The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in...The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg^(-1) potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg^(-1) was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase(XDH) and xanthine oxidase(XOD), regulated renal m RNA and protein levels of urate transporter 1(URAT1), glucose transporter 9(GLUT9), organic anion transporter 1(OAT1), organic cation transporter 1(OCT1), OCT2, organic cation/carnitine transporter 1(OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3(NLRP3), apoptosis-associated speck-like(ASC), and Caspase-1, resulting in the reduction of interleukin(IL)-1β, IL-18, IL-6 and tumor necrosis factor-α(TNF-α) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.展开更多
Food-derived peptides are gradually becoming a safe and effective candidate for relieving hyperuricemia(HUA).Using xanthine oxidase(XOD)inhibitory activity and HUA cell model as screening indicators,peptides DGFDGL(N-...Food-derived peptides are gradually becoming a safe and effective candidate for relieving hyperuricemia(HUA).Using xanthine oxidase(XOD)inhibitory activity and HUA cell model as screening indicators,peptides DGFDGL(N-to C-terminus,DL-6)and HWGTDSF(N-to C-terminus,HF-7)from yellowfin tuna(Thunnus albacares)were purified by IEC,GFC,and RP-HPLC,with IC50 values of 641.49 and 324.94μg/mL,respectively.According to molecular docking,hydrogen bonding and hydrophobic interactions played important roles in interactions between peptides and XOD.In vitro digestion suggested that HF-7 exhibited good gastrointestinal stability,while DL-6 required structural optimization due to significant degradation.Besides,in the adenosine-induced HUA HK-2 cell model,1 mM of DL-6 and HF-7 decreased UA levels by 28.49%and 31.08%via regulating urate transporters(GLUT9,ABCG2,and MRP4)and the TLR4/MyD88/NF-κB signaling pathway.Meanwhile,in the monosodium urate-induced gout RAW264.7 cell model,DL-6 and HF-7 reduced IL-1βand TNF-αlevels via regulating the TLR2/MyD88/NF-κB signaling pathway.This study indicated that DL-6 and HF-7 exhibited anti-hyperuricemic and antigout activity,and had great potential as functional food ingredients.展开更多
In this study,two novel xanthine oxidase inhibitory peptides,PDEAVAYG(820.3602 Da)and IAAGLQNTG(843.4450 Da),were purified and identified from tea protein hydrolysate,and their IC_(50) values were 0.09 mg/mL(109.71μM...In this study,two novel xanthine oxidase inhibitory peptides,PDEAVAYG(820.3602 Da)and IAAGLQNTG(843.4450 Da),were purified and identified from tea protein hydrolysate,and their IC_(50) values were 0.09 mg/mL(109.71μM)and 0.24 mg/mL(284.55μM),respectively.During the gastrointestinal simulation digestion,PDEAVAYG was broken down into new peptides,while IAAGLQNTG exhibited some stability.Molecular docking results showed that hydrogen bonding,π-πstacking,and hydrophobic interactions exerted crucial effects on the interaction between peptides and xanthine oxidase.In the hyperuricemia cell model,compared to the model group,1.0 mg/mL of PDEAVAYG and IAAGLQNTG decreased cellular uric acid levels by 40.80%and 33.33%,respectively.The RNA-seq experiments revealed that PDEAVAYG could alleviate hyperuricemia by regulating mRNA expression for pro-inflammatory factors,growth factors associated with cardiovascular disease,and uric acid efflux transporter proteins in cells.This study provides a new theoretical reference for the development of functional foods or nutritional supplements using peptides with anti-hyperuricemic activity.展开更多
Hyperuricemia(HUA)endangers renal function and induces gout.Although peptides from Antarctic Krill(AKP)showed anti-hyperuricemic effects,the underlying mechanism remained unclear.The study investigated the anti-hyperu...Hyperuricemia(HUA)endangers renal function and induces gout.Although peptides from Antarctic Krill(AKP)showed anti-hyperuricemic effects,the underlying mechanism remained unclear.The study investigated the anti-hyperuricemic effect via xanthine oxidase(XOD)inhibitory activity,an adenosine-induced HK-2 cell model,and a potassium oxonate(PO)-induced mouse model.The AKP prepared using alkaline protease exhibited a strong XOD inhibitory activity with a low IC50 value of 3.232 mg/mL.AKP(5 mg/mL)reduced the uric acid(UA)content by 40.50%in HK-2 cells(p<0.01).In addition,AKP(600 mg/kg/d)reduced serum UA level by 54.37%in a mouse model(p<0.01)and had an alleviating effect on HUA-induced inflammation.Besides,AKP supplementing could regulate the mRNA levels of renal UA urate transporters(GLUT9,ABCG2,OAT1,OAT3,and NPT1)to promote UA excretion.According to non-targeted metabolomics,AKP regulated metabolic disorders in HUA mice by proximal tubule bicarbonate reclamation,taurine and hypotaurine metabolism,and butanate metabolism,etc,providing useful clues for research on the molecular mechanism of AKP.In addition,AKP alleviated gout by reducing paw swelling and inflammatory factors(IL-6,TNF-α,IL-1β)levels.展开更多
基金supported by grants from Program for Changjiang Scholars and Innovative Research Team in University(IRT_14R271020)
文摘The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg·kg^(-1) potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg·kg^(-1) was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase(XDH) and xanthine oxidase(XOD), regulated renal m RNA and protein levels of urate transporter 1(URAT1), glucose transporter 9(GLUT9), organic anion transporter 1(OAT1), organic cation transporter 1(OCT1), OCT2, organic cation/carnitine transporter 1(OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3(NLRP3), apoptosis-associated speck-like(ASC), and Caspase-1, resulting in the reduction of interleukin(IL)-1β, IL-18, IL-6 and tumor necrosis factor-α(TNF-α) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.
基金supported by the National Natural Science Foundation of China(No.32272307)Hainan province key R&D projects(No.ZDYF2024XDNY190)+4 种基金Qingdao key technology research project(No.25-1-1-gjgg-53-hy)Guangxi province key research and development projects(No.GuikeAB25069114)Shandong province key research and development projects(No.2024TZXD049)Leading the Charge with Open Competition Project of the State Key Laboratory of Marine Food Processing and Safety Control(No.20250401)Taishan Scholar Foundation of Shandong Province(No.tsqn202103033).
文摘Food-derived peptides are gradually becoming a safe and effective candidate for relieving hyperuricemia(HUA).Using xanthine oxidase(XOD)inhibitory activity and HUA cell model as screening indicators,peptides DGFDGL(N-to C-terminus,DL-6)and HWGTDSF(N-to C-terminus,HF-7)from yellowfin tuna(Thunnus albacares)were purified by IEC,GFC,and RP-HPLC,with IC50 values of 641.49 and 324.94μg/mL,respectively.According to molecular docking,hydrogen bonding and hydrophobic interactions played important roles in interactions between peptides and XOD.In vitro digestion suggested that HF-7 exhibited good gastrointestinal stability,while DL-6 required structural optimization due to significant degradation.Besides,in the adenosine-induced HUA HK-2 cell model,1 mM of DL-6 and HF-7 decreased UA levels by 28.49%and 31.08%via regulating urate transporters(GLUT9,ABCG2,and MRP4)and the TLR4/MyD88/NF-κB signaling pathway.Meanwhile,in the monosodium urate-induced gout RAW264.7 cell model,DL-6 and HF-7 reduced IL-1βand TNF-αlevels via regulating the TLR2/MyD88/NF-κB signaling pathway.This study indicated that DL-6 and HF-7 exhibited anti-hyperuricemic and antigout activity,and had great potential as functional food ingredients.
基金supported by the open fund of Guangdong provincial key laboratory of tea plant resources innovation and utilization(2020KF01)the Guangdong province key laboratory for green pro-cessing of natural products and product safety(202210)the Natural science foundation of Guangdong province(2023A1515010006).
文摘In this study,two novel xanthine oxidase inhibitory peptides,PDEAVAYG(820.3602 Da)and IAAGLQNTG(843.4450 Da),were purified and identified from tea protein hydrolysate,and their IC_(50) values were 0.09 mg/mL(109.71μM)and 0.24 mg/mL(284.55μM),respectively.During the gastrointestinal simulation digestion,PDEAVAYG was broken down into new peptides,while IAAGLQNTG exhibited some stability.Molecular docking results showed that hydrogen bonding,π-πstacking,and hydrophobic interactions exerted crucial effects on the interaction between peptides and xanthine oxidase.In the hyperuricemia cell model,compared to the model group,1.0 mg/mL of PDEAVAYG and IAAGLQNTG decreased cellular uric acid levels by 40.80%and 33.33%,respectively.The RNA-seq experiments revealed that PDEAVAYG could alleviate hyperuricemia by regulating mRNA expression for pro-inflammatory factors,growth factors associated with cardiovascular disease,and uric acid efflux transporter proteins in cells.This study provides a new theoretical reference for the development of functional foods or nutritional supplements using peptides with anti-hyperuricemic activity.
基金supported by Major Scientific and Technological Innovation Project in Shandong Province(No.2022CXGC020414)ajor Scientific and Technological Innovation Project of Qingdao West Coast New Area(No.ZDKC-2022-01)+3 种基金,Qingdao Marine Science and Technology Center(No.2022QNLM030002-4)Hainan province key R&D projects(No.ZDYF2024XDNY190)Qingdao West Coast University President Fund(No.XZJJ-2024204)Taishan Scholar Foundation of Shandong Province(No.tsqn202103033).
文摘Hyperuricemia(HUA)endangers renal function and induces gout.Although peptides from Antarctic Krill(AKP)showed anti-hyperuricemic effects,the underlying mechanism remained unclear.The study investigated the anti-hyperuricemic effect via xanthine oxidase(XOD)inhibitory activity,an adenosine-induced HK-2 cell model,and a potassium oxonate(PO)-induced mouse model.The AKP prepared using alkaline protease exhibited a strong XOD inhibitory activity with a low IC50 value of 3.232 mg/mL.AKP(5 mg/mL)reduced the uric acid(UA)content by 40.50%in HK-2 cells(p<0.01).In addition,AKP(600 mg/kg/d)reduced serum UA level by 54.37%in a mouse model(p<0.01)and had an alleviating effect on HUA-induced inflammation.Besides,AKP supplementing could regulate the mRNA levels of renal UA urate transporters(GLUT9,ABCG2,OAT1,OAT3,and NPT1)to promote UA excretion.According to non-targeted metabolomics,AKP regulated metabolic disorders in HUA mice by proximal tubule bicarbonate reclamation,taurine and hypotaurine metabolism,and butanate metabolism,etc,providing useful clues for research on the molecular mechanism of AKP.In addition,AKP alleviated gout by reducing paw swelling and inflammatory factors(IL-6,TNF-α,IL-1β)levels.
