The medical term for this is oxidative stress. Free radicals are unstable molecules in the body that can increase the risk of disease and quicken aging.

The body produces free radicals through regular metabolic processes such as energy production. Quercetin is a more powerful antioxidant than vitamin C, E , or beta carotene.

However, chronic inflammation can harm the body and contribute to specific health conditions. Quercetin can help inhibit inflammation in the body. While consuming a diet high in quercetin-rich foods may help regulate inflammation, it is unclear whether taking high dose quercetin supplements is beneficial for reducing inflammatory markers.

Research shows that a diet high in flavonoid-rich fruit and vegetables can lower the risk of certain cancers and slow cancer cell growth. However, more research is necessary to assess the direct links between quercetin intake and cancer risk. Oxidative stress contributes to the development of neurodegenerative diseases.

Oxidative stress occurs when there is an imbalance of free radicals in the body. The antioxidant properties of quercetin may help fight free radicals. A study found that consuming quercetin-rich onion for 24 weeks reduces age-related cognitive decline.

Additional findings from Pharmacognosy Review suggest that quercetin might be an effective antihistamine , as it restricts histamine from being released from cells.

These anti-allergy properties indicate that quercetin may be a helpful supplement for those with allergic diseases, especially rhinitis. However, more research is needed to confirm this potential benefit.

People with allergies should not supplement with quercetin unless directed to do so by their healthcare professional. Quercetin has antibacterial and antiviral properties. Lab tests show that quercetin can inhibit the growth of many bacteria, including. Quercetin, along with other flavonoids, may help inhibit the growth of many viruses.

Diet plays an essential role in reducing the risk of cardiovascular diseases , such as heart disease and strokes. Because fruit and vegetables contain flavonoids, eating more may help reduce the risk of these diseases.

Research suggests that quercetin may help protect heart health by mitigating blood vessel dysfunction mitigating endothelial dysfunction, and reducing heart disease risk factors like high blood pressure and atherosclerosis.

According to a analysis , taking quercetin supplements could be an effective way to reduce blood pressure. Further research shows that people who were overweight and took a quercetin supplement of milligrams mg per day had lower levels of harmful cholesterol in their blood and reduced systolic blood pressure.

Systolic blood pressure measures the pressure in the blood vessels during a heartbeat. People can get quercetin through their diet by eating a range of fruit and vegetables daily.

Onions are amongst the richest sources of dietary flavonoids you can eat, providing Quercetin is available as a nutritional supplement, typically in doses of to mg daily.

Supplements may also include other substances, such as bromelain or vitamin C, which may help the body absorb quercetin more effectively. The natural antioxidants found in fruits and vegetables can be beneficial when consumed as part of a balanced and nutritious diet.

However, quercetin may interact with some medications, so people should ask their doctor before taking a supplement. Quercetin is a flavonoid found in fruit and vegetables.

It has a wide range of benefits, which people can get by including a variety of fruit and vegetables in their diet. Although many studies have found several potential benefits of quercetin, many have been animal or in vitro studies. If people want to supplement their diet with quercetin, they should seek advice from a healthcare professional first.

Free radicals are unstable atoms that can cause damage to cells and lead to illnesses and the aging process. Exactly what impact do they have on the…. Dementia describes symptoms affecting memory and cognitive function. Learn about both….

Eucalyptus leaves contain antioxidants and may help to reduce inflammation. For thousands of years, and throughout the world, preparations of…. Cut-off blood flow in the arteries is one of the primary risk factors for experiencing a heart attack or stroke, which is why cardiac arrest is less likely among people who eat a nutrient-packed diet.

Certain studies show that quercetin prevents damage to LDL cholesterol particles, and it seems that people who eat the most flavonoid-rich foods typically have healthier and lower cholesterol levels , plus fewer incidences of hypertension and high blood pressure.

Taking quercetin supplements may help lower pain associated with autoimmune conditions such as arthritis, as well as infections, including those of the prostate and respiratory tract. Flavonoids are also linked to reduced symptoms of prostatitis inflammation of the prostate and rheumatoid arthritis RA.

While improvements were at times small, it makes sense that antioxidants could boost physical performance since they help increase the health of blood vessels, which carry oxygen and nutrients to muscle and joint tissue.

Other studies also show that it helps increase immune function and prevents susceptibility to illnesses that can occur when someone trains intensely and experiences exhaustion.

One study found evidence that taking milligrams of quercetin twice daily helped protect cyclists from developing exercise-induced respiratory infections following periods of heavy exercise.

Because it can boost your energy level, does quercetin affect sleep? For example, is there a link between quercetin and insomnia? One study found evidence that it may alter the sleep-wake cycle partly through activation of GABA gamma-aminobutyric acid receptors.

However, insomnia is generally not believed to be a common side effect of taking it in dietary supplement form. A Boston University School of Medicine study published in the Journal of Biological Regulators and Homeostatic Agents shows a link between a nutrient-dense diet rich in quercetin plus other antioxidants and a lowered risk of cancer.

Quercetin seems to have potential chemo-preventive activity and might have a unique antiproliferative effect on cancerous cells, making it an effective addition to any natural cancer treatment approach. Research shows that this may result from the modulation of either EGFR or estrogen-receptor pathways.

Other studies have found quercetin can help stop the processes involved in cell proliferation and mutation, the growth of tumors, and symptoms related to typical cancer treatments, such as radiation or chemotherapy. This is especially true when taken in high doses above the amount someone would get from a healthy diet.

Studies have found that this compound has antioxidant and anti-inflammatory effects that help fight allergic and inflammatory diseases, as well as some prescriptions, when taken in oral supplement form. For example, some people take quercetin for eczema since it can inhibit the secretion of histamine and pro-inflammatory markers.

Research has shown that this antioxidant has protective effects when administered to rats with ethanol-induced acute liver injury.

A study found evidence indicating that quercetin attenuates liver inflammation and fibrosis in mice through inhibiting macrophages infiltration. What foods have the most quercetin? All types of tasty red, green and purple-pigmented plants come packed with quercetin — for example, red wine, blueberries, apples, red onion and even green tea are some of the best sources.

Quercetin is actually believed to be the most abundant flavonoid in the human diet. Some of the most common types of dietary supplements include: quercetin 3, quercetin 3 glucoside, quercetin aglycone, isoquercetin, quercetin 7 rutinoside, and quercetin 3 0 rhamnoside.

Some quercetin supplements are also labeled as quercetin dihydrate, which is mostly insoluble in water and may not be absorbed as well as other kinds. Quercetin supplements are available in all types of pills or capsules and are commonly used in formulas along with other anti-inflammatory ingredients.

For example, quercetin with bromelain an anti-inflammatory enzyme found in pineapples may be taken to help manage allergies. What are side effects of quercetin? According to a report, most studies have found little to no side effects in people eating nutrient-dense diets high in quercetin or taking supplements by mouth short term.

Is quercetin safe to take daily? Amounts up to milligrams taken twice daily for 12 weeks appear to be safe. However, of course, in very high doses there are some risks. Side effects can include headaches and tingling of the arms and legs. Very high doses taken intravenously have also been linked to cases of kidney damage, although this seems very rare.

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In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Keywords: Antioxidant; Anxiety; Cognition; Depression; Quercetin; Stress. Abstract It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders.

Substances Antioxidants Cytokines RNA, Messenger Nitric Oxide Quercetin Catalase. You should take periodic breaks from taking quercetin. If you are being treated with any of the following medications, you should not use quercetin supplements without talking to your health care provider first.

There is some concern that quercetin may reduce the effectiveness of certain antibiotics. Speak with your doctor. Quercetin may enhance the effect of these drugs, increasing your risk for bleeding. Anticoagulants include:.

Test tube and animal studies suggest that quercetin may enhance the effects of doxorubicin and cisplatin, which are two chemotherapy medications used to treat cancer. In addition, some doctors believe taking antioxidants at the same time as chemotherapy can be harmful, while others believe it can be helpful.

In one study, combining quercetin with the anti-tumor drug doxorubicin, increased the drug's beneficial effects on breast cancer cells. In another, taking quercetin alongside cisplatin reduced the medicines' therapeutic effects in ovarian cancer cells. Talk to your oncologist before taking any supplements if you are undergoing chemotherapy.

Quercetin may interfere with the body's absorption of this drug, which is used to suppress the immune system. Since quercetin affects the liver, concomitant use with medications that are changed by the liver may alter how the body metabolizes these medications.

Speak with your physician. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. Boots AW, Li H, Schins RP, Duffin R, Heemskerk JW, Bast A, Haenen GR. The quercetin paradox. Toxicol Appl Pharmacol. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP.

Oxidative damage and protection of the RPE. Prog Retin Eye Res. Chan MM, Mattiacci JA, Hwang HS, Shah A, Fong D. Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway.

Bio Pharm. Chuang CC, Martinez K, Xie G, et al. Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-{alpha}-mediated inflammation and insulin resistance in primary human adipocytes.

Am J Clin Nutr. Dajas F. Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol. Dower JI, Geleijnse JM, Gijsbers L, Zock PL, Kromhout D, Hollman PC.

Effects of the pure flavonoids epicatechin and quercetin on vascular function and cariometabolic health: a randomized, double-blind, placebo-controlled, crossover trial. Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T.

Quercetin reduces blood pressure in hypertensive subjects. J Nutr. Egert S, Bosy-Westphal A, Seiberl J, et al. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a doule-blinded, placebo-controlled cross-over study.

Br J Nutr. Gates MA, Tworoger SS, Hecht JL, De Vivo I, Rosner B, Hankinson SE. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer.

Int J Cancer. Giuliani C, Noguchi Y, Harii N, Napolitano G, Tatone D, Bucci I, Piantelli M, Monaco F, Kohn LD. The flavonoid quercetin regulates growth and gene expression in rat FRTL-5 thyroid cells. Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids.

Effects of rutin, quercetin, and hesperidin on adjuvant arthritis in rat. Hanninen, Kaartinen K, Rauma AL, Nenonen M, Torronen R, Hakkinen AS, Adlercreutz H, Laakso J. Antioxidants in vegan diet and rheumatic disorders. Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC.

Food Chem Toxicol. Kleemann R, Verschuren L, Morrison M, et al. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Knekt P, Isotupa S, Rissanen H, Heliovaara M, Jarvinen R, Hakkinen S et al.

Quercetin intake and the incidence of cerebrovascular disease. Eur J Clin Nut. Kurowska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piche LA, Serratore P. HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia.

BDNF-Quercetin nanogels significantly increased the corresponding positive cells. At the same time, these impairments of pyramidal cells were also found in the prefrontal cortex of CUMS rats Figure S6 , and BDNF-Quercetin nanogels showed the same therapeutic effects as in the hippocampus.

CUMS-induced cell apoptosis and proliferation in the hippocampus of rats. a TUNEL staining. b The nerve cells by TUNEL staining. c Ki67 staining. d Number of cell proliferation by Ki67 staining. Apoptosis is an essential mechanism of CUMS-induced depression [ 48 ].

As an anti-apoptotic endogenous membrane protein, B cell lymphoma-2 Bcl-2 prevents cells from entering the apoptotic program. B-cell lymphoma extra-large Bcl-xL , like Bcl-2, is another antiapoptotic factor supporting neuronal survival but not promoting axon regeneration.

BCL2-associated X Bax was a pro-apoptotic protein promoting cells to enter apoptosis. The study findings indicated that CUMS increased Bax mRNA expression in the hippocampal and prefrontal cortex tissues Figure S7 a, b and selectively decreased hippocampal Bcl-xL mRNA levels Figure S7 c, d without changing Bcl-2 mRNA expression Figure S7 e, f.

BDNF-quercetin nanogels exerted antidepressant effects on CUMS rats, mainly through anti-stress, anti-inflammation, and neuroprotection. BDNF-quercetin nanogels can restore HPA axis function, inhibit neuron cell apoptosis, and promote neuron cell regeneration. To elucidate the impact of BDNF-Quercetin nanogels on CUMS rats, a comprehensive, integrated omics approach was used to investigate potential antidepressant mechanisms.

Gene expression of total mRNA isolated from rat hippocampus was assessed using RNA sequencing. The transcriptomic volcano map revealed that compared to CUMS group, genes were differentially expressed in the BDNF-quercetin nanogels group, with significantly up-regulated genes and significantly down-regulated genes Fig.

The most enriched GO terms in Fig. Gene set enrichment analysis GSEA was next performed using the KEGG Kyoto Encyclopedia of Genes and Genomes database, revealing significant enrichment including TGF-β and PI3K-Akt signaling pathway, glutamatergic synapse, alanine, aspartate, and glutamate metabolism Fig.

Additionally, GO terms associated with antioxidant activity were identified in Table S4. Oxidative phosphorylation was further found in KEGG pathway enrichment analysis. In line with previous studies on depression, it was found that there are glutamate receptor-related terms, PI3K-Akt, glutamatergic synapse, and glutamate metabolism signaling pathways.

These transcriptomic findings suggested that BDNF-Quercetin nanogels not only induced antioxidant activities via oxidative phosphorylation but also exerted antidepressant effects on CUMS rats by improving the glutamatergic system and PI3K-Akt signaling pathway.

A metabolomic analysis was then performed to investigate the changes in hippocampal metabolites. Partial least square analysis PLS-DA in Fig. Further analysis in Fig. The metabolic pathways associated with the antidepressant effects primarily encompassed the following biochemical process: 1 biotin metabolism; 2 citrate cycle; 3 tryptophan metabolism; 4 Alanine, aspartate, and glutamate metabolism; 5 thiamine metabolism Fig.

Taken together, transcriptomic and metabonomic data showed that the glutamatergic system and PI3K-Akt signaling pathway were the primary antidepressant mechanism of BDNF-Quercetin nanogels in CUMS rats. Western blot experiments were performed to verify related protein expression.

Protein expression of the glutamatergic system was demonstrated in Fig. These results presented that chronic stress significantly reduced the GRIA3 the receptor of AMPA protein content and increased the GRIN2B the receptor of NMDA protein content in the hippocampus of rats.

Moreover, BDNF-Quercetin nanogels regulated the PI3K-Akt signaling pathway by improving the abnormal expression of BDNF, TrkB, GSK3β, and p-mTOR after CUMS Fig. These results showed that exogenously supplemented BDNF might bind to its receptor TrkB and further activate the PI3K-Akt signaling pathway, thereby regulating the expression of abnormal GSK3β and p-mTOR proteins.

In summary, the protective effects of quercetin nanogels on BDNF were achieved by antioxidant activities associated with oxidative phosphorylation. By integrating omics prediction and protein expression verification, the results showed that BDNF-Quercetin nanogels exerted antidepressant effects on CUMS rats by modulating the glutamatergic system and PI3K-Akt signaling pathway.

Antidepressant mechanism of BDNF-Quercetin nanogels in the thermosensitive gel on the CUMS rats. a Volcano map. b GO enrichment analysis. c KEGG pathway enrichment analysis of BDNF-quercetin nanogels vs.

CUMS model. d Partial least squares-discriminant analysis PLS-DA. e VIP analysis. f Major metabolic pathways that BDNF-Quercetin nanogels improve CUMS rats.

g-h Expression of GRIA3, BDNF, TrkB, P-mTOR, GRIN2B, and GSK3β in the hippocampus of rats. In conclusion, quercetin nanogels were successfully prepared and characterized. Quercetin nanogels showed protective effects against protein damage, exhibited antioxidant activities without affecting cell viability, proliferation, and immune response, and increased in vitro inflammatory cytokine levels.

The intranasally administered quercetin nanogels rapidly distributed in the brain within 30 min and improved the bioavailability of quercetin nearly fold at a lower dose. The BDNF-quercetin nanogels in the thermosensitive gel exhibited excellent thermosensitivity and co-delivered quercetin and BDNF slowly and sustainably.

As a protein drug carrier, quercetin nanogels exerted antidepressant effects on reserpine-induced rats and alleviated the depletion of monoamine neurotransmitters.

BDNF-quercetin nanogels effectively reversed despair behavior in mice, alleviated weight loss and anhedonia in rats, ameliorated dramatic pyramidal cell damage in hippocampal CA1 and CA3 subregions and inflammatory cytokine levels, and ameliorated CUMS-induced cell apoptosis and proliferation in rat hippocampus.

Further omics analysis and protein verification revealed that the treatment of BDNF-Quercetin nanogels on depressive disorder was mainly related to the glutamatergic system, PI3K-Akt, and BDNF-TrkB signaling pathway. These results showed that the brain delivery of BDNF- Quercetin nanogels via intranasal administration has a significant potential for the combination treatment of depressive disorder.

Chemicals and Materials and animals are described in Additional file 1 : S1 Chemicals and Materials and S2 Animals, respectively. BDNF-Quercetin nanogels were prepared using the previous study with slight modifications [ 49 ].

Preparation and characterization of BDNF-Quercetin nanogels are described in Additional file 1 : S3 Preparation and characterization of BDNF-Quercetin nanogels.

In vitro release of quercetin nanogels was investigated in 0. In vitro release of BDNF-Quercetin nanogels was investigated in 0. Quercetin nanogels and BDNF-Quercetin nanogels were placed in a dialysis bag molecular weight of 10, and suspended in 40 mL of release medium at 34 °C on a shaker at 50 rpm.

Each release sample was taken at appropriate intervals and added by fresh release medium. The analysis was conducted three times for each batch.

Antioxidant activities of quercetin nanogels : The protective effects of quercetin on protein were determined using the method of Coomassie brilliant blue. The methods are described in the Additional file 1 : S4 Antioxidant activities of quercetin nanogels.

BDNF-Quercetin nanogels in the thermosensitive gel were obtained using two steps. One step was that BDNF-Quercetin nanogels were dissolved in normal saline at room temperature, cooling to 4 °C.

The gelation temperature was observed through changes in the modulus [ 50 ]. In vitro release of BDNF-Quercetin nanogels in the thermosensitive gel was explored using PBS to mimic intranasal release behavior.

Each release sample was taken at appropriate intervals and added to fresh PBS. The residual weight was weighed and compared with the initial weight to calculate the weight loss rate. Each batch was analyzed in triplicate. RAW Cell biology evaluation and immune response were performed in Additional file 1 : S5 Cell biology evaluation and immune response.

For brain distribution studies, the Sprague-Dawley SD rats, intranasally administered to RBITC-labeled quercetin nanogels in the thermosensitive gel, were investigated after being sacrificed for 0. In a pharmacokinetic study, SD rats were randomly divided into intranasal quercetin nanogels in the thermosensitive gel and oral administration quercetin solution at the dose of 0.

The hippocampi were collected, detected, and analyzed as described in Additional file 1 : S6 Pharmacokinetic study. Open field test OFT , forced swim test FST , tail suspension test TST , and reserpine-induced depression model are described in Additional file 1 : S7 Open field test OFT and forced swim test FST , tail suspension test TST , and reserpine-induced depression model.

The chronic unpredictable mild stress CUMS model was used to investigate the antidepressant effect of BDNF-Quercetin nanogels in the thermosensitive gel and its mechanism. The protocol was approved by the Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine TCME The experiments are reported by the Animal Research: Reporting in Vivo Experiments ARRIVE guidelines.

The SD rats were divided into control and CUMS groups treated with drugs. CUMS involved exposure to various mild stressors.

After administration, the locomotor activity was evaluated by the OFT, consisting of the number of rearings and total distance.

The rat heparinized plasma was collected by centrifugation at × g for 10 min after the behavioral despair test. The inflammatory levels TNF-α and IL-6 and HPA axis function CRH, ACTH, corticosterone, and testosterone were measured by ELISA Assay Kit.

The CA1 and CA3 regions in the hippocampus were observed and photographed by a light microscope OLYMPUS, Japan. At the same time, the mRNA expression of the apoptosis gene was performed in a Bio-Rad C Bio-Rad, Pleasanton, CA, USA.

The real-time RT-PCR primers of GAPDH, Bcl-2, Bax, and Bcl-xL were demonstrated in Table S3. To measure pyramidal neuron proliferation in the hippocampus, the slides were incubated with an anti-MKI67 polyclonal antibody overnight at 4 °C, then a secondary antibody anti-rabbit IgG.

The number of positive cells was counted using a Nikon Eclipse Ti-U inverted fluorescent microscope Nikon, Japan.

The antidepressant mechanism of BDNF-Quercetin nanogels was explored by combining RNA sequencing, metabolomic analysis, and Western blot analysis. Transcriptome sequencing was accomplished by Beijing Novogene Technology Co. Ltd, as presented in Additional file 1 : S8 The procedure of RNA sequencing.

Metabolite levels in the hippocampal tissues were determined using our previous methods in Additional file 1 : S9 Determination of hippocampal tissues in metabolite levels. The protein expressions of GRIA3, GRIN2B, BDNF, TrkB, GSK3β, and p-mTOR were determined by western blotting according to Additional file 1 : S10 Western blotting detection.

Statistical analyses were calculated by the Origin Pro software Origin Lab, Northampton, MA. Li W, Ali T, Zheng C, He K, Liu Z, Shah FA, Li N, Yu Z-J, Li S. Mol Psychiatry. Article CAS PubMed Google Scholar. Carniel BP, da Rocha NS. Brain-derived neurotrophic factor BDNF and inflammatory markers: perspectives for the management of depression.

Prog Neuropsychopharmacol Biol Psychiatry. Article PubMed Google Scholar. Woodburn SC, Asrat HS, Flurer JK, Schwierling HC, Bollinger JL, Vollmer LL, Wohleb ES. Depletion of microglial BDNF increases susceptibility to the behavioral and synaptic effects of chronic unpredictable stress. Brain Behav Immun.

Huang F, Chen T, Chang J, Zhang C, Liao F, Wu L, Wang W, Yin Z. A conductive dual-network hydrogel composed of oxidized dextran and hyaluronic-hydrazide as BDNF delivery systems for potential spinal cord injury repair.

Int J Biol Macromol. Ma X, Gao F, Su W, Ran Y, Bilalijiang T, Tuolhen Y, Tian G, Ye L, Feng Z, Xi J. Multifunctional injectable hydrogel promotes functional recovery after Stroke by modulating microglial polarization, angiogenesis and neuroplasticity. Chem Eng J. Article CAS Google Scholar.

Park SB, Cho H-J, Moon SR, Choi KJ, Jung WH, Kim KY, Koh B. Gold nanoparticle-assisted delivery of brain-derived neurotrophic factor to cerebral organoids.

Nano Res. Kraus A, Huertas M, Ellis L, Boudinot P, Levraud J-P, Salinas I. Intranasal delivery of SARS-CoV-2 spike protein is sufficient to cause olfactory damage, inflammation and olfactory dysfunction in zebrafish. Article CAS PubMed PubMed Central Google Scholar.

Zhang L, Deng L, Ma C, Zhang H, Dang Y. Brain-derived neurotrophic factor delivered Intranasally relieves post-traumatic stress disorder symptoms caused by a single prolonged stress in rats. Zhou X, Deng X, Liu M, He M, Long W, Xu Z, Zhang K, Liu T, So K-F, Fu Q-L. Intranasal delivery of BDNF-loaded small extracellular vesicles for cerebral ischemia therapy.

J Control Release. Long Y, Yang Q, Xiang Y, Zhang Y, Wan J, Liu S, Li N, Peng W. Nose to brain drug delivery-a promising strategy for active components from herbal medicine for treating cerebral ischemia reperfusion. Pharmacol Res. Cristea IA, Naudet F. US Food and Drug Administration approval of esketamine and brexanolone.

Lancet Psychiatry. Kryst J, Kawalec P, Pilc A. Efficacy and safety of intranasal esketamine for the treatment of major depressive disorder. Expert Opin Pharmacother.

Quintana DS, Steen NE, Andreassen OA. The Promise of Intranasal Esketamine as a Novel and effective antidepressant. JAMA Psychiatry. Kandemir K, Tomas M, McClements DJ, Capanoglu E. Recent advances on the improvement of quercetin bioavailability. Trends Food Sci Technol.

Onugwu AL, Nwagwu CS, Onugwu OS, Echezona AC, Agbo CP, Ihim SA, Emeh P, Nnamani PO, Attama AA, Khutoryanskiy VV. Nanotechnology based drug delivery systems for the treatment of anterior segment eye Diseases.

Liu W, Ma Z, Wang Y, Yang J. Multiple nano-drug delivery systems for intervertebral disc degeneration: current status and future perspectives. Bioact Mater. PubMed Google Scholar.

Chen YB, Zhang YB, Wang YL, Kaur P, Yang BG, Zhu Y, Ye L, Cui YL. A novel inhalable quercetin-alginate nanogel as a promising therapy for acute lung injury. J Nanobiotechnol. Article Google Scholar.

Correa D, Scheuber MI, Shan H, Weinmann OW, Baumgartner YA, Harten A, Wahl A-S, Skaar KL, Schwab ME. Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.

Liu Z, Tang W, Liu J, Han Y, Yan Q, Dong Y, Liu X, Yang D, Ma G, Cao H. A novel sprayable thermosensitive hydrogel coupled with zinc modified metformin promotes the healing of skin wound. CAS PubMed Google Scholar. Madry H, Gao L, Rey-Rico A, Venkatesan JK, Muller-Brandt K, Cai X, Goebel L, Schmitt G, Speicher-Mentges S, Zurakowski D, et al.

Thermosensitive hydrogel based on PEO-PPO-PEO poloxamers for a controlled in situ release of recombinant Adeno-Associated viral vectors for effective gene therapy of cartilage defects. Adv Mater.

Donati I, Christensen BE. Alginate-metal cation interactions: macromolecular approach. Carbohydr Polym. Li X, Liu Y, Yu Y, Chen W, Liu Y, Yu H. Nanoformulations of quercetin and cellulose nanofibers as healthcare supplements with sustained antioxidant activity.

Tan Y, Zi Y, Peng J, Shi C, Zheng Y, Zhong J. Gelatin as a bioactive nanodelivery system for functional food applications. Food Chem. Kumar MN, Kalarikkal SP, Bethi CM, Singh SN, Narayanan J, Sundaram GM. An eco-friendly one-pot extraction process for curcumin and its bioenhancer, piperine, from edible plants in exosome-like nanovesicles.

Green Chem. Huang K, Zhong P, Xu B. Discrimination on potential adulteration of extra virgin olive oils consumed in China by differential scanning calorimeter combined with dimensionality reduction classification techniques. Guo S, Kim WJ, Lok J, Lee SR, Besancon E, Luo BH, Stins MF, Wang X, Dedhar S, Lo EH.

Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Xu D, Hu MJ, Wang YQ, Cui YL. Antioxidant activities of Quercetin and its complexes for Medicinal Application.

Xu D, Qiao T, Wang Y, Wang QS, Cui YL. Alginate nanogels-based thermosensitive hydrogel to improve antidepressant-like effects of albiflorin via intranasal delivery.

Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious Elevated Plus Maze and Open Field , showed depressive-like behavior sucrose preference task , performed poorly in short-term and long-term associative memory task passive avoidance step-through task and displayed reduced locomotion open field.

Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers TBARS, nitric oxide , lowered antioxidants total thiol, catalase , enhanced expression of pro-inflammatory cytokines IL-6, TNF-α, IL-1β and COX-2 in the hippocampus and damaged hippocampal neurons.

Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress.

In fact, there are a number of studies linking depression, anxiety, and in rare cases, even mental illness with deficient levels of omega-3 fats. For those of us that are Vegan, we need to convert alpha linoleic acid, which is a plant based form of omega-3, into the EPA and DHA the brain can use, and in some people with variants in the FADS1 genes, the conversion rate can be very low, so algal oil is a good option for a plant based product that has actual bioavailable EPA and DHA your brain can use.

Rhodiola rosea or roseroot is an adaptogenic herb that helps improve our resilience to stress and helps calm anxiety while promoting mental and physical energy.

Rhodiola appears to be safe to use in combination with common antidepressants and has demonstrated benefits for insomnia, emotional instability and somatization in people with depression and anxiety.

The effects of rhodiola are linked to its ability to modulate levels of neurotransmitters including adrenaline, dopamine, serotonin , and acetylcholine in the brain, in part by inhibiting the enzymes such as monoamine oxidase that break down these substances — the result being enhanced mood regulation.

Taking a single dose of rhodiola before a stressful event seems to help prevent stress-induced disruptions in performance 6 , while long-term use of mg of rhodiola in two mg doses daily has been associated with an anti-fatigue effect, improved mental performance, and reduced burnout, including improvements in anxiety, irritability, concentration, and zest for life.

I wrote a full blog post on Ashwaganda which you can read here. Ashwagandha Withania somnifera is another adaptogenic herb with a long history of traditional use.

Also called Indian ginseng and winter cherry, ashwagandha has been used for over years in Ayurvedic medicine to support vitality and longevity. More recently, research has found that this herb has antioxidant properties, supports immune function, and helps to settle nerves to promote healthy sleep, mood, and reductions in anxiety.

In fact, ashwagandha is used as a natural tranquilizer in India. Ashwagandha is thought to induce its calming effects through the activity of alkaloids and steroidal lactones called withanolides. These substances inhibit overactive nerve cells in the brain, 8 and help to decrease elevated levels of stress hormones such as cortisone in the brain.

In one day placebo-controlled clinical study, people with a history of chronic stress who took mg of an Ashwagandha root extract had significant reductions in stress and a Specifically, ashwagandha led to reductions in scores on the Hamilton Anxiety Scale in two studies, and in one study people taking ashwagandha has a We did a blog post devoted to L-Theanine which you can read here.

L-theanine is an amino acid found in tea leaves, particularly green tea. This amino acid helps to promote feelings of relaxation without causing drowsiness, which makes it a good go-to for daytime anxiety such as before a big meeting or a first date.

L-theanine works by influencing levels of neurotransmitters in the brain. Specifically, theanine increases production of the inhibitory neurotransmitter gamma amino butyric acid GABA and moderates the production of dopamine and serotonin.

Theanine supplementation leads to increased relaxation, reduced feelings of stress, and improvements in focus. L-theanine also results in a switch towards alpha brain wave patterns associated with calm alertness away from beta brain waves associated with anxiety and stress , particularly in the occipital and parietal regions of the brain, indicating a relaxation effect.

L-theanine has also been seen to improve responses in volunteers undertaking a stress task. Gene Food uses a proprietary algorithm to divide people into one of twenty diet types based on genetics. We score for fat metabolism, histamine clearance, carbohydrate tolerance, and more.

Where do you fit? Vitamin B6 is required by the body to produce important neurotransmitters such as serotonin, dopamine, and GABA, as well as the neurohormone melatonin, which regulates the sleep-wake cycle.

High doses of B6 have been linked to nerve damage and even cancer over the long term, so consult with your doctor before starting a regimen and keep doses on the low side less than 10mg. For more, see: B Vitamins and Cancer Risk: How to Make Smart Decisions.

Magnesium is also an important nutrient for nerve health, relaxation, and sleep. This mineral is needed for muscles to relax, so can be helpful for anxiety-related muscle tension. Conversely, deficiencies can cause cramping and muscle spasms, as well as poor quality sleep and other issues.

A combination of magnesium and vitamin B6 has been shown to help relieve anxiety in people with premenstrual syndrome PMS. In one study, people who took mg of magnesium and 50 mg of vitamin B6 over four menstrual cycles had significant relief from PMS-related anxiety, compared to those taking a placebo or magnesium by itself.

In fact, the reported benefits of quercetin are wide ranging, from heart health to a natural remedy for leaky gut , however, it has also shown promise as a calming agent. Studies show that quercetin helps to keep a lid on the fight or flight response of the adrenal system, leading to increased social interaction and a reduction in corticotropin releasing factor CRF which is a neuropeptide associated with anxiety and fear.

Hops, like the ingredient in beer?

For example, eating lots of deeply colored fruits and veggies that contain flavonoids is linked to a lower risk of cardiovascular disease, and even death, in older adults, among reduced risk for vascular diseases. Studies done in animal and some human populations show that various types of flavonoids quercetin, resveratrol and catechins, for example can help reduce the risk of atherosclerosis, which is a dangerous condition caused by plaque building up within the arteries.

Cut-off blood flow in the arteries is one of the primary risk factors for experiencing a heart attack or stroke, which is why cardiac arrest is less likely among people who eat a nutrient-packed diet.

Certain studies show that quercetin prevents damage to LDL cholesterol particles, and it seems that people who eat the most flavonoid-rich foods typically have healthier and lower cholesterol levels , plus fewer incidences of hypertension and high blood pressure.

Taking quercetin supplements may help lower pain associated with autoimmune conditions such as arthritis, as well as infections, including those of the prostate and respiratory tract.

Flavonoids are also linked to reduced symptoms of prostatitis inflammation of the prostate and rheumatoid arthritis RA. While improvements were at times small, it makes sense that antioxidants could boost physical performance since they help increase the health of blood vessels, which carry oxygen and nutrients to muscle and joint tissue.

Other studies also show that it helps increase immune function and prevents susceptibility to illnesses that can occur when someone trains intensely and experiences exhaustion. One study found evidence that taking milligrams of quercetin twice daily helped protect cyclists from developing exercise-induced respiratory infections following periods of heavy exercise.

Because it can boost your energy level, does quercetin affect sleep? For example, is there a link between quercetin and insomnia? One study found evidence that it may alter the sleep-wake cycle partly through activation of GABA gamma-aminobutyric acid receptors.

However, insomnia is generally not believed to be a common side effect of taking it in dietary supplement form. A Boston University School of Medicine study published in the Journal of Biological Regulators and Homeostatic Agents shows a link between a nutrient-dense diet rich in quercetin plus other antioxidants and a lowered risk of cancer.

Quercetin seems to have potential chemo-preventive activity and might have a unique antiproliferative effect on cancerous cells, making it an effective addition to any natural cancer treatment approach. Research shows that this may result from the modulation of either EGFR or estrogen-receptor pathways.

Other studies have found quercetin can help stop the processes involved in cell proliferation and mutation, the growth of tumors, and symptoms related to typical cancer treatments, such as radiation or chemotherapy.

This is especially true when taken in high doses above the amount someone would get from a healthy diet. Studies have found that this compound has antioxidant and anti-inflammatory effects that help fight allergic and inflammatory diseases, as well as some prescriptions, when taken in oral supplement form.

For example, some people take quercetin for eczema since it can inhibit the secretion of histamine and pro-inflammatory markers.

Research has shown that this antioxidant has protective effects when administered to rats with ethanol-induced acute liver injury. A study found evidence indicating that quercetin attenuates liver inflammation and fibrosis in mice through inhibiting macrophages infiltration.

What foods have the most quercetin? All types of tasty red, green and purple-pigmented plants come packed with quercetin — for example, red wine, blueberries, apples, red onion and even green tea are some of the best sources.

Quercetin is actually believed to be the most abundant flavonoid in the human diet. Some of the most common types of dietary supplements include: quercetin 3, quercetin 3 glucoside, quercetin aglycone, isoquercetin, quercetin 7 rutinoside, and quercetin 3 0 rhamnoside.

Some quercetin supplements are also labeled as quercetin dihydrate, which is mostly insoluble in water and may not be absorbed as well as other kinds. Quercetin supplements are available in all types of pills or capsules and are commonly used in formulas along with other anti-inflammatory ingredients.

For example, quercetin with bromelain an anti-inflammatory enzyme found in pineapples may be taken to help manage allergies. What are side effects of quercetin? According to a report, most studies have found little to no side effects in people eating nutrient-dense diets high in quercetin or taking supplements by mouth short term.

Is quercetin safe to take daily? Amounts up to milligrams taken twice daily for 12 weeks appear to be safe. However, of course, in very high doses there are some risks.

Side effects can include headaches and tingling of the arms and legs. Very high doses taken intravenously have also been linked to cases of kidney damage, although this seems very rare.

Popular Nutrition Posts All Time This Week {position} Detox Your Liver: A 6-Step Liver Cleanse. More Nutrition Dr. Axe on Facebook 82 Dr. Axe on Twitter 4 Dr. Axe on Instagram Dr. Axe on Google Plus Dr. We found that MA-induced anxiety-like behavior in mice, as previously described Ru et al.

Consistent with our findings, Iwazaki et al. As an organelle generating secondary ROS, which can disturb protein folding and cause mitochondrial DNA mutations, mitochondria are regarded as both a source and a target of oxidative stress Song et al. Furthermore, ER-misfolded proteins have been reported to accumulate at ER-mitochondria contact regions, where they eventually imported into mitochondrial matrix and resulted in impaired mitochondrial function Saito and Imaizumi, ; Cortés et al.

In summary, MA exposure facilitated mitochondrial damage, intracellular ROS production Cao et al. In this article, pathways related to mitochondria were markedly changed, and mitochondria were found to be short, fragmented with abnormal morphology after MA treatment in vivo and in vitro.

Multiple parameters about mitochondria function were then displayed aberrant, such as ROS and ATP production, MMP, and OCR, implying that mitochondria as a target organelle in MA-treatment. Based on these, we speculate that mitochondria represent a primary target organelle of MA treatment in the HIPP.

Accumulating data has highlighted the contributions of brain mitochondria and bioenergetics to the development of psychiatric disorders and stress-related pathologies Einat et al. The damaged mitochondria accumulation induced synaptic loss, and neuron apoptosis de la Mata et al.

In addition, The fundamental role played by mitochondria in the synthesis of the primary excitatory neurotransmitter glutamate and the inhibitory neurotransmitter γ-aminobutyric acid, GABA suggest that the mitochondrial adaptations observed in the context of anxiety may contribute to an imbalance in neural excitation and inhibition, which is thought to underlie several neuropsychiatric disorders Filiou and Sandi, Mitochondria-targeting drugs have been reported to show good outcomes in anxiety-related studies in both humans and rodents Filiou and Sandi, In this article, we further demonstrated that modification of mitochondrial function and morphology might represent a potential strategy for alleviating anxiety-like behaviors induced by MA, since chronic MA exposure resulted in the dysregulation of mitochondrial morphology and mitochondrial dysfunction.

Quercetin, as a bioactive compound with diverse pharmacologic effects, has been reported to exert several beneficial effects, including neuroprotective effects Costa et al.

In this study, quercetin supplementation significantly mitigated MA-induced anxiety-like behavior by improving mitochondrial morphology and function, alleviating neuronal injury, both in vivo and in vitro. Here, we also identified the novel pharmacological efficacy of quercetin in the treatment of anxiety induced by MA.

As a major source of glycogen and lactate, astrocytes provided neurons with additional energy and play key metabolic roles in the CNS Shirakawa et al. Moreover, astrocytes can dispose of and recycle damaged mitochondria released by neurons, and release healthy extracellular mitochondrial particles to neuron Hayakawa et al.

Astrocyte dysfunction has been shown to facilitate the pathogenesis of neurological and psychiatric disorders Tian et al. Hence, astrocytes and the mitochondria may represent an important target of neurological and psychiatric disorders.

Thus, we intended to focus this study on astrocytes in subsequent experiments. Research has shown MA exposure facilitated dysfunction and morphological abnormalities of mitochondrial Valian et al.

In this work, we observed MA-induced morphological abnormalities of mitochondria in vivo and in vitro , and mitochondrial dysfunction in astrocytes, and the phenotypes were rescued by quercetin.

As we know, except for microglia, astrocytes also serve as crucial regulators of the innate and adaptive immune responses, and play critical roles in neuroinflammation Colombo and Farina, In this study, we found that MA treatment accelerated astrocyte activation, accompanied by the elevation of interleukin IL -1β, IL-6, and tumor necrosis factor TNF α in the HIPP and MA-treated astrocytes Figure 5.

Quercetin, as a bioactive compound with antioxidant and anti-inflammatory properties Khan et al. These results suggested that MA treatment accelerated astrocytes activation and facilitated the release of inflammatory factors, which can trigger neuronal apoptosis and synaptic loss Garwood et al.

Moreover, the excessive accumulation of damaged mitochondria, combined with astrocyte activation and the increase in inflammatory factors, induces neurotoxicity and promotes neuronal apoptosis Nicholls, , which initiates a vicious cycle that aggravates the anxiety process Garwood et al.

These findings also confirmed the neuroprotective activity of quercetin, through modulating astrocytes and rebalancing neuroinflammation levels activation. Nevertheless, the mechanisms by which quercetin exerts its anti-neuroinflammation activity and modulates mitochondrial function remain unclear.

According to previous reports, Nr4a1 also known as TR3 or NGFI-B , which was upregulated in our RNA-seq results, is an orphan member of the nuclear receptor superfamily. It migrates from the nucleus to the mitochondria, where it binds to Bcl-2 to induce apoptosis and cause the release of cytochrome c Liu et al.

Nr4a1 evoked cellular oxidative stress and disrupt ATP generation Zhang and Yu, , and the expression and activity of Nr4a1 are sustained by chronic stress in animal models and in human studies of neuropathologies sensitive to the buildup of chronic stress Akiyama et al.

Nr4a1 has also been shown to be important for regulating metabolic and morphological aspects of neuronal functions by modifying the expression of several mitochondrial regulatory genes, including Mfn1 , Mfn2, Fis1 and OPA1 Jeanneteau et al.

Therefore, we speculated that quercetin might modulate genes associated with mitochondrial function via downregulating Nr4a1. Future work will explore the molecular mechanism extensively. In conclusion, our study indicated that MA cause damage to brain cells, including neurons and astrocytes, by influencing mitochondrial metabolism, energy production, and morphology in astrocytes, which participated in the development of neuropsychiatric disorders, such as anxiety.

The oral supplementation of quercetin neutralized the neuropsychiatric status of MA-treated mice; our findings indicated the potential of quercetin as a candidate agent for alleviating MA-induced anxiety and support the hypothesis that mitochondria mediate anxiety progression.

Further study is necessary to illustrate the contributions and mechanisms of mitochondria in the progression of anxiety induced by MA. The raw reads data from mRNA-seq are available at NCBI GEO with the accession number: GSE and Supplementary Material , further inquiries can be directed to the corresponding authors.

The animal study was reviewed and approved by Committee on Ethics in the Use of Animals from Kunming Medical University. FC and JY designed the experiments and participated in the data analysis. FC, JY, QW, and YL wrote the manuscript. JS and CC performed the sequence alignment and bioinformatics.

MC, YZ, and WT performed the animal experiments. FC, LZ, and ZZ performed the cell experiments. HW, HL, YX, and MZ participated in data analysis. JY and KW conceived of the study and supervised the project. All authors read and approved the final manuscript.

This work was supported by grants from the National Natural Science Foundation of China Grant Nos. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. We would like to thank Jie Bai and Xiangyang Kong for the technical support of behavioral test.

We would also like to thank the technical support of Shaoyou Li for the Flow Cytometry test. Supplementary Figure 1 The effect of quercetin on mitochondrial morphology and function in MA-treated in PC A Representative images of mitochondria in PC Alive cells were incubated with MitoTraker Green as a probe for mitochondria in each group.

B Enlarged images of the areas marked in A with a white box. C Quantification of the mitochondrial membrane potential MMP. D Quantification of the total ATP in PC E Total ROS production quantification by flow cytometry in each group. Supplementary Figure 2 Confocal microscopic analysis of neuron and astrocytes using immunofluorescence stainings.

A—C Immunofluorescence was performed with anti-NeuN [green, C ] and DAPI [blue, B ], C Merged image of panels A,B. D—F Immunofluorescence was performed with anti-Iba [green, D ] and DAPI [blue, E ], F Merged image of panels D,E. Supplementary Figure 3 Quercetin rescued MA-induced Nr4a1 upregulation in gene and protein level.

A Representative band pattern of the WB of different treatment of HIPP using antibodies for Nr4a1 and GAPDH. B Summary bar graphs of Nr4a1 and GAPDH levels in different groups in hippocampus. C Expression of Nr4a1 and GAPDH by qPCR in HIPP. Akiyama, K.

mRNA expression of the Nurr1 and NGFI-B nuclear receptor families following acute and chronic administration of methamphetamine. Psychiatry 32, — doi: PubMed Abstract CrossRef Full Text Google Scholar. Allsop, S. Optogenetic insights on the relationship between anxiety-related behaviors and social deficits.

Andres, S. Safety aspects of the use of quercetin as a dietary supplement. Food Res. Bader, V. Mitochondria at the interface between neurodegeneration and neuroinflammation.

Cell Dev. Baksh, R. The association between anxiety disorders and hippocampal volume in older adults. Aging 36, — Çalışkan, G. Long-Term impact of early-life stress on hippocampal plasticity: spotlight on astrocytes.

Cao, J. Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium iii complexes. Chang, L. Structural and metabolic brain changes in the striatum associated with methamphetamine abuse.

Addiction Abingdon, England Suppl. Chen, F. Acta , — Cheng, M. Chronic methamphetamine treatment reduces the expression of synaptic plasticity genes and changes their DNA methylation status in the mouse brain.

Brain Res. Chiang, M. Methamphetamine-associated psychosis: clinical presentation, biological basis, and treatment options. Colombo, E. Astrocytes: key regulators of neuroinflammation. Trends Immunol.

Cortés, S. ER-misfolded proteins become sequestered with mitochondria and impair mitochondrial function. Costa, L. Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more. Dang, J. Glial cell diversity and methamphetamine-induced neuroinflammation in human cerebral organoids.

Psychiatry 26, — de la Mata, M. Coenzyme Q10 partially restores pathological alterations in a macrophage model of Gaucher disease.

Orphanet J. Rare Dis. Dhiman, P. Quercetin and related chromenone derivatives as monoamine oxidase inhibitors: targeting neurological and mental disorders. Molecules Basel, Switzerland Duncan, Z. Correlates of anxiety and depression in a community cohort of people who smoke methamphetamine.

Psychiatry Einat, H. Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disorders.

Fang, D. Fiebig, C. Mitochondrial dysfunction in astrocytes impairs the generation of reactive astrocytes and enhances neuronal cell death in the cortex upon photothrombotic lesion. Filiou, M. Anxiety and brain mitochondria: a bidirectional crosstalk.

Trends Neurosci. Gallitano, A. Editorial: the role of immediate early genes in neuropsychiatric illness. Garwood, C. Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture. Cell Death Dis. Glasner-Edwards, S. Methamphetamine psychosis: epidemiology and management.

CNS Drugs 28, — Anxiety disorders among methamphetamine dependent adults: association with post-treatment functioning. Golsorkhdan, S. Methamphetamine administration impairs behavior, memory and underlying signaling pathways in the hippocampus. Hayakawa, K. Transfer of mitochondria from astrocytes to neurons after stroke.

Nature , — Hellem, T. A review of methamphetamine dependence and withdrawal treatment: a focus on anxiety outcomes. Abuse Treat. Homer, B. Methamphetamine abuse and impairment of social functioning: a review of the underlying neurophysiological causes and behavioral implications.

Houghton, M. Quercetin preserves redox status and stimulates mitochondrial function in metabolically-stressed HepG2 cells. Free Radic. Huang, R.

Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIRHG. Autophagy 13, — Iwazaki, T. Protein expression profile in the amygdala of rats with methamphetamine-induced behavioral sensitization.

Jayanthi, S. Neurotoxicity of methamphetamine: main effects and mechanisms. Jeanneteau, F. The stress-induced transcription factor NR4A1 adjusts mitochondrial function and synapse number in prefrontal cortex. Joshi, A. Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration.

Kambe, D. Effects of quercetin on the sleep-wake cycle in rats: involvement of gamma-aminobutyric acid receptor type A in regulation of rapid eye movement sleep.

Khan, I. Novel quercetin derivative TEF induces ER stress and mitochondria-mediated apoptosis in human colon cancer HCT cells. Kohno, M.

The relationship between interleukin-6 and functional connectivity in methamphetamine users. Kosari-Nasab, M. Quercetin mitigates anxiety-like behavior and normalizes hypothalamus-pituitary-adrenal axis function in a mouse model of mild traumatic brain injury.

Kwon, H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Lee, B. Protective effects of quercetin on anxiety-like symptoms and neuroinflammation induced by lipopolysaccharide in rats.

Based Complement. eCAM Li, P. Mitochondrial respiratory dysfunctions of blood mononuclear cells link with cardiac disturbance in patients with early-stage heart failure. Liu, J. Modulation of orphan nuclear receptor Nurmediated apoptotic pathway by acetylshikonin and analogues.

Cancer Res. Manji, H. Impaired mitochondrial function in psychiatric disorders. Manning, E. BDNF-deficient mice show reduced psychosis-related behaviors following chronic methamphetamine. May, A. Dark times: the role of negative reinforcement in methamphetamine addiction.

McCoy, M. Chronic methamphetamine exposure suppresses the striatal expression of members of multiple families of immediate early genes IEGs in the rat: normalization by an acute methamphetamine injection.

Psychopharmacology , — Meredith, C. Implications of chronic methamphetamine use: a literature review. Psychiatry 13, — Morava, E. Mitochondria and the economy of stress mal adaptation. Nicholls, D. Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures.

Nie, L. The relationship between duration of abstinence and gray-matter brain structure in chronic methamphetamine users. Drug Alcohol Abuse 47, 65— Pei, L.

Mitochondrial etiology of neuropsychiatric disorders. Psychiatry 83, — Ru, Q. Withdrawal from chronic treatment with methamphetamine induces anxiety and depression-like behavior in mice. Psychiatry Res. Saito, A. Unfolded protein response-dependent communication and contact among endoplasmic reticulum, mitochondria, and plasma membrane.

Samad, N. Quercetin protects against stress-induced anxiety- and depression-like behavior and improves memory in male mice.

Satpute, A. Human anterior and posterior hippocampus respond distinctly to state and trait anxiety. Emotion 12, 58— Shin, E. Current understanding of methamphetamine-associated dopaminergic neurodegeneration and psychotoxic behaviors.

Shirakawa, H. Transient receptor potential canonical 3 TRPC3 mediates thrombin-induced astrocyte activation and upregulates its own expression in cortical astrocytes. Shoptaw, S. Treatment for amphetamine psychosis. Cochrane Database Syst.

Smith, M. Prevalence of psychotic symptoms in substance users: a comparison across substances. Psychiatry 50, — Song, X.

Transcriptomics and proteomic studies reveal acaricidal mechanism of octadecanoic acid-3, 4 — tetrahydrofuran diester against Sarcoptes scabiei var.

Srisurapanont, M. Psychotic symptoms in methamphetamine psychotic in-patients. Su, H. Anxiety level and correlates in methamphetamine-dependent patients during acute withdrawal.

Medicine e Sun, J. Intestinal mRNA expression profile and bioinformatics analysis in a methamphetamine-induced mouse model of inflammatory bowel disease. Tian, H.