Morin is a functional flavonoid commonly found in human diet.Compared to being used solely,it is evident that morin can be more effective as a drug adjuvant.However,research on the combined effect and its correspondin...Morin is a functional flavonoid commonly found in human diet.Compared to being used solely,it is evident that morin can be more effective as a drug adjuvant.However,research on the combined effect and its corresponding mechanism is limited.Here,we found that morin significantly potentiated the inhibitory effects of the natural compound celastrol on the proliferation of lung cancer cells.Morin and celastrol synergistically exhibit marked apoptosis induction in lung cancer cells,accompanied by changes in the abundance of apoptosis-related proteins.Transcriptome analyses revealed that the combination of morin and celastrol had a significant impact on the number of differentially expressed genes in lung cancer cells.Among these genes,BIRC3 was one of the most significantly different ones,which plays a crucial role in the process of tumor resistance to apoptosis.In addition,several genes identified are primarily associated with intracellular signal transduction pathways,specifically the NF-κB signaling pathway.Importantly,the treatment combining morin and celastrol in tumor-bearing mice results in a synergistic effect that significantly suppressed tumor growth.These findings indicate that morin could be a promising functional adjuvant,and the combination of morin and celastrol has potential for the treating lung cancer.展开更多
Objective:Gastric cancer(GC)is one of the most common malignancies seen in clinic and requires novel treatment options.Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant ...Objective:Gastric cancer(GC)is one of the most common malignancies seen in clinic and requires novel treatment options.Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L.,which exhibits an anti-cancer effect in multiple types of tumors.However,the therapeutic effect and underlying mechanism of morin in treating GC remains elusive.The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC.Methods:For in vitro experiments,the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45,human gastric adenocarcinoma cell line AGS,and human gastric epithelial cell line GES-1;for apoptosis analysis,microscopic photography,Western blotting,ubiquitination analysis,quantitative polymerase chain reaction analysis,flow cytometry,and RNA interference technology were employed.For in vivo studies,immunohistochemistry,biomedical analysis,and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC.Results:Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose-and timedependent manner,but did not inhibit human gastric epithelial cells GES-1.Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells,suggesting that apoptosis was the main type of cell death during the treatment.Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells,which mainly relied on B cell leukemia/lymphoma 2(BCL-2)associated agonist of cell death(BAD)but not phorbol-12-myristate-13-acetate-induced protein 1.The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD,rather than the transcription regulation and the phosphorylation of BAD.Furthermore,the combination of morin and BCL-2 inhibitor navitoclax(also known as ABT-737)produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals.In addition,morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway.Conclusion:Morin suppressed GC by inducing apoptosis,which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD.The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells,which may overcome the drug resistance of the BCL-2 inhibitor.These findings indicated that morin was a potent and promising agent for GC treatment.展开更多
Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is...Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is a bioflavonoid mainly extracted from white mulberry,a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties.This study examines whether morin can alleviate atherosclerosis by suppressing End MT and seeks to elucidate the underlying mechanism.Methods:We induced an in vitro End MT model in human umbilical vein endothelial cells(HUVECs)by stimulating the cells with transforming growth factor-β1(TGF-β1)(10 ng/m L)for 48 h.The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E(Apo E)^(-/-)mice fed with a high-fat diet(HFD).Mice in the intervention group were given morin(50 mg/kg)orally for 4 weeks.Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase-9(MMP-9).Results:Morin inhibited the expression of End MT markers in a dose-dependent manner in TGF-β1-treated HUVECs.Administering 50μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced End MT.Moreover,the overexpression of MMP-9 activated Notch-1 signaling,thereby reversing morin's inhibitory effect on End MT.In the HFD-induced atherosclerotic Apo E^(-/-)mice,morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing End MT.Furthermore,morin demonstrated a strong binding affinity for MMP-9.Conclusion:Morin acts as an MMP-9 inhibitor to disrupt End MT in atherosclerosis by limiting the activation of Notch-1 signaling.This study underscores morin's potential utility in the development of antiatherosclerotic medication.展开更多
AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control gro...AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride(CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimenswere obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin(α-SMA), collagen Ⅰ, collagen Ⅲ, Nrf2, heme oxygenase(HO-1), and quinone oxidoreductase 1(NQO1) using frozen liver specimens.RESULTS Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower m RNA and protein expression of α-SMA, collagen Ⅰ, and collagen Ⅲ, but significantly higher m RNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only(P < 0.05).CONCLUSION Morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors(HO-1 and NQO1) and reducing the expression of α-SMA, collagen Ⅰ, and collagen Ⅲ in CCl4-induced liver fibrosis rats.展开更多
Objective:To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate(DOCA)-salt induced hypertension in male Wistar rats.Methods:Hypertension was induced in uninephrectomized rats by ...Objective:To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate(DOCA)-salt induced hypertension in male Wistar rats.Methods:Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA(25 mg/kg bw) and 1% NaCl in the drinking water for six consecutive weeks. Effect of morin against DOCA-salt induced hypertension was evaluated by measuring blood pressure and performing biochemical estimations and histopathological examination of renal tissues.Results:DOCA-salt hypertensive rats showed considerably increased systolic and diastolic blood pressure,serum hepatic marker enzyme activities such as aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and gamma-glutamyl transpeptidase(GGT)and renal function markers(urea, uric acid and creatinine) in plasma. Oral administration of morin(25, 50 and 75 mg/kg bw) brought back all the above parameters to near normal level.Histopathology of kidney also confirmed the biochemical findings of this study. The effect at a dose of 50 mg/kg bw of morin was more pronounced than that of the other two doses(25 and 75 mg/kg bw).Conclusions:These findings indicate that morin exhibits strong antihypertensive effect against DOCA-salt induced hypertension.展开更多
Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p....Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p.) administration of PTZ(90 mg/kg). Mice were either pretreated with morin(10, 20 and 40 mg/kg) or vehicle(distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production(P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin(20 and 40 mg/kg) administration. The PTZinduced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin(20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin(20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na^+K^+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent.展开更多
Flavonols are plant nature. Morin and other related pigments that are ubiquitous in plant flavonols have come into recent prominence because of their usefulness as anticancer, antitumor, anti-AIDS, and other important...Flavonols are plant nature. Morin and other related pigments that are ubiquitous in plant flavonols have come into recent prominence because of their usefulness as anticancer, antitumor, anti-AIDS, and other important therapeutic activities of significant potency and low systemic toxicity. The heat of combustion of morin （molecular formula, C15H10O7·H2O） in oxygen was measured by a rotating-bomb type combustion calorimeter, the standard molar enthalpy of combustion of morin at T = 298.15 K was determined to be △cH^ m （C15H10O7·H2O, s） = - （5 937.99±2.99） kJ·mol^-1. The derived standard molar enthalpy of the formation of morin in solid powder state at T = 298.15 K, △fH^ m（C15H10O7·H2O, s）, was -（1 682.12 ± 3.58） kJ·mol^1, which provide an accurate data of the stability of morin to the pharmacy and pharmacology.展开更多
Objective:To explore the therapeutic role of morin against L-arginine-induced acute pancreatitis in rats.Methods:The group 1 received two intraperitoneal injections of normal saline,and groups 2-4 were given two intra...Objective:To explore the therapeutic role of morin against L-arginine-induced acute pancreatitis in rats.Methods:The group 1 received two intraperitoneal injections of normal saline,and groups 2-4 were given two intraperitoneal injections of L-arginine(250 mg/100 g body weight)at 1 h interval to induce acute pancreatitis.Subsequently,group 2 received no further treatment while groups 3 and 4 were treated with morin(30 mg/kg)and diclofenac sodium(30 mg/kg),respectively.Blood glucose and serum levels of insulin,α-amylase,malondialdehyde,myeloperoxidase,alanine aminotransferase,aspartate aminotransferase and cholesterol were measured.Moreover,histopathological study was carried out to investigate the effect of morin treatment on physiology of the pancreas.Results:L-arginine significantly altered the level of blood glucose and serum levels of insulin,α-amylase,malondialdehyde,myeloperoxidase,alanine aminotransferase,aspartate aminotransferase and cholesterol.Treatment with morin or diclofenac sodium significantly improved the levels of these biomarkers.Furthermore,morin showed more significant effect than diclofenac sodium.Histopathological analysis verified that morin protected the pancreas from deleterious effects of L-arginine.Conclusions:Morin plays a protective role against L-arginineinduced acute pancreatitis via reducing lipid peroxidation and tissue inflammation,and attenuating acute pancreatitis-associated alteration in insulin secretion and glucose metabolism.展开更多
Morin (MR) is an anticancer drug present in fruits and Chinese herbs. Fe3O4 magnetic nanoparticles (MNPs) coated on 3-aminopropyl triethoxysilane (APTES) were synthesized (MNPs-APTES) as carriers for MR. The character...Morin (MR) is an anticancer drug present in fruits and Chinese herbs. Fe3O4 magnetic nanoparticles (MNPs) coated on 3-aminopropyl triethoxysilane (APTES) were synthesized (MNPs-APTES) as carriers for MR. The characterization of drug delivery system was confirmed by Fourier Transform Infrared (FTIR), Transmission Electron Microscope (TEM), X-Ray Diffraction (XRD), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). The adsorbed APTES on the magnetite surface (MNPs-APTES) was examined by FTIR. The TEM image showed that the average particle size is obtained to be about 26.7 nm for MNPs-APTES. The MR loading and release behavior of MNPs-APTES were studied and the results showed that up to 60% of the adsorbed drug was released within 4 h. In summary, the MNPs-APTES nanocarriers are based on the results, promising for targeted morin drug delivery.展开更多
A highly sensitive and fairly selective spectrofluorimetric method has been developed for the determination of germanium with morin in tap water and health drink. The fluorescent reaction and optimal conditions of ger...A highly sensitive and fairly selective spectrofluorimetric method has been developed for the determination of germanium with morin in tap water and health drink. The fluorescent reaction and optimal conditions of germanium with morin in phosphoric acid medium were studied. The detection limits of germanium in tap water and health drink were found to be 0.2 and 0.7μd/L respectively.展开更多
Background:Alcohol use and traumatic events have a connecting relationship owing to the rising number of people adopting alcoholism as a coping strategy.Objectives:This study examined the cardiorenal protective effect...Background:Alcohol use and traumatic events have a connecting relationship owing to the rising number of people adopting alcoholism as a coping strategy.Objectives:This study examined the cardiorenal protective effect of morin,a bioflavonoid,in mice comorbidly exposed to alcohol use disorder(AUD)and posttraumatic stress disorder(PTSD).Methods:Mice exposed to single-prolong-stress(SPS)-induced PTSD were submitted to every-other-day ethanol(2 g/kg,oral gavage)for AUD induction,alongside treatments with morin(50 mg/kg and 100 mg/kg)or fluox-etine(10 mg/kg),from days 8-21 once daily.After that,mice were euthanized on day 22,markers of oxidative stress(glutathione,catalase,superoxide dismutase,malondialdehyde,nitrite)and inflammatory cytokines(tumor necrosis factor(TNF-α),interleukin-6(IL-6))in the kidney and heart were assayed.Results:Our result showed that mice exposed to SPS+EtOH-induced PTSD-AUD had reduced levels of glutathione,catalase,and superoxide dismutase,with increased malondialdehyde and nitrite concentrations in the heart and kidney relative to SPS+EtOH group.Also,the SPS+EtOH group showed increased concentrations of TNF-αand IL-6 in the heart and kidney tissues,suggesting inflammatory activity relative to normal control.Treatment with morin(50 mg/kg and 100 mg/kg)significantly reduced the SPS-EtOH-induced oxidative and nitrergic stress relative to the SPS+EtOH group.Additionally,the increased release of TNF-αand IL-6 following PTSD-AUD induction was profoundly inhibited by morin in a similar manner to fluoxetine.Conclusion:Our findings suggest that AUD-PTSD interaction-induced organ dysfunction,such as cardiorenal impairments,was reversed by morin via mechanisms associated with attenuation of oxidative/nitrergic stress and release of pro-inflammatory cytokines in mice.展开更多
Nimodipine(NMD),a calcium channel blocker,is classified as a Biopharmaceutical Classification System Class II drug,with low oral bioavailability(3%-30%)due to extensive first-pass metabolism.Self-nanoemulsifying drug ...Nimodipine(NMD),a calcium channel blocker,is classified as a Biopharmaceutical Classification System Class II drug,with low oral bioavailability(3%-30%)due to extensive first-pass metabolism.Self-nanoemulsifying drug delivery systems(SNEDDS)offer a novel approach to improving the bioavailability of such drugs.Morin hydrate(MH),a flavonoid,may enhance NMD’s bioavailability by modulating CYP3A4 and P-glycoprotein during metabolism.This study aimed to optimize an MHloaded NMD-SNEDDS formulation using a three-factor,three-level Box-Behnken design(BBD).Independent variables were Capmul MCM(X_(1))as the oil,Cremophor RH-40(X_(2))as the surfactant,and Transcutol-P(X_(3))as the co-surfactant.Dependent variables included droplet size(Y_(1)),polydispersity index(Y_(2)),and cumulative drug release in 15 minutes(Y_(3)).The optimized formulation(X_(1)=10.0 mg,X_(2)=62.0 mg,X_(3)=40.0 mg)predicted Y_(1),Y_(2),and Y_(3)values of 124.3 nm,0.105,and 97.2%,respectively,with a desirability of 0.8850.Pharmacokinetic studies showed that NMDSNEDDS and MH-loaded NMD-SNEDDS increased oral bioavailability 3-fold and 4-fold,respectively,compared to pure drug suspension.MH-loaded NMD-SNEDDS demonstrated P-gp inhibition,enhancing NMD absorption.BBD effectively optimized the SNEDDS formulation,and MH-loaded NMD-SNEDDS is a promising approach to enhance NMD’s oral bioavailability.展开更多
基金supported by the National Nature Science Foundation Project(32202067)the Young Talent Fund of Association for Science and Technology in Shaanxi,China(20230203)。
文摘Morin is a functional flavonoid commonly found in human diet.Compared to being used solely,it is evident that morin can be more effective as a drug adjuvant.However,research on the combined effect and its corresponding mechanism is limited.Here,we found that morin significantly potentiated the inhibitory effects of the natural compound celastrol on the proliferation of lung cancer cells.Morin and celastrol synergistically exhibit marked apoptosis induction in lung cancer cells,accompanied by changes in the abundance of apoptosis-related proteins.Transcriptome analyses revealed that the combination of morin and celastrol had a significant impact on the number of differentially expressed genes in lung cancer cells.Among these genes,BIRC3 was one of the most significantly different ones,which plays a crucial role in the process of tumor resistance to apoptosis.In addition,several genes identified are primarily associated with intracellular signal transduction pathways,specifically the NF-κB signaling pathway.Importantly,the treatment combining morin and celastrol in tumor-bearing mice results in a synergistic effect that significantly suppressed tumor growth.These findings indicate that morin could be a promising functional adjuvant,and the combination of morin and celastrol has potential for the treating lung cancer.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202208)2021 Shanghai Science and Technology Innovation Action Plan—Medical Innovation Research Project(No.31801153)the National Natural Youth Science Foundation of China(No.21MC1930500)。
文摘Objective:Gastric cancer(GC)is one of the most common malignancies seen in clinic and requires novel treatment options.Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L.,which exhibits an anti-cancer effect in multiple types of tumors.However,the therapeutic effect and underlying mechanism of morin in treating GC remains elusive.The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC.Methods:For in vitro experiments,the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45,human gastric adenocarcinoma cell line AGS,and human gastric epithelial cell line GES-1;for apoptosis analysis,microscopic photography,Western blotting,ubiquitination analysis,quantitative polymerase chain reaction analysis,flow cytometry,and RNA interference technology were employed.For in vivo studies,immunohistochemistry,biomedical analysis,and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC.Results:Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose-and timedependent manner,but did not inhibit human gastric epithelial cells GES-1.Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells,suggesting that apoptosis was the main type of cell death during the treatment.Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells,which mainly relied on B cell leukemia/lymphoma 2(BCL-2)associated agonist of cell death(BAD)but not phorbol-12-myristate-13-acetate-induced protein 1.The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD,rather than the transcription regulation and the phosphorylation of BAD.Furthermore,the combination of morin and BCL-2 inhibitor navitoclax(also known as ABT-737)produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals.In addition,morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway.Conclusion:Morin suppressed GC by inducing apoptosis,which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD.The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells,which may overcome the drug resistance of the BCL-2 inhibitor.These findings indicated that morin was a potent and promising agent for GC treatment.
基金supported by grants from the National Key R&D Program of China(No.2019YFA0210100)the Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University(No.PY2022010[NP22])。
文摘Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is a bioflavonoid mainly extracted from white mulberry,a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties.This study examines whether morin can alleviate atherosclerosis by suppressing End MT and seeks to elucidate the underlying mechanism.Methods:We induced an in vitro End MT model in human umbilical vein endothelial cells(HUVECs)by stimulating the cells with transforming growth factor-β1(TGF-β1)(10 ng/m L)for 48 h.The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E(Apo E)^(-/-)mice fed with a high-fat diet(HFD).Mice in the intervention group were given morin(50 mg/kg)orally for 4 weeks.Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase-9(MMP-9).Results:Morin inhibited the expression of End MT markers in a dose-dependent manner in TGF-β1-treated HUVECs.Administering 50μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced End MT.Moreover,the overexpression of MMP-9 activated Notch-1 signaling,thereby reversing morin's inhibitory effect on End MT.In the HFD-induced atherosclerotic Apo E^(-/-)mice,morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing End MT.Furthermore,morin demonstrated a strong binding affinity for MMP-9.Conclusion:Morin acts as an MMP-9 inhibitor to disrupt End MT in atherosclerosis by limiting the activation of Notch-1 signaling.This study underscores morin's potential utility in the development of antiatherosclerotic medication.
文摘AIM To investigate whether morin can reduce hepatic fibrosis by activating the NF-E2-related factor 2(Nrf2) signaling pathway.METHODS Twenty male Sprague-Dawley rats were randomly divided into four groups: control group, morin group, carbon tetrachloride(CCl4) group, and morin + CCl4 group. Rats in both the CCl4 and morin + CCl4 groups were injected intraperitoneally with CCl4 at a dose of 2 mL/kg twice a week. Rats in both the morin and morin + CCl4 groups were treated orally with morin at a dose of 50 mg/kg twice a week. Control rats were treated with vehicle only twice a week. At the end-point of the 8 wk of the experimental period, serum AST, ALT, and ALP were measured, and the liver specimenswere obtained for pathological assessment. Real-time PCR and Western blot methods were used to analyze the expression of α-smooth muscle actin(α-SMA), collagen Ⅰ, collagen Ⅲ, Nrf2, heme oxygenase(HO-1), and quinone oxidoreductase 1(NQO1) using frozen liver specimens.RESULTS Morin-treated rats in the morin + CCl4 group had less hyperplasia of fiber tissue, minimal inflammatory cells, and less body weight loss with favorable liver enzyme measurements compared to rats treated with CCl4 only. Additionally, morin-treated rats had significantly lower m RNA and protein expression of α-SMA, collagen Ⅰ, and collagen Ⅲ, but significantly higher m RNA and protein expression of Nrf2, HO-1, and NQO1 compared to rats treated with CCl4 only(P < 0.05).CONCLUSION Morin could play a protective role by inducing the expression of Nrf2 and its downstream antioxidant factors(HO-1 and NQO1) and reducing the expression of α-SMA, collagen Ⅰ, and collagen Ⅲ in CCl4-induced liver fibrosis rats.
基金financially supported by Department of Science and Technology,New Delhi,India(grant No.SR/FT/LS-150/2008)
文摘Objective:To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate(DOCA)-salt induced hypertension in male Wistar rats.Methods:Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA(25 mg/kg bw) and 1% NaCl in the drinking water for six consecutive weeks. Effect of morin against DOCA-salt induced hypertension was evaluated by measuring blood pressure and performing biochemical estimations and histopathological examination of renal tissues.Results:DOCA-salt hypertensive rats showed considerably increased systolic and diastolic blood pressure,serum hepatic marker enzyme activities such as aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and gamma-glutamyl transpeptidase(GGT)and renal function markers(urea, uric acid and creatinine) in plasma. Oral administration of morin(25, 50 and 75 mg/kg bw) brought back all the above parameters to near normal level.Histopathology of kidney also confirmed the biochemical findings of this study. The effect at a dose of 50 mg/kg bw of morin was more pronounced than that of the other two doses(25 and 75 mg/kg bw).Conclusions:These findings indicate that morin exhibits strong antihypertensive effect against DOCA-salt induced hypertension.
文摘Objective: To evaluate the protective effect of morin against pentylenetetrazol(PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice(18-22 g) was used to induce convulsions by intraperitoneal(i.p.) administration of PTZ(90 mg/kg). Mice were either pretreated with morin(10, 20 and 40 mg/kg) or vehicle(distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production(P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin(20 and 40 mg/kg) administration. The PTZinduced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin(20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin(20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na^+K^+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent.
基金Supported by the National Natural Science Foundation of China (30570015, 20621502)the Natural Science Foundation of Hubei Prov-ince (2005ABC002)the Research Foundation of Chinese Ministry of Edu-cation ([2006]8-IRT0543)
文摘Flavonols are plant nature. Morin and other related pigments that are ubiquitous in plant flavonols have come into recent prominence because of their usefulness as anticancer, antitumor, anti-AIDS, and other important therapeutic activities of significant potency and low systemic toxicity. The heat of combustion of morin （molecular formula, C15H10O7·H2O） in oxygen was measured by a rotating-bomb type combustion calorimeter, the standard molar enthalpy of combustion of morin at T = 298.15 K was determined to be △cH^ m （C15H10O7·H2O, s） = - （5 937.99±2.99） kJ·mol^-1. The derived standard molar enthalpy of the formation of morin in solid powder state at T = 298.15 K, △fH^ m（C15H10O7·H2O, s）, was -（1 682.12 ± 3.58） kJ·mol^1, which provide an accurate data of the stability of morin to the pharmacy and pharmacology.
基金financially supported by the research grant(5661/Punjab/NRPU/R&D/HEC/2016,6429/Punjab/NRPU/R&D/HEC/2016 and 8365/Punjab/NRPU/R&D/HEC/2017)received from Higher Education Commission of Pakistan
文摘Objective:To explore the therapeutic role of morin against L-arginine-induced acute pancreatitis in rats.Methods:The group 1 received two intraperitoneal injections of normal saline,and groups 2-4 were given two intraperitoneal injections of L-arginine(250 mg/100 g body weight)at 1 h interval to induce acute pancreatitis.Subsequently,group 2 received no further treatment while groups 3 and 4 were treated with morin(30 mg/kg)and diclofenac sodium(30 mg/kg),respectively.Blood glucose and serum levels of insulin,α-amylase,malondialdehyde,myeloperoxidase,alanine aminotransferase,aspartate aminotransferase and cholesterol were measured.Moreover,histopathological study was carried out to investigate the effect of morin treatment on physiology of the pancreas.Results:L-arginine significantly altered the level of blood glucose and serum levels of insulin,α-amylase,malondialdehyde,myeloperoxidase,alanine aminotransferase,aspartate aminotransferase and cholesterol.Treatment with morin or diclofenac sodium significantly improved the levels of these biomarkers.Furthermore,morin showed more significant effect than diclofenac sodium.Histopathological analysis verified that morin protected the pancreas from deleterious effects of L-arginine.Conclusions:Morin plays a protective role against L-arginineinduced acute pancreatitis via reducing lipid peroxidation and tissue inflammation,and attenuating acute pancreatitis-associated alteration in insulin secretion and glucose metabolism.
文摘Morin (MR) is an anticancer drug present in fruits and Chinese herbs. Fe3O4 magnetic nanoparticles (MNPs) coated on 3-aminopropyl triethoxysilane (APTES) were synthesized (MNPs-APTES) as carriers for MR. The characterization of drug delivery system was confirmed by Fourier Transform Infrared (FTIR), Transmission Electron Microscope (TEM), X-Ray Diffraction (XRD), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). The adsorbed APTES on the magnetite surface (MNPs-APTES) was examined by FTIR. The TEM image showed that the average particle size is obtained to be about 26.7 nm for MNPs-APTES. The MR loading and release behavior of MNPs-APTES were studied and the results showed that up to 60% of the adsorbed drug was released within 4 h. In summary, the MNPs-APTES nanocarriers are based on the results, promising for targeted morin drug delivery.
文摘A highly sensitive and fairly selective spectrofluorimetric method has been developed for the determination of germanium with morin in tap water and health drink. The fluorescent reaction and optimal conditions of germanium with morin in phosphoric acid medium were studied. The detection limits of germanium in tap water and health drink were found to be 0.2 and 0.7μd/L respectively.
文摘Background:Alcohol use and traumatic events have a connecting relationship owing to the rising number of people adopting alcoholism as a coping strategy.Objectives:This study examined the cardiorenal protective effect of morin,a bioflavonoid,in mice comorbidly exposed to alcohol use disorder(AUD)and posttraumatic stress disorder(PTSD).Methods:Mice exposed to single-prolong-stress(SPS)-induced PTSD were submitted to every-other-day ethanol(2 g/kg,oral gavage)for AUD induction,alongside treatments with morin(50 mg/kg and 100 mg/kg)or fluox-etine(10 mg/kg),from days 8-21 once daily.After that,mice were euthanized on day 22,markers of oxidative stress(glutathione,catalase,superoxide dismutase,malondialdehyde,nitrite)and inflammatory cytokines(tumor necrosis factor(TNF-α),interleukin-6(IL-6))in the kidney and heart were assayed.Results:Our result showed that mice exposed to SPS+EtOH-induced PTSD-AUD had reduced levels of glutathione,catalase,and superoxide dismutase,with increased malondialdehyde and nitrite concentrations in the heart and kidney relative to SPS+EtOH group.Also,the SPS+EtOH group showed increased concentrations of TNF-αand IL-6 in the heart and kidney tissues,suggesting inflammatory activity relative to normal control.Treatment with morin(50 mg/kg and 100 mg/kg)significantly reduced the SPS-EtOH-induced oxidative and nitrergic stress relative to the SPS+EtOH group.Additionally,the increased release of TNF-αand IL-6 following PTSD-AUD induction was profoundly inhibited by morin in a similar manner to fluoxetine.Conclusion:Our findings suggest that AUD-PTSD interaction-induced organ dysfunction,such as cardiorenal impairments,was reversed by morin via mechanisms associated with attenuation of oxidative/nitrergic stress and release of pro-inflammatory cytokines in mice.
文摘Nimodipine(NMD),a calcium channel blocker,is classified as a Biopharmaceutical Classification System Class II drug,with low oral bioavailability(3%-30%)due to extensive first-pass metabolism.Self-nanoemulsifying drug delivery systems(SNEDDS)offer a novel approach to improving the bioavailability of such drugs.Morin hydrate(MH),a flavonoid,may enhance NMD’s bioavailability by modulating CYP3A4 and P-glycoprotein during metabolism.This study aimed to optimize an MHloaded NMD-SNEDDS formulation using a three-factor,three-level Box-Behnken design(BBD).Independent variables were Capmul MCM(X_(1))as the oil,Cremophor RH-40(X_(2))as the surfactant,and Transcutol-P(X_(3))as the co-surfactant.Dependent variables included droplet size(Y_(1)),polydispersity index(Y_(2)),and cumulative drug release in 15 minutes(Y_(3)).The optimized formulation(X_(1)=10.0 mg,X_(2)=62.0 mg,X_(3)=40.0 mg)predicted Y_(1),Y_(2),and Y_(3)values of 124.3 nm,0.105,and 97.2%,respectively,with a desirability of 0.8850.Pharmacokinetic studies showed that NMDSNEDDS and MH-loaded NMD-SNEDDS increased oral bioavailability 3-fold and 4-fold,respectively,compared to pure drug suspension.MH-loaded NMD-SNEDDS demonstrated P-gp inhibition,enhancing NMD absorption.BBD effectively optimized the SNEDDS formulation,and MH-loaded NMD-SNEDDS is a promising approach to enhance NMD’s oral bioavailability.
