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International Archives of Allergy and... 2021Cough-variant asthma (CVA) is a special type of asthma, solely manifesting with coughing. Studies suggest that airway inflammation is associated with CVA pathogenesis....
Amygdalin Attenuates Airway Epithelium Apoptosis, Inflammation, and Epithelial-Mesenchymal Transition through Restraining the TLR4/NF-κB Signaling Pathway on LPS-Treated BEAS-2B Bronchial Epithelial Cells.
BACKGROUND
Cough-variant asthma (CVA) is a special type of asthma, solely manifesting with coughing. Studies suggest that airway inflammation is associated with CVA pathogenesis. Amygdalin is found to have an anti-inflammatory potential, while how it affects CVA remains unexplored.
METHODS
Cytotoxicity delivered by various concentrations of LPS and amygdalin on BEAS-2B cells was determined by Cell Counting Kit-8 assay. CVA in vitro models were established via LPS exposure on BEAS-2B cells which underwent amygdalin pretreatment. Cell apoptosis was determined by flow cytometry. Production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and mucin 5AC (MUC5AC) in BEAS-2B cells was measured by ELISA and qRT-PCR. Expressions of TLR4, E-cadherin, N-cadherin, α-smooth muscle actin (SMA), vimentin, phosphorylated-p65 (p-p65), p65, phosphorylated-IκBα (p-IκBα), and IκBα in BEAS-2B cells were measured by qRT-PCR or Western blot.
RESULTS
LPS and high concentrations of amygdalin (over 600 μg/mL) decreased BEAS-2B cell toxicity. Exposure to LPS inhibited toxicity, enhanced apoptosis; and promoted production of TNF-α, IL-6, IL-8, and MUC5AC, increased the levels of N-Cadherin, α-SMA, vimentin, p-p65, and p-IκBα, and decreased the levels of E-cadherin and IκBα in BEAS-2B cells. Amygdalin pretreatment counteracted the effects of LPS on BEAS-2B cells. Overexpressing TLR4 reversed amygdalin-exerted effects in LPS-exposed BEAS-2B cells.
CONCLUSION
Amygdalin attenuated airway epithelium apoptosis, inflammation and epithelial-mesenchymal transition through restraining the TLR4/NF-κB signaling pathway in CVA.
Topics: Amygdalin; Anti-Inflammatory Agents; Apoptosis; Cell Line; Cytokines; Epithelial-Mesenchymal Transition; Humans; Lipopolysaccharides; NF-kappa B; Respiratory Mucosa; Signal Transduction; Toll-Like Receptor 4
PubMed: 34428767
DOI: 10.1159/000514209 -
Journal of Applied Microbiology Mar 2022Based on the gut microbiota and plasma metabolites, the underlying mechanism was analysed for the anti-hepatocellular carcinoma (HCC) effects of Ganfule capsule (GFL) in...
AIMS
Based on the gut microbiota and plasma metabolites, the underlying mechanism was analysed for the anti-hepatocellular carcinoma (HCC) effects of Ganfule capsule (GFL) in the study.
METHODS AND RESULTS
The UPLC-Q-TOF/MS results showed that 13 key compounds were identified in GFL and the major active ingredients included amygdalin, saikosaponin A, astragaloside I, etc. The nude mice received HepG2 injection, and GFL showed lower volume and weight of the tumour. In addition, the apoptosis proteins (Bax and Bcl2) were altered in response to GFL treatment, and apoptosis cells were increased, indicating an anti-HCC effect. Interestingly, 16S rDNA results showed that GFL treatment improved gut microbiota diversity and compositions, especially for the beneficial bacteria, such as Bacilli, Lactobacillales, Lactobacillus, Lactobacillaceae, Firmicutes, Lactobacillus_reuteri and Lactobacillus_gasseri. Metabonomics further identified 426 metabolites and 343 metabolites variation in the positive and negative ion modes after GFL treatment, which might be associated with amino acid, lipid metabolism and carbohydrate metabolism pathways, indicating these metabolites might involve in the protective role of GFL in HCC. Correlation analysis showed a significant relationship between gut microbiota and plasma metabolites.
CONCLUSION
In conclusion, GFL exerted an anti-HCC effect in the nude murine model, which might be associated with microbial and metabolic improvements.
SIGNIFICANCE AND IMPACT OF THE STUDY
This study is the first to report the anti-HCC effect of GFL associated with gut microbiota and plasma metabolites. GFL may improve the gut microbiota structure, such as increasing probiotics - Lactobacillus. It also provides a new strategy for the scientific demonstration of the modernization of traditional Chinese medicine.
Topics: Animals; Carcinoma, Hepatocellular; Gastrointestinal Microbiome; Liver Neoplasms; Metabolome; Mice; Mice, Nude
PubMed: 34564943
DOI: 10.1111/jam.15307 -
Life Sciences Jan 2021To explore the protective efficacies and potent mechanism of amygdalin on high glucose-cultured renal cell HBZY-1 in vitro and streptozotocin (STZ)-induced diabetic...
AIMS
To explore the protective efficacies and potent mechanism of amygdalin on high glucose-cultured renal cell HBZY-1 in vitro and streptozotocin (STZ)-induced diabetic nephropathy (DN) rat in vivo.
MAIN METHODS
The cellar proliferation and generation of ROS in high-glucose cultured HBZY-1 cell were assessed by MTT and DCFH-DA assay, respectively. The fasting blood glucose levels, renal function and inflammation indexes as well as oxidative stress markers in STZ-induced diabetic rats were all measured. The histologic renal section was stained with Mason and periodic acid-Schiff (PAS) method. Immunohistochemistry and western blotting methods were applied to assess expression levels of extracellular matrix (ECM), epithelial-mesenchymal transition (EMT)-related as well as TGF-β1/Smad signaling pathway-related proteins.
KEY FINDINGS
Firstly, amygdalin significantly suppressed the excessive cell proliferation and ROS generation in HBZY-1 cells cultured with high glucose. The hyperglycemia, 24 h-UP excretion, BUN and Scr of DN rats were significantly attenuated after the chronic treatment of amygdalin. Moreover, MDA, SOD, IFN-γ and IL-12 levels in kidney tissues were all effectively reduced. Besides, amygdalin can suppress the ECM accumulation and EMT transformation by inhibiting Smad/TGF-β pathway to alleviate the renal fibrosis in renal tissues of DN model rats.
SIGNIFICANCE
Amygdalin ameliorates excessive oxidative stress, inflammation and renal tissue fibrosis of DN mainly by suppressing TGF-β1/Smad signaling pathway and regulating the key enzymes of ECM degradation.
Topics: Amygdalin; Animals; Cell Line; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Epithelial-Mesenchymal Transition; Female; Fibrosis; Glucose; Inflammation; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction; Streptozocin; Transforming Growth Factor beta1
PubMed: 33253723
DOI: 10.1016/j.lfs.2020.118835 -
Food Additives & Contaminants. Part A,... Oct 2019This work is focused on separation and determination of amygdalin and its unnatural form neoamygdalin in natural food supplements. Reversed-phase high-performance liquid...
This work is focused on separation and determination of amygdalin and its unnatural form neoamygdalin in natural food supplements. Reversed-phase high-performance liquid chromatography with a high-stability silica-based column with C functional group has been used for solving this problem. The effect of the mobile phase composition as well as the column temperature on the separation of the amygdalin epimers has been investigated. Isocratic elution using a mobile phase composed of 0.05% aqueous formic acid and acetonitrile achieved the required separation within 17 min. Under optimum chromatographic conditions, the developed method was validated and was applied for the determination of amygdalin epimers in natural food supplements containing apricot or peach kernels. A simple extraction method using methanol as an extractant supported by an ultrasonic bath was used with recovery in the range of 94.8% to 104.3%. The limit of detection and limit of quantification values for R-amygdalin were 0.13 mg/L and 0.40 mg/L, respectively. The developed method proved to be precise with the intra-day and inter-day relative standard deviation values less than 2.23%.
Topics: Amygdalin; Antineoplastic Agents, Phytogenic; Chromatography, High Pressure Liquid; Dietary Supplements; European Union; Food Analysis; Food Contamination; Molecular Conformation; Silicon Dioxide
PubMed: 31397641
DOI: 10.1080/19440049.2019.1650962 -
Pharmacological Research Sep 2019The dynamic and delicate interactions amongst intestinal microbiota, metabolome and metabolism dictates human health and disease. In recent years, our understanding of... (Review)
Review
The dynamic and delicate interactions amongst intestinal microbiota, metabolome and metabolism dictates human health and disease. In recent years, our understanding of gut microbial regulation of intestinal immunometabolic and redox homeostasis have evolved mainly out of in vivo studies associated with high-fat feeding induced metabolic diseases. Techniques utilizing fecal transplantation and germ-free mice have been instrumental in reproducibly demonstrating how the gut microbiota affects disease pathogenesis. However, the pillars of modern drug discovery i.e. evidence-based pharmacological studies critically lack focus on intestinal microflora. This is primarily due to targeted in vitro molecular-approaches at cellular-level that largely overlook the etiology of disease pathogenesis from the physiological perspective. Thus, this review aims to provide a comprehensive understanding of the key notions of intestinal microbiota and dysbiosis, and highlight the microbiota-phytochemical bidirectional interactions that affects bioavailability and bioactivity of parent phytochemicals and their metabolites. Potentially by focusing on the three major aspects of gut microbiota i.e. microbial abundance, diversity, and functions, I will discuss phytochemical-microbiota reciprocal interactions, biotransformation of phytochemicals and plant-derived drugs, and pre-clinical and clinical efficacies of herbal medicine on dysbiosis. Additionally, in relation to phytochemical pharmacology, I will briefly discuss the role of dietary-patterns associated with changes in microbial profiles and review pharmacological study models considering possible microbial effects. This review therefore, emphasize on the timely and critically needed evidence-based phytochemical studies focusing on gut microbiota and will provide newer insights for future pre-clinical and clinical phytopharmacological interventions.
Topics: Animals; Biotransformation; Diet; Gastrointestinal Microbiome; Humans; Phytochemicals; Phytotherapy
PubMed: 31344423
DOI: 10.1016/j.phrs.2019.104367 -
Journal of Microbiology and... Oct 2023Infectious diseases caused by drug-resistant () pose a critical concern for medical institutions as they can lead to high morbidity and mortality rates. In this study,...
Infectious diseases caused by drug-resistant () pose a critical concern for medical institutions as they can lead to high morbidity and mortality rates. In this study, amygdalin exhibited anti-inflammatory and antioxidant activities, as well as other potentials. However, whether it could influence the drug-resistant -infected cells remained unanswered. Amygdalin was therefore tested in a cellular model in which human macrophages were exposed to resistant . Apoptosis was measured by flow cytometry and the lactate dehydrogenase (LDH) assay. Western immunoblotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to quantify interleukin-18 (IL-18), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The production of reactive oxygen species (ROS) in macrophages was detected by ROS kit. The expression of panapoptotic proteins in macrophages was measured by qRT-PCR and Western immunoblotting. Drug-Resistant inhibited cell viability and enhanced apoptosis in the cellular model. In cells treated with amygdalin, this compound can inhibit cell apoptosis and reduce the expression of pro - inflammatory cytokines such as IL-1β, IL-18 and IL-6. Additionally, it decreases the production of PANoptosis proteins, Furthermore, amygdalin lowered the levels of reactive oxygen species induced by drug-resistant , in cells, demonstrating its antioxidant effects. Amygdalin, a drug with a protective role, alleviated cell damage caused by drug-resistant in human macrophages by inhibiting the PANoptosis signaling pathway.
Topics: Humans; Amygdalin; Interleukin-6; Interleukin-18; Escherichia coli; Reactive Oxygen Species; Macrophages
PubMed: 37559205
DOI: 10.4014/jmb.2306.06030 -
Molecules (Basel, Switzerland) Oct 2021The inflammatory reaction accompanies in part or in full any disease process in the vascularized metazoan. This complicated reaction is controlled by regulatory... (Review)
Review
The inflammatory reaction accompanies in part or in full any disease process in the vascularized metazoan. This complicated reaction is controlled by regulatory mechanisms, some of which produce unpleasant symptomatic manifestations of inflammation. Therefore, there has been an effort to develop selective drugs aimed at removing pain, fever, or swelling. Gradually, however, serious adverse side effects of such inhibitors became apparent. Scientific research has therefore continued to explore new possibilities, including naturally available substances. Amygdalin is a cyanogenic glycoside present, e.g., in bitter almonds. This glycoside has already sparked many discussions among scientists, especially about its anticancer potential and related toxic cyanides. However, toxicity at different doses made it generally unacceptable. Although amygdalin given at the correct oral dose may not lead to poisoning, it has not yet been accurately quantified, as its action is often affected by different intestinal microbial consortia. Its pharmacological activities have been studied, but its effects on the body's inflammatory response are lacking. This review discusses the chemical structure, toxicity, and current knowledge of the molecular mechanism of amygdalin activity on immune functions, including the anti-inflammatory effect, but also discusses inflammation as such, its mediators with diverse functions, which are usually targeted by drugs.
Topics: Amygdalin; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 1; Cyclooxygenase 2; Cytokines; Humans; Inflammation; Inflammation Mediators
PubMed: 34641516
DOI: 10.3390/molecules26195972 -
Food Chemistry Feb 2022Samples containing cyanide were incubated at 85 °C in the presence of the fluorogenic reagent 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ) and glutamic acid, and...
Samples containing cyanide were incubated at 85 °C in the presence of the fluorogenic reagent 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ) and glutamic acid, and analyzed by capillary electrophoresis utilizing post-separation laser-induced fluorescence detection in a sheath flow cuvette. The separation time on a 25 cm long capillary at 800 Vcm was 3 min with the fluorescent product eluting at 107 s. Flushing of the capillary was not required between runs. Signal was proportional with cyanide concentration from 50 nM to 1.5 μM. LOD and LOQ were determined to be 26 and 87 nM respectively. As an application, free cyanide in five individual apple seeds was measured and found to range from 12 to 86 ng/mg, with a mean of 55 ± 32 ng/mg. As a means for the detection of amygdalin, cyanide was enzymatically produced from amygdalin using the enzymes β-glucosidase and mandelonitrile lyase. The cyanide was then reacted with FQ and injected onto the capillary. Amygdalin was detected at a concentration of 1 μM.
Topics: Cyanides; Electrophoresis, Capillary
PubMed: 34788967
DOI: 10.1016/j.foodchem.2021.131377 -
International Immunopharmacology Jan 2021The activation of hepatic stellate cells (HSCs) has been considered one of the major events in hepatic fibrosis. Amygdalin has been used to treat cancers and alleviate...
The activation of hepatic stellate cells (HSCs) has been considered one of the major events in hepatic fibrosis. Amygdalin has been used to treat cancers and alleviate pain; however, its role and mechanism in HSC activation and hepatic fibrosis remain unclear. In the present study, transforming growth factor-beta 1 (TGF-β1) stimulated the activation of HSCs, as indicated by significantly increased alpha-smooth muscle actin (α-SMA), desmin, collagen I, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein levels. Amygdalin treatment dramatically suppressed TGF-β1-induced HSC proliferation and activation. Moreover, amygdalin treatment also reduced the TGF-β1-induced secretion of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), platelet-derived growth factor (PDGF), and chemokine (C-C motif) ligand 2 (CCL2), as well as the phosphorylation of Smad2, Smad3, and p65. In the CCl-stimulated liver fibrosis rat model, amygdalin treatment improved liver fibrosis and liver damage by reducing focal necrosis, collagen fiber accumulation, and the protein levels of α-SMA, desmin, collagen I, and TIMP-1 in hepatic tissue samples and reducing serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In conclusion, we demonstrated the suppressive effects of amygdalin in TGF-β1-induced HSC activation through modulating proliferation, fibrogenesis, and inflammation signaling in vitro and the antifibrotic effects of amygdalin in CCl-stimulated hepatic fibrosis in rats in vivo.
Topics: Amygdalin; Animals; Anti-Inflammatory Agents; Carbon Tetrachloride; Cell Line; Cell Proliferation; Chemical and Drug Induced Liver Injury; Cytokines; Gene Expression Regulation; Humans; Inflammation Mediators; Kupffer Cells; Liver; Liver Cirrhosis, Experimental; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta1; Rats
PubMed: 33296784
DOI: 10.1016/j.intimp.2020.107151 -
Acta Biochimica Et Biophysica Sinica Sep 2022Mounting evidence supports that long-term exposure to fine particle pollutants (PM2.5) is closely implicated in cardiovascular diseases, especially atherosclerosis....
Mounting evidence supports that long-term exposure to fine particle pollutants (PM2.5) is closely implicated in cardiovascular diseases, especially atherosclerosis. Amygdalin is reported to attenuate external stimuli-induced cardiovascular diseases. However, the underlying mechanisms are still not understood. In this study, we aim to explore the protective effects of amygdalin on PM2.5-induced human umbilical vein endothelial cell (HUVEC) injury and unravel the specific mechanisms by MTT, DCFH-DA, biochemical, immunofluorescence, ELISA, RT-qPCR, flow cytometry, TUNEL and western blot analysis. The results reveal that amygdalin reverses PM2.5-induced cytotoxicity and attenuates intracellular ROS production. Moreover, amygdalin increases the levels of SOD and GSH and alleviates the MDA content. Additionally, amygdalin causes a decline of IL-6, IL-1β, TNF-α and COX-2 levels. Moreover, amygdalin inhibits NF-κB p50 and TLR4 protein expressions and NF-κB p65 nuclear translocation. Concomitantly, a decline of phospho-NF-κB p65/NF-κB p65 and phospho-IκB-α/IκB-α is detected. Meanwhile, amygdalin pretreatment reduces HUVEC apoptosis. In addition, amygdalin triggers an upregulation of Bcl-2 and a downregulation of Bax after stimulation with PM2.5. Collectively, these results suggest that amygdalin suppresses PM2.5-induced HUVEC injury by regulating the TLR4/NF-κB and Bcl-2/Bax signaling pathways, indicating that amygdalin may be a novel target for atherosclerosis treatments.
Topics: Humans; NF-kappa B; Amygdalin; bcl-2-Associated X Protein; NF-KappaB Inhibitor alpha; Human Umbilical Vein Endothelial Cells; Toll-Like Receptor 4; Cardiovascular Diseases; Signal Transduction; Particulate Matter
PubMed: 36178164
DOI: 10.3724/abbs.2022136