Astragalus membranaceus and Panax notoginseng, the Novel Renoprotective Compound, Synergistically Protect against Podocyte Injury in Streptozotocin-Induced Diabetic Rats

Abstract

This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.

TUNEL Assay: A Powerful Tool for Kidney Injury Evaluation

“…If the injury continues or the dose of the damaging agent increases, cytoplasmic TUNEL can be converted to a “messy” picture of dispersed TUNEL ( Figure 3 G) attributed to late stages of cell destruction due to necrosis and spillage of cellular cytoplasm and debris. For example, both cytoplasmic and dispersed TUNEL was observed in cisplatin-treated mice [ 71 , 72 ] and rats [ 144 ], and in podocyte injury in streptozotocin-induced diabetic rats [ 145 ]. Dispersed necrotic TUNEL was also observed during uranyl acetate-induced nephrotoxicity in mice [ 101 ].…”

Sanqi Oral Solution Ameliorates Renal Ischemia/Reperfusion Injury via Reducing Apoptosis and Enhancing Autophagy: Involvement of ERK/mTOR Pathways

“…Moreover, some of the components in SQ have been scientifically proven to possess anti-apoptosis or autophagy-regulating properties. Previous researches have reported that Astragalus membranaceus plus Panax notoginseng can synergistically ameliorate renal injury in diabetic nephropathy partly through inhibiting apoptosis ( Zhai et al., 2019 ) or promoting autophagy ( Wen et al., 2020 ). Calycosin, one of the major components in Astragalus membranaceus, has been verified to inhibit oxidative stress-induced cardiomyocyte apoptosis via activating estrogen receptor-α/β ( Liu B. et al., 2016 ).…”

“…In our previous study, we have identified that the major compositions of SQ include ginsenosides, notoginsenoside R1, calycosin, and so on (Tian et al, 2019;Xu et al, 2019). Among these compositions, ginsenoside Rg 1, notoginsenoside R1 and calycosin are capable of reducing apoptosis (Chen et al, 2001;Liu B. et al, 2016;Huang et al, 2017;Tong et al, 2019;Zhai et al, 2019), notoginsenoside R1 and calycosin also exhibit effects on activating autophagy in HT29 cells, podocytes or renal mesangial cells (Huang et al, 2017;Wen et al, 2020). Yet, their roles on renal I/R injury and tubular cells have never been elucidated and deserves to be addressed.…”

Network Pharmacology-Based Investigation into the Mechanisms of Qibangyishen Formula for the Treatment of Diabetic Kidney Disease

“…Previously, we found that HUANG QI combined with SAN QI reduces urinary protein excretion, decreases renal pathological changes, and improves apoptosis and shedding of kidney podocytes in DKD rats [33]. NIU BANG ZI extract reduces podocyte damage and proteinuria symptoms of DKD mice by enhancing PP2A activity in podocytes and protects kidney function [34].NIU BANG ZI extract also signi cantly reduces blood sugar in DKD mice and reduces the damage to the kidney [35].…”