Research On The Mechanism Of Baicalin And Baicalein Against Hyperuricemic Nephropathy

Hyperuricemia nephropathy(HN)was a metabolic disease that seriously endangered human health;inflammation and oxidative stress played an important role in its pathological process.Although the current drugs for the treatment of HN,such as allopurinol,benzbromarone and dexamethasone,had certain curative effects,these drugs also had seriously adverse reactions.Baicalin and baicalein were two flavonoids extracted from the roots of the traditional Chinese medicine Scutellaria baicalensis which could be converted into each other in the body.Studies have shown that baicalin and baicalein have broad pharmacological activities such as anti-inflammatory and antioxidant activities.This article first explored the anti-HN mechanism of baicalin and baicalein through network pharmacology and molecular docking technology,and predicted the signal pathways.Effects and mechanism of baicalin and baicalein against HN were investigated using the HN mouse model established by yeast extract combined with potassium oxazinate in vivo and the HK-2cell injury model induced by monosodium urate(MSU)crystals in vitro,and through blood-bochemistry examination,histopathological examination,and western blooting technology,and so on.(1)Molecular docking and network pharmacology were used to explore the targets and pathways of baicalin and baicalin against HN.The results indicated that the target of xanthine oxidase(XO),AKT,TLR4 and MAPK1 might play a key role in the anti-HN effects of baicalin and baicalein.Baicalin and baicalein might treat HN by down-regulating TLRs/NLRP3/NF-κB,MAPK,PI3K/AKT/NF-κB pathways.(2)In vivo studies,the HN mouse model was established by using yeast extract combined with potassium oxazinate,and the anti-HN effects of baicalin and baicalein was studied through two administration routes at the dose of 50 mg/kg: intragastric administration and intraperitoneal injection.The results showed that both baicalin and baicalein had the effects of inhibiting XO activity in liver and lowering serum uric acid.In addition,intraperitoneal injection of baicalin and baicalein could also reduce the levels of serum creatinine and urea nitrogen,ameliorate the oxidative stress level of HN mice,reduce inflammation,tube necrosis and dilation,and renal tissue fibrosis and other pathological damage,could inhibit PI3K/AKT/NF-κB pathway,and protected the kidney function of HN mice..(3)In vitro studies explored the effects of baicalin and baicalein(20,40,80 μM)on MSU-induced human renal tubular epithelial cell(HK-2)damage.The results showed that both baicalin and baicalein could reduce the levels of NO and lactate dehydrogenase in the cell supernatant,improve the level of oxidative stress in HK-2cells in a dose-dependent manner,and inhibit the PI3K/AKT/NF-κB pathway.