Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury

Abstract

Objective. To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. Methods. Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injection of 1, 3, and 5 mg/(kg·d) APS for 3 consecutive days. The severity of kidney injury was then scored by histopathological analysis, and the concentrations of serum urea nitrogen (BUN) and serum creatinine (SCr) and the levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were determined as well. In in vitro experiments, lipopolysaccharide (LPS) was used to induce HK-2 cell injury to establish a sepsis-induced AKI cell model, and the cell counting kit-8 (CCK-8) method was performed to determine the cytotoxicity and appropriate experimental concentration of APS. Then, cells were divided into the control, LPS, and APS+LPS groups. Cell apoptosis and inflammation-related TNF-α, IL-1β, IL-6, and IL-8 were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The microscope was used to observe the morphological changes of cells, and the cell migration ability was measured by wound healing assay. RT-qPCR and Western blot assay were used to determine the mRNA and protein levels of apoptosis-related factors including caspase-3, caspase-9, Bax, and Bcl-2; endoplasmic reticulum stress- (ERS-) related biomarkers including C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78); and epithelial-mesenchymal transition- (EMT-) related biomarkers including E-cadherin, Snail, α-smooth muscle actin (α-SMΑ), and Vimentin. Results. In vivo experiments in mice showed that APS can reverse LPS-induced kidney damage in a concentration-dependent manner ( P < 0.05 ); the concentrations of BUN and Scr were increased (all P < 0.05 ); similarly, the levels of TNF-α and IL-1β were increased as well (all P < 0.05 ). In in vitro experiments, the results showed that LPS can significantly cause HK-2 cell damage and induce apoptosis, inflammation, ERS, and EMT. When APS concentration was in the range of 0-200 μg/mL, it had no cytotoxicity in HK-2 cells, and 100 μg/mL APS pretreatment could significantly mitigate the decrease of cell activity induced by LPS ( P < 0.05 ). Compared with the LPS group, APS pretreatment could inhibit the expression of inflammatory factors including TNF-α, IL-1 β, IL-6, and IL-8 (all P < 0.05 ), reducing the number of apoptotic cells ( P < 0.05 ), suppressing the expression of caspase-3, caspase-9, and Bax, but upregulating the expression levels of Bcl-2. In ERS, APS pretreatment inhibited LPS-induced upregulation of CHOP and GRP78. Moreover, in EMT, APS pretreatment could inhibit the morphological changes of cells, downregulate the migration, decrease the expression of EMT biomarkers, and inhibit the process of EMT. Conclusion. APS could alleviate sepsis-induced AKI by regulating inflammation, apoptosis, ERS, and EMT.

Aqueous Two-Phase Extraction, Antioxidant and Renal Protective Effects of Polysaccharides from Spores of Cordyceps cicadae

“…Recently, Echinacea polysaccharide have been demonstrated to decrease ROS, malondialdehyde, and oxidized glutathione levels as well as increase SOD, CAT, and glutathione reductase while decreasing glutathione activity [32]. Astragalus polysaccharide could have increased T-SOD and GSH-Px activities as well as inhibited oxidative stress marker 3-NT expression in cisplatin-induced AKI mice [33]. Our results are consistent with these studies.…”

“…Studies have also found that natural polysaccharides can improve numerous types of kidney diseases, including diabetic nephropathy [26,27], drug-related kidney injury [28,29], and renal ischemia-reperfusion injury [30]. Polysaccharides from Sanguisorba officinalis [31], Lycium barbarum [23], Echinacea [32], and Astragalus [33] have been reported to alleviate sepsis AKI via the suppression of oxidative stress and inflammatory responses. It has been demonstrated that C. cicadae and its extracts exert a protective role in kidney diseases.…”

Astragalus polysaccharide protects sepsis model rats after cecum ligation and puncture

“…The binding of free sICAM-1 to LFA-1 can promote the killing process involving CTL and NK cells, enhance the immune response of helper T cells, and involve in antibody-dependent cell-mediated cytotoxicity (ADCC) ( Gross et al, 2010 ). Sun et al (2021) showed that APS inhibited the expression of TNF-α, IL-1 β, IL-6, and IL-8 in a concentration-dependent manner to reverse sepsis-induced acute kidney injury in mice. Dong et al (2019b ) demonstrated that APS reduced the mRNA expression levels of TNF-α, IL-1 β, IL-6, and IL-17 in diarrheic mice.…”

Astragalus Polysaccharide Reduces Blood Pressure, Renal Damage, and Dysfunction Through the TGF-β1-ILK Pathway

“…HK-2 cells and iBMDMs were cultivated in DMEM (Gibco) basic medium supplemented with 5% fetal bovine serum and 100 U/ml penicillin-100 μg/ml streptomycin antibiotics at 37 °C under a 5% CO 2 -humidified environment. For the in vitro study, HK-2 cells were pretreated with APS (100 μg/ml) or an inhibitor of TGF-β (disitertide, P144, 100 μg/ml) for 3 h and then treated with saline or Ang II (100 nM) for 24 h (Sun et al, 2021;Jun et al, 2019).…”

“…Astragalus polysaccharides are the main bioactive components extracted from Astragalus membranaceus. Astragalus polysaccharide extract (APS) is famous for its various pharmacological activities (Yang et al, 2019;Sun et al, 2021). APS is a critical active ingredient responsible for various bioactivities of Astragalus membranaceus.…”