PMID: 

Asian Pac J Cancer Prev. 2020 Feb 1 ;21(2):363-370. Epub 2020 Feb 1. PMID: 32102512

Abstract Title: 

Ethanolic Extract of Ocimum sanctum Leaves Reduced Invasion and Matrix Metalloproteinase Activity of Head and Neck Cancer Cell Lines.

Abstract: 

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a yearly incidence of 600,000 cases worldwide with a low survival rate. Ocimum sanctum L. or Ocimum tenuiflorum L. (Holy basil; Tulsi in Hindi), is a traditional medicine herb that demonstrates numerous effects including anti-oxidant, anti-microbial, and anti-tumor effects. The aim of this study was to evaluate the anti-invasive effect of O. sanctum leaf extract on HNSCC cell lines.METHODS: Ethanolic extract of O. sanctum leaf (EEOS) was prepared and the phenolic compounds were identified using high-performance liquid chromatography-electrospray ionization-time of flight-mass spectrometry. Genetically matched HNSCC cell lines derived from primary (HN30 and HN4) and metastatic sites (HN31 and HN12) from the same patient were used in this study. The EEOS cytotoxicity to the cell lines was determined using an MTT assay. The invasion and matrix metalloproteinase (MMP)-2 and -9 activity of EEOS-treated cells were tested using a modified Boyden chamber assay and zymography, respectively.RESULTS: We found that EEOS significantly inhibited the invasion and MMP-2 and MMP-9 activity of HN4 and HN12 cells, but not HN30 and HN31 cells. Rosmarinic acid, caffeic acid, and apigenin were detected in EEOS. Moreover, rosmarinic acid was found as the major phenolic compound.CONCLUSION: EEOS exerted its anti-invasive effect on HNSCC cells by attenuating MMP activity. The active compounds identified in EEOS might be promising as an alternative therapeutic agent for HNSCC.

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PMID: 

Mol Biol Rep. 2020 Feb ;47(2):1021-1032. Epub 2019 Nov 26. PMID: 31773385

Abstract Title: 

Quercetin, caffeic acid and resveratrol regulate circadian clock genes and aging-related genes in young and old human lung fibroblast cells.

Abstract: 

The circadian timing system of mammals is synchronized in concert with a central clock, but is also influenced by additional stimuli, including nutrients. However, little research has been done on polyphenols other than resveratrol and there seem to be no studies on their influence on young and old cells. The purpose of this study was to analyse the potential effects of quercetin, caffeic acid, and resveratrol on young and old fibroblast cells in the expressions of different clock genes and aging-related genes, and further investigate the mechanism. The mRNA expression of different clock genes and aging-related genes was assessed by quantitative real-time PCR. The protein levels of clock genes (BMAL1, PER1 and SIRT1) and glucocorticoid receptorα (GRα) were assessed by ELISA. Quercetin and caffeic acid in old fibroblast cells showed higher clock gene expression than resveratrol, quercetin increased Sirt1 expression, and caffeic acid increased Sirt6 expression indicating the possibility of an anti-aging effect. Also, quercetin and caffeicacid showed higher clock-controlled gene (Sirt1 and NR1D1) expression than resveratrol in young fibroblast cells. It appears that caffeic acid acts on NRF2 expression, and in turn to the actions of GRα, GDF11, Sirt1, and Sirt6. Regarding the increased expression of Per1, the activation effect on NR1D1 was confirmed only for caffeic acid in young fibroblast cells. Our results have confirmed the interplay of the circadian clock genes and cellular aging.

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PMID: 

J Cell Mol Med. 2020 Jan 30. Epub 2020 Jan 30. PMID: 32000299

Abstract Title: 

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice.

Abstract: 

Epidemiological studies have found that diabetes and cognitive dysfunction are closely related. Quercetin has been certified with the effect on improving diabetes mellitus (DM) and cognitive impairment. However, the effect and related mechanism of quercetin on diabetic encephalopathy (DE) are still ambiguous. In this study, we used the db/db mice (diabetic model) to discover whether quercetin could improve DE through the Sirtuin1/NLRP3 (NOD-, LRR- and pyrin domain-containing 3) pathway. Behavioural results (Morris water maze and new object recognition tests) showed that quercetin (70 mg/kg) improved the learning and memory. Furthermore, quercetin alleviated insulin resistance and the level of fasting blood glucose. Besides, Western blot analysis also showed that quercetin increased the protein expressions of nerve- and synapse-related protein, including postsynapticdensity 93(PSD93), postsynapticdensity 95 (PSD95), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of db/db mice. Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation-related proteins, including NLRP3, the adaptor protein ASC and cleaved Caspase-1, the pro-inflammatory cytokines IL-1β and IL-18. In conclusion, the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.

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PMID: 

J Ovarian Res. 2020 Jan 31 ;13(1):11. Epub 2020 Jan 31. PMID: 32005271

Abstract Title: 

Quercetin and polycystic ovary syndrome, current evidence and future directions: a systematic review.

Abstract: 

Polycystic ovary syndrome (PCOS) is a polygenic endocrine disorder and the most common gynecological endocrinopathy among reproductive-aged women. Current remedies are often used only to control its signs and symptoms, while they are not thoroughly able to prevent complications. Quercetin is an herbal bioactive flavonoid commonly used for the treatment of metabolic and inflammatory disorders. Thus, this systematic review was conducted to evaluate the efficacy of quercetin supplementation in subjects with PCOS. Databases until March 2019 were searched. All human clinical trials and animal models evaluating the effects of quercetin on PCOS women were included. Out of 253 articles identified in our search, 8 eligible articles (5 animal studies and 3 clinical trials) were reviewed. The majority of studies supported the beneficial effects of quercetin on the ovarian histomorphology, folliculogenesis, and luteinisation processes. The effects of quercetin on reducing the levels of testosterone, luteinizing hormone (LH), and insulin resistance were also reported. Although quercetin improved dyslipidemia, no significant effect was reported for weight loss. It is suggested that the benefits of quercetin may be more closely related to antioxidant and anti-inflammatory features of quercetin rather than weight-reducing effects. Therefore, this review article provides evidence that quercetin could be considered as a potential agent to attenuate PCOS complications. However, due to the paucity of high-quality clinical trials, further studies are needed.

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PMID: 

Front Pharmacol. 2019 ;10:1544. Epub 2020 Jan 17. PMID: 32009956

Abstract Title: 

Quercetin Alleviates LPS-Induced Depression-Like Behavior in RatsRegulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC.

Abstract: 

Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.

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PMID: 

Biomed Res Int. 2019 ;2019:7039802. Epub 2019 Oct 28. PMID: 31781635

Abstract Title: 

Quercetin and Quercitrin Attenuates the Inflammatory Response and Oxidative Stress in LPS-Induced RAW264.7 Cells: In Vitro Assessment and a Theoretical Model.

Abstract: 

Background: Nowadays, atmospheric pollutants, ultraviolet rays, and other factors cause the imbalance of cell redox, resulting in skin oxidative damage. There is an interaction between inflammatory response and oxidative stress, which often involve networks of reactions and serve to amplify each other. Quercetin and quercitrin, with strong antioxidant and anti-inflammatory properties, were widely applied in cardiovascular disease, osteoporsis, pulmonary disease, etc. However, the regulation mechanism of quercetin and quercitrin on various inflammatory skin diseases is still not clear.Purpose: In this study, quercetin and quercitrin were used to investigate whether they had anti-inflammatory and anti-ROS effects. Besides, theoretical calculation method was also adopted to preliminarily explore the mechanism of the anti-inflammatory and antioxidant effects of these two substances.Methods: CCK-8 assay was employed to investigate the cytotoxicity. The concentration of NO measured by Griess Reaction System. Moreover, the inflammatory factors (TNF-, IL-1, and IL-6) were reduced in LPS-stimulated RAW264.7 cells were tested by ELISA kits. The trend of ROS changes was detected by DCFH-DA method. Finally, the mechanism of the anti-inflammatory and antioxidant effects of these two substances was carried out by DMol3 package in Materials Studio.Results: CCK-8 assay results guided that the safe concentration of quercetin and quercitrin was lower than 15.0 g/mL and 22.4 g/mL, respectively. Also, the concentration of NO could significantly be inhibited by quercetin and quercitrin. Besides, the ELISA results showed that TNF-, IL-1, and IL-6 were reduced in LPS-stimulated RAW264.7 cells after interfering with quercetin and quercitrin. The trend of ROS changes was similar to that of inflammatory factors. Finally, the theoretical calculation illustrated that the oxygen atom on B rings may be the main site of electron cloud density changes, which may suggest a possible mechanism for the anti-inflammatory and ROS scavenging effects of quercetin and quercitrin.Conclusions: This experiment shows that LPS can induce the overactivating of macrophages and the activated macrophages can subsequently induce inflammatory storms and oxidative stress. Both quercetin and quercitrin can inhibit LPS-induced macrophage inflammation and oxidative stress by experiment and theoretical calculations.

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PMID: 

Acta Biochim Biophys Sin (Shanghai). 2019 Dec 13 ;51(12):1250-1257. PMID: 31781748

Abstract Title: 

Quercetin improves endothelial insulin sensitivity in obese mice by inhibiting Drp1 phosphorylation at serine 616 and mitochondrial fragmentation.

Abstract: 

Studies have shown that endothelial insulin resistance induced by oxidative stress contributes to vascular dysfunction in metabolic disorders. Quercetin, a natural antioxidant, has been recently shown to exert protective effects on endothelial function. However, the effects of quercetin on endothelial insulin resistance and its underlying mechanism are unclear. Here, we found that chronic oral treatment of obese mice with quercetin increased vascular endothelial insulin sensitivity, accompanied by alleviated mitochondrial fragmentation as revealed by confocal imaging. In addition, western blot analysis showed that quercetin treatment suppressed the levels of dynamin-related protein 1 (Drp1) and phosphorylation at serine 616 in endothelial cells of obese mice. Mechanistically, quercetin specifically suppressed Drp1 phosphorylation at serine 616, whereas it showed little effects on the Drp1 level and its phosphorylation at serine 637 in cultured endothelial cells under oxidative stress. Furthermore, our results also showed that quercetin suppressed Drp1 phosphorylation at serine 616 by inhibiting PKCδ as revealed by western blot analysis. Knockdown of PKCδ with siRNA alleviated the protective effects of quercetin on endothelial-mitochondrial dynamics and insulin sensitivity. These results suggest that chronic oral treatment with quercetin exerts endothelial protective effects through inhibition of PKCδ and the resultant mitochondrial fragmentation.

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PMID: 

Int J Mol Sci. 2019 Dec 3 ;20(23). Epub 2019 Dec 3. PMID: 31816893

Abstract Title: 

Quercetin Suppresses the Progression of Atherosclerosis by Regulating MST1-Mediated Autophagy in ox-LDL-Induced RAW264.7 Macrophage Foam Cells.

Abstract: 

OBJECTIVE: To investigate the process by which quercetin suppresses atherosclerosis by upregulating MST1-mediated autophagy in RAW264.7 macrophages.METHODS: An in vitro foam cell model was established by culturing RAW264.7 macrophages with oxidized low-density lipoprotein (ox-LDL). The cells were treated with quercetin alone or in combination with the autophagy inhibitor, 3-methyladenine, and autophagy agonist, rapamycin. Cell viability was detected with a CCK-8 kit. Lipid accumulation was detected by oil red O staining, senescence was detected by SA-β-gal (senescence-associated β-galactosidase) staining, reactive oxygen species were detected by ROS assay kit. Autophagosomes and mitochondria were detected by transmission electron microscope (TEM), and expression of MST1, LC3-II/I, Beclin1, Bcl-2, P21, and P16 were detected by immunofluorescence and Western blot.RESULTS: Ox-LDL induced RAW264.7 macrophage-derived foam cell formation, reduced survival, aggravated cell lipid accumulation, and induced a senescence phenotype. This was accompanied by decreased formation of autophagosome; increased expression of P53, P21, and P16; and decreased expression of LC3-II/I and Beclin1. After intervention with quercetin, the cell survival rate was increased, and lipid accumulation and senescence phenotype were reduced. Furthermore, the expression of LC3-II/I and Beclin1 were increased, which was consistent with the ability of quercetin to promote autophagy. Ox-LDL also increased the expression of MST1, and this increase was blocked by quercetin, which provided a potential mechanism by which quercetin may protect foam cells against age-related detrimental effects.CONCLUSION: Quercetin can inhibit the formation of foam cells induced by ox-LDL and delay senescence. The mechanism may be related to the regulation of MST1-mediated autophagy of RAW264.7 cells.

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PMID: 

Front Microbiol. 2019 ;10:2536. Epub 2019 Nov 22. PMID: 31824439

Abstract Title: 

Mechanism of Synergy Between Tetracycline and Quercetin Against Antibiotic Resistant.

Abstract: 

Treatment of multi-drug resistant (MDR)intestinal infections are being hampered by the presence of the-1 (colistin) and(tetracycline) resistance genes in these strains. We screened seven traditional Chinese medicines for their ability to synergize with tetracycline to provide an effective new drug for the treatment of animal intestinal diseases caused by MDR. Our primary screen identified quercetin as a compound that reduced the minimum inhibitory concentration (MIC) of tetracycline against thestandard test strain American Type Culture Collection (ATCC) 25922 and clinical isolates fourfold from 4 and 256μg/mL to 1 and 64 μg/mL, respectively. Low levels of quercetin in combination with tetracycline were bactericidal for clinicalisolates and after 24 h, the differences between this combination and each drug singly were 10CFU/mL. We used this combination therapy in a mouse infection model and found 100% survival after 48 h compared with

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PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2019 Dec 14. Epub 2019 Dec 14. PMID: 31836917

Abstract Title: 

Resveratrol and quercetin attenuate depressive-like behavior and restore impaired contractility of vas deferens in chronic stress-exposed rats: involvement of oxidative stress and inflammation.

Abstract: 

Chronic stress is associated with male sexual problems including ejaculatory dysfunctions. The aim of this study was to determine whether resveratrol (RS) or quercetin (QE) has protective effects on vas deferens (VD) contractility in the unpredictable chronic mild stress (UCMS) rat model of depression. Animals were separated into six groups: control, control + RS and control + QE, stress, stress + RS, and stress + QE. Stress groups were subjected to UCMS procedure for 5 weeks. Animals in treatment groups were injected intraperitoneally with RS (20 mg/kg) or QE (30 mg/kg) for 5 weeks during UCMS period. UCMS caused depressive-like behaviors and enhanced systemic levels of corticosterone. The nerve-evoked contractile responses of VD significantly impaired and, noradrenaline- and ATP-induced contractile responses of VD significantly increased in stressed rats. UCMS exposure also markedly enhanced oxidative stress and inflammationin VD tissues. Treatment with RS or QE significantly ameliorated all the aforementioned parameters. The current study demonstrated that RS or QE protected against chronic stress-induced VD dysfunction by their antioxidant and anti-inflammatory effects on VD, suggesting that oxidative stress and inflammation may be synergistic parts in the development of VD dysfunction associated with chronic stress-induced depression.

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