression of key downstream transcription factors and enzymes, including SREBP-1, FAS, and ACC. Additionally, Sap treatment significantly attenuated TNF-α-stimulated cortisol secretion and inflammatory cytokine (IL-1β, IL-6, and IL-8) production in NHEK cells through the inhibition of the 11β-HSD1/TLR2/NF-κB signaling pathway. Conclusion: Sap demonstrated dual inhibitory effects, suppressing both emotional-stress-induced sebum overproduction and inflammatory cytokines secretion. Full article

Background: Hormonal fluctuations significantly influence skin physiology, affecting collagen production, sebum regulation, pigmentation, and tissue repair. Hormonal therapies are increasingly used in cosmetic dermatology to address age-related and hormone-dependent skin changes. Methods: This narrative review synthesizes the current literature on the mechanisms, clinical applications, and future directions of hormonal therapies in dermatologic aesthetics. Studies were selected through a comprehensive search on PubMed, Scopus, and Web of Science. Results: Estrogens, androgens, progesterone, and other hormones act on skin through specific receptors, modulating fibroblast, sebocyte, and melanocyte activity. Clinical applications include hormone-based strategies for anti-aging, acne, melasma, alopecia, and postmenopausal atrophy. Both systemic (e.g., HRT) and topical (e.g., clascoterone, phytoestrogens) approaches are discussed. Safety concerns, including systemic absorption and off-label use, require careful evaluation. Emerging technologies such as SERMs, nanocarriers, and regenerative combinations suggest promising future avenues. Conclusions: Hormonal therapies offer a biologically rational and increasingly evidence-based tool in cosmetic dermatology. Responsible integration into clinical practice depends on personalized approaches, ethical prescribing, and further research on long-term safety and efficacy. Full article

Sebum secreted by sebaceous glands mixes with sweat to form a protective film that aids in maintaining skin health. Reduced sebum production compromises such barrier functions, potentially leading to severe itchiness and inflammation. Therefore, incorporating moisturizers with ingredients promoting sebum secretion is desirable. Wild watermelon possesses moisturizing and antioxidant properties, and its extracts are utilized in skin cosmetics and supplements. This study investigates whether seed watermelon (Citrullus mucosospermus (Fursa))—a species closely related to wild watermelon—influences sebum synthesis and can serve as a skin cosmetic raw ingredient. Several bioactive compounds—including coniferyl alcohol, coniferin, and p-coumaryl alcohol—were identified in the active third fraction of the fruit extract. Subsequently, SZ95 sebocytes stimulated with linoleic acid were stained using Oil Red O to detect lipogenesis facilitated by the identified bioactive compounds. Coniferyl alcohol promoted linoleic acid-stimulated lipogenesis by approximately 2.2-fold at a concentration of 300 µM. Lipidomic analyses confirmed an increase in total lipid content following coniferyl alcohol treatment, with notable increases in cholesterol ester, cardiolipin, and simple lipid content. Overall, these findings suggest that seed watermelon contains compounds that do influence sebum synthesis. Consequently, skin cosmetics containing seed watermelon fruit extracts with linoleic acid may benefit individuals with dry skin. Full article

Galectin-12, a member of the galectin family of glycan-binding proteins, exhibits restricted tissue distribution, primarily in adipocytes and sebocytes. In sebocytes, it modulates the cell cycle, influences lipid metabolism through interactions with peroxisome proliferator-activated receptor γ (PPARγ), and exerts immunomodulatory functions by activating immune signaling pathways. Dysregulation of sebocyte homeostasis, lipid metabolism, and immune responses contributes to the pathogenesis of a number of skin diseases, underscoring the therapeutic potential of targeting galectin-12. The review summarizes and discusses current developments in the field to foster future research in this important but underexplored galectin. Full article