Acrolein scavengers and detoxification: From high-throughput screening of flavonoids to mechanistic study of epigallocatechin gallate.

Acrolein (ACR) is a widespread, highly toxic substance that poses significant health risks. Flavonoids have been recognized as effective ACR scavengers, offering a possible way to reduce these risks. However, the lack of specific high-throughput screening methods has limited the identification of ACR scavengers, and their actual detoxifying capacity on ACR remains unknown. To address this, we developed a high-throughput screening platform to assess the ACR scavenging capacity of 322 flavonoids. Our results showed that 80.7 % of the flavonoids could scavenge ACR, but only 34.4 % exhibited detoxifying effects in an ACR-injured QSG7701 cell model. Some flavonoids even increased toxicity. Structure-activity relationship (SAR) analysis indicated that galloyl and pyrogallol units enhance scavenging but worsen ACR-induced cytotoxicity. Further investigation revealed that epigallocatechin gallate (EGCG) could exacerbate ACR-induced redox disorder, leading to cell apoptosis. Our findings provide crucial data on the scavenging and detoxifying capacities of 322 flavonoids, highlighting that ACR scavengers might not mitigate ACR-induced toxicity and could pose additional safety risks.

Identification of acrolein as a novel diagnostic odor biomarker for 1,2,3-trichloropropane-induced hepatotoxicity in Sprague Dawley rats.

Body odor is considered a diagnostic indicator of various infectious and chronic diseases. But, few studies have examined the odor markers for various toxic effects in the mammalian system. This study attempted to identify the novel diagnostic odor biomarkers for chemical-induced hepatotoxicity in animals. The changes in the concentration of odors were analyzed in the urine of Sprague Dawley (SD) rats treated with two dosages (100 or 200 mg/kg) of 1,2,3-trichloropropane (TCP) using gas chromatography-mass spectrometry (GC-MS). The TCP treatment induced significant toxicity, including a decrease in body weight, an increase in serum biochemical factors, and histopathological changes in the liver of SD rats. During this hepatotoxicity, the concentrations of six odors (ethyl alcohol, acrolein (2-propenal), methanesulfonyl chloride, methyl ethyl ketone, cyclotrisiloxane, and 2-heptanone) in urine changed significantly after the TCP treatment. Among them, acrolein, an acrid and pungent compound, showed the highest rate of increase in the TCP-treated group compared to the Vehicle-treated group. In addition, this increase in acrolein was accompanied by enhanced spermine oxidase (SMOX) expression, an acrolein metabolic enzyme, and the increased level of IL-6 transcription as a regulator factor that induces SMOX production. The correlation between acrolein and other parameters was conformed using correlagram analyses. These results provide scientific evidence that acrolein have potential as a novel diagnostic odor biomarker for TCP-induced hepatotoxicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00253-0.

Hydrogen sulfide protects against toxicant acrolein-induced ferroptotic cell death in Sertoli cells.

Acrolein (ACR) is a ubiquitous environmental pollutant and byproduct of lipid peroxidation that has been implicated in male infertility. However, the molecular mechanisms underlying ACR-induced toxicity in Sertoli cells remain unclear. Given its role in inducing oxidative stress, we examined whether ferroptosis, an iron-dependent form of regulated cell death, could mediate ACR toxicity in Sertoli cells. We also tested if hydrogen sulfide (H2S), which has antioxidant and ACR detoxifying properties, could protect Sertoli cells from ACR-induced ferroptosis. ACR exposure decreased Sertoli cell viability, increased protein carbonylation and p38 MAPK phosphorylation, indicating oxidative injury. ACR also depleted glutathione (GSH), downregulated the cystine importer SLC7A11, increased intracellular ferrous iron (Fe2+) and lipid peroxidation, suggesting activation of ferroptosis. Consistently, the ferroptosis inhibitor deferoxamine (DFO) markedly attenuates ACR-induced cell death. Further studies revealed that ACR-induced ferroptotic changes were prevented by exogenous H2S and exaggerated by inhibition of endogenous H2S production. Furthermore, H2S also suppressed GPX4 inhibitor RSL3-induced intracellular ACR accumulation and ferroptosis. In summary, our study demonstrates that ACR induces ferroptotic cell death in Sertoli cells, which can be prevented by H2S through multiple mechanisms. Targeting the H2S pathway may represent a therapeutic strategy to mitigate ACR-induced Sertoli cell injury and preserve male fertility.

Novel fluorescent nanoplatform for all-in-one sensing and removal of acrolein: An ultrasensitive probe to evaluate its removal efficiency.

As a highly toxic aldehyde, acrolein is widely found in diet and environment, and can be produced endogenously, posing a serious threat to human health. Herein, we designed a novel fluorescent nanoplatform integrating carbon dots­manganese dioxide (CDs-MnO2) and glutathione (GSH) for all-in-one sensing and removal of acrolein. By converting Mn4+ to free Mn2+, GSH inhibited the inner filter effect (IFE) of MnO2 nanosheets, and the Michael addition of acrolein with GSH inhibited the GSH-induced Mn4+ conversion, forming an "off-on-off" fluorescence response of CDs. The developed fluorescent nanoplatform exhibited high sensitivity (LOD was 0.067 µM) and selectivity for the simultaneous detection and removal of acrolein. The combination of CDs-MnO2 hydrogels with smartphones realized the point-of-care detection of acrolein, yielding satisfactory results (recovery rates varied between 97.01-104.65%, and RSD ranged from 1.42 to 4.16%). Moreover, the capability of the nanoplatform was investigated for on-site evaluating acrolein scavengers' efficacy, demonstrating excellent potential for practical application.

Acrolein exposure affects ovarian function by interfering with glycolysis and mitochondrial energy metabolism in mouse.

Acrolein is a widespread contaminant found in both diet and environment, entering the human body through food, alcohol, smoking, and exposure to fuel combustion fumes. While prior studies have highlighted acrolein's harmful impact on oocyte quality and early embryonic development in vitro, the specific mechanisms by which acrolein affects the female reproductive system in vivo remain poorly understood. This study first confirmed that in vitro acrolein exposure disrupts spindle morphology and chromosome alignment during the mid-MI stage of oocyte development, thus hindering oocyte maturation. Besides, exposure to acrolein not only stunts growth in mice but also impairs ovarian development, decreases the ovarian coefficient, disrupts follicular development, and increases the count of atretic follicles in vivo. Additional research has shown that acrolein exposure reduces the activity of key enzymes in glycolysis, pyruvate metabolism, and the tricarboxylic acid cycle within the ovaries. It also suppresses mitochondrial complex expression and disturbs the balance between mitochondrial fission and fusion, as confirmed by metabolomic analyses. Moreover, acrolein exposure in vivo induced granulosa cell apoptosis and reduced oocyte number. In summary, acrolein exposure impairs glucose metabolism and induces mitochondrial dysfunction in the ovaries.

Capture of single or multiple reactive carbonyl species by mangiferin under high temperatures.

Reactive carbonyl species (RCS), including acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO), are typically generated in food processing and accumulate in the body for ages, triggering various chronic diseases. Here, we investigated the capture capability and reaction pathways of mangiferin one-to-one and one-to-many on RCS in high temperatures using UPLC-MS/MS. We found that mangiferin can capture ACR/MGO/GO to form their adducts, yet, the ability to capture RCS is arranged in different orders, with ACR > MGO > GO for a single RCS and MGO > ACR > GO for multiple RCS. After synthesizing and identifying the structures of the ACR- and MGO-adducts of MGF, our results indicated that MGF-ACR-MGO produced in the multiple-RCS-MGF system was formed by capturing MGO through MGF-ACR rather than through MGF-MGO capturing ACR, which resulting in higher inhibitory activity of MGF against MGO than against ACR. Then, the capture ability and path of MGF on RCS were verified in the coffee-leaves tea and cake.

Time dependency and individual variation in human sensory irritation from acrolein - a controlled exposure study.

Acrolein is considered a risk factor for indoor air health problems due to its reactivity. An objective of the study was to investigate prevalence of sensory irritation in terms of time-dependent detection and perceived intensity of symptoms in human volunteers. Another objective was to investigate individual variation in sensory irritation. Participants (n=40) were exposed twice in an exposure chamber (15 min), once to heptane and once to acrolein and heptane. Symptoms and sensory irritation thresholds were rated continuously and 70% of the participants detected eye irritation from the acrolein exposure. A significant interaction between time and exposure (ƞp2=0.19) was identified, indicating time-dependent activation. This group also reported a higher level of stress and lower self-reported health (p<0.05). The results suggest that the eye is the primary system affected by exposure to acrolein, and that duration of exposure and perceived stress play important roles in symptom reactions due to acrolein exposure.

Intermolecular Interactions between Aldehydes and Alcohols: Conformational Equilibrium and Rotational Spectra of Acrolein-Methanol Complex.

The rotational spectra of the 1:1 complex formed by acrolein and methanol and its deuterated isotopologues have been analyzed. Two stable conformations in which two hydrogen bonds between the two moieties are formed were detected. The rotational lines show a hyperfine structure due to the methyl group internal rotation in the complex and the V3 barriers hindering the motion were determined as 2.629(5) kJ mol-1 and 2.722(5) kJ mol-1 for the two conformations, respectively. Quantum mechanical calculations at the MP2/aug-cc-pVTZ level and comprehensive analysis of the intermolecular interactions, utilizing NCI and SAPT approaches, highlight the driving forces of the interactions and allow the determination of the binding energies of complex formation.

Singlet-Oxygen-Mediated Regulation of Photosynthesis-Specific Genes: A Role for Reactive Electrophiles in Signal Transduction.

During photosynthesis, reactive oxygen species (ROS) are formed, including hydrogen peroxide (H2O2) and singlet oxygen (1O2), which have putative roles in signalling, but their involvement in photosynthetic acclimation is unclear. Due to extreme reactivity and a short lifetime, 1O2 signalling occurs via its reaction products, such as oxidised poly-unsaturated fatty acids in thylakoid membranes. The resulting lipid peroxides decay to various aldehydes and reactive electrophile species (RES). Here, we investigated the role of ROS in the signal transduction of high light (HL), focusing on GreenCut2 genes unique to photosynthetic organisms. Using RNA seq. data, the transcriptional responses of Chlamydomonas reinhardtii to 2 h HL were compared with responses under low light to exogenous RES (acrolein; 4-hydroxynonenal), ß-cyclocitral, a ß-carotene oxidation product, as well as Rose Bengal, a 1O2-producing photosensitiser, and H2O2. HL induced significant (p < 0.05) up- and down-regulation of 108 and 23 GreenCut2 genes, respectively. Of all HL up-regulated genes, over half were also up-regulated by RES, including RBCS1 (ribulose bisphosphate carboxylase small subunit), NPQ-related PSBS1 and LHCSR1. Furthermore, 96% of the genes down-regulated by HL were also down-regulated by 1O2 or RES, including CAO1 (chlorophyllide-a oxygnease), MDH2 (NADP-malate dehydrogenase) and PGM4 (phosphoglycerate mutase) for glycolysis. In comparison, only 0-4% of HL-affected GreenCut2 genes were similarly affected by H2O2 or ß-cyclocitral. Overall, 1O2 plays a significant role in signalling during the initial acclimation of C. reinhardtii to HL by up-regulating photo-protection and carbon assimilation and down-regulating specific primary metabolic pathways. Our data support that this pathway involves RES.

Identifying high-risk volatile organic compounds in residences of Chinese megacities: A comprehensive health-risk assessment.

Indoor volatile organic compounds (VOCs) pose considerable health hazards. However, research on hazardous VOCs in Chinese residences has been conducted on a limited spectrum. This study used Monte Carlo simulations with data from Beijing, Shanghai, and Shenzhen to assess VOC health risks in Chinese homes. We identified high-risk VOCs and analyzed the impact of geographic location, age group, activity duration, and inhalation rate on VOC exposure, including lifetime risks. Formaldehyde, acrolein, naphthalene, and benzene posed the highest risks. Notably, acrolein made the leading contribution to non-cancer risks across all megacities. Naphthalene had elevated cancer and non-cancer risks in Shenzhen. This study highlights the need to investigate acrolein and naphthalene, which are currently unregulated but pose substantial health risks. The cumulative cancer risk (TCR) decreases from adults to children, while the cumulative non-cancer risk (HI) is higher for children. In all cities, the average TCR for adults exceeds the tolerable threshold of 10-4, and the average HI values surpass the safety threshold of 1. Nearly 100 % of the population faces a lifetime cancer risk above 10-4, and over 71 % face a non-cancer risk exceeding 10 (tenfold the benchmark). This study underscores the critical need for developing control strategies tailored to VOCs.

The roles and regulatory mechanisms of cigarette smoke constituents in vascular remodeling.

Vascular remodeling is a dynamic process involving cellular and molecular changes, including cell proliferation, migration, apoptosis and extracellular matrix (ECM) synthesis or degradation, which disrupt the homeostasis of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Cigarette smoke exposure (CSE) is thought to promote vascular remodeling, but the components are complex and the mechanisms are unclear. In this review, we overview the progression of major components of cigarette smoke (CS), such as nicotine and acrolein, involved in vascular remodeling in terms of ECs injury, VSMCs proliferation, migration, apoptosis, and ECM disruption. The aim was to elucidate the effects of different components of CS on different cells of the vascular system, to discover the relevance of their actions, and to provide new references for future studies.

MgO Modified by X2, HX, or Alkyl Halide (X = Cl, Br, or I) Catalytic Systems and Their Activity in Chemoselective Transfer Hydrogenation of Acrolein into Allyl Alcohol.

A new type of catalyst containing magnesium oxide modified with various modifiers ranging from bromine and iodine, to interhalogen compounds, hydrohalogenic acids, and alkyl halides have been prepared using chemical vapor deposition (CVD) and wet impregnation methods. The obtained systems were characterized using a number of methods: determination of the concentration of X- ions, surface area determination, powder X-ray diffraction (PXRD), surface acid-base strength measurements, TPD of probe molecules (acetonitrile, pivalonitrile, triethylamine, and n-butylamine), TPD-MS of reaction products of methyl iodide with MgO, and Fourier transform infrared spectroscopy (FTIR). The catalysts' activity and chemoselectivity during transfer hydrogenation from ethanol to acrolein to allyl alcohol was measured. A significant increase in the activity of modified MgO (up to 80% conversion) in the transfer hydrogenation of acrolein was found, while maintaining high chemoselectivity (>90%) to allyl alcohol. As a general conclusion, it was shown that the modification of MgO results in the suppression of strong basic sites of the oxide, with a simultaneous appearance of Brønsted acidic sites on its surface. Independently, extensive research on the reaction progress of thirty alkyl halides with MgO was also performed in order to determine its ability to neutralize chlorinated wastes.

Urinary Volatile Organic Compound Metabolites are Associated with High Blood Pressure Among Non-smoking Participants in the National Health and Nutrition Examination Survey (2011-2018).

Background: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants. Exposure to VOCs is associated with cardiovascular disease (CVD) risk factors, including elevated blood pressure (BP) in susceptible populations. However, research in the general population, particularly among non-smoking adults, is limited. We hypothesized that higher VOC exposure is associated with higher BP and hypertension, among non-smokers. Methods: We included four cycles of data (2011-2018) of non-smoking adults (n=4,430) from the National Health and Nutrition Examination Survey (NHANES). Urinary VOC metabolites were measured by ultra-performance liquid chromatography-mass spectrometry, adjusted for urine dilution, and log-transformed. We estimated mean differences in BP using linear models and prevalence ratio of stage 2 hypertension using modified Poisson models with robust standard errors. Models were adjusted for age, sex, race and ethnicity, education, body mass index, estimated glomerular filtration rate and NHANES cycle. Results: Participants were 54% female, with a median age of 48 years, 32.3% had hypertension, and 7.9% had diabetes. The mean differences (95% CI) in systolic BP were 1.61 (0.07, 3.15) and 2.46 (1.01, 3.92) mmHg when comparing the highest to lowest quartile of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA) metabolites. The prevalence ratios (PR) for hypertension were 1.06 (1.02, 1.09) and 1.05 (1.01, 1.09) when comparing the highest to lowest quartiles of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA), respectively. Conclusions: Exposure to VOCs may be relevant yet understudied environmental contributors to CVD risk in the non-smoking, US population.

Chemical Implications of apo-8, 6' Carotendial versus Intact Lycopene on Mechanism of Enhanced Cell-cell Communication and Apoptosis Induction in Breast Cancer Cells.

Investigation on carotenoids and its cleavage products is crucial to combat the development of chronic diseases, including cancer. Therefore, this study aimed to explore the effect of lycopene oxidative products versus equivalent concentration of lycopene (LYC) on major molecular events of cancer cells (MCF-7). Primarily, LYC-oxidized products were generated chemically, then collected its rich fraction. Based on cell-based assays, the antiproliferation potency of rich fraction of chemically-oxidized lycopene (COL) identified as apo-8, 6' carotendial was compared with LYC. Interestingly, the inhibition of cell migration by COL strongly demonstrated anti-metastatic activity. Further, the increased connexin-43 expression confirms enhanced gap-junctional communication activity of COL than LYC and control. Fortunately, apo-8, 6' carotendial did not affect normal breast epithelial cells. We anticipated that, the chemical properties of apo-8, 6'-carotendial is similar and mimic a model compound acrolein (α, ß-conjugated aldehyde) which is involved in Michael addition/Schiff base formation with specific amino acids and regulates redox signaling, reactive oxygen species sensing and cellular buffering. The chemistry of apo-8, 6' carotendial reveals a greater insight into the mechanism of selective inhibition of cancer cells proliferation. In this context, speculations of putative action of lycopeneoids through chemical biology approach facilitate greater insights in tandem with synthetic chemistry.

Puerarin inhibits HDAC1-induced oxidative stress disorder by activating JNK pathway and alleviates acrolein-induced atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.

Theanine Capture of Reactive Carbonyl Species in Humans after Consuming Theanine Capsules or Green Tea.

Acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO) are a class of reactive carbonyl species (RCS), which play a crucial role in the pathogenesis of chronic and age-related diseases. Here, we explored a new RCS inhibitor (theanine, THE) and investigated its capture capacity on RCS in vivo by human experiments. After proving that theanine could efficiently capture ACR instead of MGO/GO by forming adducts under simulated physiological conditions, we further detected the ACR/MGO/GO adducts of theanine in the human urine samples after consumption of theanine capsules (200 and 400 mg) or green tea (4 cups, containing 200 mg of theanine) by using ultraperformance liquid chromatography-time-of-flight-high-resolution mass spectrometry. Quantitative assays revealed that THE-ACR, THE-2ACR-1, THE-MGO, and THE-GO were formed in a dose-dependent manner in the theanine capsule groups; the maximum value of the adducts of theanine was also tested. Furthermore, besides the RCS adducts of theanine, the RCS adducts of catechins could also be detected in the drinking tea group. Whereas, metabolite profile analysis showed that theanine could better capture RCS produced in the renal metabolic pathway than catechins. Our findings indicated that theanine could reduce RCS in the body in two ways: as a pure component or contained in tea leaves.

The autoxidation of polyether-polyurethane open cell soft foam: An analytical aging method to reproducibly determine VOC emissions caused by thermo-oxidative degradation.

We present a new method for investigating the oxidation and emission behavior of air-permeable materials. Employing this method, a differentiated statement can be made about the extent to which critical volatile organic compounds (VOCs) such as formaldehyde, acetaldehyde, and acrolein are contained in the material as impurities or formed by thermo-oxidative degradation of the polymer matrix in the use phase. The parameters affecting methods of VOC analysis are reviewed and considered for the developed method. The molecular mechanisms of VOC formation are discussed. Toxicological implications of the reaction kinetics are put into context with international guidelines and threshold levels. This new method enables manufacturers of cellular materials not only to determine the oxidative stability of their products but also to optimize them specifically for higher durability. ENVIRONMENTAL IMPLICATION: Cellular materials are ubiquitous in the technosphere. They play a crucial role in various microenvironments such as automotive interiors, building insulation, and cushioning. These materials are susceptible to oxidative breakdown, leading to the release of formaldehyde, acetaldehyde, and acrolein. The ecotoxicological profiles of these compounds necessitate monitoring and regulation. The absence of reproducible and reliable analytical methods restricts research and development aimed at risk assessment and mitigation. This work significantly enhances the toolbox for optimizing the oxidative stability of any open-cell cellular material and evaluating these materials in terms of their temperature-dependent oxidation and emission behavior.

Acrolein Induces Changes in Cell Membrane and Cytosol Proteins of Erythrocytes.

High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the induction and progression of many diseases. The high reactivity of acrolein towards the thiol and amino groups of amino acids may cause damage to cell proteins. Acrolein may be responsible for the induction of oxidative stress in cells. We hypothesized that acrolein may contribute to the protein damage in erythrocytes, leading to the disruption of the structure of cell membranes. The lipid membrane fluidity, membrane cytoskeleton, and osmotic fragility were measured for erythrocytes incubated with acrolein for 24 h. The levels of thiol, amino, and carbonyl groups were determined in cell membrane and cytosol proteins. The level of non-enzymatic antioxidant potential (NEAC) and TBARS was also measured. The obtained research results showed that the exposure of erythrocytes to acrolein causes changes in the cell membrane and cytosol proteins. Acrolein stiffens the cell membrane of erythrocytes and increases their osmotic sensitivity. Moreover, it has been shown that erythrocytes treated with acrolein significantly reduce the non-enzymatic antioxidant potential of the cytosol compared to the control.

Toxicity mechanism of acrolein on energy metabolism disorder and apoptosis in human ovarian granulosa cells.

Acrolein (ACR), an unsaturated, highly reactive aldehyde, is a widespread environmental toxin. ACR exerts permanent and irreversible side effects on ovarian functions. Granulosa cells play a crucial role in supporting ovarian function. Thus, in this study, we investigated the toxicity effects of granulosa cells induced by ACR. Following treatment with varying ACR concentrations (0, 12.5, 25, 50, and 100 µM), we observed that ACR exposure induced reactive oxygen species accumulation, mitochondrial energy metabolism disorder, and apoptosis in KGN cells (a human ovarian granulosa cell line) in a dose-dependent manner. In addition, mitochondrial biogenesis in KGN cells displayed biphasic changes after ACR exposure, with activation at a low ACR dose (12.5 µM), but inhibition at higher ACR doses (≥50 µM). SIRT1/PGC-1α-mediated mitochondrial biogenesis is crucial for maintaining intracellular mitochondrial homeostasis and cellular function. The inhibition/activation of the SIRT1/PGC-1α pathway in KGN cells validated its role in ACR-induced damage. The results indicated that the inhibition of the SIRT1/PGC-1α pathway aggravated ACR-induced cell damage, whereas its activation partially counteracted ACR-induced cell damage. This study attempted to uncover a novel mechanism of ACR-induced ovarian toxicity so as to provide an effective treatment option for safeguarding female reproductive health from the adverse effects of ACR.

Puerarin alleviates acrolein-induced atherosclerosis by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit the activation of inflammasome.

Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.