Shenqi granule upregulates CD2AP and α-actinin4 and activates autophagy through regulation of mTOR/ULK1 pathway in MPC5 cells

Wei, Li-feng; Yong, Jun; Zhang, Xianwen; Ling, Chunyan; Wu, Yi‐Long; Xu, Zheng; Zhang, Hengzhou; Cao, Xueqing; Sheng, Lingli; Zhang, Quan; Wang, Lin

doi:10.1016/j.jep.2022.115942

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…The thirteen herbs contained in SQ granule were supplied by Wanshicheng Pharmaceutical Co., Ltd. (Shanghai, Wanshicheng, China). The thirteen herbs were consistent with some published literature [9,15]. Speci c methods of drug dissolution and freezing have been described in detail in previous articles, using high performance liquid chromatography (HPLC) and control standards, it was con rmed that SQ granule complied with the authentic drug regulations of the Chinese Pharmacopoeia (version 2020).…”

Section: Herbal Materials and Sq Preparationsupporting

confidence: 76%

“…Changes in the actin cytoskeleton within a cell are necessary for maintenance of cell shape, cell motility and intracellular transport [24]. Our previous study demonstrated that SQ offers protection against podocyte cytoskeletal proteins, including CD2AP and α-actinin4 [15,25,26]. In this study, upon further examination of the podocytes' cytoskeletal protein, it was observed that PAN induces impairment in the F-actin protein, resulting in polymerization breakdown.…”

Section: Discussionmentioning

confidence: 68%

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Analysis of the regulating PI3K/AKT/mTOR signaling pathway and anti-apoptosis activity of Shenqi granule through Network Pharmacology and in vitro experiments

Wei,

Guo,

Zhu

et al. 2024

Preprint

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Idiopathic membranous nephropathy (IMN), a common pathological type of nephrotic syndrome. Shenqi granule(SQ) is a traditional Chinese medical formula that has been used for decades to treat IMN, and there is a large amount of clinical data confirming its effectiveness,but the mechanism is unclear. This study explores the potential mechanisms and targets of action of SQ through network pharmacology and validates them through in vitro experiments and molecular docking techniques. Network pharmacology is a method that can determine how TCM works through pharmacokinetic evaluation, allowing us to study its molecular mechanisms. Through in vitro experiments, MPC5 cells are used to establish puromycin aminonucleoside (PAN)-induced podocytes damage models to extract cell protein, western blot detection signal pathway protein and related target proteins, molecular docking was performed for the validation. The network pharmacology study results indicate that SQ has 106 compounds, and 195 shared targets with MN. The treatment of IMN with SQ is mainly related to the apoptosis, PI3K/AKT/mTOR signaling pathway and other significant signaling pathways. In vitro experiments showed that SQ could effectively inhibit the activity of the PI3K/AKT/mTOR signaling pathway, increase the expression of Bcl2, and suppress the expression levels of apoptosis-related proteins such as Calaspase-3 and Bax in MPC5 cells. This study initially investigated the pharmacological effects of SQ, which effectively ameliorates IMN by potentially regulating the phosphorylation level of the AKT/mTOR pathway, inhibiting apoptotic activity, and restoring skeletal proteins.

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Section: Herbal Materials and Sq Preparationsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 68%

Analysis of the regulating PI3K/AKT/mTOR signaling pathway and anti-apoptosis activity of Shenqi granule through Network Pharmacology and in vitro experiments

Wei,

Guo,

Zhu

et al. 2024

Preprint

Self Cite

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“…A compound phloretin from a natural plant was capable of restoring the expression of nephrin and podocin in DKD, thus protecting the podocyte cytoskeleton and the integrity of SD [ 221 ]. In PAN-induced podocyte injury, the expression of ACTN4 and CD2AP was significantly reduced, and Shenqi granule was able to upregulate the expression of ACTN4 and CD2AP [ 222 ].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Cytoskeleton Rearrangement in Podocytopathies: An Update

Ma,

Qiu,

Zhang

2024

IJMS

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Podocyte injury can disrupt the glomerular filtration barrier (GFB), leading to podocytopathies that emphasize podocytes as the glomerulus’s key organizer. The coordinated cytoskeleton is essential for supporting the elegant structure and complete functions of podocytes. Therefore, cytoskeleton rearrangement is closely related to the pathogenesis of podocytopathies. In podocytopathies, the rearrangement of the cytoskeleton refers to significant alterations in a string of slit diaphragm (SD) and focal adhesion proteins such as the signaling node nephrin, calcium influx via transient receptor potential channel 6 (TRPC6), and regulation of the Rho family, eventually leading to the disorganization of the original cytoskeletal architecture. Thus, it is imperative to focus on these proteins and signaling pathways to probe the cytoskeleton rearrangement in podocytopathies. In this review, we describe podocytopathies and the podocyte cytoskeleton, then discuss the molecular mechanisms involved in cytoskeleton rearrangement in podocytopathies and summarize the effects of currently existing drugs on regulating the podocyte cytoskeleton.

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Insights into the Therapeutic Potential of Phytoconstituents as an Epigenetic Modulators in Diabetic Nephropathy

Thapa,

Khan,

Grewal

et al. 2023

Curr. Pharmacol. Rep.

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Shenqi granule upregulates CD2AP and α-actinin4 and activates autophagy through regulation of mTOR/ULK1 pathway in MPC5 cells

Cited by 5 publications

References 34 publications

Analysis of the regulating PI3K/AKT/mTOR signaling pathway and anti-apoptosis activity of Shenqi granule through Network Pharmacology and in vitro experiments

Analysis of the regulating PI3K/AKT/mTOR signaling pathway and anti-apoptosis activity of Shenqi granule through Network Pharmacology and in vitro experiments

Cytoskeleton Rearrangement in Podocytopathies: An Update

Insights into the Therapeutic Potential of Phytoconstituents as an Epigenetic Modulators in Diabetic Nephropathy

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