Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis

Zhang, Jing-Tian; Xie, Li-ya; Shen, Qiong; Liu, Wei; Li, Ming-Han; Hu, Rui-Yi; Hu, Jun‐Nan; Wang, Zi; Chen, Chen; Li, Wei

doi:10.1016/j.jep.2023.116294

Cited by 7 publications

(4 citation statements)

References 51 publications

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“…Zhang et al showed that PD activates AMPK to enhance antioxidant capacity and exert neuroprotective effects in vivo and in vitro. 52 We also used PyMOL and BIOVIA Discovery Studio 2019 software to visualize the binding mode of PD and AMPK, and the binding energy was −8.2 kcal/mol, indicating that the component and the target can be tightly bound. In addition, the AMPK activator can upregulate the expression of AMPK protein and reduce cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

“…The activation of AMPK by PD has also been demonstrated in previous articles of the research group. Zhang et al showed that PD activates AMPK to enhance antioxidant capacity and exert neuroprotective effects in vivo and in vitro . We also used PyMOL and BIOVIA Discovery Studio 2019 software to visualize the binding mode of PD and AMPK, and the binding energy was −8.2 kcal/mol, indicating that the component and the target can be tightly bound.…”

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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“…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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“…1 ). This plant has been utilized for medicinal and culinary purposes for thousands of years ( Sun et al, 2018 , Zhang et al, 2023 ). P. grandiflorum is predominantly distributed in Asian countries in the Northern Hemisphere, including China, Japan, North Korea, and Eastern Siberia.…”

Section: Introductionmentioning

confidence: 99%

Ethnopharmacology, phytochemistry, pharmacology and product application of Platycodon grandiflorum: A review

Zhang,

Wang,

Zhang

et al. 2024

Chinese Herbal Medicines

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Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis

Cited by 7 publications

References 51 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

Ethnopharmacology, phytochemistry, pharmacology and product application of Platycodon grandiflorum: A review

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