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Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin‐3′‐O‐sulfate (M3′S), AMP, and ampelopsin‐4′‐O‐sulfate (A4′S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion‐transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3′S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3′S, AMP, and A4′S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3′S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3′S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR‐containing dietary supplements may affect the OATP‐mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3′S. [ABSTRACT FROM AUTHOR]

Abstract Myricetin (MYR) and ampelopsin (AMP, or dihydromyricetin) are flavonoid aglycones found in certain plants and dietary supplements. During the presystemic biotransformation of flavonoids, mainly sulfate and glucuronide derivatives are produced, which are the dominant metabolites in the circulation. In this study, we tested the interactions of MYR, myricetin‐3′‐O‐sulfate (M3′S), AMP, and ampelopsin‐4′‐O‐sulfate (A4′S) with human serum albumin (HSA), cytochrome P450 enzymes (CYPs), and organic anion‐transporting polypeptides (OATPs) using in vitro models, including the recently developed method for measuring flavonoid levels in living cells. M3′S and MYR bound to albumin with high affinity, and they showed moderate displacing effects versus the Site I marker warfarin. MYR, M3′S, AMP, and A4′S exerted no or only minor inhibitory effects on CYP2C9, CYP2C19, and CYP3A4 enzymes. M3′S and MYR caused considerable inhibitory actions on OATP1B1 at low micromolar concentrations (IC50 = 1.7 and 6.4 μM, respectively), while even their nanomolar levels resulted in strong inhibitory effects on OATP2B1 (IC50 = 0.3 and 0.4 μM, respectively). In addition, M3′S proved to be a substrate of OATP1B1 and OATP2B1. These results suggest that MYR‐containing dietary supplements may affect the OATP‐mediated transport of certain drugs, and OATPs are involved in the tissue uptake of M3′S.

Ampelopsin (AMP) had a wound-healing effect in rat skin wounds with or without purulent infection. However, the role of AMP in diabetic wound healing remains poorly defined. Wounds were created on the dorsal skin of type 2 diabetic mouse model, and the histological features of wounds were examined by hematoxylin and eosin (HE) staining. Caspase-1 activity and the secretion of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability and migration were examined through cell counting kit-8 (CCK-8) and wound healing assays, respectively. AMP facilitated wound healing in vivo. AMP notably facilitated platelet endothelial cell adhesion molecule-31 (CD31), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA), and inhibited matrix metallopeptidase 9 (MMP9) and cyclooxygenase 2 (Cox2) expression in diabetic wounds. The inflammasome pathway was implicated in skin injury. AMP inhibited pro-inflammatory factor secretions and NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in diabetic wounds and high glucose-treated THP-1 macrophages. AMP-mediated NLRP3 inflammasome inhibition in THP-1 macrophages increased cell viability and migratory capacity in HaCaT cells. AMP facilitated diabetic wound healing and increased keratinocyte cell viability and migratory ability by inhibiting the NLRP3 inflammasome pathway in macrophages. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.

Parkinson's disease (PD) is a progressive neurodegenerative disease associated with loss of dopaminergic neurons in the substantia nigra pars compacta. Although aging is the primary cause, environmental and genetic factors have also been implicated in its etiology. In fact, the sporadic nature of PD (i.e., unknown etiology) renders the uncovering of the exact pathogenic mechanism(s) or development of effective pharmacotherapies challenging. In search of novel neuroprotectants, we showed that butyrate (BUT), a short-chain fatty acid, protects against salsolinol (SALS)-induced toxicity in human neuroblastoma-derived SH-SY5Y cells, which are considered an in-vitro model of PD. Dihydromyricetin (DHM), a flavonoid derived from Asian medicinal plant, has also shown effectiveness against oxidative damage and neuroinflammation, hallmarks of neurodegenerative diseases. Here we show that pretreatment of SH-SY5Y cells with DHM concentration-dependently prevented SALS-induced toxicity and that a combination of DHM and BUT resulted in a synergistic protection. The effects of both DHM and BUT in turn could be completely blocked by flumazenil (FLU), a GABAA antagonist acting at benzodiazepine receptor site, and by bicuculline (BIC), a GABAA antagonist acting at orthosteric site. Beta-hydroxybutyrate (BHB), a free fatty acid 3 (FA3) receptor antagonist, also fully blocked the protective effect of DHM. BHB was shown previously to only partially block the protective effect of BUT. Thus, there are some overlaps and some distinct differences in protective mechanisms of DHM and BUT against SALS-induced toxicity. It is suggested that a combination of DHM and BUT may have therapeutic potential in PD. However, further in-vivo verifications are necessary. [ABSTRACT FROM AUTHOR]

Cancer is being considered as a serious threat to human health globally due to limited availability and efficacy of therapeutics. In addition, existing chemotherapeutic drugs possess a diverse range of toxic side effects. Therefore, more research is welcomed to investigate the chemo-preventive action of plant-based metabolites. Ampelopsin (dihydromyricetin) is one among the biologically active plant-based chemicals with promising anti-cancer actions. It modulates the expression of various cellular molecules that are involved in cancer progressions. For instance, ampelopsin enhances the expression of apoptosis inducing proteins. It regulates the expression of angiogenic and metastatic proteins to inhibit tumor growth. Expression of inflammatory markers has also been found to be suppressed by ampelopsin in cancer cells. The present review article describes various anti-tumor cellular targets of ampelopsin at a single podium which will help the researchers to understand mechanistic insight of this phytochemical.

Background: Breast cancer (BC) is the most frequent type of gynecology tumors with high morbidity and mortality. Ampelopsin, the main active compound of Ampelopsis grossedentata, exerts an anti-tumor effect on a variety of cancers. However, the anti-cancer role of ampelopsin in BC remains unclear. The aim of this study is to explore the mechanism of ampelopsin against breast cancer. Materials and Methods: The target genes of ampelopsin in the treatment of breast cancer were determined and analyzed by network pharmacology and molecular docking. Cytoscape software was used to identify the core target genes and construct a protein--protein interaction (PPI) network. Discovery Studio software was used to perform the molecular docking of ampelopsin and core genes and glycolytic metabolic enzymes. Results: In total, 25 potential target genes of ampelopsin were screened out. The core target genes of ampelopsin against breast cancer were AKT1, ESR1, ESR2, NCOA1, HSP90AA1, NCOA2, BECN1, COMT, HMOX1, and CDK6, with AKT1, ESR1 and ESR2 considered as the key target proteins. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that ampelopsin inhibited breast cancer via modulating the estrogen signaling pathway, apoptosis regulation, carbohydrate metabolism, and inflammation. Molecular docking analysis showed that ampelopsin possessed a stable binding ability to regulate the three target proteins and glycolytic metabolic enzymes such as ALDOA and LDHA. Conclusions: Ampelopsin may inhibit the proliferation of breast cancer cells by acting on AKT and estrogen-related glucose metabolic pathways and inhibiting the enzymes involved in glycolysis and oxidative phosphorylation. [ABSTRACT FROM AUTHOR]

Toxicity induced by binge alcohol drinking, particularly in adolescent and young adults, is of major medical and social consequence. Recently, we reported that butyrate, a short chain fatty acid, can protect against ethanol (ETOH)-induced toxicity in an in vitro model. In this study, we sought to evaluate the potential effectiveness of dihydromyricetin (DHM), a natural bioactive flavonoid, alone or in combination with butyrate in the same model. Exposure of SH-SY5Y cells for 24 h to 500 mM ETOH resulted in approximately 40% reduction in cell viability, which was completely prevented by 0.1 μM DHM. Combinations of DHM and butyrate provided synergistic protection against alcohol toxicity. Whereas butyrate effect was shown to be mediated primarily through fatty acid receptor 3 activation, DHM protection appears to be mediated primarily via benzodiazepine receptor site of GABAA receptor. This is based on the finding that DHM's effect could be completely prevented by pretreatment with flumazenil, a selective antagonist at this site, but not by bicuculline, a selective antagonist at the actual GABAA receptor binding site. These findings suggest potential utility of DHM alone or in combination with butyrate against ETOH-induced toxicity. [ABSTRACT FROM AUTHOR]

In ischemic stroke, reperfusion after thrombolysis is associated with secondary brain damage. Dihydromyricetin (DHM), a flavonoid, has shown neuroprotective effects through anti-oxidant, anti-inflammatory and anti-apoptotic properties. This study investigates the potential of DHM, given postreperfusion in middle cerebral artery occlusion (MCAo) model of stroke in rats. MCAo surgery was performed in male Wistar rats. Reperfusion was performed after 90 min of ischemia. DHM (50 and 100 mg/kg) was administered 10–15 min and 2 h postreperfusion followed by daily dosing for 2 more days. Neurobehavioral parameters and infarct size (TTC staining) were assessed after 72 h. The effective dose (100 mg/kg) was then used to study reduction in infarct size (measured by MRI) and effect on apoptosis (evaluated by protein expression of Bax, Bcl-2 and cleaved caspase-3 and TUNEL assay) in peri-infarct cortex. Furthermore, effects of DHM on neuronal damage and activation of astrocytes were studied by immunofluorescence. Poststroke DHM (100 mg/kg) administered for 3 days showed significant improvements in motor-coordination and infarct damage (TTC staining and MRI). MCAo-induced altered apoptotic proteins were normalized to a significant extent in peri-infarct cortex with DHM treatment. Data from TUNEL assay were complementary to the effects on apoptotic proteins. Additionally, DHM caused a significant reduction in the number of reactive astrocytes when compared with the MCAo group. This study demonstrated the efficacy of subacute DHM treatment in ischemia/reperfusion injury by modulating apoptosis and astrogliosis in the peri-infarct cortex. This suggests the potential of DHM in attenuating disease progression. [ABSTRACT FROM AUTHOR]

Herbal teas like vine tea (Ampelopsis grossedentata) have been traditionally consumed worldwide because of their health-promotion and pleasant taste. Vine tea and its main bioactive component, dihydromyricetin, have gained attention because of their potential applications in food, material, and pharmaceutical sciences. Vine tea and dihydromyricetin have been suggested as potential natural antioxidants to extend shelf life of foods. Studies have also suggested potential application in packaging and food safety. Additionally, dietary supplementation with vine tea extract have shown great potential to prevent metabolic diseases, which can justify its application in novel functional foods. This review discusses the chemistry, functional properties, and potential applications of vine tea and dihydromyricetin in the food industry. Although vine tea extracts and dihydromyricetin have shown promising results, further studies on optimal application, thermal stability, synergetic effect with other natural antioxidants, consumer acceptability, and sensory profile of vine tea are needed to support food product innovation.

• Two flavonoids and one ellagic acid derivative were isolated from the roots of Euphorbia tirucalli. • 13 compounds were identified by HPLC-MS/MS analysis. • Ethanol extract from roots of E. tirucalli and the isolated compounds displayed significant antimicrobial activity. Euphorbia tirucalli (Euphorbiaceae) is a species widely utilized for popular medicine in northeast of Brazil because of its innumerable reported medicinal properties. The HPLC-Qtrap-MS/MS analysis from E. tirucalli roots ethanol extract revealed that this species presents 8 flavonoids and 5 shikimate derivative compounds. Chemical studies of these ethanolic extract using chromatographic procedures allowed the isolation of four previously unreported compounds for this species: myricetin, 3,3'-dimethoxy-4- O -α-rhamnopyranoside-ellagic acid, 4- O -methyl-gallic acid and ampelopsin. All structures were determined using 1D and 2D NMR spectroscopy analysis. The ethanol extract and four isolated compounds were evaluated for antimicrobial activity against Staphylococcus aureus , Escherichia coli , Sporothrix brasiliensis and Candida albicans. All the analyzed compounds presented activity against all evaluated bacteria and fungi, with MIC values ranging from 8 to 2048 μg/mL. [ABSTRACT FROM AUTHOR]

Dihydromyricetin (DHM) dramatically improved the quality of life for Streptozotocin (STZ)-induced diabetic rats and significantly increased the activity of antioxidant enzymes in the liver. Moreover, DHM successfully ameliorated diabetes-induced liver damage by suppression of apoptosis in the liver, as indicated by the decreased levels of Bax and cleaved caspase-3. In diabetic rats, the levels of tumor necrosis factor-α and interleukin-1β in the liver were significantly increased. However, the administration of DHM (100–400 mg/kg/day) for 6 weeks restored the cytokine levels to their normal values in a dose-dependent manner in diabetic rats by the regulation of nuclear factor-kappa B signaling pathway. In addition, DHM significantly induced 5′ AMP-activated protein kinase (AMPK) phosphorylation and decreased MyD88, TLR4, p38, GSK-3β protein expression levels in the liver of diabetic rats. In conclusion, DHM could improve STZ-induced liver impairment by preventing oxidative stress, apoptosis, and inflammation.

Ampelopsis grossedentata (AG) is an ancient medicinal plant that is mainly distributed and used in southwest China. It exerts therapeutic effects, such as antioxidant, anti-diabetic, and anti-inflammatory activities, reductions in blood pressure and cholesterol and hepatoprotective effects. Researchers in China recently reported the anti-obesity effects of AG extract in diet-induced obese mice and rats. To verify these findings, we herein investigated the effects of AG extract and its principal compound, ampelopsin, in high-fat diet (HFD)- and alcohol diet-fed mice, olive oil-loaded mice, and differentiated 3T3-L1 cells. The results obtained showed that AG extract and ampelopsin significantly suppressed increases in the weights of body, livers and abdominal fat and also up-regulated the expression of carnitine palmitoyltransferase 1A in HFD-fed mice. In olive oil-loaded mice, AG extract and ampelopsin significantly attenuated increases in serum triglyceride (TG) levels. In differentiated 3T3-L1 cells, AG extract and ampelopsin promoted TG decomposition, which appeared to be attributed to the expression of hormone-sensitive lipase. In alcohol diet-fed mice, AG extract and ampelopsin reduced serum levels of ethanol, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) and liver TG. An examination of metabolic enzyme expression patterns revealed that AG extract and ampelopsin mainly enhanced the expression of aldehyde dehydrogenase and suppressed that of cytochrome P450, family 2, subfamily e1. In conclusion, AG extract and ampelopsin suppressed diet-induced intestinal fat accumulation and reduced the risk of fatty liver associated with HFD and alcohol consumption.

The aim of this study was to investigate the effects of ampelopsin (AMP) on injuries of ovarian and lung tissues generated by bilateral ovarian torsion/detorsion (TD) model in rats. In the present study, 32 Sprague Dawley female rats were randomly divided into four groups. Groups planned as sham, TD, 80 mg/kg dose of AMP+TD, and 160 mg/kg dose of AMP+TD. In the sham group, the abdomen was opened applying an incision and closed again without TD model. In TD group, 3 hours of torsion followed 3 hours of detorsion were made. In the 80 and 160 mg/kg dose groups, respectively, AMP was given orally 80 and 160 mg/kg doses before detorsion and TD was performed as defined in TD group. At the end of detorsion period, rats were sacrificed and the ovarian and lung tissues were quickly removed. All results were analyzed using statistically appropriate tests. Malondialdehyde (MDA) level, myeloperoxidase (MPO) activity, tumor necrosis faktor-α (TNF-α), interleukin-1beta (IL-1ß), total oxidant status (TOS) and oxidative stress index (OSI) values increased significantly in TD group when compared to sham group (p≤0.05). However, superoxide dismutase (SOD) enzyme activity and total antioxidant status (TAS) values decreased in ovarian and lung tissues of TD group. Conversely, SOD enzyme activity increased, while TOS and OSI values, MPO activity and TNF-α, IL-1ß, MDA levels decreased significantly due to administration of AMP in 80 and 160 mg/kg dose groups (p≤0.05). As a conclusion, in this study, it was demonstrated that 80 and 160 mg/kg doses of AMP administrations protected against oxidative damage of the ovarian and lung tissues that generated by experimental TD in rats. [ABSTRACT FROM AUTHOR]

Background: Cancer-induced bone pain (CIBP) is the pain caused by bone metastasis from malignant tumors, and the largest source of pain for cancer patients. miR-300 is an important miRNA in cancer. It has been shown that miR-300 regulates tumorigenesis of various tumors. Purpose: This study aims to investigate the role of miR-300 in CIBP and its underlying molecular mechanisms in vitro and in vivo. Methods: We constructed CIBP model in rats and investigated the mechanism through which miR-300 affects CIBP. We first examined expression level of miR-300 in CIBP rats and then tested the effect of its overexpression. Next, we identified the target of miR-300 using TargetScan analysis and double luciferase assay. Finally, we studied genetic interactions between miR-300 and its target and their roles in CIBP. Results: We found that miR-300 was downregulated in CIBP rats. Overexpression of miR-300 significantly attenuated cancer-induced neuropathic pain (p < 0.01). Furthermore, TargetScan analysis and double luciferase assay show High Mobility Group Box 1 (HMGB1) is a target of miR-300. Notably, HMGB1 is overexpressed in CIBP rats, while up-regulation of miR-300 significantly suppresses expression of HMGB1 (p < 0.01). Moreover, knockdown of HMGB1 by siRNA significantly relieves cancer-induced neuropathic pain in rats (p < 0.01). On the other hand, HMGB1 overexpression partially blocked the effect of miR-300 on cancer-induced nerve pain. Conclusion: miR-300 relieves cancer-induced neuropathic pain by inhibiting HMGB1 expression. These results may be beneficial for the treatment of CIBP in clinical practice. [ABSTRACT FROM AUTHOR]

Ampelopsin, also known as dihydromyricetin, is a commonly found flavonoid in medicinal plants. The cancer stem cell (CSC) population is a promising target for triple-negative breast cancer (TNBC). In this study, flavonoid screening was performed in the established MDA-MB-231/IR cell line, which is enriched in CSCs. Ampelopsin suppressed the proliferation and colony formation of stem cell-rich MDA-MB-231/IR, while inducing their apoptosis. Importantly, ampelopsin displayed an inhibitory impact on the stemness features of MDA-MB-231/IR cells, demonstrated by decreases in mammosphere formation, the CD44+/CD24−/low population, aldehyde dehydrogenase activity, and the levels of stem cell markers (e.g., CD44, MRP1, β-catenin, and KLF4). Ampelopsin also suppressed the epithelial–mesenchymal transition, as evidenced by decreases in migration, invasion capacity, and mesenchymal markers, as well as an increase in the epithelial marker E-cadherin. Moreover, ampelopsin significantly impaired oxidative phosphorylation by reducing the oxygen consumption rate and adenosine triphosphate production in MDA-MB-231/IR cells. Notably, ampelopsin treatment significantly reduced the levels of the phosphorylated forms of IκBα and NF-κB p65, as well as the levels of tumor necrosis factor (TNF)-α-stimulated phosphorylation of IκBα and NF-κB p65. These results demonstrated that ampelopsin prevents the TNF-α/NF-κB signaling axis in breast CSCs.

Ampelopsin (APS) is the main bioactive component from Ampelopsis grossedentata and has anti-inflammatory properties. We hypothesize that it could reduce the acute phase response (APR) and help to maintain balance between inflammation-mediated oxidative damage and APS-induced protective mechanisms in liver. In the present study, APS possessed strong DPPH, ABTS, H2O2 and O2· radical scavenging activities in different in vitro antioxidant assays. Further study demonstrated that APS alleviated APR as reflected in the changes in the whole body metabolic rate, physical conditions, and production of cytokines in LPS-treated piglets. Moreover, APS has the potential to prevent Akt-mediated activation of NF-κB and decreased the levels of STAT3 in inflammation. The administration of APS ameliorated mitochondrial dysfunction and moderated the involvement of Ref-1 and Nrf2 in the attenuation in LPS-induced APR. The present results suggest that the APS attenuate LPS induced inflammation and oxidative stress in liver of piglets.

Brain aging and neurodegenerative diseases share the hallmarks of slow and progressive loss of neuronal cells. Flavonoids, a subgroup of polyphenols, are broadly present in food and beverage and numerous studies have suggested that it could be useful for preventing or treating neurodegenerative diseases in humans. Dihydromyricetin (DHM) is one of the main flavonoids of some Asian medicinal plants that are used to treat diverse illness. The effects of DHM have been studied in different in vitro systems of oxidative damage and neuroinflammation, as well as in animal models of several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Here we analyzed the most important effects of DHM, including its antioxidant, anti-inflammatory, and neuroprotective effects, as well as its ability to restore GABA neurotransmission and improve motor and cognitive behavior. We propose new areas of research that might contribute to a better understanding of the mechanism of action of this flavonoid, which could help develop a new therapy for aging and age-related brain diseases.

Brain aging and neurodegenerative diseases share the hallmarks of slow and progressive loss of neuronal cells. Flavonoids, a subgroup of polyphenols, are broadly present in food and beverage and numerous studies have suggested that it could be useful for preventing or treating neurodegenerative diseases in humans. Dihydromyricetin (DHM) is one of the main flavonoids of some Asian medicinal plants that are used to treat diverse illness. The effects of DHM have been studied in different in vitro systems of oxidative damage and neuroinflammation, as well as in animal models of several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Here we analyzed the most important effects of DHM, including its antioxidant, anti-inflammatory, and neuroprotective effects, as well as its ability to restore GABA neurotransmission and improve motor and cognitive behavior. We propose new areas of research that might contribute to a better understanding of the mechanism of action of this flavonoid, which could help develop a new therapy for aging and age-related brain diseases. [ABSTRACT FROM AUTHOR]

Luteolin, naringenin, myricetin, and ampelopsin are abundant flavonoids in nature, and several dietary supplements also contain them at very high doses. After the peroral intake, flavonoids go through extensive presystemic biotransformation; therefore, typically their sulfate/glucuronic acid conjugates reach high concentrations in the circulation. Xanthine oxidase (XO) enzyme is involved in uric acid production, and it also takes part in the elimination of certain drugs (e.g., 6-mercaptopurine). The inhibitory effects of flavonoid aglycones on XO have been widely studied; however, only limited data are available regarding their sulfate and glucuronic acid conjugates. In this study, we examined the impacts of luteolin, naringenin, myricetin, ampelopsin, and their sulfate/glucuronide derivatives on XO-catalyzed xanthine and 6-mercaptopurine oxidations employing in vitro enzyme incubation assays and molecular modeling studies. Our major results/conclusions are the following: (1) Sulfate metabolites were stronger while glucuronic acid derivatives were weaker inhibitors of XO compared to the parent flavonoids. (2) Naringenin, ampelopsin, and their metabolites were weak inhibitors of the enzyme. (3) Luteolin, myricetin, and their sulfates were highly potent inhibitors of XO, and the glucuronides of luteolin showed moderate inhibitory impacts. (4) Conjugated metabolites of luteolin and myricetin can be involved in the inhibitory effects of these flavonoids on XO enzyme. [Display omitted] • Effects of flavonoid conjugates on XO enzyme were tested. • Inhibitory actions were examined on XO-catalyzed xanthine and 6-MP oxidation. • Glucuronides were weaker inhibitors of XO than their parent flavonoids. • Sulfates showed stronger inhibitory effects on XO than the respective aglycones. • Luteolin, myricetin and their sulfates are potent inhibitors of XO. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a prevalent cause of lung infections in hospitals and communities, and can cause a wide spectrum of human infections. Due to the bottleneck caused by antibiotic resistance and substantial increases in morbidity and mortality, targeting the virulence factors released by S. aureus as an alternative prevention and treatment method has become a promising approach. Ampelopsin, a component of vine tea, has promising potential for treating S. aureus -induced acute lung injury. In this study, the effects of ampelopsin were investigated on a mouse model of acute lung injury established using S. aureus 8325–4 and the α-hemolysin (hla) silent strain DU1090. The hla silent strain did not cause mortality in mice, whereas lethal and sublethal concentrations of S. aureus 8325–4 caused high mortality. Notably, ampelopsin treatment protected against mortality stemming from S. aureus infection. Ampelopsin yielded enhancements in lung barrier function, decreased total protein leakage in the alveolar lavage fluid, and modulated inflammatory signaling pathway-related proteins, thereby reducing the release of pro-inflammatory factors and improving respiratory dysfunction. Moreover, ampelopsin prevented the upregulation of ADAM10 activity, leading to E-cadherin mucin cleavage. In conclusion, our findings establish the key role of alpha -toxin in infectious lung injury in S. aureus and provide support for ampelopsin as an effective therapeutic approach to improve lung injury. [Display omitted] • Alpha-Toxin secreted by S. aureus facilitates bacterial colonization of the lungs for infection. • Alpha-Toxin secreted by S. aureus was able to activate the metalloproteinase ADAM10 and cleave E-cadherin. • Compared with the alpha-toxin silent strain DU1090, S. aureus 8325-4 secreting alpha-toxin was able to cause massive leakage of proteins in alveolar lavage fluid. • Ampelopsin has been shown to attenuate infectious lung injury through a combination of anti-inflammatory, antimicrobial, and alpha-toxin inhibition effects. [ABSTRACT FROM AUTHOR]

The commercial method for isolation of ampelopsin, one of the most common flavonoids isolated from the plant species Ampelopsis grossedentata, is a simple hydrothermal extraction at high temperature. To develop an improved process to isolate ampelopsin, the effects of treatment of cellulase on hydrolysis of the dried fruit of A. grossedentata were investigated. The treatment of cellulase was found to decrease the temperature and time for hydrolysis of the dried fruit of A. grossedentata. The conditions of the filter press and continuous flow centrifuge for removal of insoluble materials from the hydrolysate of the dried fruit of A. grossedentata were optimized. The recovery yield of ampelopsin from the dried fruits of A. grossedentata was 39.4%, as determined by HPLC chromatographic analysis. A safe and economical process at low temperature with treatment of cellulase for the isolation of ampelopsin was developed in this study.

Increasing evidence has demonstrated that oxidative stress is involved in the pathogenesis of Parkinson's disease (PD), suggesting that pharmacological targeting of the antioxidant machinery may have therapeutic potential. Ampelopsin, a natural flavonoid compound, has been reported to possess various pharmacological functions, including anti-inflammatory, anti-oxidative and anti-cancer effects. However, its neuroprotective effect and neurotoxicity-attenuating role as well as underlying mechanisms are still unclear. In the present study, we investigated the potential role of ampelopsin in neuroprotective function and neurotoxicity attenuation, and explored its corresponding mechanisms against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the cell model of PD. The pretreatment with ampelopsin for 1 h significantly improved cell viability, reduced the release of lactate dehydrogenase (LDH) and inhibited the accumulation of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells. In addition, ampelopsin treatment attenuated 6-OHDA-induced apoptosis of PC12 cells by inhibiting the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Moreover, ampelopsin treatment significantly increased the localization of nuclear factor-erythroid 2-related factor 2 (Nrf2) and subsequent activation of haem oxygenase-1 (HO-1) gene associated with antioxidant response element (ARE) pathway in a dose-dependent manner. Further study demonstrated that ampelopsin treatment suppressed the expression of glycogen synthase kinase-3β (GSK-3β). The present results suggest that the neuroprotective role of ampelopsin is due to the increased expression of Nrf2 through suppressing GSK-3β signalling, thereby correspondingly inhibiting ROS/p-p38/p-JNK MAPK signalling pathway. Therefore, ampelopsin has promising therapeutic potential for PD.

Ampelopsin (Amp) is bioactive natural product and exerts anti‑cancer effects against several cancer types. The present study investigated the anti‑colon cancer activity of Amp and explored its mechanism of action. The treatment of colon cancer cells with Amp resulted in the dose‑ and time‑dependent induction of apoptosis via the activation of endoplasmic reticulum (ER) stress, 5' adenosine monophosphate‑activated protein kinase (AMPK), and c‑Jun N‑terminal protein kinase (JNK)/p38 mitogen‑activated protein kinases (MAPKs). Salubrinal, an ER stress inhibitor, prevented the upregulation of ER stress‑associated proteins, including phosphorylated protein kinase RNA‑like ER kinase, phosphorylated eukaryotic translation initiation factor 2α, glucose‑regulated protein 78, and CCAAT/enhancer‑binding protein homologous protein, as well as suppressing AMPK activation and the MAPK signaling pathway. Knockdown of AMPK by RNA interference failed to block ER stress. Additionally, SP600125 (a JNK inhibitor) and SB203580 (a p38‑MAPK inhibitor) effectively inhibited apoptosis and attenuated the expression of X‑linked IAP‑associated factor 1 (XAF1) and apoptotic Bcl‑2 family proteins (BCL2 antagonist/killer 1 and BCL2‑associated X protein) in Amp‑treated colon cancer cells. Furthermore, reactive oxygen species (ROS)‑mediated ER stress/AMPK apoptotic signaling pathway in Amp‑treated colon cancer cells were markedly inhibited by treatment with N‑acetyl‑L‑cysteine, a ROS scavenger. These results demonstrate that treatment with Amp induces the apoptotic death of colon cancer cells through ER stress‑initiated AMPK/MAPK/XAF1 signaling. These results also provide experimental information for developing Amp as therapeutic drug against colon cancer. [ABSTRACT FROM AUTHOR]

Ampelopsin (AMP) is an active ingredient of flavonoid compounds that is extracted from Ampelopsis megalophylla Diels et Gilg. The present study aimed at investigating the antitumor activities of AMP and the possible underlying molecular mechanisms in HeLa cells. A total of three types of tumor cell were selected to screen antitumor activities for AMP using the MTT assay. Flow cytometry was used to analyze the cell apoptotic proportion and the cell cycle. Rhodamine 123 staining was used to determine changes in mitochondrial transmembrane potential. Western blot analysis was used to determine the expression of apoptosis-associated proteins. The results of the present study demonstrated that AMP may inhibit the viability of HeLa cells in a dose- and time-dependent manner. Changes in morphology were observed using fluorescence microscopy. In addition, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) double staining revealed that AMP induced apoptosis in a concentration-dependent manner and PI staining indicated that HeLa cells were arrested in S phase. Furthermore, western blot analysis demonstrated that AMP treatment induced apoptosis through activation of caspases 9 and 3, which was validated by the increasing ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein to Bcl-2. Additionally, the loss of mitochondrial transmembrane potential and the release of cytochrome c suggested that AMP-induced apoptosis was associated with the mitochondrial pathway. Taken together, these results indicate that AMP may induce apoptosis via the mitochondrial signaling pathway in HeLa cells. [ABSTRACT FROM AUTHOR]

Ampelopsin (APS) is the main bioactive component from Ampelopsis grossedentata and has anti-inflammatory properties. We hypothesize that it could reduce the acute phase response (APR) and help to maintain balance between inflammation-mediated oxidative damage and APS-induced protective mechanisms in liver. In the present study, APS possessed strong DPPH, ABTS, H 2 O 2 and O 2 radical scavenging activities in different in vitro antioxidant assays. Further study demonstrated that APS alleviated APR as reflected in the changes in the whole body metabolic rate, physical conditions, and production of cytokines in LPS-treated piglets. Moreover, APS has the potential to prevent Akt-mediated activation of NF-κB and decreased the levels of STAT3 in inflammation. The administration of APS ameliorated mitochondrial dysfunction and moderated the involvement of Ref-1 and Nrf2 in the attenuation in LPS-induced APR. The present results suggest that the APS attenuate LPS induced inflammation and oxidative stress in liver of piglets. [ABSTRACT FROM AUTHOR]

Ampelopsin (AMP) is isolated from the Chinese medicinal herb Ampelopsis grossedentata (Hand-Mazz) and has been associated with numerous biological and pharmacological activities. However, it is not clear whether AMP has a direct protective effect on cerebral ischemia reperfusion injury. Therefore, the present study investigated its role in acute brain injury following focal cerebral ischemia in rats. The current study induced transient focal cerebral ischemia by performing middle cerebral artery occlusion (MCAO) for 60 min, followed by 24 h of reperfusion. Rats were exposed to 40, 80 and 160 mg/kg AMP by oral administration 30 min prior to MCAO and the cysteinyl leukotriene receptor 1-antagonist, pranlukast (0.1 mg/kg, i.p.) was used as a positive control. Neurological deficit scores were observed and an inclined board test was used to assess behavioral dysfunction. The coronal slices were stained with 3,5-triphenyltetrazolium chloride to determine the infarct volume and brain edema. Neuronal morphology was assessed in brain sections stained with cresyl violet and degenerating neurons were identified using Fluoro-Jade B staining. Blood-brain barrier permeability was determined with immunoglobulin (Ig)G immunohistochemistry. Interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) in serum and cerebrospinal fluid were measured using ELISA kits. AMP at 80 and 160 mg/kg attenuated neurological deficits, reduced infarct volume, brain edema, IgG exudation and neuron degeneration and loss. Similar to pranlukast, AMP also inhibited the MCAO-induced IL-1β and TNF-α release. Thus, AMP has a neuroprotective effect on acute brain injury following focal cerebral ischemia in rats at an effective oral dose of 80-160 mg/kg. The results of the current study indicate a therapeutic role for AMP in the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Objectives Erlotinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), has been shown to have a dramatic effect in non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, the presence of primary resistance or acquired resistance to EGFR-TKI is the most common reason for switching to other anti-cancer agents. Even though there are newer agents that have activity in the presence of the T790 M mutation, identification of potential agents that could overcome resistance to EGFR-TKI is still needed for the treatment of NSCLC patients. Materials and methods In this study, we used erlotinib-resistant NSCLC cell lines to investigate the effects of combination treatment with erlotinib and ampelopsin. After treatment with either single or combination, cell viability and cell death were determined with WST-1 assay, trypan blue exclusion method, colony forming assay, annexin-V staining assay and western blot assay. The content of ROS was evaluated by FACS analysis using H 2 DCF-staining method. To determine the effect of Nox2 and Bim on the combined treatment with erlotinib and ampelopsin-induced cell death, we transfected with Nox2 or Bim specific siRNA and performed with western blot assay for evaluation of its expression. Results Combined treatment with erlotinib and ampelopsin at non-cytotoxic concentrations significantly induced caspase-dependent cell death in erlotinib-resistant NSCLC cells. Furthermore, cell death resulted in the accumulation of reactive oxygen species (ROS) through upregulation of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2) expression, a direct source of ROS. The expression level of Bim increased with combination treatment, but not with either treatment alone. Conclusion Here in this study, we demonstrate that the combination of erlotinib and ampelopsin induces cell death via the Nox2-ROS-Bim pathway, and ampelopsin could be used as a novel anti-cancer agent combined with EGFR-TKI to overcome resistance to erlotinib in EGFR-mutant NSCLC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cytotoxic effects of ampelopsin sodium (Amp-Na) and carboplatin (CBP) used alone or in combination on human non-small cell lung cancer (NSCLC) cells SPC-A1 in vitro and its related mechanism. Methods: Cytotoxic effects were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The synergistic effects of the drugs were calculated with coefficient of drug interaction (CDI). Cell cycle was determined by flow cytometry (FCM). The levels of p53, p21, cyclinE, cyclinD1, and phosphorylated cyclin-dependent kinase-2 (p-CDK2) were evaluated by Western blot. Results: Amp-Na (6.25-200 μg/mL) and CBP (3.13-100 μg/mL) alone exhibited prominent cytotoxic activity in a concentration-dependent manner on SPC-A1 cells with 50% inhibitive concentration values of 57.07±14.46 and 34.97±6.30 μg/mL, respectively. Drug combinations were associated with significantly higher cytotoxic effects than each drug alone ( P<0.05 or 0.01). The CDI analysis confirmed the synergy of Amp-Na and CBP on inhibiting cancer cell viability across a wide concentration range (CDI <1). FCM and Western blot showed that synergistic cytotoxic effects of Amp-Na and CBP were related to G arrested which mainlym ediated by p 21 through the inhibition of CDK2 activity independent of the p53 tumor suppressor pathway. Conclusions: Amp-Na exhibits anticancer activities and enhances the antitumor activities of CBP through up-regulation of p21 and inhibition of CDK2 activity in human NSCLC cells SPC-A1. These results suggest that Amp-Na may be applied to enhance the anticancer action of CBP. [ABSTRACT FROM AUTHOR]

This study reports two novel 5-fluorouracil-substituted ampelopsin derivatives. The structures of two new derivatives were characterized by elemental analysis, 1H-NMR, 13C-NMR, IR and MS. Their anticancer activities in vitro against two cancer cell lines, K562 and K562/ADR, were investigated using the MTT assay, and the results showed that the two new compounds were more effective than reference drugs such as ampelopsin and verapamil.

Ampelopsin has been suggested as a novel anticancer agent, however, there is no evidence regarding its direct effect on the migration and invasion of osteosarcoma cells. The aims of the present study were to investigate the influence of ampelopsin on the migration and invasion of osteosarcoma cells and to clarify the underlying mechanisms. Scratch wound healing and Transwell assays were used to measure the migratory and invasive activities of the cells, respectively. The protein and RNA levels of matrix metalloproteinase-2 (MMP-2) were detected with western blot and RT-qPCR, respectively, following stimulation with tumor necrosis factor-α (TNF-α) and ampelopsin. The expression levels of phospho- and total-p38MAPK were detected using western blot analysis. Additionally, SB203580, an inhibitor of p38MAPK, was used to investigate the effect of TNF-α and ampelopsin. The results demonstrated that TNF-α upregulated the expression level of MMP-2 and promoted the migration and invasion of osteosarcoma cells. TNF-α also activated the p38MAPK pathway, and SB203580 significantly inhibited the effect of TNF-α on MMP-2 expression. The application of ampelopsin abolished the effects of TNF-α on the activation of the p38MAPK pathway and the expression of MMP-2, and downregulated the migration and invasion of the osteosarcoma cells. These results demonstrated that ampelopsin inhibits the TNF-α-induced migration and invasion of osteosarcoma cells, and that the effect of ampelopsin was mediated by p38MAPK/MMP-2 signaling. [ABSTRACT FROM AUTHOR]

Increasing evidence has demonstrated that oxidative stress is involved in the pathogenesis of Parkinson's disease (PD), suggesting that pharmacological targeting of the antioxidant machinery may have therapeutic potential. Ampelopsin, a natural flavonoid compound, has been reported to possess various pharmacological functions, including anti-inflammatory, anti-oxidative and anti-cancer effects. However, its neuroprotective effect and neurotoxicity-attenuating role as well as underlying mechanisms are still unclear. In the present study, we investigated the potential role of ampelopsin in neuroprotective function and neurotoxicity attenuation, and explored its corresponding mechanisms against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the cell model of PD. The pretreatment with ampelopsin for 1 h significantly improved cell viability, reduced the release of lactate dehydrogenase (LDH) and inhibited the accumulation of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells. In addition, ampelopsin treatment attenuated 6-OHDA-induced apoptosis of PC12 cells by inhibiting the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Moreover, ampelopsin treatment significantly increased the localization of nuclear factor-erythroid 2-related factor 2 (Nrf2) and subsequent activation of haem oxygenase-1 (HO-1) gene associated with antioxidant response element (ARE) pathway in a dose-dependent manner. Further study demonstrated that ampelopsin treatment suppressed the expression of glycogen synthase kinase-3β (GSK-3β). The present results suggest that the neuroprotective role of ampelopsin is due to the increased expression of Nrf2 through suppressing GSK-3β signalling, thereby correspondingly inhibiting ROS/p-p38/p-JNK MAPK signalling pathway. Therefore, ampelopsin has promising therapeutic potential for PD. [ABSTRACT FROM AUTHOR]

Diabetic angiopathy is a major diabetes-specific complication that often begins with endothelial dysfunction induced by hyperglycemia; however, the pathological mechanisms of this progression remain unclear. Ampelopsin is a natural flavonol that has strong antioxidant activity, but little information is available regarding its antidiabetic effect. This study focused on the effect of ampelopsin on hyperglycemia-induced oxidative damage and the underlying mechanism of this effect in human umbilical vein endothelial cells (HUVECs). We found that hyperglycemia impaired autophagy in HUVECs through the inhibition of AMP-activated protein kinase (AMPK), which directly led to endothelial cell damage. Ampelopsin significantly attenuated the detrimental effect of hyperglycemiainduced cell dysfunction in a concentration-dependent manner in HUVECs. Ampelopsin significantly upregulated LC3-II, Beclin1, and Atg5 protein levels but downregulated p62 protein levels in HUVECs. Transmission electron microscopy and confocal microscopy indicated that ampelopsin notably induced autophagosomes and LC3-II dots, respectively. Additionally, the autophagy-specific inhibitor 3-MA, as well as Atg5 and Beclin1 siRNA pretreatment, markedly attenuated ampelopsin-induced autophagy, which subsequently abolished the protective effect of ampelopsin against hyperglycemia in HUVECs. Moreover, ampelopsin also increased AMPK activity and inhibited mTOR (mammalian target of rapamycin) complex activation. Ampelopsin-induced autophagy was attenuated by the AMPK antagonist compound C but strengthened by the AMPK agonist AICAR (5-minoimidazole-4-carboxamide ribonucleotide). Furthermore, AMPK siRNA transfection eliminated ampelopsin's alleviation of cell injury induced by hyper-glycemia. The protective effect of ampelopsin against hyperglycemia-induced cell damage, which functions by targeting autophagy via AMPK activation, makes it a promising pharmacological treatment for type-2 diabetes. [ABSTRACT FROM AUTHOR]

Our results showed that ampelopsin significantly inhibited cell viability of hepatoma HepG2 cells using MTT assay. We further investigated the mechanism of anticancer activity by ampelopsin, it showed that ampelopsin induced apoptosis of HepG2 cells using DAPI assay and flow cytometry, which was confirmed by activation of PARP. Next, activation of the caspase cascades were demonstrated, including caspase-8, -9 and -3. We also found that ampelopsin increased the levels of death receptor 4 (DR4), death receptor 5 (DR5) and decreased the expression of Bcl-2 protein, which led to an increase of the Bax/Bcl-2 ratio. Meanwhile, the release of cytochrome c from mitochondria was observed. Ampelopsin decreased the levels of iNOS and COX-2 but had no impact on the level of reactive oxygen species (ROS). In addition, ampelopsin activated ERK1/2 and P38, but little JNK1/2 activation was detected. Further investigation showed that suppression of P38 activation by SB203580 increased the cell viability and also prevented cleavage of caspase-3 and PARP, inhibition of ERK1/2 with U0126 had the opposite action. In conclusion, our results indicated that ampelopsin mainly elicited apoptosis through extrinsic and intrinsic pathway and that ERK1/2 and P38 had opponent effects on the apoptosis. [ABSTRACT FROM AUTHOR]

Ampelopsin (AMP), a plant flavonoid, has been reported to inhibit cell growth and/or induce apoptosis in various types of tumor. The aim of the present study was to assess the apoptosis-inducing activity of AMP in A549 human lung adenocarcinoma epithelial cells and the associated underlying mechanism. A549 cells were incubated with different concentrations of AMP in culture medium. Cell growth and apoptosis were evaluated by MTT assay and Annexin V/propidium iodide double staining and flow cytometry, respectively. In addition, western blotting and reverse transcription quantitative polymerase chain reaction analysis were used to examine the time-dependent changes in protein expression. Certain changes in apoptotic protein expression were detected following exposure to AMP, including X-linked inhibitor of apoptosis protein release, reduced B-cell lymphoma 2, myeloid cell leukemia 1 and survivin expression levels, increased Bcl-2-associated X protein expression levels and cleaved-poly ADP ribose polymerase expression. The results revealed that AMP was a potent inhibitor of A549 cell proliferation. The c-Myc/S-phase kinase-associated protein 2 (Skp2) and histone deacetylase (HDAC)1/2 pathways were found to exert an important role in AMP-induced A549 cell apoptosis, as increased levels of c-Myc mRNA and reduced levels of c-Myc/Skp2 and HDAC1 and 2 proteins following AMP treatment were observed. The levels of F-box and WD repeat-containing protein 7α (Fbw7α), Fbw7β, Fbw7γ, phosphorylated-(p-) c-Myc (Thr58) and glycogen synthase kinase 3β (GSK3β) proteins involved in c-Myc ubiquitin-dependent degradation were also analyzed. Following exposure to AMP, the expression levels of Fbw7α, Fbw7γ and GSK3β were reduced and p-c-Myc (Thr58) expression levels were increased. The results suggest that AMP exerts an anticancer effect, which is associated with the degradation of c-Myc, Skp2 and HDAC1 and 2. The ability of AMP to induce apoptosis independently of Fbwα and Fbw7γ suggests a possible use in drug-resistant cancer associated with Fbw7 deficiency. Understanding the exact underlying mechanism requires further investigation of the association between c-Myc and Fbw7α/γ reversal, and analysis of whether Thr58 phosphorylation of c-Myc is dependent on GSK3β. [ABSTRACT FROM AUTHOR]

Our previous study has shown that ampelopsin ( AMP), a flavonol mainly found in Ampelopsis grossedentata, could induce cell death in human breast cancer cells via reactive oxygen species generation and endoplasmic reticulum ( ER) stress pathway. Here, we examined whether autophagy is activated in AMP-treated breast cancer cells and, if so, sought to find the exact role and underlying molecular profile of autophagy in AMP-induced cell death. Our results showed that AMP treatment activated autophagy in MDA- MB-231 and MCF-7 breast cancer cells, as evidenced by the accumulation of autophagosomes, an increase of microtubule-associated protein 1 light chain 3 beta-2 ( LC3 B- II) and the conversion of LC3 B- I to LC3 B- II, the degradation of the selective autophagic target p62/ SQSTM1, and the formation of green fluorescent protein ( GFP)- LC3 puncta. Blockage of autophagy augmented AMP-induced cell death, suggesting that autophagy has cytoprotective effects. Meanwhile, AMP treatment suppressed Akt-mammalian target of rapamycin (m TOR) pathway as evidenced by dose- and time-dependent decrease of the phosphorylation of Akt, m TOR and ribosomal protein S6 kinase (p70 S6 K), whereas Akt activator insulin-like growth factor-1 ( IGF-1) pretreatment partially restored Akt-m TOR pathway inhibited by AMP and decreased AMP-inuduced autophagy, signifying that AMP activated autophagy via inhibition of the Akt-m TOR pathway. Additionally, blocking ER stress not only reduced autophagy induction, but also alleviated inhibition of the Akt-m TOR pathway induced by AMP, suggesting that activation of ER stress was involved in induction of autophagy and inhibition of the Akt-m TOR pathway. Taken together, these findings indicate that AMP induces protective autophagy in human breast cancer cells through Akt-m TOR pathway via ER stress. [ABSTRACT FROM AUTHOR]

• 37 °C in DMEM, dihydromyricetin was gradually converted into several new products. • At 6 °C, the stability of dihydromyricetin in DMEM improved obviously, ascorbic acid significantly enhanced it. Dihydromyricetin has shown many bioactivities in cell level. However, dihydromyricetin was found to be highly instable in cell culture medium DMEM. Here, the underlying degradation mechanism was investigated via UPLC-MS/MS analysis. Dihydromyricetin was mainly converted into its dimers and oxidized products. At lower temperature, dihydromyricetin in DMEM showed higher stability. Vitamin C increased the stability of dihydromyricetin in DMEM probably due to its high antioxidant potential. [ABSTRACT FROM AUTHOR]

Cancer is being considered as a serious threat to human health globally due to limited availability and efficacy of therapeutics. In addition, existing chemotherapeutic drugs possess a diverse range of toxic side effects. Therefore, more research is welcomed to investigate the chemo-preventive action of plant-based metabolites. Ampelopsin (dihydromyricetin) is one among the biologically active plant-based chemicals with promising anti-cancer actions. It modulates the expression of various cellular molecules that are involved in cancer progressions. For instance, ampelopsin enhances the expression of apoptosis inducing proteins. It regulates the expression of angiogenic and metastatic proteins to inhibit tumor growth. Expression of inflammatory markers has also been found to be suppressed by ampelopsin in cancer cells. The present review article describes various anti-tumor cellular targets of ampelopsin at a single podium which will help the researchers to understand mechanistic insight of this phytochemical., Competing Interests: 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., (© 2022 The Authors.)