The increasing elderly population has brought healthy aging into focus. Aging is a multifactorial process characterized by the progressive decline of cellular and tissue functions, largely due to cumulative oxidative stress. Antioxidant-based strategies have therefore gained prominence as potential interventions. This study investigated the protective and therapeutic effects of Squalene (SQ) and Saponin (SP), individually and in combination, on aging-related biomarkers in brain tissue using a D-Galactose (D-Gal)-induced rat model. Forty-eight male Sprague-Dawley rats (200-250g) were randomly divided into eight groups (n = 6). Aging was induced in four groups via intraperitoneal administration of D-Gal (300mg/kg/day) for six weeks. One group received no antioxidants, while others were treated orally with SQ (2.66mL/kg/day), SP (100mg/kg/day), or their combination. Non-aging groups received the same antioxidant treatments without D-Gal. At the end of the intervention, brain tissues were collected for biochemical analysis. Spectrophotometric assessments included Malondialdehyde (MDA), Glutathione (GSH), Nitric oxide derivatives (NOx), Ascorbic acid (AA), and Protein carbonyls (PC). Forkhead Box O3A (FOXO3A), Nuclear factor erythroid 2-related factor 2 (NRF2), Sirtuin 1 (SIRT1), Paraoxonase 1 (PON1), and Klotho were quantified by ELISA. Combined SQ and SP treatment significantly decreased oxidative stress markers (MDA, NOx, PC) and increased antioxidant defenses (GSH, AA) as well as aging-related molecules (FOXO3A, NRF2, SIRT1, PON1, Klotho) (p < 0.05). Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels were also reduced. These findings demonstrate, for the first time, that combined SQ and SP administration can mitigate aging-related oxidative stress and molecular alterations in brain tissue.

This study investigated the effects of four antioxidative substances, α-tocopherol (α-TP), phytosterols (PS), squalene (SQ), and propyl gallate (PG), on micronutrient retention and antioxidative capacity of rapeseed oil during ethanol steam deodorization (ESD, 140-220 °C). Results demonstrated that supplementation with these antioxidants increased the retention rates (percentage relative to initial content) of tocopherols, phenols, carotenoids, phytosterols, and squalene by up to 2.92%, 46.25%, 25.82%, 1.03%, and 60.15%, respectively. These improvements are attributed to the protective effects of the supplemental antioxidative substances against thermal and oxidative degradation. Moreover, α-TP and PG increased the antioxidative capacity of the oil after ESD at 180 °C for 60 min by 10.37% and 5.35%, respectively, which can be attributed to their increased concentrations and synergistic interactions with endogenous antioxidants. A model oil system of caprylic triglyceride supplemented with binary mixtures of antioxidative substances revealed synergistic behavior in blends of α-TP with PG or CE (β-carotene), and of CE with PG or PS, through complementary interactions, whereas antagonism occurred in blends of PS with PG, and of SQ at a high concentration (40.10 mg/100 g) with α-TP, PG or CE, due to unfavorable molecular interactions.

Recent studies emphasize the pivotal role of endoplasmic reticulum (ER) stress in Alzheimer's disease (AD), highlighting the need for further investigation into this critical link. In response to ER stress, cells increase reactive oxygen species (ROS) production, leading to heightened oxidative stress. This interplay has sparked interest in antioxidant molecules such as squalene (SQ) as potential therapeutic agents. The primary objective of this study was to examine the impact of SQ on the unfolded protein response (UPR) pathway triggered by ER stress in an in vitro AD model. Herein, molecular docking analysis was performed to evaluate SQ interactions with target proteins, followed by in vitro assays. Human bone marrow-derived mesenchymal stem cells were differentiated into neuronal-like cells and characterized via immunostaining. The cells were then exposed to Aβ1-42 toxicity to establish an in vitro AD model. To assess the effects of SQ treatment following Aβ1-42 exposure, UPR-related proteins (BIP, p-PERK, PERK, eIF2α, p-eIF2α, ATF4, CHOP) were analysed by Western blotting; ROS levels were quantified to evaluate oxidative stress, and a TUNEL assay was performed to assess apoptosis. Our findings indicate that SQ alters protein expression within the UPR pathway in the AD experimental model. Notably, amyloid-β levels were significantly reduced in the SQ-treated group (p˂0.001). Furthermore, SQ reduced ROS levels. These results suggest that SQ holds potential as a therapeutic agent for mitigating amyloid-β toxicity.

Comparison of electrospray ionization-lithium adduct formation and atmospheric pressure chemical ionization for lipid analysis by normal phase liquid chromatography.

Squalene (SQE) is a key triterpene used in pharmaceuticals, nutraceuticals and cosmetics. Although olive pomace (OP) is a sustainable source of SQE, conventional hexane extraction raises environmental and health concerns. This study investigates the potential of 2-methyltetrahydrofuran (2-MeTHF) as a greener alternative for SQE extraction and catalytic hydrogenation to squalane (SQA); a high-value compound in industrial applications. 2-MeTHF provided 83% SQE recovery from OP, which was further concentrated in deodorizer distillates during refining. SQE hydrogenation in 2-MeTHF significantly improved reaction efficiency at lower temperatures (60 °C, 3 bar H2, 0.5 mol % Pd/C), enabling full conversion within 1 h. This represents a major advantage over conventional industrial hydrogenation, which requires harsher conditions (200 °C, 4-30 bar H2) and longer reaction times (6-7 h). In order to assess industrial feasibility, SQE from OP deodorizer distillates (6.8 wt %) was concentrated via saponification and molecular distillation (∼34 wt %), followed by flash chromatography (59 wt % purity, 85% recovery). However, residual impurities caused catalyst poisoning, lowering the SQA yield to 19.8%. This study highlights 2-MeTHF's potential for industrial-scale SQE valorization via integrated extraction and hydrogenation. Future efforts should focus on improving SQE purification from OP-DDs and enhancing catalyst recyclability.

Squalene (SQ), a naturally occurring triterpenoid, is a key precursor in steroid biosynthesis, particularly cholesterol. Its role in lung surfactant contributes to the enhancement of pulmonary function. This study aimed to quantify squalene levels in lung tissues affected by acute respiratory distress syndrome (ARDS) and in hydroalcoholic pre-treated extract Gymnema sylvestre (HAEGS). A highly selective and validated gas chromatography-mass spectrometry (GC-MS) method was developed, utilizing solvent extraction and squalane as the internal standard. The method demonstrated excellent sensitivity, with a limit of detection (LOD) of 0.05 μg mL-1 and a limit of quantification (LOQ) of 0.5 μg mL-1. In this study, selective ion monitoring (SIM) mode was employed to monitor ions at m/z 69 for squalene and m/z 71 for squalane (internal standard). In ARDS-affected rat lungs, squalene levels were reduced by 50% compared to healthy controls. Pre-treatment with HAEGS significantly restored squalene levels, showing a 1.8-fold increase at a high dose (250 mg kg-1) and a 1.2-fold increase at a low dose (125 mg kg-1) relative to untreated ARDS lungs.

Pandan, a tropical crop, is rich in squalene (SQ), known for its antioxidant and hypoglycemic properties, and 2-acetyl-1-pyrroline (2-AP), which imparts a characteristic aroma. This study focuses on the extraction of the two bioactive compounds from Pandan leaves and investigates the effects of drying methods, extraction solvents, and conditions on the yield of SQ and 2-AP. Results show that hot air-dried Pandan leaves when extracted using the binary solvent system of ethanol and n-hexane (EH), yield higher SQ content while maintaining an adequate content of 2-AP. To further optimize the extraction process, a single-factor experiment was followed by optimization using Box–Behnken design (BBD) and response surface methodology (RSM). The optimal extraction conditions were determined as follows: ultrasound time of 60 min, a temperature of 50 °C, power of 300 W, and a solid-to-liquid ratio of 1:5 g/mL. Under these conditions, an SQ yield of 1229.98 ± 13.09 μg/DW 1 g Pandan leaves and a 2-AP yield of 80.72 ± 0.88 μg/DW 1 g Pandan leaves were achieved, representing increases of 3.30% and 9.82% compared to pre-optimization values. Additionally, the antioxidant activities of EH extracts were evaluated through various in vitro assays. The extracts demonstrated significant DPPH and ABTS free radical scavenging activity (12.46 μmol TE/g DW and 22.14 μmol TE/g DW, respectively), along with ferric and cupric ion reducing power (10.629 μmol TE/g DW and 14.275 μmol TE/g DW, respectively). The extracts also exhibited notable inhibitory effects on α-amylase and α-glucosidase. The findings suggest that these extracts are a promising natural source of antioxidants with potential applications in health and nutrition.

Raman imaging for monitoring deuterated squalene-gemcitabine nanomedicines in single living breast cancer cells

The aluminum nanoparticle-encircled SQ-in-water emulsions (ANSWE) as a vaccine adjuvant-delivery system (VADS) for developing robust mucosal subunit vaccines

Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer

Squalene (SQ) is a well-known antioxidant and anti-inflammatory agent that provides promising anti-aging and UV-protective roles on human skin. However, its strong hydrophobic nature, accompanied by issues such as poor solubility and limited tissue permeation, has created challenges for scientists to investigate its untapped potential in more complex conditions, including cancer progression. The present study assessed the potent anti-metastatic properties of a newly synthesized amphiphilic ethylene glycol SQ derivative (SQ-diEG) in melanoma, the most fatal skin cancer. In vitro and in vivo experiments have discovered that SQ-diEG may exert its potential on melanoma malignancy through the mitochondria-mediated caspase activation apoptotic signaling pathway. The potent anti-metastatic effect of SQ-diEG was observed in vitro using highly proliferative and aggressive melanoma cells. Administration of SQ-diEG (25 mg/kg) significantly decreased the tumor burden on the lung and inhibited the metastasis-associated proteins and gene markers in B16F10 lung colonization mice model. Furthermore, global gene profiling also revealed a promising role of SQ-diEG in tumor microenvironment. We anticipated that the amphiphilic nature of the SQ compound bearing ethylene glycol oligomers could potentially augment its ability to reach the pathology site, thus enhancing its therapeutic potential in melanoma.

Fatty acids and squalene and quality parameters of extra virgin olive oil (Olea europaea L.) produced in Mexico

De novo hair follicle (HF) regeneration, achieved through the replenishment of the dermal papilla (DP), acknowledged as the principal orchestrator of the hair growth cycle, is emerging as a prospective therapeutic intervention for alopecia. Nonetheless, multiple attempts have shown that these cells lose key inductive properties when cultured in a two-dimensional (2D) monolayer, leading to precocious senescence engendered by oxidative stress and inflammatory processes. Consequently, the three-dimensional (3D) spheroid technique is presently widely employed for DP cell culture. Nevertheless, substantiating the regenerative potential of these cells within the hair follicle (HF) milieu remains a challenge. In this current study, we aim to find a new approach to activate the inductive properties of DP cells. This involves the application of hair-growth-stimulating agents that not only exhibit concurrent protective efficacy against the aging process but also induce HF regeneration. To achieve this objective, we initially synthesized a novel highly amphiphilic derivative derived from squalene (SQ), named triethylene glycol squalene (Tri-SQ). Squalene itself is a potent antioxidant and anti-inflammatory compound traditionally employed as a drug carrier for alopecia treatment. However, its application is limited due to its low solubility. Subsequently, we applied this newly synthesized derivative to DP cells. The data obtained demonstrated that the derivative exhibits robust antioxidant and anti-inflammatory activities while concurrently promoting the expression of genes associated with hair growth. Moreover, to further assess the hair regrowth inductive properties of DP cells, we cultured the cells and treated them with Tri-SQ within a 3D spheroid system. Subsequently, these treated cells were injected into the previously depilated dorsal area of six-week-old male C57BL/6 mice. Results revealed that 20 days postinjection, a complete regrowth of hair in the previously hairless area, particularly evident in the case of 3D spheroids treated with the derivative, was observed. Additionally, histological and molecular analyses demonstrated an upregulation of markers associated with hair growth and a concurrent decrease in aging hallmarks, specifically in the 3D spheroids treated with the compound. In summary, our approach, which involves the treatment of Tri-SQ combined with a 3D spheroid system, exhibited a notably robust stimulating effect. This effect was observed in the induction of inductive properties in DP cells, leading to HF regeneration, and concurrently, it demonstrated an inhibitory effect on cellular and follicular aging.

Body odors change during development, and this change influences the interpersonal communication between parents and their children. The molecular basis for this chemical communication has not been elucidated yet. Here, we show by combining instrumental and sensory analyses that the qualitative odorant composition of body odor samples is similar in infants (0-3 years) and post-pubertal children (14-18 years). The post-pubertal samples are characterized by higher odor dilution factors for carboxylic acids and by the presence of 5α-androst-16-en-3-one and 5α-androst-16-en-3α-ol. In addition to the olfaction-guided approach, the compounds 6-methylhept-5-en-2-one (6MHO), geranyl acetone (GA) and squalene (SQ) were quantified. Both age groups have similar concentrations of 6MHO and GA, whereas post-pubertal children tend to have higher concentration of SQ. In conclusion, sexual maturation coincides with changes to body odor chemical composition. Whether those changes explain differences in parental olfactory perception needs to be determined in future studies with model odors.

A comparative transcriptomics analysis reveals ethylene glycol derivatives of squalene ameliorate excessive lipogenesis and inflammatory response in 3T3-L1 preadipocytes

Lipid cyclic peroxides are a rarely reported and documented class of compounds in the human organism. Recently, we reported the formation of squalene (SQ) hydroperoxy cyclic peroxides derived from SQ monohydroperoxide isomers (SQ-OOHs) for the first time. Notably, we successfully detected and quantified cis-2-OOH-3-(1,2-dioxane)-SQ in the human skin. Nevertheless, the underlying mechanism governing the formation of these compounds remained elusive. Therefore, in the current study, we set to determine the reaction’s mechanism. To this end, a comprehensive analysis of the precise conditions involved in the onset and propagation of this conversion was carried out by oxidizing total SQ-OOHs under different conditions, including singlet oxygen (1O2), thermal, and photoinduced oxidations monitored by quantifying the generated 2-OOH-3-(1,2-dioxane)-SQ using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Radical intermediates were thoroughly investigated using Electron Spin Resonance (ESR) with the aid of spin traps and radical references. Moreover, calculations of SQ-OOHs’ electrostatic charges were performed on Spartan 18 software. We found that the reaction is ideally induced and favored under photooxidation in the presence of 3O2 in hexane, and that superoxide radical (O2•−) is the first key intermediate in this mechanism, whereas peroxyl radicals were the major species observed throughout the oxidation. Chemical calculations provided an explanation for the targeting of tertiary SQ-OOHs by this reaction and gave further evidence on the proposed heterolytic cleavage initiating the reaction. The novel oxidation mechanism suggested herein offers new insights into understanding lipid secondary oxidation and is a promising finding for further studying lipid cyclic peroxides in general.

Plant-derived squalene supplementation improves growth performance and alleviates acute oxidative stress-induced growth retardation and intestinal damage in piglets

Abstract BackgroundA wiped‐film molecular distillation (WFMD) pilot plant was used to evaluate process conditions for enriching phytonutrients (PN) from a novel vegetable oil deodorizer distillate (VODD) of the margarine and shortenings industry. This byproduct results from the incorporation of new blends of vegetable oils, such as soybean and palm oil, making it of interest due to its distinct chemical composition and matrix, which differ from those of deodorizer distillates studied previously. The significance of the present investigation is related to the properties of the oil blend, requiring the establishment of new process conditions for this specific VODD. Experimental design was used to evaluate the WFMD process variables, with the aim of removing free fatty acids and enabling eight PN to be concentrated in the reprocessing stages.ResultsThe product obtained after three WFMD stages presented a fivefold increase in the total PN concentration, compared to the raw material. Notably, the procedure provided enrichment ratios of 7.2‐fold for total tocopherols (including α‐, β‐, λ‐ and δ‐tocopherols), 4.5‐fold for total phytosterols (including campesterol, stigmasterol and β‐sitosterol) and 1.2‐fold for squalene, together with a deacidification efficiency of 78.93%.ConclusionThe proposed process provided significant concentration gains for all eight PN evaluated, resulting in a value‐added product. These excellent results were achieved using only three WFMD stages, without any need for additional processing steps. The data obtained at the pilot scale provide valuable insights for predicting the scalability of the process and facilitating potential industrial implementation. © 2023 Society of Chemical Industry.

Purification of artemisinin precursor amorphadiene from microbial metabolites containing isomeride farnesene: Solid-Pd chemocatalysis of farnesene to squalene with high boiling point

Alfalfa as a vegetable source of β-carotene: The change mechanism of β-carotene during fermentation