Danshen injection induces autophagy in podocytes to alleviate nephrotic syndrome via the PI3K/AKT/mTOR pathway

Chen, Junqi; Yuan, Shengliang; Zhou, Jie; Huang, Xiuye; Wu, Wenjia; Cao, Yiwen; Liu, Hong; Hu, Qinghong; Li, Xiaojie; Guan, Xueping; Yin, Simin; Jiang, Jiaying Christine; Zhou, Yuan; Zhou, Jiuyao

doi:10.1016/j.phymed.2022.154477

Cited by 24 publications

(13 citation statements)

References 28 publications

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“…In addition, we found that biological activities of identified key metabolites that were enriched by NSND processing have consistently been proved in previous studies, 28,52,55,57,65,67,73‐78 supporting our findings (Table 3). Among them, gallocatechin and furoaloesone showed the largest binding energy with most of the targeted proteins.…”

Section: Resultssupporting

confidence: 91%

“…We conducted molecular docking to further investigate the binding ability between key targets – that is, TNF, VEGF, STAT3, IL6, STOR, GCKR, GLIT4, HIF1, and INSR – that were closely related to oxidative stress, inflammation, and hyperglycemia, and 13 main metabolites that were significantly abundant in aqueous extracts of processed PK compared with crude PK. Results collectively demonstrated great ability of processed PK‐enriched metabolites to combat abnormal oxidative stress and inflammation status, as well as hyperglycemia, partly via regulating multi‐pathways, consistent with previous study 28,63‐70 …”

Section: Resultssupporting

confidence: 89%

“…Results collectively demonstrated great ability of processed PK-enriched metabolites to combat abnormal oxidative stress and inflammation status, as well as hyperglycemia, partly via regulating multi-pathways, consistent with previous study. 28,[63][64][65][66][67][68][69][70] We found that the binding energy ranged from −3.3 to −9.4 kcal mol −1 between selected targets and metabolites. A total of 11 compounds had a docking score of less than −5.0 with core targets, indicating that they had strong binding activity with each other.…”

Section: Molecular Dockingmentioning

confidence: 99%

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'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

Zhou,

Liu,

Yan

et al. 2023

J Sci Food Agric

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BACKGROUNDPolygonatum kingianum Coll. & Hemsl (PK), a prominent medicine and food homology plant, has been consumed as a decoction from boiling water for thousands of years. 'Nine Steaming Nine Sun‐drying' processing has been considered an effective method for enriching tonic properties, but studies investigating such impacts on PK and underlying mechanisms are extremely rare.RESULTSWe first demonstrated substantial improvements in the anti‐oxidative, anti‐inflammatory and anti‐hyperglycemia effects of the Nine Steaming Nine Sun‐drying processed PK water extracts compared with crude PK in cell models (i.e., HepG2 and Raw 264.7 cells). We then integrated foodomics and network pharmacology analysis to uncover the key compounds responsible for the improved benefits. A total of 551 metabolites of PK extracts were identified, including polyphenols, flavonoids, alkaloids, and organic acids. During processing, 204 metabolites were enhanced, and 32 metabolites were recognized as key constituents of processed PK responsible for the improved health‐promoting activities, which may affect PI3K‐Akt‐, MAPK‐, and HIF‐1 pathways. We further confirmed the high affinity between identified key constituents of processed PK and their predicted acting targets using molecular docking.CONCLUSIONOur results provide novel insights into bioactive compounds of processed PK, elaborating the rationality of processing from the perspective of tonic effects. Consuming processed PK could be an efficacious strategy to combat the high prevalence of metabolic diseases that currently affect millions of people worldwide. © 2023 Society of Chemical Industry.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 89%

Section: Molecular Dockingmentioning

confidence: 99%

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'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

Zhou,

Liu,

Yan

et al. 2023

J Sci Food Agric

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“… 37 Excessive ROS leads to Ca 2+ influx, which in turn ROS production, reduces the MMP and promotes apoptosis. 28 , 38 , 39 Chen et al 40 found that Danshen injection could improve adriamycin‐induced nephropathy by reducing apoptosis through PI3K/AKT signaling. In our study, PA and EPI decreased the levels of Ca 2+ and apoptosis and increased MMP levels in primary renal cells, upregulated Bcl‐2, and downregulated Bax and Cleaved caspase‐3.…”

Section: Discussionmentioning

confidence: 99%

Epimedium sagittatum Maxim ameliorates adriamycin‐induced nephropathy by restraining inflammation and apoptosis via the PI3K/AKT signaling pathway

Wang,

Zeng,

Zhang

et al. 2023

Immunity Inflam & Disease

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Background: Modern pharmacological studies show that Epimedium sagittatum Maxim (EPI) has antioxidant, antiapoptotic, anti-inflammatory effects. However, the effects of EPI on adriamycin-induced nephropathy are unclear. Aim:The main purpose of this study is to investigate the effects of EPI on adriamycin-induced nephropathy in rats. Methods: The chemical composition of EPI was detected by high performance liquid chromatography. Network pharmacology was used to collect the effects of EPI on adriamycin nephropathy; renal histological changes, podocyte injury, inflammatory factors, oxidative stress levels, apoptosis levels, and the PI3K/AKT signaling pathway were examined. Moreover, analyze the effects of icariin (the representative component of EPI) on adriamycin-induced apoptosis and PI3K/AKT signaling pathway of NRK-52e cells. Results: Network pharmacological results suggested that EPI may ameliorate adriamycin-induced nephropathy by inhibiting inflammatory response and regulating the PI3K/AKT signaling pathway. The experimental results showed that EPI could improve pathological injury, renal function, podocyte injury, and inhibit inflammation, oxidative stress, apoptosis in adriamycin-induced nephropathy rats through the PI3K/AKT signaling pathway. Furthermore, icariin inhibited adriamycin-induced mitochondrial apoptosis in NRK-52e cells. Conclusion: This study suggested that EPI ameliorates adriamycin-induced nephropathy by reducing inflammation and apoptosis through the PI3K/AKT signaling pathway, icariin may be the pharmacodynamic substance basis for this effect.

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“…It can be seen that the anti-inflammatory effect of DanShen is one of the mechanisms of improving renal function. Otherwise, DanShen extracts can induce podocyte autophagy by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of a rapamycin signaling pathway to make renal function better and reduce pathological injury in mice with nephrotic syndrome ( Chen et al, 2022 ), can also reduce BP in rats through inhibiting angiotensin-converting enzyme and relaxing vascular smooth muscle ( Kang et al, 2002 ; Zhang X D et al, 2018 ). In clinical research, many studies have confirmed that salvianolate can lower BP and improve renal function-related indicators ( Fu et al, 2012 ), significantly reduce Scr, BUN and 24-hour UP in CKD patinets ( Zhang et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Salvianolate injection for hypertensive nephropathy patients who were using valsartan: A systematic review and meta-analysis

Shen

Zhao

et al. 2023

Front. Pharmacol.

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Background: The treatment of hypertensive nephropathy has remained unchanged for many years. Salvianolate is the main active component extracted from Salvia Miltiorrhiza. The current studies seem to suggest that salvianolate has a certain therapeutic effect on hypertensive nephropathy.Objective: The purpose of this meta-analysis is to evaluate the effect and safety of salvianolate on hypertensive nephropathy under the condition of standardized use of valsartan.Methods: We conducted a systematic search (unlimited initial date to 22 October 2022) in PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Data knowledge service platform, China Science and Technology Journal Database, China Biomedical Literature Service System. Searching for the study of salvianolate on hypertensive nephropathy. Two reviewers independently included the study that met the inclusion criteria, and extracted data, evaluated the quality of the study. We use RevMan5.4 and stata15 software for this meta-analysis. We use GRADEprofiler 3.2.2 software for evidence quality assessment.Results: This meta-analysis included seven studies (525 patients). Compared with the use of valsartan combined with conventional treatment, salvianolate combined with valsartan and conventional treatment can further improve the efficacy (RR = 1.28, 95%CI:1.17 to 1.39), reduce blood pressure [systolic blood pressure (MD = 8.98, 95%CI:−12.38 to −5.59); diastolic blood pressure (MD = 5.74, 95%CI:−7.20 to −4.29)], serum creatinine (MD = −17.32, 95%CI:−20.55 to −14.10), blood urea nitrogen (MD = −1.89, 95%CI:−3.76 to −0.01), urine microalbumin (MD = −23.90, 95%CI:−26.54 to −21.26), and urinary protein to creatinine ratio (MD = −1.92, 95%CI:−2.15 to −1.69), cystatin C (MD = −1.04, 95%CI: −1.63 to −0.45) and increase calcitonin gene-related peptide (MD = 18.68, 95%CI:12.89 to 24.46) without increasing adverse reactions (RR = 2.20, 95%CI:0.52 to 9.40). But it has no additional effect on endothelin-1 and malondialdehyde. The quality of evidence ranged from moderate to very low.Conclusion: This meta-analysis shows that the salvianolate can further improve renal function of hypertensive nephropathy patients based on valsartan was used. Therefore, salvianolate can be used as a clinical supplement for hypertensive nephropathy. However, the quality of the evidence is not high due to the uneven quality of the included studies and the insufficient sample size, we still need a lot of large sample size studies with more perfect design to confirm these results.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373256, identifier CRD42022373256

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Danshen injection induces autophagy in podocytes to alleviate nephrotic syndrome via the PI3K/AKT/mTOR pathway

Cited by 24 publications

References 28 publications

'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

'Nine Steaming Nine Sun‐drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia

Epimedium sagittatum Maxim ameliorates adriamycin‐induced nephropathy by restraining inflammation and apoptosis via the PI3K/AKT signaling pathway

Salvianolate injection for hypertensive nephropathy patients who were using valsartan: A systematic review and meta-analysis

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