Azelaic Research Articles

A Pilot Study on the Comparative Efficacy and Tolerability of a Novel Dermo-cosmetic Cream with 15% Azelaic Acid for Mild to Moderate Acne: A New Approach to Acne Treatment.

Acne is a one of the most frequent skin conditions among teenagers and young adults. It is currently managed with topical retinoids and antibiotics, which can present numerous side effects, thus reducing treatment adherence and effectiveness. We evaluated the efficacy and tolerability of a novel dermo-cosmetic cream (α-AZ) in treating mild to moderate acne. Subjects were randomized into three groups: group1 received α-AZ cream, group2 was treated with α-AZ combined with an oral acne treatment routine, and group3 received a topical acne treatment, for 84days. All treated patients underwent a 28-day maintenance period with α-AZ cream. Total acne and post-inflammatory hyperpigmentation (PIH) scoring, quality of life (QoL), and skin tolerance were all evaluated during the treatment and maintenance periods. Acne and PIH lesions significantly decreased in group1 compared to group3 (p < 0.001), with a reduction in acne of 66.52 ± 2.92% in group1 versus 52.55 ± 3.90% in group3. Patients in group1 achieved nearly clear skin by the end of the treatment. α-AZ cream treatment was well tolerated and all participants experienced an enhanced QoL. Participants expressed high satisfaction. Additional enhancements in all groups were noted during the maintenance phase across all clinical parameters. The novel dermo-cosmetic α-AZ cream could serve as a valuable new approach to current treatments for mild and moderate acne. It can be used alone, as a once-daily adjuvant to oral acne treatments, or as part of a maintenance regimen. ISRCTN registry, ISRCTN70142596, registered retrospectively on 11/12/2023.

Comprehensive Phytochemical Profiling of Ulva lactuca from the Adriatic Sea

The potential of the green macroalga Ulva lactuca is increasingly recognized, not only for its environmental benefits, but also for its applications in various industries, including food, pharmaceuticals, and cosmetics. Given this insight, a comprehensive analysis of the chemical profile of U. lactuca from the Adriatic Sea was carried out. The hydrodistillate, rich in (Z,Z,Z)-hexadeca-7,10,13-trienal and hexadecanoic acid, underlines its importance for health-related uses, particularly in lipid metabolism and cellular integrity. Fatty acid analysis showed a predominance of palmitic acid and a favorable n-6/n-3 polyunsaturated fatty acid ratio, suggesting that U. lactuca can make a valuable contribution to a balanced diet. In addition, essential amino acids, including leucine, valine, and isoleucine, support its use as a functional ingredient for muscle repair and metabolic health. The ethanol extract contained 56 compounds, including derivatives of fatty acids, phenolic acids, pigments, flavonoids, and steroids. Many of them, such as hexadecasphinganine, azelaic acid, 5-sulfosalicylic acid, and pheophytin a, have proven roles or potentials in promoting human health. These results confirm that U. lactuca is a rich source of bioactive compounds, emphasizing its potential in scientific research and its expanding industrial applications in health, nutrition, and cosmetics.

The Effect of the Surface Treatment on TiO2 Particles When Used as a Filler on Crystallization and Mechanical Properties of Polylactic Acid Composites. Case of Study: Silane Coupling Agents and Dicarboxylic Acids Were Used as Surface Modifiers

ABSTRACT This article analyzes the effect of the type of surface modification (using silane coupling agents and dicarboxylic acids) on titanium dioxide particles used as fillers in polylactic acid composites, which were exposed to a photodegradative process. The thermomechanical properties of the composites were analyzed; it was found that the silane coupling agent with Imidazole allowed the composites to have Young’s modulus values 60% lower than the composite without filler. On the other hand, the crystallization rate was 30% higher for composites with azelaic Acid attached to TiO2 particles than for composites without filler at a cooling rate of 5°C min−1. Once degraded composites containing azelaic acid were the least brittle, with a minor increment in Young’s Modulus compared to pure polylactic acid composites. When a mixture of modified titanium dioxide particles (with imidazole and either azelaic acid or pimelic acid) was used, there was a synergistic effect regarding photostability.

Surgical Management of Moderate Rhinophyma with Nasal Nodules: An Electrosurgery Approach

Introduction: Rhinophyma, a severe manifestation of rosacea, is characterized by hypertrophy of sebaceous glands and fibrosis of the nose, often leading to significant aesthetic and functional impairments. Surgical treatment is the preferred approach for advanced cases to restore nasal appearance and function. Case Report: We present the case of a 60-year-old man with moderate rhinophyma and nodules on the nostrils. Surgical management under local anesthesia involved the use of thermal loops for excision of the lesions and bipolar electrosurgery for hemostasis. The patient was also treated for rosacea with topical agents, including metronidazole and azelaic acid, and oral doxycycline for inflammatory lesions. Directed healing followed the surgery, along with LED phototherapy and ablative erbium laser sessions to optimize results. Discussion: The use of thermal loops and electrosurgery allowed for precise excision and control of bleeding. Postoperative care, including daily greasy vaseline dressings, facilitated rapid healing. Mild infection at the excision sites was treated with topical and prophylactic antibiotics. Six sessions of LED therapy combining four types of light (infrared, red, yellow, and blue) improved healing and reduced inflammation. Ablative erbium laser was proposed to further enhance the aesthetic outcome. Conclusion: A combined surgical approach and careful postoperative management yielded satisfactory results in the treatment of rhinophyma.

A Prospective Randomized Trial Comparing Quality of Life in Adult Female Acne Treated with Azelaic Acid 15% Gel versus Oral Spironolactone.

In several countries, recent research has shown an increase in the prevalence of adult female acne (AFA), defined as the acne that appears in women aged over 25. This disease brings some particularities and challenges, such as a greater impact on quality of life (QoL) and chronicity. A negative impact on QoL has been observed, as well as anxiety, depression, anger, low self-esteem, and feelings of embarrassment and frustration. To quantify AFA's impact on QoL and the influence of two dermatological treatments. A prospective study including 40 women, aging from 25 to 44 years old, with mild-to-moderate acne was conducted. Participants underwent clinical, laboratory, and photographic evaluations. They were randomized into two treatment groups: group 1 - azelaic acid (AZA) 15% gel twice daily; group 2 - spironolactone (SPIRO) 100 mg/day and treated for 6 months. At baseline and at the end of treatments, a specific QoL questionnaire for acne, already translated and validated for Brazilian Portuguese (Acne-QoL-BR), was applied. It contains 19 questions allotted in four domains. Each item within a domain is scored from 0 to 6. The total score ranges from 0 to 114 and domains are distributed as follows: 0-30 (self-perception), 0-30 (role-emotional), 0-24 (role-social), 0-30 (acne-symptoms). Higher scores reflect better QoL. The mean age was 32.7 (SD: 5.42); 85% presented persistent acne. After treatment regardless of group, there was a significant improvement in total score and all domains' scores of acne QoL-BR (p < 0.001), with no difference between groups, despite one treatment being topical and the other systemic (p=0.918). Acne-QoL-BR is a useful tool for quantifying the impact of acne and should be used as an efficacy parameter in clinical trials.

Recognition of carboxylic acids and phosphonic acids using a 1,8-diphenylanthracene-based diguanidine in solution and solid states

A 1,8-diphenylanthracene-based diguanidine 1 has been designed and synthesized for the recognition of carboxylic acids and phosphonic acid derivatives. The diguanidine 1a forms 1:1 complexes with the dicarboxylic acids and the diphosphonic acid derivatives in a DMSO solution, and the formation of these complexes was confirmed by a DOSY NMR analysis. The binding mode towards the guanidyl group (Type I, Type II, two existing types of binding modes toward three nitrogen atoms) with a diphosphonic acid derivative was successfully demonstrated by the 2D NOESY analysis. The diguanidine 1a does not show any fluorescence in a DMSO solution, but after the addition of carboxylic acids, the formation of a stable complex or the formation of the protonated guanidinium (1a+2H+) were distinguishable by the observation of a light-blue fluorescence around 430 nm. These fluorescence observations can be determined the stability of the complexes of the diguanidine 1a with carboxylic acids. On the other hand, the DMSO solution of diguanidine 1a showed a light-blue fluorescence after the addition of phosphonic acids. Interestingly, diguanidine 1a recognized methylphosphonic acid 9a in the solid state by grinding and showed a green fluorescence, while the other phosphonic acids 9 and dicarboxylic acids (4d: pimelic acid, 4f: azelaic acid) showed a light-blue fluorescence in the solid state, and a selectivity was observed. These fluorescence characteristics of the diguanidine 1 are applicable for the detection of carboxylic acids and phosphonic acids, especially for methylphosphonic acid 9a in the solid state.

Azelaic acid-based lyotropic liquid crystals gel for acne vulgaris: Formulation optimization, antimicrobial activity and dermatopharmacokinetic study

The proposed study aimed to develop a topical gel containing azelaic acid (AZA)-based lyotropic liquid crystals (LLCs) for the treatment of acne vulgaris. AZA-based LLCs were optimized by varying Poloxamer-407 and polyvinyl alcohol concentration using a central composite design, which showed that both independent variables had a significant effect on the formulation. The highest desirable trial of AZA-based LLCs (Batch-7) containing 300 mg poloxamer-407 and 100 mg polyvinyl alcohol depicted the particle size, zeta potential, and entrapment efficiency of 184.2 nm, −16.1 mV, and 79.96 %, respectively. TEM images confirmed the globular vesicles of LLCs, and ATR-FTIR and DSC results confirmed the compatibility of formulation excipients. In vitro, the release of AZA, AZA-based LLCs, AZA-based LLC gel, and marketed gel showed a release of 23.29, 95.24, 91.07 and 59.88 %, respectively, after 24 h in phosphate buffer pH 6.8. Ex vivo release of AZA-based LLC gel displayed an 86.56 % release after 24 h. The antimicrobial activity of AZA-based LLC gel exhibited a comparable efficacy with marketed gel against Cutibacterium acnes, Staphylococcus epidermis and Staphylococcus aureus. The acute dermal irritation study indicated excellent safety and skin compatibility of AZA-based LLC gel without any erythema and edema. The dermatopharmacokinetic study displayed an enhanced drug retention for AZA-based LLC gel (146.121 ± 21.13 µg/cm2) than marketed gel (58.58 ± 15.95 µg/cm2) in the dermal layer, which would improve its therapeutic effect. These outcomes proved that AZA-based LLC gel has the potential to enhance skin penetration and retention for effective management of acne vulgaris.

Azelaic Acid: Mechanisms of Action and Clinical Applications.

AZA is a non-phenolic, saturated dicarboxylic acid with nine carbon atoms, naturally produced by the yeast Malassezia. It has diverse physiological activities, including antibacterial, anti-keratinizing, antimelanogenic, antioxidant and anti-inflammatory effects. AZA is widely used in dermatology and is FDA-approved for treating papulopustular rosacea. It also shows significant efficacy in acne vulgaris and melasma. This review summarizes the mechanisms of action and clinical applications of AZA, aiming to provide theoretical support for its clinical and cosmetic use and to facilitate further research.

Extraction Condition Optimization, Quantitative Analysis, and Anti-AD Bioactivity Evaluation of Acorn Polyphenols from Quercus variabilis, Quercus aliena, and Quercus dentata

In the present study, Quercus variabilis (Q. variabilis), Quercus aliena (Q. aliena), and Quercus dentata (Q. dentata) acorn kernels were taken as the research objects, and the free polyphenols and bound polyphenols in acorn kernels were extracted using improved ultrasound-assisted ethanolic and alkaline extraction methods, after which the contents of gallic acid, quercetin, azelaic acid, ellagic acid, and ferulic acid were quantified by LC-MC/MS. The results demonstrated that Q. variabilis and Q. aliena acorns were suitable as raw materials to extract ellagic acid, the contents of ferulic acid and bound gallic acid in them were different, and Q. aliena acorns were more suitable for the research of gallic acid, but not for azelaic acid. Results on APP/PS1 transgenic mice verified that five polyphenols significantly suppressed the progression of AD. This study provides a theoretical basis for the drug development of acorn polyphenols.

Comparative Analysis of the Effects of Crude Metabolic Extracts of Three Biocontrol Bacteria on Microbial Community Structure Provides a New Strategy for the Biological Control of Apple Replant Disease

The crude metabolic extract from plant biocontrol bacteria plays a very important role in sustainable agricultural production. These extracts help maintain healthy plants and have very important application prospects in biotechnology related to alleviating apple replant disease (ARD). In this study, Bacillus velezensis XC1 (T1), Bacillus amyloliquefaciens QSB-6 (T2), and Lactobacillus reuteri LBR (T3) were examined to characterize the ability of their crude metabolic extracts to alleviate ARD. The high-throughput sequencing data of the soil microbial community structure were analyzed in relation to LBR crude metabolic extracts, and an extensive untargeted metabolomic analysis of UHPLC-Qex active components was performed. Active LC-MS/MS revealed that the main secondary metabolites involved in the biological control exerted by L. reuteri included 3-hydroxypropionaldehyde, extracellular polysaccharides (EPS), p-hydroxybenzoic acid, and azelaic acid. These crude metabolic extracts significantly inhibited the growth of soil pathogenic fungi, reduced the abundance of Fusarium, promoted the abundance of beneficial bacteria such as Pseudomonas, and optimized the soil microbial community structure. Improved modern extraction and purification technologies will be able to offer additional insights into the mechanism of action of these secondary metabolites and enable them to be used in biological preparations to prevent and control ARD in the future, as well as to allow harmful chemical fumigants to be discontinued.

The Characteristics of Component of Lime Mortars with Perilla Oil

A lime is a traditional material that has been used for a long time and has been used in ancient tumb, fortress walls, ondol, buildings, and lime-mortar barrier tombs. Based on the literature records used lime with additive materials, in this study, observed changes in the composition of perilla oil according to curing environment, sampling position, and time tor time mixed or applied with perilla oil among traditional lime additive materials by pyrosis gas chromatography mass spectrometery (Py-GC-MS) and Fourier Transform infrared spectroscopy(FT-IR) analysis. For perilla oil, unsaturated fatty acids such as oleic acid, and linoleic acid, saturated fatty acid, palmitic acid were identified as the main component, and as perilla oil was cured, the ratio of saturated fatty acids such as azelaic acid, palmitic acid, and stearic acid tended to increase. This trend has also been confirmed in lime mortars using perilla oil. In limes mixed with perilla oil, oleic acid is predominantly detected. In the case of lime coated with perilla oil, no characteristic component was identified in the internal sample, and a change in characteristic components were confirmed according to the indoor and outdoor environments on the coated surface. Palmitic acid, stearic acid, and oleic acid were detected as main components in a stable indoor environment, but azelaic acid, palmitic acid, and stearic acid were identified as main components as they were exposed to the climate environment(outdoor). In particular, it is characterized by the fact that it was detected only in mortar applied with azelaic acid. However the possibility of grasping perilla oil using FT-IR was expected to have a detection limit depending on the concentration of perilla oil. Such analysis results are expected to contribute to the discovery of lime additive materials used in cultural heritage and the research on construction technology in the future.

Need of ethosomes as a transdermal drug delivery system

Transdermal Drug Delivery (TDD) TDD is a painless method of delivering drugs systemically by applying a drug formulation onto intact and healthy skin. Ethosomes are soft malleable vesicles composed mainly of phospholipids, ethanol (relatively high concentration) and water. In vitro and in vivo skin permeation experiments have shown that ethosomal formulations can improve the penetration of both hydrophobic and hydrophilic compounds when compared to traditional liposomes. Cold method and hot method are the two types of method of preparation of ethosomes. In comparison to traditional liposomes, antigen-loaded ethosomes for transcutaneous immunization against Hepatitis B were synthesized and described, demonstrating better entrapment effectiveness, appropriate size range, and a unilamellar, spherical shape.As a topical medium (gel), ethosomes and liposomes of azelaic acid (an anti-keratinizing agent used in the treatment of acne) were created, and the results showed that ETHOS 40 might be responsible for a larger azelaic acid concentration than ETHOS 20 and liposomes.

The possibilities of improving the effectiveness of acne therapy

Acne is one of the most urgent problems of dermatology, since this dermatosis is widespread, often occurs during puberty, is accompanied by cosmetic defects, causes increased anxiety, dysmorphic phobia and depressive states. As a result, the quality of life and the possibility of social adaptation decrease in patients. Therefore, it is necessary to optimize the treatment of this disease with the inclusion of modern highly effective drugs. When prescribing treatment, it is necessary to take into account all links in the pathogenesis of acne, and also remember that inflammation plays an important role in the development of dermatosis (especially severe course). With mild acne, it is recommended to prescribe only external therapy, with medium – external therapy and, if necessary, systemic, with severe systemic therapy is used as the main one. The appointment of antibiotics for this dermatosis is dictated by the presence of bacterial flora. Clindamycin is one of the antibiotics that effectively reduce colonization of C. аcnes. To ensure the high efficiency and safety of topical therapy, as well as the prevention of the development of resistance of microorganisms, there is a need to use a combination of at least two drugs. Thus, the combination of clindamycin with benzoyl peroxide makes it possible to increase the effectiveness of therapy due to bactericidal, bacteriostatic, anti-inflammatory and keratolytic actions. The convenient mode of use and the rapid therapeutic effect make it possible to include this combination in the group of priority drugs for the treatment of acne. Comedonolytic, anti-inflammatory and bactericidal effects are also observed in azelaic acid, and therefore drugs containing this component show a high pathogenetic effect in acne.

Integration of network pharmacology and experimental verification to reveal the active components and molecular mechanism of modified Danzhi Xiaoyao San in the treatment of depression

Ethnopharmacological relevanceModified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. Aim of the studyTo reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro. Materials and methodsUPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. ResultsThere were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. ConclusionsThese results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.

Metabolome and Mycobiome of Aegilops tauschii Subspecies Differing in Susceptibility to Brown Rust and Powdery Mildew Are Diverse.

The present study demonstrated the differences in the seed metabolome and mycobiome of two Aegilops tauschii Coss accessions with different resistance to brown rust and powdery mildew. We hypothesized that the seeds of resistant accession k-1958 Ae. tauschii ssp. strangulata can contain a larger number of metabolites with antifungal activity compared with the seeds of susceptible Ae. tauschii ssp meyeri k-340, which will determine differences in the seed fungal community. Our study emphasizes the differences in the seed metabolome of the studied Ae. tauschii accessions. The resistant accession k-1958 had a higher content of glucose and organic acids, including pyruvic, salicylic and azelaic acid, as well as pipecolic acids, galactinol, glycerol and sitosterol. The seeds of Ae. tauschii-resistant accession k-1958 were found to contain more active substances with antifungal activity. The genera Cladosporium and Alternaria were dominant in the seed mycobiome of the resistant accession. The genera Alternaria, Blumeria and Cladosporium dominated in seed mycobiome of susceptible accession k-340. In the seed mycobiome of the resistant k-1958, a higher occurrence of saprotrophic micromycetes was found, and many of the micromycetes were biocontrol agents. It was concluded that differences in the seed metabolome of Ae. tauschii contributed to the determination of the differences in mycobiomes.

Characterization, sources, and formation processes of dicarboxylic acids, oxocarboxylic acids and α-dicarbonyls in PM2.5 aerosols in New Delhi

Daytime and nighttime fine aerosol (PM2.5) samples were collected during a heavy pollution episode in November 2020, January 2021, and also during clean event (August 2020) in New Delhi. These samples (n = 20) were analyzed for water-soluble dicarboxylic acids (diacids) and related compounds, carbonaceous components, and inorganic ions to identify their sources and atmospheric processing in different episodes/seasons. Among the measured organics, oxalic acid (C2) was found to be the most abundant species followed by terephthalic (tPh), succinic (C4), phthalic (Ph), and azelaic (C9) acids. Such high abundance of tPh were different from those in other Asian cities where C3 is generally the second or third dominant species. tPh very well correlated with OC, Cl− and K+, indicating combustion of biomass and plastic-containing waste may be the possible sources. Significant high contents of diacids, oxoacids, and dicarbonyls were observed during heavy pollution episode, implying an enhanced emission and/or atmospheric processing of these species. Additionally, two important secondary formation pathways for C2 diacid were discussed in New Delhi, i.e. (i) biomass burning derived (biogenic) volatile organic precursors lead to formation of C2 diacid through transformation of oxoacids and dicarbonyls by oxidation, and (ii) oxidative degradation of the unsaturated fatty acids results in formation of C5 and C4 which subsequently decompose to C2 diacid. This study demonstrated that both primary emissions in clean event and secondary production during polluted event are important sources of aerosols in New Delhi.

Deciphering the complexity of the chemicals in food packaging materials using molecular networks

Chemicals from packaging materials might be transferred into food resulting in consumer exposure. Identifying these migrated chemicals is highly challenging and crucial to perform their safety assessment, usually starting by the understanding of the chemical composition of the packaging material itself. This study explores the use of the Molecular Networking (MN) approach to support identification of the extracted chemicals. Two formulations of bioplastics were analyzed using Liquid Chromatography hyphenated to High-Resolution Mass Spectrometry. Data processing and interpretation using a conventional manual method was performed as a point of comparison to understand the power of MN. Interestingly, only the MN approach facilitated the identification of unknown chemicals belonging to a novel oligomer series containing the azelaic acid monomer. The MN approach provided a faster visualization of chemical families in addition to the highlight of unrelated chemicals enabling to prioritize chemicals for further investigation improving the safety assessment of packaging materials.

Water-mediated chelation dynamics of dicarboxylic acid functionalized TiO2 nanoparticles for β-nucleation enhancement in isotactic polypropylene composites

ABSTRACT Isotactic polypropylene (iPP) is the most prominent form of polypropylene, and β-phase is the most resistant to impact compared to the crystalline forms. However, β-phase is the least frequently obtained under conventional operating conditions. TiO2 nanoparticles were functionalized with dicarboxylic acids as nucleating agents to promote β-crystal formation in iPP. The effects of three dicarboxylic acids – glutaric, pimelic, and azelaic – were characterized on TiO2-modified surfaces. Additionally, the interactions between TiO2 and water molecules, crucial for the formation of chelating or bridging linkages, were analyzed using Fourier Transform Infrared spectroscopy. For pimelic and azelaic acids at the polymer processing temperature, the carboxyl group band disappeared, suggesting a transition of the acid-calcium union from a bridging to a chelating linkage due to the presence of water molecules. These molecules help maintain the stability of the chains during processing. X-ray diffraction (XRD) analysis confirmed a higher content of β-crystalline structures in iPP when modified with pimelic and azelaic acids. The research indicates that water molecules, desorbed during manufacturing, facilitate the chelating form, thereby enhancing β-nucleation and improving the surface properties of iPP composites. These β-nucleated PP composites represent a promising material solution for medical device applications, offering a compelling combination of enhanced properties and cost-effectiveness.

Curcumenol regulates Histone H3K27me3 demethylases KDM6B affecting Succinic acid metabolism to alleviate cartilage degeneration in knee osteoarthritis

BackgroundCartilage metabolism dysregulation is a crucial driver in knee osteoarthritis (KOA). Modulating the homeostasis can mitigate the cartilage degeneration in KOA. Curcumenol, derived from traditional Chinese medicine Curcuma Longa L., has demonstrated potential in enhancing chondrocyte proliferation and reducing apoptosis. However, the specific mechanism of Curcumenol in treating KOA remains unclear. This study aimed to demonstrate the molecular mechanism of Curcumenol in treating KOA based on the transcriptomics and metabolomics, and both in vivo and in vitro experimental validations. Materials and methodsIn this study, a destabilization medial meniscus (DMM)-induced KOA mouse model was established. And the mice were intraperitoneally injected with Curcumenol at 4 and 8 mg/kg concentrations. The effects of Curcumenol on KOA cartilage and subchondral was evaluated using micro-CT, histopathology, and immunohistochemistry (IHC). In vitro, OA chondrocytes were induced with 10 μg/mL lipopolysaccharide (LPS) and treated with Curcumenol to evaluate the proliferation, apoptosis, and extracellular matrix (ECM) metabolism through CCK8 assay, flow cytometry, and chondrocyte staining. Furthermore, transcriptomics and metabolomics were utilized to identify differentially expressed genes (DEGs) and metabolites. Finally, integrating multi-omics analysis, virtual molecular docking (VMD), and molecular dynamics simulation (MDS), IHC, immunofluorescence (IF), PCR, and Western blot (WB) validation were conducted to elucidate the mechanism by which Curcumenol ameliorates KOA cartilage degeneration. ResultsCurcumenol ameliorated cartilage destruction and subchondral bone loss in KOA mice, promoted cartilage repair, upregulated the expression of COL2 while downregulated MMP3, and improved ECM synthesis metabolism. Additionally, Curcumenol also alleviated the damage of LPS on the proliferation activity and suppressed apoptosis, promoted ECM synthesis. Transcriptomic analysis combined with weighted gene co-expression network analysis (WGCNA) identified a significant downregulation of 19 key genes in KOA. Metabolomic profiling showed that Curcumenol downregulates the expression of d-Alanyl-d-alanine, 17a-Estradiol, Glutathione, and Succinic acid, while upregulating Sterculic acid and Azelaic acid. The integrated multi-omics analysis suggested that Curcumenol targeted KDM6B to regulate downstream protein H3K27me3 expression, which inhibited methylation at the histone H3K27, consequently reducing Succinic acid levels and improving KOA cartilage metabolism homeostasis. Finally, both in vivo and in vitro findings indicated that Curcumenol upregulated KDM6B, suppressed H3K27me3 expression, and stimulated collagen II expression and ECM synthesis, thus maintaining cartilage metabolism homeostasis and alleviating KOA cartilage degeneration. ConclusionCurcumenol promotes cartilage repair and ameliorates cartilage degeneration in KOA by upregulating KDM6B expression, thereby reducing H3K27 methylation and downregulating Succinic Acid, restoring metabolic stability and ECM synthesis.

The use of azelaic acid in the reduction of acne vulgaris and post-inflammatory hyperpigmentation. Case report

Acne vulgaris is considered as one of the most common skin disorders. Its etiopathogenesis is based mainly on sebaceous gland overactivity, the influence of hormones, the presence of Cutibacterium acnes bacteria, abnormal keratinization of the outlets of the hair follicles and sebaceous glands, genetic factors and immunological disorders. Post-inflammatory hyperpigmentation occurs as a consequence of inflammatory skin conditions, such as acne vulgaris, and other similar diseases. They arise as a result of persistent inflammation, which stimulates melanocytes to synthesize melanin. The aim of this study was to evaluate the efficacy of 30% azelaic acid in a 25-year-old man with symptoms of acne vulgaris and post-inflammatory hyperpigmentation.