Anal Pathologies: What Management at the Reference Health Center of Bamako’s Commune V?

Anal pathologies are conditions affecting the anal margin and the anal canal. The aim of our study was to update data on anal diseases. Non-specific, it can reveal an emergency, a serious illness, a chronic disease or a benign condition. It was a prospective, descriptive and analytical study from April 2022 to March 2023, carried out in the hepato-gastroenterology unit of the Centre de Santé de Référence de la commune V du District de Bamako in Mali. Out of seven hundred and forty-nine (749) patients seen in consultation, 98 had anal pathology, i.e. a prevalence of 13.08%. The mean age was 40 ± 15.15 years and the sex ratio was 1.5. Hemorrhoidal disease and anal fissure were the most frequent pathologies in 66.4% and 24.4% of cases respectively. Medical treatment was initiated in 91.9% of patients with hemorrhoidal disease and 91.7% with anal fissure. Anal pathologies are common in young male patients. In our context, they are dominated by benign conditions.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac dysfunction.Methods Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity.At embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western blotting.Results They demonstrated that the heart presented inflammatory responses after LPS induction.The LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three dosages.Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS group.Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS group.Quercetin significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS induction.Quercetin significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS group.Quercetin significantly decreased protein expressions of AMPKα1,LC3-I,and LC3-II.Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.Conclusion Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy,programmed cell death,and myocardiocytes permeability.

Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments

BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.

Protective effects of quercetin against H2O2 induced KGN cells injury

Background:Oxidative stress is one of the key contributors to cellular senescence and ovarian aging.Quercetin has a variety of physiological activities such as antioxidant.Given that hydrogen peroxide can cause oxidative damage to cells,the present study is designed to verify the protective effect of quercetin on human ovarian granulosa tumor cell line under oxidative stress.Methods:Cell counting kit-8 and lactate dehydrogenase assays examined cell viability and toxicity.Flow cytometry detected reactive oxygen species accumulation.Glutathione level was measured to analyze the oxidation resistance.Cell apoptosis was evaluated by Hoechst 33258 staining,acridine orange/Ethidium Bromide staining and western blot.The mitochondrial structure was observed under a transmission electron microscope.Mitochondrial membrane integrity was detected by JC-1 staining and western blot.Results:Hydrogen peroxide could induce cell injury,promote reactive oxygen species accumulation,and lead to glutathione depletion.hydrogen peroxide also resulted in mitochondrial morphological damage and depolarization,which activate caspase3/9 subsequently.However,quercetin could mitigate these damages.Conclusions:Present study found that hydrogen peroxide induced oxidative stress and mitochondrial apoptosis of human ovarian granulosa tumor cell line cells,which could be attenuated by quercetin.

Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.

Protective mechanism of quercetin compounds against acrylamide-induced hepatotoxicity

Quercetin compounds have antioxidant,anti-inflammatory and anticancer pharmacological functions.Longterm exposure to acrylamide(AA)can cause liver injury and endanger human health.However,whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear.Here,we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro.In vivo studies found that quercetin-like compounds protect against AAinduced liver injury by reducing oxidative stress levels,activating the Akt/m TOR signaling pathway to attenuate autophagy,and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis.In vitro studies found that quercetin compounds protected Hep G2 cells from AA by attenuating the activation of AA-induced autophagy,lowering reactive oxygen species(ROS)levels by exerting antioxidant effects and thus attenuating oxidative stress,increasing mitochondrial membrane potential(MMP),and improving apoptosis-related proteins,thus attenuating AA-induced apoptosis.Furthermore,the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity,with quercetin showing the best protective capacity due to its strongest antioxidant activity.In conclusion,quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress,autophagy and apoptosis,and their protective capacity correlates with antioxidant activity.

Perianal disease in inflammatory bowel disease:Broadening treatment and surveillance strategies for anal cancer

The perianal disease affects up to one-third of individuals with Crohn's disease(CD),causing disabling symptoms and significant impairment in quality of life,particularly for those with perianal fistulising CD(PFCD).The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing.Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents,endoscopic procedures and surgical techniques that show promising results.Among these,mesenchymal stem cells injection is a particularly hopeful therapy.In addition to the burden of fistulas,individuals with perianal CD may face an increased risk of developing anal cancer.This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes.Currently,there is no established formal anal screening programme.In this review,we provide an overview of the current state of the art in managing PFCD,including novel medical,endoscopic and surgical approaches.The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD,intending to propose a risk-based surveillance algorithm.The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

A comparative study of acupuncture combined with rehabilitation gymnastics on postoperative anal function of lower rectal cancer

BACKGROUND From the anal function,inflammatory response and other indicators,acupuncture combined with rehabilitation gymnastics was applied to patients with cancer undergoing low resection,aiming to improve the prognosis of patients.AIM To explore the effects of acupuncture combined with rehabilitation gymnastics on anal function after lower rectal cancer surgery.METHODS From January 2020 to December 2022,128 patients who underwent rectal cancer surgery in the Department of Oncology of Hebei Provincial Hospital of Traditional Chinese Medicine Hospital were selected and divided into two groups using the random number table method,with 64 patients in each group.Patients in the control group were not treated with acupuncture or rehabilitation gymnastics and served as blank controls.Patients in the study group were treated with acupuncture and rehabilitation gymnastics from the 7th postoperative day.The anal incontinence scores,changes in serum interleukin-4,interleukin-6,and interleukin-10 Levels,and serum motilin,5-hydroxytryptamine,and vasoactive intestinal peptide levels were compared.RESULTS There were no significant differences in serum interleukin-4,interleukin-6,and interleukin-10 Levels between the groups before treatment(P>0.05).After treatment,these levels were better than those of the control group(P<0.05).There was no significant difference in the anal incontinence scores between the groups before and 7 d after surgery(P>0.05).Anal incontinence scores in the study group were lower than those in the control group at 14 d,21 d,and 28 d postoperatively(P<0.05).There were no significant differences in serum motilin,5-hydroxytryptamine,or vasoactive intestinal peptide levels between the groups before treatment(P>0.05).After treatment,these levels were higher in the study group than in the control group,and vasoactive intestinal peptide level was lower in the study group than in the control group(P<0.05).CONCLUSION Acupuncture combined with rehabilitation gymnastics can promote the recovery of anal function and reduce the inflammatory response in patients with lower rectal cancer after surgery.

Identification of key genes regulating the synthesis of quercetin derivatives in Rosa roxburghii through integrated transcriptomics and metabolomics

Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together,these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.

Anal pruritus:Don’t look away

Anal pruritus is a common anorectal symptom that can significantly impair a patient’s quality of life,including their mental health.It can be one of the most difficult proctological conditions to treat.Patients often delay seeking medical attention,since it is an embarrassing but non-life-threatening situation.Pruritus ani can be associated with idiopathic and secondary causes,such as anorectal diseases,cancer(anal or colorectal),dermatological and sexually transmitted diseases,fungal infections and systemic diseases.If patients are referred for a colonoscopy,this can sometimes provide the first opportunity to evaluate the perianal area.Classifications of anal pruritus are based on the abnormalities of the perianal skin,one of the most commonly used being the Washington classi-fication.A proper digital anorectal examination is important,as well as an anoscopy to help to exclude anorectal diseases or suspicious masses.Endoscopists should be aware of the common etiologies,and classification of the perianal area abnormalities should be provided in the colonoscopy report.Information on treatment possibilities and follow-up can also be provided.The treatment normally consists of a triple approach:proper hygiene,elimination of irritants,and skin care and protection.Several topical therapies have been described as possible treatments,including steroids,capsaicin,tacrolimus and methylene blue intradermal injections.

Evaluating the clinical application and effect of acupuncture therapy in anal function rehabilitation after low-tension rectal cancer surgery

BACKGROUND According to the indexes of serum and anal function,acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications.AIM To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery.METHODS From the anorectal surgery cases,we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group(n=60),observation group(n=60),and control group after surgery for lifestyle intervention(including smoking cessation and exercise),dietary factor adjustment,anal movement,and oral loperamide treatment.The serum levels of motilin,5-hydroxytryptamine,and vasoactive intestinal peptide(VIP),Wexner score for anal incontinence,and incidence of complications were compared between groups.RESULTS After treatment,the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group(P<0.05).The motilin level was higher than that in the control group(P<0.05).Postoperative anal incontinence was better in the observation group than in the control group(P<0.05).The incidence of complications in the observation group was 6.67%,which was significantly lower than that in the control group(21.67%;P<0.05).CONCLUSION Acupuncture therapy has a positive effect on the rehabilitation of anal function after low-tension rectal cancer surgery;it can effectively help to improve the serum indices of patients,avoid the occurrence of anal incontinence,and reduce the incidence of complications.Popularizing and applying it will be valuable.

Effects of Quercetin Extracted from Flower Buds of Sophora japonica cv.jinhuai on Proliferation and Apoptosis of Human Breast Cancer MCF-7 Cells

[Objectives]To investigate the effects of quercetin extracted from flower buds of Sophora japonica cv.jinhuai on the proliferation,apoptosis and migration of human breast cancer MCF-7 cells.[Methods]MTT assay,inverted microscope observation,hoechst33342 staining,flow cytometry(FCM)and wound healing assay were adopted to investigate the proliferation,morphological changes,apoptosis level and cell migration ability of human breast cancer MCF-7 cells,respectively.[Results]The morphological changes of cells in the treatment groups included gradually decreased number,reduced volume,vague cell contour,loose intercellular connection,uneven cytoplasm distribution and increased cell debris.With the increase of drug concentration,quercetin significantly inhibited the proliferation of human breast cancer MCF-7 cells(P<0.05).The number of apoptotic bodies increased gradually.When the concentration reached 100μmol/L,a large number of nuclear fragments appeared,and the level of apoptosis was statistically different(P<0.05).The mobility and migration ability of cells showed a decreasing trend,and the differences were statistically significant(P<0.05).[Conclusions]This study can provide experimental basis for clinical application of quercetin against breast cancer.

Quercetin regulates depression-like behavior in CUMS rat models via TLR4/NF-κB signaling

Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.

Based on network pharmacology,molecular docking and experimental validation to reveal the potential molecular mechanism of quercetin for the treatment of diarrheal irritable bowel syndrome

Objective:To explore the potential mechanism of action of quercetin in the treatment of diarrhea irritable bowel syndrome(IBS-D).Methods:The potential targets of quercetin were obtained from the TCMSP,SwissTar-getPrediction,and BATMAN-TCM databases.The targets of IBS-D were obtained by searching the GeneCards database with"diarrhea irritable bowel syndrome"as the keyword,and the targets of quercetin and IBS-D were intersected.The PPI network was constructed by Cytoscape 3.7.1 software.The intersected targets were imported into the DAVID database for GO functional analysis and KEGG pathway enrichment analysis.The binding ability of quercetin to the core targets was observed using molecular docking.Based on this,we established an IBS-D rat model,administered quercetin for intervention,and experimentally validated the network pharmacology prediction results by HE staining and ELISA assay.Results:Network pharmacology analysis showed that TP53,TNF-α,AKT1,VEGF-A,IL-6 factors and MAPK,PI3K-Akt signaling pathway as the core targets and pathways of quercetin for the treatment of IBS-D.The results of animal experiments revealed that quercetin could inhibit the secretion of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,reduce the inflammatory response and improve IBS-D.Conclusion:Quercetin could protect colon tissue by regulating the expression of TP53,TNF-α,AKT1,VEGF-A,IL-1βand IL-6,thereby treating IBS-D.

Clinical Study on the Treatment of Low Anal Fistula in Infants and Young Children by Anal Gland Excision and Virtual Hanging Procedure

Objective:To compare the efficacy of anal adenectomy with virtual hanging wire and anal fistulotomy in the treatment of low anal fistula in infants and children.Methods:60 children with low anal fistula who were admitted to our hospital from October 2021 to March 2022 and met the inclusion criteria were randomly divided into two groups of 30 cases each;the treatment group was treated with anal adenectomy and virtual hanging wire surgery,and the control group was treated with anal fistula resection.The clinical efficacy after treatment was compared.Results:The total effective rate of both groups was 96.67%and the difference between the two groups was not statistically significant(P>0.05).The postoperative pain score of the treatment group was lower than that of the control group(P<0.05).The length of hospitalization and healing time of the treatment group was lower than that of the control group(P<0.05).The anal function of the patients in both groups was normal,and there was no adverse reaction.Conclusion:Anal gland excision and virtual hanging surgery for the treatment of low anal fistula in infants and children have the advantages of mild pain,reduced length of hospitalization,short healing time,and better patient experience as compared to anal fistula excision.

A case study illustrating the use of an integrated approach to treat secondary Anal Fistula Post I&D of Perianal Abscess

Background:Anal fistula is a long-term disease characterized by a tubular structure with one end opening in the anorectal canal and the other end opening on the surface of the perineum or perianal skin with chronic pus drainage.It is linked to Bhagandar in Ayurveda,and in Sushruta Samhita,Acharya has mentioned 5 forms of Bhagandar.The boil in the present case was Shukla,sthira i.e.hard and firm,with Picchila strava and Kandu resembling the features of Parisraavi bhagandar.Aim and objective:The current case was diagnosed as Parisravi bhagandar,which resembles trans-sphincteric or intersphincteric fistula in modern ano.In Ayurveda,the management of Parisraavi Bhagandar,Shastra,kshara,and Agnikarma is advised and the use of Ksharasutra,which contributes to complete cutting and healing of the track without reoccurrence,similarly Modern surgeon depends on surgery i.e radical excision of the track,ligation with Seton,and use of chemical irritants like urethane,silver nitrates,etc.A cutting seton(tight)gently slices the confined muscle to close the fistula with the least interruption to continence.This operation is especially advised when a one-stage fistulotomy poses a considerable risk of incontinence.Material and methods:The method performed here was Core Partial Fistulectomy followed by Ksharasutra application till complete healing of the wound.Discussion and conclusion:This case study provides the successful management of Parisraavi Bhagandara(high anal,trans-sphincteric fistula in ano)in 61-year-old male patient with an integrated surgical&Ayurvedic management approach.

Effects of Quercetin on Blood Pressure in Animals:A Systematic Review and Meta-analysis

[Objectives] To make a systematic evaluation of the efficacy and safety of quercetin on animal blood pressure.[Methods] The CNKI,Wan Fang,VIP,CBM,Pubmed,and Cochrane Library databases were searched for the literature about the effects of quercetin on blood pressure in the period from the creation of databases to April 2018.Two researchers separately screened literature and extracted data.Meta-analysis was carried out with the aid of Rev Men 5.3 software.[Results]A total of 10 articles were included,involving 288 animals.All animals were rodents.Meta-analysis results showed that there was a statistically significant difference in Systolic Blood Pressure(SBP) between the quercetin group and the control group.MD =-21.43,95% CI(-28.99,-13.86),P < 0.000 01;subgroup analysis,hypertensive animal group,MD =-29.52,95% CI(-36.05,-22.98),P < 0.000 01;the ability of quercetin group in lowering blood pressure was better than that of the control group,and the difference was statistically significant;in the normal blood pressure group,MD =-0.49,95% CI(-3.74,2.77),P = 0.77,the quercetin group was basically the same as the control group,the difference was not statistically significant.[Conclusions] Compared with the blank control group,quercetin can effectively reduce the blood pressure of hypertensive animals,but it has little effect on the blood pressure of normal animals.Besides,further study is needed on the safety of quercetin.

Anti-leishmanial,immunomodulatory and anti-oxidative activity of quercetin against cutaneous leishmaniasis caused by Leishmania major

Objective:To evaluate the in vitro and in vivo efficacy of quercetin and its immunomodulatory and anti-oxidative activity against Leishmania major(L.major).Methods:L.major promastigotes and amastigotes were incubated with different concentrations of quercetin to estimate EC_(50).For in vivo study,the base of tails of mice was infected with L.major.After developing ulcers in the inoculation site,mice were treated with 50 mg/kg quercetin orally for 28 consecutive days.The wound-healing potential of quercetin was evaluated by histopathological analysis of tissue sections stained by hematoxylin and eosin as well as Masson's trichrome.In addition,the levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and adiponectin,the ferric reducing ability of plasma,as well as superoxide dismutase and glutathione peroxidase activities were measured.Results:The EC_(50)values of quercetin against L.major promastigotes and intracellular amastigotes were 0.27 and 0.85μM,respectively.Histopathological analysis showed that fewer inflammatory cells,more fibroblasts,and more collagen deposition were observed in tissue sections of quercetin-treated mice.In addition,treatment with quercetin markedly increased glutathione peroxidase activity,the ferric reducing ability of plasma and adiponectin levels while decreasing malondialdehyde,interleukin-6,and tumor necrosis factor-αlevels.Conclusions:Quercetin shows anti-leishmanial activity,immunomodulatory,anti-oxidative,and anti-inflammatory effects.Therefore,it may be further explored as an effective drug in treating leishmaniasis.

Quercetin-derivatives painting the yellow petals of American lotus(Nelumbo lutea)and enzymatic basis for their accumulation

American lotus(Nelumbo lutea)is one of the two species in Nelumbo and has only yellow flower.Identification of total flavonoids showed wild American lotus contained almost only flavonols with quercetin 3-O-glucuronide to be the dominant pigment.The variation tendency of the total flavonol content was coincident with yellow color variation of petals during flower development.To understand the mechanism of accumulation and constituent of pigments in petals,three pivotal genes,NlFLS1,NlFLS2 and NlFLS3,which were predicted to encode flavonol synthases were isolated and characterized by analyses of basic bioinformatics,temporal and spatial expression patterns and enzymatic activity.Their temporal expression levels showed the same variation tendency,which was also consistent with the development-dependent variation of total flavonol content.Spatial expression patterns indicated the three genes should function in petals.All the three proteins were demonstrated to be bifunctional dioxygenase,possessing both flavonol synthase activity and flavanone 3-hydroxylase activity.Besides,other flavonol biosynthesis related genes were also investigated on their expression levels to give more clues on the mechanism.Substrate preferences of the three FLSs,substrate competitions between the FLSs and other flavonol biosynthesis related enzymes,and the greatly differential expression levels between F3’H(flavonoid 3-hydroxylase)and F3’5’H(flavonoid 3,5-hydroxylase)contributed to the flavonol constituent in the petals of America lotus,namely abundant quercetin-derivatives while very few kaempferol-derivatives and myricetin-derivatives.

Protocatechuic acid and quercetin attenuate ETEC-caused IPEC-1 cell inflammation and injury associated with inhibition of necroptosis and pyroptosis signaling pathways

Background:Necroptosis and pyroptosis are newly identified forms of programmed cell death,which play a vital role in development of many gastrointestinal disorders.Although plant polyphenols have been reported to protect intestinal health,it is still unclear whether there is a beneficial role of plant polyphenols in modulating necroptosis and pyroptosis in intestinal porcine epithelial cell line(IPEC-1)infected with enterotoxigenic Escherichia coli(ETEC)K88.This research was conducted to explore whether plant polyphenols including protocatechuic acid(PCA)and quercetin(Que),attenuated inflammation and injury of IPEC-1 caused by ETEC K88 through regulating necroptosis and pyroptosis signaling pathways.Methods:IPEC-1 cells were treated with PCA(40μmol/L)or Que(10μmol/L)in the presence or absence of ETEC K88.Results:PCA and Que decreased ETEC K88 adhesion and endotoxin level(P<0.05)in cell supernatant.PCA and Que increased cell number(P<0.001)and decreased lactate dehydrogenases(LDH)activity(P<0.05)in cell supernatant after ETEC infection.PCA and Que improved transepithelial electrical resistance(TEER)(P<0.001)and reduced fluorescein isothiocyanate-labeled dextran(FD4)flux(P<0.001),and enhanced membrane protein abundance of occludin,claudin-1 and ZO-1(P<0.05),and rescued distribution of these tight junction proteins(P<0.05)after ETEC infection.PCA and Que also declined cell necrosis ratio(P<0.05).PCA and Que reduced mRNA abundance and concentration of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8(P<0.001),and down-regulated gene expression of toll-like receptors 4(TLR4)and its downstream signals(P<0.001)after ETEC infection.PCA and Que down-regulated protein abundance of total receptor interacting protein kinase 1(t-RIP1),phosphorylated-RIP1(p-RIP1),p-RIP1/t-RIP1,t-RIP3,p-RIP3,mixed lineage kinase domain-like protein(MLKL),p-MLKL,dynamin-related protein 1(DRP1),phosphoglycerate mutase 5(PGAM5)and high mobility group box 1(HMGB1)(P<0.05)after ETEC infection.Moreover,PCA and Que reduced protein abundance of nod-like receptor protein 3(NLRP3),nod-like receptors family CARD domain-containing protein 4(NLRC4),apoptosis-associated speck-like protein containing a CARD(ASC),gasdermin D(GSDMD)and caspase-1(P<0.05)after ETEC infection.Conclusions:In general,our data suggest that PCA and Que are capable of attenuating ETEC-caused intestinal inflammation and damage via inhibiting necroptosis and pyroptosis signaling pathways.