Platycodin D ameliorates hyperglycaemia and liver metabolic disturbance in HFD/STZ-induced type 2 diabetic mice

Shen, Qiong; Zhong, Yute; Liu, Xiangxiang; Hu, Jun‐Nan; Qi, Si-Min; Li, Ké; Wang, Zi; Zhu, Hongyan; Li, Xin-Dian; Wang, Ying‐Ping; Li, Wei

doi:10.1039/d2fo03308a

Cited by 15 publications

(15 citation statements)

References 55 publications

(64 reference statements)

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“…An early report indicated that PD inhibits Aβ-induced oxidative stress and inflammatory responses in BV-2 cells by modulating the TLR4/NF-κB (p65) and Nrf2/HO-1 signaling pathways . Moreover, PD could protect mice from hippocampal ischemia/reperfusion injury by increasing antioxidant enzymes . Our previous work demonstrated that PD not only ameliorated diabetic nephropathy and liver disease , but also ameliorated Alcl 3 +D-gal-induced neuronal apoptosis and cognitive dysfunction via activating AMPK activity .…”

Section: Introductionmentioning

confidence: 90%

“…Fasting blood glucose (FBG) levels were measured at days 7, 14, 21, and 28 after STZ injection using blood taken from the tail vein using an ACCU-CHEK Performa FBG monitor. Mice with stable FBG values in the range of 7.8–16.67 mmol/L were selected for the study. , After 13 weeks of dietary manipulation with a high-fat and high-sugar regimen, the T2DM mice were randomly assigned to three groups: (1) normal group (mice received 0.5% CMC-Na, n = 10); (2) model group, (mice received HFD + STZ at 100 mg/kg, n = 10); and (3) HFD + STZ + PD (2.5 mg/kg, n = 10) . The optimal dose of PD was determined based on the results of previous pre-experiments by the subject group.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 90%

Section: Methodsmentioning

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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“…PD (purity, ≥98%) was isolated from the aerial parts of P. grandiflorum and extracted by our research group. 25 Streptozocin (STZ) and wheat germ agglutinin (WGA) were purchased from Solarbio (Beijing, China). The high-fat diet (HFD) comprised 60% of total kilocalories based on D12492 (Beijing Hua Fukang guidelines).…”

Section: Methodsmentioning

confidence: 99%

“…The mice were randomly assigned to three groups (n = 8): a normal group, a diabetes group, and a PD group (2.5 mg/kg). 25 All experimental animals underwent adaptive feeding for 7 days prior to the induction of diabetes in mice. After 8 weeks of HFD feeding combined with STZ (100 mg/kg) dissolved in preprepared citrate buffer (pH = 4.2−4.4) in an ice bath, a single dose of STZ was intraperitoneally injected into mice to induce diabetes.…”

Section: Methodsmentioning

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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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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“…In addition, PD may have a potential direct effect on AMPK and other key glycolipid metabolism proteins. To summarize, PD modulation of hepatic glycolipid metabolism abnormalities is promising for T2D therapy in the future ( Shen et al, 2023 ). Diabetes mellitus is a group of physiological dysfunctions associated with hyperglycemia-mediated oxidative stress and apoptosis in pancreatic β-cells.…”

Section: Pharmacology Of Pldmentioning

confidence: 99%

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus

et al. 2023

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Chinese doctors widely prescribed Platycodon grandiflorus A. DC. (PG) to treat lung carbuncles in ancient China. Modern clinical experiences have demonstrated that PG plays a crucial role in treating chronic pharyngitis, plum pneumonia, pneumoconiosis, acute and chronic laryngitis, and so forth. Additionally, PG is a food with a long history in China, Japan, and Korea. Furthermore, Platycodin D (PLD), an oleanane-type triterpenoid saponin, is one of the active substances in PG. PLD has been revealed to have anti-inflammatory, anti-viral, anti-oxidation, anti-obesity, anticoagulant, spermicidal, anti-tumor etc., activities. And the mechanism of the effects draws lots of attention, with various signaling pathways involved in these processes. Additionally, research on PLD’s pharmacokinetics and extraction processes is under study. The bioavailability of PLD could be improved by being prescribed with Glycyrrhiza uralensis Fisch. or by creating a new dosage form. PLD has been recently considered to have the potential to be a solubilizer or an immunologic adjuvant. Meanwhile, PLD was discovered to have hemolytic activity correlated. PLD has broad application prospects and reveals practical pharmacological activities in pre-clinical research. The authors believe that these activities of PLD contribute to the efficacy of PG. What is apparent is that the clinical translation of PLD still has a long way to go. With the help of modern technology, the scope of clinical applications of PLD is probable to be expanded from traditional applications to new fields.

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Platycodin D ameliorates hyperglycaemia and liver metabolic disturbance in HFD/STZ-induced type 2 diabetic mice

Abstract: In this work, we investigated the ameliorative effects of platycodin D (PD), a major active chemical ingredient isolated from the roots of Platycodon grandiflorum (PG), on a high-fat diet (HFD)/streptozotocin...

Cited by 15 publications

References 55 publications

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

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

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

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus

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