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AbstractContext The toxicity of atractyloside/carboxyatractyloside is generally well recognized and commonly ascribed to the inhibition of mitochondrial ADP/ATP carriers, which are pivotal for oxidative phosphorylation. However, these glycosides may 'paralyze' additional target proteins.Objective This review presents many facts about atractyloside/carboxyatractyloside and their plant producers, such as Xanthium spp. (Asteraceae), named cockleburs.Methods Published studies and other information were obtained from databases, such as 'CABI - Invasive Species Compendium', 'PubMed', and 'The World Checklist of Vascular Plants', from 1957 to December 2022. The following major keywords were used: 'carboxyatractyloside', 'cockleburs', 'hepatotoxicity', 'mitochondria', 'nephrotoxicity', and 'Xanthium'.Results In the third decade of the twenty first century, public awareness of the severe toxicity of cockleburs is still limited. Such toxicity is often only perceived by specialists in Europe and other continents. Interestingly, cocklebur is among the most widely distributed invasive plants worldwide, and the recognition of new European stands of Xanthium spp. is provided here. The findings arising from field and laboratory research conducted by the author revealed that (i) some livestock populations may instinctively avoid eating cocklebur while grazing, (ii) carboxyatractyloside inhibits ADP/GDP metabolism, and (iii) the direct/indirect target proteins of carboxyatractyloside are ambiguous.Conclusions Many aspects of the Xanthium genus still require substantial investigation/revision in the future, such as the unification of the Latin nomenclature of currently distinguished species, bur morphology status, true fruit (achene) description and biogeography of cockleburs, and a detailed description of the physiological roles of atractyloside/carboxyatractyloside and the toxicity of these glycosides, mainly toward mammals. Therefore, a more careful interpretation of atractyloside/carboxyatractyloside data, including laboratory tests using Xanthium-derived extracts and purified toxins, is needed.

The toxicity of atractyloside/carboxyatractyloside is generally well recognized and commonly ascribed to the inhibition of mitochondrial ADP/ATP carriers, which are pivotal for oxidative phosphorylation. However, these glycosides may 'paralyze' additional target proteins. This review presents many facts about atractyloside/carboxyatractyloside and their plant producers, such as Xanthium spp. (Asteraceae), named cockleburs. Published studies and other information were obtained from databases, such as 'CABI - Invasive Species Compendium', 'PubMed', and 'The World Checklist of Vascular Plants', from 1957 to December 2022. The following major keywords were used: 'carboxyatractyloside', 'cockleburs', 'hepatotoxicity', 'mitochondria', 'nephrotoxicity', and 'Xanthium'. In the third decade of the twenty first century, public awareness of the severe toxicity of cockleburs is still limited. Such toxicity is often only perceived by specialists in Europe and other continents. Interestingly, cocklebur is among the most widely distributed invasive plants worldwide, and the recognition of new European stands of Xanthium spp. is provided here. The findings arising from field and laboratory research conducted by the author revealed that (i) some livestock populations may instinctively avoid eating cocklebur while grazing, (ii) carboxyatractyloside inhibits ADP/GDP metabolism, and (iii) the direct/indirect target proteins of carboxyatractyloside are ambiguous. Many aspects of the Xanthium genus still require substantial investigation/revision in the future, such as the unification of the Latin nomenclature of currently distinguished species, bur morphology status, true fruit (achene) description and biogeography of cockleburs, and a detailed description of the physiological roles of atractyloside/carboxyatractyloside and the toxicity of these glycosides, mainly toward mammals. Therefore, a more careful interpretation of atractyloside/carboxyatractyloside data, including laboratory tests using Xanthium-derived extracts and purified toxins, is needed. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of atractyloside, a promoter of the mitochondrial membrane permeability transition pore (MPTP), on mitochondrial membrane permeability, cristae structure, cytochrome c release and tenderness of postmortem beef and to explore the effect of injury on meat tenderness by releasing cytochrome c and activating caspases. The postmortem longissimus dorsi muscle of adult crossbred cattle was treated or not treated (control) with atractyloside, stored at 4 ℃ and evaluated for mitochondrial ultrastructure, membrane potential, the amount of cytochrome c released to the cytoplasm, cell apoptotic rate, caspase-3 and myofibrillary fragmentation index (MFI) after 0, 12, 24, 72, and 120 h. With postmortem aging time, the number of mitochondrial cristae decreased significantly, and swelling and rupture were observed. The mitochondrial membrane potential decreased significantly, and cytochrome c was released gradually. Starting from 72 h postmortem, the activity of caspase-3 and the apoptosis rate of myocytes increased, and so did MFI. Compared with the control group, atractyloside treatment induced mitochondrial damage by destroying mitochondrial cristae structure, reducing the membrane potential and causing cytochrome c release. In addition, the apoptosis of muscle cells and the fragmentation of myofibrils were accelerated by atractyloside. The opening of the MPTP significantly affected mitochondrial injury in beef after slaughter. Apart from increasing cell membrane permeability, atractyloside also significantly altered the structure of mitochondrial cristae. The internal and external mitochondrial membranes could synergistically regulate the release of cytochrome c, which in turn could affect postmortem tenderization of beef.

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This study is aimed to determine the toxicity of Xanthium strumarium L. (cocklebur) or its seeds to human or an animal. Cocklebur, potentially toxic plants is found abundantly in meadows and pastures. One of the most significant ingredients that causes toxicity is atractyloside (ATR). In this study, the concentration of ATR in cocklebur seeds was determined as 4 mg/g seed. The study involved 54 rats which were divided into a total of 9 groups including one control group. A single dose of cocklebur seed extract was provided by gavage after being concentrated by 2 ml for each animal (80 mg ATR/kg) except for those in the control group, and time-dependent hepatotoxic, nephrotoxic, hematological and biochemical effects were analyzed. No histopathological change was detected in the liver and kidney tissues of the rats in the experimental groups. Both hematological and serum biochemical values (Ca, P, TBIL, ALT, AST, ALP, Urea, and Creatinine) were within the physiological limits in all groups. Consequently, in light of the obtained data, it was observed that the rats were not exposed to any toxic effect even when they consumed a stomach full of cocklebur fruit at once. [ABSTRACT FROM AUTHOR]

Atractyloside is a traditional Chinese medicine used to treat nasal congestion, and allergic rhinitis; however, its effects on cancer are unknown. Non-small cell lung cancer (NSCLC) is associated with high mortality rates worldwide, and relapse due to epidermal growth factor receptor mutations is a problem in clinical therapy. Therefore, novel biomarkers are required for the diagnosis and treatment of NSCLC. Brother of the regulator of imprinted sites ( BORIS ; also known as CTCFL ) is a potential therapeutic target in NSCLC. BORIS promotes cisplatin resistance and it has been suggested that it may account for multidrug resistance. The present study examined BORIS expression in tyrosine kinase inhibitor (TKI)-resistant NSCLC cells. Subsequently, small interfering RNA was used to knock down BORIS expression, and the effects of this knockdown were assessed on TKI-resistant NSCLC cell viability. The present study also investigated the effect of atractyloside on the proliferation of NSCLC cells using MTT assay. The results of the present study indicated that the inhibition of BORIS or its related downstream pathways may have potential for the treatment of TKI-resistant NSCLC. In addition, atractyloside mimicked BORIS knockdown, regulated its downstream genes and inhibited the proliferation of TKI-resistant NSCLC cells. In conclusion, the findings of the present study supported the potential application of atractyloside in TKI-resistant NSCLC therapy., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Yao et al.)

Atractyloside (ATR) may cause severe liver and kidney damage. However, there is a lack of information about levels of ATR in parts of Xanthium strumarium and the concentrations and kinetics of ATR in the serum. In this study, we determined atractyloside levels in Xanthium strumarium parts, its serum concentrations and some kinetic parameters concerning time with the gas chromatography-mass selective (GC-MS) method. After administering (80 mg/kg ATR) X. strumarium seed extract to rats through gastric gavage, blood samples were collected at the 0th, 4th, 6th, 8th, 12th, 24th, 36th, 48th, 60th, 72nd, 96th, and 120th h. After extraction, hydrolysis and derivatization of the plant and serum samples were analyzed by the GC-MS instrument. The ATR level in the X. strumarium seeds was 3.043 mg/g in August, 3.502 mg/g in September and 3.800 mg/g in October. ATR was not detected in other parts of the plant. After ATR administration to rats, the Cmax value of ATR was calculated as 10.77 μg/mL at Tmax of 48 h and t1/2 of 6.07 h. A thorough understanding of ATR circulation in the blood will aid in determining the course of its toxic effects in the bloodstream, the onset of symptoms and the general management plan for ATR poisoning. Moreover, the results obtained from this study will contribute to the antidote studies for ATR poisoning.

Objective : Adenine nucleotide translocase (ANT) can transport ADP from cytoplasm to mitochondrial matrix and provide raw materials for ATP synthesis by oxidative phosphorylation. Dysfunction of ANT leads to limitation of ADP transport and decrease of ATP production. Atractyloside (ATR) is considered as a cytotoxic competitive inhibitor binding to ANT, making ANT vulnerable to transport ADP, and reduces ATP synthesis. Moreover, the blockage of ANT by ATR may increase ADP/ATP ratio, activate AMPK-mTORC1-autophagy signaling pathway, and promote lipid degradation in steatosis hepatocytes. The present study was conducted to investigate the mechanism of ATR, regulate ANT-AMPK-mTORC1 signaling pathway to activate autophagy, and promote the degradation of lipid droplets in high-fat diet (HFD) induced liver steatosis. Methods : ICR mice were fed with HFD for 8 weeks to induce liver steatosis, and ATR solution was given by intraperitoneal injection. Intracellular triglyceride level and oil red O staining-lipid droplets (LDs) were assessed, the expression of proteins related to ANT-AMPK-mTORC1 signaling pathway and autophagy were determined, and the colocalization of LC3B and Perilipin 2 was performed. Results : ATR treatment decreased the serum AST level, relative weight of liver and epididymal fat, and body weight of HFD mice. The LDs in HFD mice livers were reduced in the presence of ATR, and the TG level in serum and liver of HFD mice was significantly reduced by ATR. In addition, ATR inhibited ANT2 expression, promoted the activation of AMPK, then increased Raptor expression, and finally decreased the mTOR activity. Furthermore, ATR increased the protein level of LC3A/B and ATG7, and a strong colocalization of LC3B and PLIN2 was observed. Conclusion : ATR treatment blocks ANT2 expression, promotes the activation of AMPK, then decreases the mTOR activity, and finally promotes autophagosomes formation, thus accelerating the degradation of HFD-induced accumulated lipids in the liver. This will provide new therapeutic ideas and experimental data for clinical prevention and treatment of non-alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Atractyloside (ATR) may cause severe liver and kidney damage. However, there is a lack of information about levels of ATR in parts of Xanthium strumarium and the concentrations and kinetics of ATR in the serum. In this study, we determined atractyloside levels in Xanthium strumarium parts, its serum concentrations and some kinetic parameters concerning time with the gas chromatography-mass selective (GCMS) method. After administering (80 mg/kg ATR) X. strumarium seed extract to rats through gastric gavage, blood samples were collected at the 0th, 4th, 6th, 8th, 12th, 24th, 36th, 48th, 60th, 72nd, 96th, and 120th h. After extraction, hydrolysis and derivatization of the plant and serum samples were analyzed by the GC-MS instrument. The ATR level in the X. strumarium seeds was 3.043 mg/g in August, 3.502 mg/g in September and 3.800 mg/g in October. ATR was not detected in other parts of the plant. After ATR administration to rats, the Cmax value of ATR was calculated as 10.77 µg/mL at Tmax of 48 h and t1/2 of 6.07 h. A thorough understanding of ATR circulation in the blood will aid in determining the course of its toxic effects in the bloodstream, the onset of symptoms and the general management plan for ATR poisoning. Moreover, the results obtained from this study will contribute to the antidote studies for ATR poisoning. [ABSTRACT FROM AUTHOR]

Objective: Adenine nucleotide translocase (ANT) can transport ADP from cytoplasm to mitochondrial matrix and provide raw materials for ATP synthesis by oxidative phosphorylation. Dysfunction of ANT leads to limitation of ADP transport and decrease of ATP production. Atractyloside (ATR) is considered as a cytotoxic competitive inhibitor binding to ANT, making ANT vulnerable to transport ADP, and reduces ATP synthesis. Moreover, the blockage of ANT by ATR may increase ADP/ATP ratio, activate AMPK-mTORC1-autophagy signaling pathway, and promote lipid degradation in steatosis hepatocytes. The present study was conducted to investigate the mechanism of ATR, regulate ANT-AMPK-mTORC1 signaling pathway to activate autophagy, and promote the degradation of lipid droplets in high-fat diet (HFD) induced liver steatosis.Methods: ICR mice were fed with HFD for 8 weeks to induce liver steatosis, and ATR solution was given by intraperitoneal injection. Intracellular triglyceride level and oil red O staining-lipid droplets (LDs) were assessed, the expression of proteins related to ANT-AMPK-mTORC1 signaling pathway and autophagy were determined, and the colocalization of LC3B and Perilipin 2 was performed.Results: ATR treatment decreased the serum AST level, relative weight of liver and epididymal fat, and body weight of HFD mice. The LDs in HFD mice livers were reduced in the presence of ATR, and the TG level in serum and liver of HFD mice was significantly reduced by ATR. In addition, ATR inhibited ANT2 expression, promoted the activation of AMPK, then increased Raptor expression, and finally decreased the mTOR activity. Furthermore, ATR increased the protein level of LC3A/B and ATG7, and a strong colocalization of LC3B and PLIN2 was observed.Conclusion: ATR treatment blocks ANT2 expression, promotes the activation of AMPK, then decreases the mTOR activity, and finally promotes autophagosomes formation, thus accelerating the degradation of HFD-induced accumulated lipids in the liver. This will provide new therapeutic ideas and experimental data for clinical prevention and treatment of non-alcoholic fatty liver disease.

Background and AimAtractyloside (ATR), a mitochondrial uncoupler, is known for its specific inhibition of mitochondrial oxidative phosphorylation. Previous studies have reported that moderate mitochondrial uncoupling effect is beneficial to increase the decomposition and clearance of hepatic lipid, prevent the occurrence of fatty liver diseases. Moreover, the beneficial effects of mitochondrial uncouplers on type 2 diabetes and metabolic syndromes have been consistently observed. The present study investigated the effect of ATR on steatosis level of HepG2 cells treated with free fatty acid (FFA).MethodsIntracellular triglyceride level and Oil Red O staining were assessed, the mitochondrial adaptation and ADP/ATP ratio were analyzed, the protein level of AMPK, mTOR and LC3B, autophagic flux, and the co-localization of LC3B with lipid droplets was performed.ResultsATR treatment inhibited the activity of mitochondrial respiratory chain complexes I and IV, decreased the mitochondrial membrane potential, and increased the ADP/ATP ratio in the FFA-treated cells. Furthermore, ATR increased the gene expression and protein level of LC3B and promoted the autophagic flux processing from early autophagosome to late autolysosome by increasing the protein level of AMPKα and decreasing the protein level of mTOR. An increased number of autophagosomes (LC3B) was also observed in the lipid droplets. ATR treatment accelerated lipid degradation in the FFA-treated cells, and the lowest lipid content was observed in the cell group with 7.5 μM ATR.ConclusionLow concentrations (2.5, 5, and 7.5 μM) of ATR treatment could activate autophagy to accelerate the degradation of TGs in steatosis HepG2 cells; the mechanism may be related to the activation of the AMPK/mTOR pathway induced by the increased ADP/ATP ratio. In addition, the ideal concentration of ATR for improving steatotic HepG2 cells was 7.5 μM.

Background: This research aimed at exploring the mechanisms of alterations of metabolites and pathways in T2D from the perspective of metabolomics and transcriptomics, as well as uncovering novel drug candidate for T2D treatment. Methods: Metabolites in human plasma from 42 T2D patients and 45 non‐diabetic volunteers were detected by liquid chromatography‐mass spectrometer (LC‐MS). Microarray dataset of the transcriptome was obtained from Gene Expression Omnibus (GEO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to conduct pathway enrichment analysis. Connectivity Map (CMap) was employed to select potential drugs for T2D therapy. In vivo assay was performed to verify above findings. The protein expression levels of ME1, ME2 and MDH1 were detected by Western blot to determine the status of NAD/NADH cofactor system. Results: In our study, differentially expressed metabolites were selected out between healthy samples and T2D samples with selection criteria P value <.05, |Fold Change| > 2, including N‐acetylglutamate and Malate. Genes set enrichment analysis (GSEA) revealed that 34 pathways were significantly enriched in T2D. Based on CMap analysis and animal experiments, Atractyloside was identified as a potential novel drug for T2D treatment via targeting ME1, ME2 and MDH1 and regulating the NAD/NADH cofactor system. Conclusion: The present research revealed differentially expressed metabolites and genes, as well as significantly altered pathways in T2D via an integration of metabolomics, transcriptomics and CMap analysis. It was also demonstrated that comprehensive analysis based on metabolomics and transcriptomics was an effective approach for identification and verification of metabolic biomarkers and alternated pathways. [ABSTRACT FROM AUTHOR]

Xanthii Fructus is extensively used as an herbal medicine. Ingestion of this herb is associated with severe hepatotoxicity and nephrotoxicity. Atractyloside and carboxyatractyloside are two dominative toxic constituents in Xanthii Fructus. However, their pharmacokinetic study is lacking. In this study, a novel high‐performance liquid chromatography‐tandem mass spectrometry method was developed to simultaneously quantify the rat plasma concentrations of atractyloside and carboxyatractyloside. After protein precipitation, the analytes were chromatographic separated on a ZORBAX Eclipse Plus column (2.1 × 150 mm id, 5 µm) under gradient elute. In the negative electrospray ionization mode, the transitions at m/z 725.3→645.4 for atractyloside, m/z 769.3→689.4 for carboxyatractyloside, and m/z 479.2→121.1 for paeoniflorin (the internal standard) were acquired by multiple reaction monitoring. This analytical method showed good linearity over 1–500 ng/mL for atractyloside and 2–500 ng/mL for carboxyatractyloside with acceptable precision and accuracy. No matrix effect, instability and carryover occurred in the analysis procedure. The extraction recoveries were greater than 85.0%. This method was applied to a preliminary pharmacokinetic study by orally administering Xanthii Fructus extract (9 g/kg) to rats, which was useful to evaluate the role of these two compounds in Xanthii Fructus‐induced toxicity. [ABSTRACT FROM AUTHOR]

Roasted coffee contains atractyligenin-2- O -β-d-glucoside and 3'- O -β-d-glucosyl-2'- O -isovaleryl-2- O -β-d-glucosylatractyligenin, which are ingested with the brew. Known metabolites are atractyligenin, atractyligenin-19- O -β-d-glucuronide ( M1 ), 2β-hydroxy-15-oxoatractylan-4α-carboxy-19- O -β-d-glucuronide ( M2 ), and 2β-hydroxy-15-oxoatractylan-4α-carboxylic acid-2- O -β-d-glucuronide ( M3 ), but the appearance and pharmacokinetic properties are unknown. Therefore, first time-resolved quantitative data of atractyligenin glycosides and their metabolites in plasma samples from a pilot human intervention study ( n = 10) were acquired. None of the compounds were found in the control samples and before coffee consumption ( t = 0 h). After coffee, neither of the atractyligenin glycosides appeared in the plasma, but the aglycone atractyligenin and the conjugated metabolite M1 reached an estimated c max of 41.9 ± 12.5 and 25.1 ± 4.9 nM, respectively, after 1 h. M2 and M3 were not quantifiable until their concentration enormously increased ≥4 h after coffee consumption, reaching an estimated c max of 2.5 ± 1.9 and 55.0 ± 57.7 nM at t = 10 h. The data suggest that metabolites of atractyligenin could be exploited to indicate coffee consumption.

Context: The toxicity of atractyloside/carboxyatractyloside is generally well recognized and commonly ascribed to the inhibition of mitochondrial ADP/ATP carriers, which are pivotal for oxidative phosphorylation. However, these glycosides may 'paralyze' additional target proteins., Objective: This review presents many facts about atractyloside/carboxyatractyloside and their plant producers, such as Xanthium spp. (Asteraceae), named cockleburs., Methods: Published studies and other information were obtained from databases, such as 'CABI - Invasive Species Compendium', 'PubMed', and 'The World Checklist of Vascular Plants', from 1957 to December 2022. The following major keywords were used: 'carboxyatractyloside', 'cockleburs', 'hepatotoxicity', 'mitochondria', 'nephrotoxicity', and ' Xanthium '., Results: In the third decade of the twenty first century, public awareness of the severe toxicity of cockleburs is still limited. Such toxicity is often only perceived by specialists in Europe and other continents. Interestingly, cocklebur is among the most widely distributed invasive plants worldwide, and the recognition of new European stands of Xanthium spp. is provided here. The findings arising from field and laboratory research conducted by the author revealed that (i) some livestock populations may instinctively avoid eating cocklebur while grazing, (ii) carboxyatractyloside inhibits ADP/GDP metabolism, and (iii) the direct/indirect target proteins of carboxyatractyloside are ambiguous., Conclusions: Many aspects of the Xanthium genus still require substantial investigation/revision in the future, such as the unification of the Latin nomenclature of currently distinguished species, bur morphology status, true fruit (achene) description and biogeography of cockleburs, and a detailed description of the physiological roles of atractyloside/carboxyatractyloside and the toxicity of these glycosides, mainly toward mammals. Therefore, a more careful interpretation of atractyloside/carboxyatractyloside data, including laboratory tests using Xanthium -derived extracts and purified toxins, is needed.

Aim: To investigate the myocardial preconditioning potential of hedgehog activator smoothened (SMO) receptor agonist purmorphamine (PUR) against ischemia-reperfusion (I/R) injury in deoxycortisone acetate (DOCA) salt-induced hypertensive rat heart. Methods: Hypertension in rats was produced by surgical removal of the kidney and DOCA salt administration for 6 weeks. Isolated rat heart was subjected to 30 min ischemia followed by 120 min of I/R. The heart was subjected to pharmacological preconditioning with the hedgehog (Hh) activator PUR (1 μM), PUR (2 μM), and atractyloside (4 μM), an mPTP opener, in the last episode of reperfusion before I/R. Elevated blood pressure was evaluated through tail-cuff method. Myocardial infarction was assessed in terms of the increase in lactate dehydrogenase, creatinine kinase-muscle/brain, and infarct size through triphenyltetrazolium chloride staining. Further, there were a decrease in the release of nitrite and coronary flow rate. Immunohistochemistry was performed for the assessment of tumor necrosis factor-α level in cardiac tissue. Results: Pharmacological preconditioning with PUR significantly attenuated I/R-induced myocardial infarction. However, atractyloside limits the ameliorative preconditioning potential of PUR and confirmed the role of Hh pathway in ischemic preconditioning. Conclusion: It may be concluded that the Hh activator PUR (SMO receptor agonist) prevents I/R injury in DOCA salt-induced hypertensive rat heart. [ABSTRACT FROM AUTHOR]

In the past, divergent results have been reported based on different methods and conditions used for enzymatic activity measurements of cytochrome c oxidase (CytOx). Here, we analyze in detail and show comparable and reproducible polarographic activity measurements of ATP-dependent inhibition of CytOx kinetics in intact and non-intact rat heart mitochondria and mitoplasts. We found that this mechanism is always present in isolated rat heart mitochondria and mitoplasts; however, it is measurable only at high ATP/ADP ratios using optimal protein concentrations. In the kinetics assay, measurement of this mechanism is independent of presence or absence of Tween-20 and the composition of measuring buffer. Furthermore, the effect of atractyloside on intact rat heart mitochondria confirms that (i) ATP inhibition occurs under uncoupled conditions [in the presence of carbonly cyanide m-chlorophenyl hydrazone (CCCP)] when the classical respiratory control is absent and (ii) high ATP/ADP ratios in the matrix as well as in the cytosolic space are required for full ATP inhibition of CytOx. Additionally, ATP inhibition measured in intact mitochondria extends in the presence of oligomycin, thus indicating further that the problem to measure the inhibitory effect of ATP on CytOx is apparently due to the lack of very high ATP/ADP ratios in isolated mitochondria. [ABSTRACT FROM AUTHOR]

Atractyloside (ATR) is found in many Asteraceae plants that are commonly used as medicinal herbs in China and other eastern Asian countries. ATR binds specifically to the adenine nucleotide translocator in the inner mitochondrial membrane and competitively inhibits ADP and ATP transport. The toxicity of ATR in medical herbs can be reduced by hydrothermal processing, but the mechanisms of ATR degradation are not well understood. In this study, GC-MS coupled with SPE and TMS derivatisation was used to detect ATR levels in traditional Chinese medicinal herbs. Our results suggest that ATR molecules were disrupted by decomposition, hydrolysis and saponification after heating with water (decoction) for a long period of time. Hydrothermal processing could decompose the endogenous toxic compounds and also facilitate the detoxification of raw materials used in the Chinese medicine industry.

Arabica roast coffee contains a substantial amount of water soluble atractyligenin-2-O-β-d-glucoside, which is ingested by consumption of coffee brew. Metabolomics data suggest this coffee compound is excreted as glucuronides, but the structures of conjugates have not been elucidated so far. We collected coffee drinkers' urine and isolated four metabolites by MS-guided liquid chromatographic fractionation. The structures were investigated by nuclear magnetic resonance (NMR) and time-of-flight mass spectrometry (ToF-MS) and identified as atractyligenin-19-O-β-d-glucuronide (M1), 2β-hydroxy-15-oxoatractylan-4α-carboxy-19-O-β-d-glucuronide (M2), and 2β-hydroxy-15-oxoatractylan-4α-carboxylic acid-2-O-β-d-glucuronide (M3). An unconjugated metabolite (M4) was confirmed as atractyligenin. We analyzed spot urines from n = 6 coffee drinking individuals and detected the metabolites M1, M2 and M4 in every sample, and M3 in four out of six samples, suggesting interindividual differences in metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Evidence supporting the occurrence of oxidative stress in Cystic Fibrosis (CF) is well established and the literature suggests that oxidative stress is inseparably linked to mitochondrial dysfunction. Here, we have characterized mitochondrial function, in particular as it regards the steps of oxidative phosphorylation and ROS production, in airway cells either homozygous for the F508del-CFTR allele or stably expressing wt-CFTR. We find that oxygen consumption, ΔΨ generation, adenine nucleotide translocator-dependent ADP/ATP exchange and both mitochondrial Complex I and IV activities are impaired in CF cells, while both mitochondrial ROS production and membrane lipid peroxidation increase. Importantly, treatment of CF cells with the small molecules VX-809 and 4,6,4′-trimethylangelicin, which act as 'correctors' for F508del CFTR by rescuing the F508del CFTR-dependent chloride secretion, while having no effect per sè on mitochondrial function in wt-CFTR cells, significantly improved all the above mitochondrial parameters towards values found in the airway cells expressing wt-CFTR. This novel study on mitochondrial bioenergetics provides a springboard for future research to further understand the molecular mechanisms responsible for the involvement of mitochondria in CF and identify the proteins primarily responsible for the F508del-CFTR-dependent mitochondrial impairment and thus reveal potential novel targets for CF therapy. [ABSTRACT FROM AUTHOR]

Espresso coffee samples prepared at various roasting degrees defined according to its basic conventional classification (light, medium, medium-dark and dark roasted) were analyzed by ultra-performance liquid chromatography/tandem mass spectrometry. Obtained raw data were processed using multivariate statistical analysis (Principal Component Analysis, PCA) to evaluate chemical differences between each roasting degrees (untargeted part of study). All four roasting degrees were resolved in appropriate Score plot. Orthogonal Projections to Latent Structures provided signals of significant markers describing the differences among particular roasting degrees. Detailed interpretation of those signals by targeted LC/MS 2 analysis revealed four groups of compounds. The first two groups involve chlorogenic acids and related lactones. The signals of other two sets of markers were ascribed to some specific atractylosides and particular melanoidins. Ratios of contents of selected representatives of each group to the sum of all identified markers were proposed as definite parameters for determination of roasting degree of Brazilian coffee Arabica. [ABSTRACT FROM AUTHOR]

Plants remain a vital source of drugs and at present, much emphasis is given to nutraceuticals. Herbal medicines have been the basis of treatment and cure for various diseases and physiological conditions in the traditional methods practiced such as ayurveda and homeopathy. Litchi chinensis belongs to the Sapindaceae family and is well-known in the Indian traditional system for its traditional uses. The parts of the plant used are leaves, flowers, fruits, seed, pulp, and pericarp. All parts of the plant are rich sources of phytochemicals-epicatechin; procyanidin A2 and procyanidin B2; leucocyanidin; cyanidin glycoside, malvidin glycoside, and saponins; butylated hydroxytoluene; isolariciresinol; kaempferol; rutin; and stigmasterol. In the present review, we explore the lychee's description, traditional medicinal uses, and phytoconstituents, and investigate the pharmacological activities in various parts of the lychee to show its importance in ethanopharmacology. This is so that this review can serve as a ready-to-use material for further research on the plant. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the mechanism underlying the rescue effect of lipid emulsion on bupivacaine (BPV)-induced cardiomyocyte toxicity. The inhibitory effects of BPV on H9c2 myoblast cell proliferation were investigated using an MTT assay. The H9c2 myoblast cells were treated with either 1 mM BPV or 1% lipid emulsion (LE) alone, or co-treated with both of the drugs. Cell apoptosis was detected using both Annexin V/propidium iodide staining and a terminal deoxynucleotidyl transferase dUTP assay. The protein expression levels of apoptosis-associated proteins were quantified using western blot analysis, and the mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction. The expression levels of reactive oxidative species, malondialdehyde, superoxide dismutase, and catalase were quantified using the optical density values obtained from a spectrophotometer. In addition, the mechanism underlying the mitochondrial function of the H9c2 myoblast cells was investigated using both JC-1 staining, and cyclosporin A and atractyloside treatment. The results indicated that the H9c2 myoblast cells treated with BPV exhibited significantly higher levels of apoptosis. Furthermore, BPV treatment increased the levels of oxidative stress, and caused mitochondrial dysfunction within the H9c2 myoblast cells. LE treatment reversed the effects of BPV treatment in the H9c2 myoblast cells. [ABSTRACT FROM AUTHOR]

A water-soluble partially purified extract from defatted flax seed was obtained and characterized; it contained proteins (828.8 g/Kg), as well as water-soluble carbohydrates (101.4 g/Kg) and phenolic compounds (22.2 g/Kg), essentially secoisolariciresinol diglucoside (SDG, 18.40 g/Kg) and ferulic acid (1.45 g/Kg) and p-coumaric acid (2.07 mg/kg) mainly in their glycoside forms. Proteins of 23-24 kDa were the main protein fractions found in the extract. In an emulsion model system, the flax extract was able to inhibit the production of oxidation products (conjugated diene, peroxides and aldehydes) as well as the degradation of flax oil carotenoids. The antioxidant effects of the flax extract were concentration dependent. Oxidation kinetics of the emulsion supplemented with 0.10 % flax extract were similar to the oxidation kinetics of the control blank, whereas, oxidation parameters of the emulsion supplemented with 0.48 % (and higher) flax extract were equal to or better than the oxidation parameters obtained with the test control emulsion containing 0.01 % BHT. These results suggested that flax seed phenolic compounds (SDG) and low molecular weight proteins, both found in the studied extract, might have very strong antioxidant properties. This is paper number 1089 of the Canadian Grain Commission. [ABSTRACT FROM AUTHOR]

RATIONALE: Grape polyphenols are antioxidant compounds, markers in vine chemotaxonomy, and involved in color stabilization of red wines. Sugar acylation usually confers higher stability on glycoside derivatives and this effect is enhanced by an aromatic substituent such as p-coumaric acid. Until now, only p-coumaroyl anthocyanins have been found in grape. METHODS: A method of 'suspect screening analysis' by ultra-high-performance liquid chromatography/high-resolution mass spectrometry (UHPLC/QTOFMS) has recently been developed to study grape metabolomics. In the present study, this approach was used to identify new polyphenols in grape by accurate mass measurement, MS/MS fragmentation, and study of correlations between fragments observed and putative structures. RESULTS: Three putative p-coumaroyl flavonoids were identified in Raboso Piave grape extract: a dihydrokaempferide-3-O-p-coumaroylhexoside-like flavanone, isorhamnetin-3-O-p-coumaroylglucoside, and a chrysoeriol-pcoumaroylhexoside-like flavone. Accurate MS provided structural characterization of functional groups, and literature data indicates their probable position in the molecule. A fragmentation scheme is proposed for each compound. CONCLUSIONS: Compounds were identified by overlapping various analytical methods according to recommendations in the MS-based metabolomics literature. Stereochemistry and the definitive position of substituents in the molecule can only be confirmed by isolation and characterization or synthesis of each compound. These findings suggest addressing research of acylated polyphenol glycosides to other grape varieties. [ABSTRACT FROM AUTHOR]

Atractyloside (ATR) and carboxyatractyloside (CATR) are diterpene glycosides that are responsible for the toxicity of several Asteraceae plants around the world. Mediterranean gum thistle (Atractylis gummifera L.) and Zulu impila (Callilepis laureola DC.), in particular, are notoriously poisonous and the cause of many accidental deaths, some suicides and even some murders. There is no current method for measuring the two toxins in biological samples that meet the criteria of specificity required in forensic medicine. We have endeavored to fill this analytical gap. Analysis was carried out using a solid-phase extraction and a high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry detection. The method was validated in the whole blood with quantification limits of 0.17 and 0.15 µg/L for ATR and CATR, respectively. The method was applied to a non-fatal case of intoxication with A. gummifera. To the best of the authors' knowledge, this is the first time that a concentration of ATR and CATR in blood (883.1 and 119.0 µg/L, respectively) and urine (230.4 and 140.3 µg/L, respectively) is reported. ATR and CATR were quantified in A. gummifera roots by the standard method addition (3.7 and 5.4 mg/g, respectively). [ABSTRACT FROM AUTHOR]

Acidosis is one of the key components in cerebral ischemic postconditioning that has emerged recently as an endogenous strategy for neuroprotection. We set out to test whether acidosis treatment at reperfusion can protect against cerebral ischemia/reperfusion injury. Adult male C57BL/6 J mice were subjected to 60-minute middle cerebral arterial occlusion followed by 24-hour reperfusion. Acidosis treatment by inhaling 10%, 20%, or 30% CO2 for 5 or 10 minutes at 5, 50, or 100 minutes after reperfusion was applied. Our results showed that inhaling 20% CO2 for 5 minutes at 5 minutes after reperfusion-induced optimal neuroprotection, as revealed by reduced infarct volume. Attenuating brain acidosis with NaHCO3 significantly compromised the acidosis or ischemic postconditioning-induced neuroprotection. Consistently, both acidosis-treated primary cultured cortical neurons and acute corticostriatal slices were more resistant to oxygen-glucose deprivation/reperfusion insult. In addition, acidosis inhibited ischemia/reperfusion-induced apoptosis, caspase-3 expression, cytochrome c release to cytoplasm, and mitochondrial permeability transition pore (mPTP) opening. The neuroprotection of acidosis was inhibited by the mPTP opener atractyloside both in vivo and in vitro. Taken together, these findings indicate that transient mild acidosis treatment at reperfusion protects against cerebral ischemia/reperfusion injury. This neuroprotection is likely achieved, at least partly, by inhibiting mPTP opening and mitochondria-dependent apoptosis. [ABSTRACT FROM AUTHOR]

Copyright of Revista Veterinaria is the property of Universidad Nacional del Nordeste and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Highlights: [•] Glucosides of atractyligenin derivatives were isolated from coffee. [•] Carboxyatractyligenin-glcp inhibits mitochondrial adenine nucleotide translocase. [•] A quantitation method was developed for atractyligenin glucoside derivatives. [•] Carboxyatractyligenin-glcp is degraded upon coffee roasting. [ABSTRACT FROM AUTHOR]

A group of 342 beef calves, corralled in the Patagonia region of Argentina, were fed alfalfa hay that had been inadvertently contaminated with Wedelia glauca. A total of 147 (43%) calves died within 4 days. Pathologic findings in 2 calves were diffuse centrilobular hepatic necrosis and hemorrhage with edema in the gallbladder, common bile duct, and choledochoduodenal junction. Epidermal fragments of W. glauca were identified in rumen contents by microscopy. Intact W. glauca plants and leaf fragments were found in the hay. Patches of defoliated W. glauca were also identified in the alfalfa pasture from which the hay had been baled. [ABSTRACT FROM PUBLISHER]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)