Quercetin alleviates chronic renal failure by targeting the PI3k/Akt pathway

Abstract

Chronic renal failure (CRF) threatens human health greatly and attracts worldwide concerns of health professionals in the public health sector. In our preliminary study, we found that Compound capsule (Shengqing Jiangzhuo Capsule, SQJZJN) had a significant therapeutic effect on CRF. Quercetin is one of the main components of this Compound capsule. In this study, we investigated the effect of Quercetin monomer on CRF and the regulation of PI3k/Akt pathway. Network pharmacology analysis methods were employed to analyze the SQJZJN/Quercetin/PIK3R1 network relationships. In this study, a CRF rat model was prepared using the gavage adenine solution method and detected the indicators of Creatinine (Cr), Blood Urea Nitrogen (BUN), and Uric Acid (UA). After treating the rat model with Quercetin and PIK3R1-interfering lentivirus, respectively, we observed the changes on the histological morphology of the kidney and detected apoptosis using TUNEL staining. Gene and protein expression associated with renal function were detected using qPCR, WB and immunofluorescence. Quercetin was identified as the main ingredient of SQJZJN by the network pharmacological screening and Quercetin at 1.5 and 3 g/(kg.d) concentrations could effectively alleviate the CRF symptoms, reduce the levels of Cr, BUN, and UA, and markedly inhibit cell apoptosis demonstrated by the intragastric administration. Furthermore, the protein expression of p-PI3K, p-AKT, NLRP3, caspase1, AQP1, and AQP2 in all groups was detected by immunofluorescence and western blot assays, indicating that Quercetin could reduce the expression of NLRP3, caspase1, p-PI3k, and p-Akt, and increase the expression of AQP1 and AQP2 in the renal tissues of CRF rats. Being labeled with biotin and incubated with the total protein extracted from kidney tissues, Quercetin could bind to PIK3R1. Following the PIK3R1 interference lentivirus was injected into the CRF model rats by tail vein, the CRF symptoms were effectively alleviated in the PIK3R1 interference group, consistent with the effect of Quercetin. Taken together, Quercetin, a major component of SQJZJN, might minimize renal fibrosis and apoptosis in CRF rats by inhibiting the PI3k/Akt pathway through targeting PIK3R1. By regulating AQP1 and AQP2, both water retention and toxin accumulation were reduced.

Translocator protein (18 kDa) regulates the microglial phenotype in Parkinson’s disease through P47

“…The samples were then treated with IBA1 (1:1000), TSPO (1:1000), and P47 (1:1000) antibodies at 37°C for 2 h. Subsequently, the samples were treated with secondary antibodies Alexa Fluor 594, 488, and 674 (Thermo Fisher) for 45 min (room temperature). Finally, the samples were treated with DAPI at room temperature for 15 min and imaged using a confocal microscope (Olympus, Tokyo, Japan) [ 22 ].…”

Does Oxidative Stress Management Help Alleviation of COVID-19 Symptoms in Patients Experiencing Diabetes?

“…Intragastric administration of quercetin (1.5 and 3 g per kg body weight daily for eight weeks) effectively reduced apoptosis of renal cells and plasma levels of blood urea nitrogen, creatinine, and uric acid in male Sprague Dawley rat model of chronic renal failure [57]. The study also reported that quercetin treated rats showed reduced inflammation by preventing phosphoinositide 3-kinase (PI3 k)/Akt (protein kinase B) signaling pathway by targeting phosphoinositide 3-kinase regulatory subunit 1 (PIK3 R1) and reduced expression NLRP3, p-PI3 k, Phospho-Akt (p-Akt), and caspase1 in kidney tissues [57]. Another study reported that in a mouse model of renal dysplasia, quercetin treatment Interestingly, some antioxidants like flavonoids have been suggested as a complementary therapy for COVID-19 [50] and diabetes [51], which could be beneficial in ameliorating kidney damage during COVID-19 infection with diabetes as a comorbidity [52].…”

“…The flavonoid quercetin reportedly acts as a prophylactic to COVID-19 [55,56], as well as an antidiabetic and antioxidant compound. Moreover, recently, a preclinical study showed quercetin's renal protective effects [57]. Intragastric administration of quercetin (1.5 and 3 g per kg body weight daily for eight weeks) effectively reduced apoptosis of renal cells and plasma levels of blood urea nitrogen, creatinine, and uric acid in male Sprague Dawley rat model of chronic renal failure [57].…”

“…Moreover, recently, a preclinical study showed quercetin's renal protective effects [57]. Intragastric administration of quercetin (1.5 and 3 g per kg body weight daily for eight weeks) effectively reduced apoptosis of renal cells and plasma levels of blood urea nitrogen, creatinine, and uric acid in male Sprague Dawley rat model of chronic renal failure [57]. The study also reported that quercetin treated rats showed reduced inflammation by preventing phosphoinositide 3-kinase (PI3 k)/Akt (protein kinase B) signaling pathway by targeting phosphoinositide 3-kinase regulatory subunit 1 (PIK3 R1) and reduced expression NLRP3, p-PI3 k, Phospho-Akt (p-Akt), and caspase1 in kidney tissues [57].…”

Quercetin inhibits fibroblasts proliferation and reduces surgery-induced epidural fibrosis via the autophagy-mediated PI3K/Akt/mTOR pathway

“…Quercetin has been reported to be critical to numerous fibrotic diseases. In vivo, quercetin inhibits PI3K/Akt pathway, thereby reducing renal fibrosis and apoptosis in CRF rats [ 20 ].…”