Platycodin D inhibits HFD/STZ-induced diabetic nephropathy via inflammatory and apoptotic signaling pathways in C57BL/6 mice

Shen, Qiong; Qi, Si-Min; Zhang, Jingtian; Li, Ming-Han; Ying-ping, Wang; Wang, Zi; Li, Wei

doi:10.1016/j.jep.2023.116596

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…grandiflorum, exhibiting diverse pharmacological activities, such as hypoglycemic and lipid-lowering, anti-inflammatory, antiapoptotic, etc. , As reported by Shen et al, the use of low-dose PD could effectively ameliorate the HFD/STZ-induced conditions of excessive glucose symbiosis and lipid metabolic disturbance, reducing the decomposition of hepatic glycogen, thus playing a protective role in the liver. In another study, PD was shown to ameliorate diabetes-induced kidney damage by modulating inflammatory and apoptotic mechanisms, PD inhibited the downregulation of Bcl2, and Bax expression in vitro and in vivo . Meanwhile, in vitro studies have shown that PD could reverse the effect of high glucose on cell death, which may have a protective effect on diabetic nephropathy .…”

Section: Discussionmentioning

confidence: 99%

“…In another study, PD was shown to ameliorate diabetes-induced kidney damage by modulating inflammatory and apoptotic mechanisms, PD inhibited the downregulation of Bcl2, and Bax expression in vitro and in vivo. 37 Meanwhile, in vitro studies have shown that PD could reverse the effect of high glucose on cell death, which may have a protective effect on diabetic nephropathy. 38 Numerous studies have shown that the development of type 2 diabetes can lead to insulin resistance and abnormal blood lipid levels.…”

Section: Discussionmentioning

confidence: 99%

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Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway

Wang,

Meng

et al. 2024

J. Agric. Food Chem.

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The current study aimed to assess the effectiveness of pharmacological intervention with Platycodin D (PD), a critically active compound isolated from the roots of Platycodon grandiflorum, in mitigating cardiotoxicity in a murine model of type 2 diabetes-induced cardiac injury and in H9c2 cells in vitro. Following oral administration for 4 weeks, PD (2.5 mg/kg) significantly suppressed the elevation of fasting blood glucose (FBG) levels, improved dyslipidemia, and effectively inhibited the rise of the cardiac injury markers creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT). PD treatment could ameliorate energy metabolism disorders induced by impaired glucose uptake by activating AMPK protein expression in the DCM mouse model, thereby promoting the GLUT4 transporter and further activating autophagy-related proteins. Furthermore, in vitro experiments demonstrated that PD exerted a concentration-dependent increase in cell viability while also inhibiting palmitic acid and glucose (HG-PA)-stimulated H9c2 cytotoxicity and activating AMPK protein expression. Notably, the AMPK activator AICAR (1 mM) was observed to upregulate the expression of AMPK in H9c2 cells after high-glucose and -fat exposure. Meanwhile, we used AMPK inhibitor Compound C (20 μM) to investigate the effect of PD activation of AMPK on cells. In addition, the molecular docking approach was employed to dock PD with AMPK, revealing a binding energy of −8.2 kcal/mol and indicating a tight interaction between the components and the target. PD could reduce the expression of autophagy-related protein p62, reduce the accumulation of autophagy products, promote the flow of autophagy, and improve myocardial cell injury. In conclusion, it has been demonstrated that PD effectively inhibits cardiac injury-induced type 2 diabetes in mice and enhances energy metabolism in HG-PA-stimulated H9c2 cells by activating the AMPK signaling pathway. These findings collectively unveil the potential cardioprotective effects of PD via modulation of the AMPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway

Wang,

Meng

et al. 2024

J. Agric. Food Chem.

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“…21 Moreover, PD could protect mice from hippocampal ischemia/reperfusion injury by increasing antioxidant enzymes. 22 Our previous work demonstrated that PD not only ameliorated diabetic nephropathy and liver disease 22,23 but also ameliorated Alcl 3 +D-gal-induced neuronal apoptosis and cognitive dysfunction via activating AMPK activity. 24 However, it is not clear whether PD has a unique modulating effect on T2DM-induced cognitive dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3β Signaling Pathway

Lu,

Xie,

et al. 2024

J. Agric. Food Chem.

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The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3β (GSK3β) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.

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Exploring the preventive effects of Jie Geng Tang on pulmonary fibrosis induced in vitro and in vivo: a network pharmacology approach

Li,

Jiang,

Liu

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Platycodin D inhibits HFD/STZ-induced diabetic nephropathy via inflammatory and apoptotic signaling pathways in C57BL/6 mice

Cited by 6 publications

References 35 publications

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway

Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3β Signaling Pathway

Exploring the preventive effects of Jie Geng Tang on pulmonary fibrosis induced in vitro and in vivo: a network pharmacology approach

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