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Intracerebral hemorrhage (ICH) is a subtype of stroke with a high mortality rate. Oxidative stress cascades play an important role in brain injury after ICH. Cannabidiol, a major non-psychotropic phytocannabinoids, has drawn increasing interest in recent years as a potential therapeutic intervention for various neuropsychiatric disorders. Here we provide a comprehensive review of the potential therapeutic effects of cannabidiol in countering oxidative stress resulting from ICH. The review elaborates on the various sources of oxidative stress post-ICH, including mitochondrial dysfunction, excitotoxicity, iron toxicity, inflammation, and also highlights cannabidiol's ability to inhibit ROS/RNS generation from these sources. The article also delves into cannabidiol's role in promoting ROS/RNS scavenging through the Nrf2/ARE pathway, detailing both extranuclear and intranuclear regulatory mechanisms. Overall, the review underscores cannabidiol's promising antioxidant effects in the context of ICH and suggests its potential as a therapeutic option.

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Background & Aims: Oxidative stress is recognized as a major driver of non-alcoholic steatohepatitis (NASH) progression. The transcription factor NRF2 and its negative regulator KEAP1 are master regulators of redox, metabolic and protein homeostasis, as well as detoxification, and thus appear to be attractive targets for the treatment of NASH. Methods: Molecular modeling and X-ray crystallography were used to design S217879 - a small molecule that could disrupt the KEAP1-NRF2 interaction. S217879 was highly characterized using various molecular and cellular assays. It was then evaluated in two different NASH-relevant preclinical models, namely the methionine and choline-deficient diet (MCDD) and diet-induced obesity NASH (DIO NASH) models. Results: Molecular and cell-based assays confirmed that S217879 is a highly potent and selective NRF2 activator with marked anti-inflammatory properties, as shown in primary human peripheral blood mononuclear cells. In MCDD mice, S217879 treatment for 2 weeks led to a dose-dependent reduction in NAFLD activity score while significantly increasing liver Nqo1 mRNA levels, a specific NRF2 target engagement biomarker. In DIO NASH mice, S217879 treatment resulted in a significant improvement of established liver injury, with a clear reduction in both NAS and liver fibrosis. αSMA and Col1A1 staining, as well as quantification of liver hydroxyproline levels, confirmed the reduction in liver fibrosis in response to S217879. RNA-sequencing analyses revealed major alterations in the liver transcriptome in response to S217879, with activation of NRF2-dependent gene transcription and marked inhibition of key signaling pathways that drive disease progression. Conclusions: These results highlight the potential of selective disruption of the NRF2-KEAP1 interaction for the treatment of NASH and liver fibrosis. Impact and implications: We report the discovery of S217879 - a potent and selective NRF2 activator with good pharmacokinetic properties. By disrupting the KEAP1-NRF2 interaction, S217879 triggers the upregulation of the antioxidant response and the coordinated regulation of a wide spectrum of genes involved in NASH disease progression, leading ultimately to the reduction of both NASH and liver fibrosis progression in mice.

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Metabolic and epigenetic reprogramming play important roles in cancer therapeutic resistance. However, their interplays are poorly understood. We report here that elevated TIGAR (TP53-induced glycolysis and apoptosis regulator), an antioxidant and glucose metabolic regulator and a target of oncogenic histone methyltransferase NSD2 (nuclear receptor binding SET domain protein 2), is mainly localized in the nucleus of therapeutic resistant tumor cells where it stimulates NSD2 expression and elevates global H3K36me2 mark. Mechanistically, TIGAR directly interacts with the antioxidant master regulator NRF2 and facilitates chromatin recruitment of NRF2, H3K4me3 methylase MLL1 and elongating Pol-II to stimulate the expression of both new (NSD2) and established (NQO1/2, PRDX1 and GSTM4) targets of NRF2, independent of its enzymatic activity. Nuclear TIGAR confers cancer cell resistance to chemotherapy and hormonal therapy in vitro and in tumors through effective maintenance of redox homeostasis. In addition, nuclear accumulation of TIGAR is positively associated with NSD2 expression in clinical tumors and strongly correlated with poor survival. These findings define a nuclear TIGAR-mediated epigenetic autoregulatory loop in redox rebalance for tumor therapeutic resistance.

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Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. However, its potential has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide DMF (IDMF), which was designed to have antipsoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is nonirritating and nonsensitizing in animal models (rat, rabbit, guinea pig). Microarray analysis of cytokine-stimulated keratinocytes showed that IDMF represses the expression of genes specifically upregulated in psoriatic skin lesions but not those of other skin diseases. IDMF also downregulated genes induced by IL-17A and TNF in keratinocytes as well as predicted targets of NF-κB and the antidifferentiation noncoding RNA (i.e., ANCR). IDMF further stimulated the transcription of oxidative stress response genes (NQO1, GPX2, GSR) with stronger NRF2/ARE activation compared to DMF. Finally, IDMF reduced erythema and scaling while repressing the expression of immune response genes in psoriasiform lesions elicited by topical application of imiquimod in mice. These data show that IDMF exhibits antipsoriatic activity that is similar or improved compared with that exhibited by DMF, without the harsh skin-sensitizing effects that have prevented topical delivery of the parent molecule.

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Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

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Tumor-specific promoters and cis-regulatory genetic elements are used for transcriptional control of therapeutic transgene expression in cancer gene therapy. HRE (hypoxia response element) and ARE (anti-oxidant response elements) cis-regulatory elements are targets for HIF1 and Nrf2 transcriptional factors, respectively, and mediate activation of gene transcription in a response to hypoxia and oxidative stress, characteristic of most solid tumors. Due to these features HREs and AREs are used in genetic constructs for cancer gene therapy to provide tumor-specific therapeutic transgene expression or replication of oncolytic adenovi-ruses. In this work on the basis of the tumor-specific promoter hTERT we have constructed hybrid promoters carrying combinations of HRE and ARE. We showed that upon imitation of hypoxia in human lung cancer cell lines the activity of the hybrid promoter HRE-ARE-hTERT is substantially higher compared to promoters carrying only ARE or HRE. Using in vitro suicide cancer gene therapy with the CD: UPRT/5-FC (cytosine deaminase; uracil phosphoribosyl transferase/5-fluorocytosine) enzyme-prodrug system as a model we showed an enhancement of the cytotoxic effect on human lung cancer cells upon imitation of hypoxia when cytosine deaminase: uracil phosphoribosyl transferase was expressed under the control of the HRE-ARE-hTERT promoter compared to HRE-hTERT and ARE-hTERT promoters. The novel hybrid promoter HRE-ARE-hTERT could be used for transcriptional targeting of therapeutic transgene expression or oncolytic adenovirus replication upon development of novel anti-cancer gene therapeutics.

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BACKGROUND: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. METHODS: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), ß2-microglobulin (ß2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. RESULTS: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and ß2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and ß2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-ß1 (TGF-ß1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. CONCLUSION: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-ß1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

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Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively. Sirt6 knockdown in AML12 cells aggravated APAP-induced hepatocyte death and oxidative stress, inhibited cell viability and proliferation, and downregulated CCNA1, CCND1 and CKD4 protein levels. Sirt6 knockdown significantly prevented APAP-induced NRF2 activation, reduced the transcriptional activities of GSTµ and NQO1 and the mRNA levels of Nrf2, Ho-1, Gstα and Gstµ. Furthermore, SIRT6 showed potential protein interaction with NRF2 as evidenced by co-immunoprecipitation (Co-IP) assay. Additionally, the protective effect of P53 against APAP-induced hepatocytes injury was Sirt6-dependent. The Sirt6 mRNA was significantly down-regulated in P53 -/- mice. P53 activated the transcriptional activity of SIRT6 and exerted interaction with SIRT6. Our results demonstrate that SIRT6 protects against APAP hepatotoxicity through alleviating oxidative stress and promoting hepatocyte proliferation, and provide new insights in the function of SIRT6 as a crucial docking molecule linking P53 and NRF2.

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Gallic acid (GA) is a known phenolic compound with anti-inflammatory, antioxidant, and anti-cancer activities. The objective of this research is to evaluate the preventive role of GA against carbon tetrachloride (CCl4) induced liver fibrosis. Thirty-five (35) male Wistar rats were used in this study and were equally distributed into five groups (7 rats each). All groups were acclimatized for a week, Group I (control) rats were administered distilled water only. Group II rats were induced with a single dose of CCl4 (1.25 mL/kg in olive oil (1:1); IP) to cause hepatic damage, while Groups III, IV, and V, rats were intoxicated with CCl4. After 24 h the rats in groups III, IV, and V were given 50 mg/kg of silymarin, 50 mg/kg of GA, and 100 mg/kg of GA daily for one week respectively. Rats were sacrificed and fasting blood was estimated for biochemical analysis while the liver was excised for molecular studies. Results from this study revealed that GA significantly decreases serum hepatic enzymes, down-regulate the expression of pro-inflammatory cytokines, interleukin 1 beta (IL-1B), interleukin 6 (IL-6), cyclooxygenase 2 (COX 2), and tumor necrosis factor-alpha (TNF α), and up-regulate antioxidant gene expression (superoxide dismutase and catalase). The use of gallic acid as natural antioxidants can be promising in ameliorating liver diseases.

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Introduction: Alzheimer's disease (AD) is a progressive brain disorder, and one of the most common causes of dementia and amnesia. Due to the complex pathogenesis of AD, the underlying mechanisms remain unclear. Although scientists have made increasing efforts to develop drugs for AD, no effective therapeutic agents have been found. Objectives: Natural products and their constituents have shown promise for treating neurodegenerative diseases, including AD. Thus, in-depth study of medical plants, and the main active ingredients thereof against AD, is necessary to devise therapeutic agents. Methods: In this study, N2a/APP cells and SAMP8 mice were employed as in vitro and in vivo models of AD. Multiple molecular biological methods were used to investigate the potential therapeutic actions of oxyphylla A, and the underlying mechanisms. Results: Results showed that oxyphylla A, a novel compound extracted from Alpinia oxyphylla, could reduce the expression levels of amyloid precursor protein (APP) and amyloid beta (Aß) proteins, and attenuate cognitive decline in SAMP8 mice. Further investigation of the underlying mechanisms showed that oxyphylla A exerted an antioxidative effect through the Akt-GSK3ß and Nrf2-Keap1-HO-1 pathways.Conclusions.Taken together, our results suggest a new horizon for the discovery of therapeutic agents for AD.

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Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

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Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, which is safe at therapeutic doses but can cause severe liver injury and even liver failure after overdoses. The mouse model of APAP hepatotoxicity recapitulates closely the human pathophysiology. As a result, this clinically relevant model is frequently used to study mechanisms of drug-induced liver injury and even more so to test potential therapeutic interventions. However, the complexity of the model requires a thorough understanding of the pathophysiology to obtain valid results and mechanistic information that is translatable to the clinic. However, many studies using this model are flawed, which jeopardizes the scientific and clinical relevance. The purpose of this review is to provide a framework of the model where mechanistically sound and clinically relevant data can be obtained. The discussion provides insight into the injury mechanisms and how to study it including the critical roles of drug metabolism, mitochondrial dysfunction, necrotic cell death, autophagy and the sterile inflammatory response. In addition, the most frequently made mistakes when using this model are discussed. Thus, considering these recommendations when studying APAP hepatotoxicity will facilitate the discovery of more clinically relevant interventions.

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Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.

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Nephropathy is a serious complication comorbid with a number of life-threatening diseases such as diabetes. Flavonoids are well known cytoprotective phytochemicals. Here, nephropathy associated with streptozotocin (STZ) treatment in experimental animals was challenged by flavonoids (CoF) isolated from Chromolaena odorata. Experimental animals were divided into control (n = 5), STZ (40 mg/kg b.w. i.p. n = 5) and STZ-CoF (CoF = 30 mg/kg b.w. oral, 60 days, n = 7) groups. Blood urea nitrogen (BUN) and serum creatinine (SC) levels were quantified using ELISA. Kidney function, inflammatory marker, and antioxidant gene expression levels were also evaluated using reverse-transcription and polymerase chain reaction protocols. Histological assessment was also performed using Haematoxylin and Eosin (H&E) staining protocols. CoF improved kidney function by restoring BUN/SC levels to pre-STZ treatment states. KIM-1, TNF-α, and MCP-1 but not TNF-R and IL-10 genes were significantly downregulated in STZ-CoF treated group in comparison with STZ-treated group (p < 0.05). Anti-oxidant genes (GPx-1, CAT) significantly (p < 0.05 vs. control) upregulated in STZ-treatment did not respond to CoF treatment. STZ treatment associated Bowman's space enlargement, thickened basement membrane, and glomerulosclerosis were completely reversed in STZ-CoF group. Finally, CoF has demonstrable anti-nephropathic via downregulation of proinflammatory genes and may represent new management option in clinical nephropathy.

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We have developed a novel vaping product (NVP) IS1.0(TT), which utilises a stainless-steel mesh to transfer and vaporise the e-liquid, mitigating some of the potential sources of toxicants that can be generated using the more traditional 'wick and coil' approach. The emissions from IS1.0(TT) have previously been found to have lower levels of toxicants overall when directly compared with a commercial wick and coil e-cig. This current study assessed the toxicological responses to aerosols from this NVP. Responses induced by IS1.0(TT)were compared to those from a 3R4F reference cigarette, using in vitro test methods which included regulatory genetic toxicological assays as well as some more contemporary screening approaches. The experimental conditions were designed to facilitate the testing of aerosol from this vaping product at doses that in most cases greatly exceeded those of the 3R4F comparator showed little to no toxicological responses and demonstrated significantly reduced effects in these in vitro assays when compared to 3R4F. Furthermore, the extreme doses tested in the present study indicate that the toxicant profile of this NVP translates to lower biological activity in vitro, and suggests that the absolute risk hazard level associated with electronic cigarettes can be reduced through continuous improvement as the technology evolves.

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Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking.

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BACKGROUND: Benfotiamine (BFT) is a synthetic thiamine precursor with high bioavailability. It is efficient in treating complications of type 2 diabetes and has beneficial effects in mouse models of neurodegenerative diseases. The mechanism of action of BFT remains unknown, though it is sometimes suggested that it may be linked to increased thiamine diphosphate (ThDP) coenzyme function. METHODS: We used a mouse neuroblastoma cell line (Neuro2a) grown in thiamine-restricted medium. The cells were stressed by exposure to paraquat (PQ) or amyloid ß1-42 peptide in the presence or absence of BFT and the cell survival was measured using the MTT method. In each case, BFT was compared with sulbutiamine (SuBT), an unrelated thiamine precursor, and thiamine. Metabolites of BFT were determined by HPLC and mass spectrometry. RESULTS: At 50 µM, BFT protects the cells against PQ and amyloid ß1-42 peptide-induced toxicity with the same efficacy. Protective effects were also observed with SuBT and with higher concentrations of thiamine. The main metabolites of BFT were thiamine and S-benzoylthiamine (S-BT). Treatment with both precursors induces a strong increase in intracellular content of thiamine. Protective effects of BFT and SuBT are directly related to thiamine (but not ThDP) levels in Neuro2a cells. CONCLUSIONS: BFT, SuBT and thiamine all protect the cells against oxidative stress, suggesting an antioxidant effect of thiamine. Our results are not in favor of a direct ROS scavenging effect of thiamine but rather an indirect effect possibly mediated by some antioxidant signaling pathway. It is however not clear whether this effect is due to thiamine itself, its thiol form or an unknown metabolite. GENERAL SIGNIFICANCE: Our results suggest a role of thiamine in protection against oxidative stress, independent of the coenzyme function of thiamine diphosphate.

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Acute watery diarrhea due to Rotavirus (RV) infection is associated with high infantile morbidity and mortality in countries with compromised socio-economic backgrounds. Although showing promising trends in developed countries, the efficacy of currently licensed RV vaccines is sub-optimal in socio-economically poor settings with high disease burden. Currently, there are no approved anti-rotaviral drugs adjunct to classical vaccination program. Interestingly, dissecting host-rotavirus interaction has yielded novel, non-mutable host determinants which can be subjected to interventions by selective small molecules. The present study was undertaken to evaluate the anti-RV potential of RA-839, a recently discovered small molecule with potent and highly selective agonistic activity towards cellular redox stress-sensitive Nuclear factor erytheroid-derived-2-like 2 (Nrf2)/Antioxidant Response Element (ARE) pathway. In vitro studies revealed that RA-839 inhibits RV RNA and protein expression, viroplasm formation, yield of virion progeny and virus-induced cytopathy independent of RV strains, RV-permissive cell lines and without bystander cytotoxicity. Anti-RV potency of RA-839 was subsequently identified to be independent of stochastic Interferon (IFN) stimulation but to be dependent on RA-839's ability to stimulate Nrf2/ARE signaling. Interestingly, anti-rotaviral effects of RA-839 were also mimicked by 2-Cyano-3, 12-dioxo-oleana-1, 9(11)-dien-28-oic acid methyl ester (CDDO-Me) and Hemin, two classical pharmacological activators of Nrf2/ARE pathway. Overall, this study highlights that RA-839 is a potent antagonist of RV propagation in vitro and can be developed as anti-rotaviral therapeutics.

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The purpose of this study was to investigate the effects of capsaicinoids (CAPs) on lipid metabolism, inflammation, antioxidant status and the changes in gene products involved in these metabolic functions in exercised rats. A total of 28 male Wistar albino rats were randomly divided into four groups (n = 7) (i) No exercise and no CAPs, (ii) No exercise + CAPs (iii) Regular exercise, (iv) Regular exercise + CAPs. Rats were administered as 0.2 mg capsaicinoids from 10 mg/kg BW/day Capsimax® daily for 8 weeks. A significant decrease in lactate and malondialdehyde (MDA) levels and increase in activities of antioxidant enzymes were observed in the combination of regular exercise and CAPs group (P < 0.0001). Regular exercise + CAPs treated rats had greater nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) levels in muscle than regular exercise and no exercise rats (P < 0.001). Nevertheless, regular exercise + CAPs treated had lower nuclear factor kappa B (NF-κB) and IL-10 levels in muscle than regular exercise and control rats (P < 0.001). Muscle sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptors (LXR), ATP citrate lyase (ACLY) and fatty acid synthase (FAS) levels in the regular exercise + CAPs group were lower than all groups (P < 0.05). However, muscle PPAR-γ level was higher in the regular exercise and CAPs alone than the no exercise rats. These results suggest CAPs with regular exercise may enhance lipid metabolism by regulation of gene products involved in lipid and antioxidant metabolism including SREBP-1c, PPAR-γ, and Nrf2 pathways in rats.

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Alcoholic beverages are enjoyed together with meals worldwide, but their excessive intake is associated with an increased risk of various diseases. We investigated whether S-allyl-L-cysteine sulfoxide (ACSO), a sulfuric odor precursor of garlic, suppresses elevation in plasma ethanol concentration by accelerating ethanol metabolism and preventing ethanol absorption from the gut in rats. ACSO and garlic extract with a high ACSO content (Garlic-H) suppressed elevation in concentrations of ethanol and acetaldehyde in plasma and promoted the activities of alcohol dehydrogenase and aldehyde dehydrogenase. However, ACSO and Garlic-H did not affect plasma acetate so much. Furthermore, we examined the change in plasma ethanol concentration by injecting ACSO or Garlic-H into the ligated stomach or jejunum together with ethanol solution. ACSO and Garlic-H suppressed the absorption of ethanol from the stomach and jejunum, but suppression in the jejunum was less than in the stomach. In conclusion, ACSO inhibits ethanol absorption and accelerates ethanol metabolism.

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