Catalpol ameliorates hepatic insulin resistance in type 2 diabetes through acting on AMPK/NOX4/PI3K/AKT pathway

Yan, Jiting; Wang, Changyuan; Jin, Yue; Meng, Qiang; Qi, Lei; Liu, Zhihao; Liu, Kexin; Sun, Huijun

doi:10.1016/j.phrs.2017.12.026

Cited by 155 publications

(114 citation statements)

References 65 publications

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“…also demonstrated globularin which is the principal compound of G. alypum , at a dose 100 mg/kg showed a hypoglycaemic effect in normalglycaemic and hyperglycaemic rats. Several reports have revealed the anti‐diabetic effect of catalpol . The presence of globularin and catalpol or derivatives in G. orientalis and G. trichosantha may justify the inhibitory activity against α‐amylase and α‐glucosidase.…”

Section: Resultsmentioning

confidence: 58%

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Chemical fingerprint and bioactivity evaluation of Globularia orientalis L. and Globularia trichosantha Fisch. & C. A. Mey. using non‐targeted HPLC‐ESI‐QTOF‐MS approach

Rodríguez‐Pérez

Zengin

Segura‐Carretero

et al. 2018

Phytochemical Analysis

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Introduction In the quest for new sources of biologically‐active compounds, the chemical, and biological profiles of two Globularia species (G. trichosantha Fisch. & C. A. Mey and G. orientalis L.) were investigated. Methodology Chemical profiles were evaluated by high‐performance liquid chromatography coupled to electrospray ionisation and quadrupole time‐of‐flight mass spectrometry (HPLC‐ESI‐QTOF‐MS), as well as by their total phenolic, flavonoids, and phenolic acids contents. The antioxidant abilities of the investigated extracts were done using different assays including free radical scavenging [1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid (ABTS)], reducing power (cupric reducing antioxidant capacity and ferric reducing antioxidant power), phosphomolybdenum, and metal chelating. Inhibitory potential against key enzymes involved in neurodegenerative diseases (cholinesterases; AChE, and BChE), diabetes (α‐glucosidase and α‐amylase), hyperpigmentation (tyrosinase) and obesity (pancreatic lipase) were evaluated. Results Globularia trichosantha and G. orientalis extracts showed remarkable antioxidant properties, with the water extracts being a better source of antioxidant compounds. Both species showed remarkable inhibitory effects against the target enzymes. However, for both species, only the acetyl acetate and methanolic extracts were potent against cholinesterases and lipase. Conclusion HPLC‐ESI‐QTOF‐MS analysis revealed the presence of 107 compounds from G. trichosantha and G. orientalis, among which, 43 compounds have been preliminarily characterised for the first time from the Globulariaceae family. To date, this study can be considered as the most comprehensive research focused on the characterisation of G. trichosantha and G. orientalis. Results amassed from this study tend to show that these plants represent a rich source of biologically active compounds which can be further explored and validated for their therapeutic potential.

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Section: Resultsmentioning

confidence: 58%

“…revealed the anti-diabetic effect of catalpol. 38,[79][80][81] The presence of globularin and catalpol or derivatives in G. orientalis and G. trichosantha may justify the inhibitory activity against α-amylase and α-glucosidase.…”

Section: Enzyme Inhibitory Abilitymentioning

confidence: 99%

Chemical fingerprint and bioactivity evaluation of Globularia orientalis L. and Globularia trichosantha Fisch. & C. A. Mey. using non‐targeted HPLC‐ESI‐QTOF‐MS approach

Rodríguez‐Pérez

Zengin

Segura‐Carretero

et al. 2018

Phytochemical Analysis

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“…AMPK is a potential target for glucose metabolism and plays a key role in the treatment of T2DM (Yan et al ., ). Hepatic gluconeogenesis was increased in T2DM and AMPK controls hepatic glucose homeostasis mainly through the inhibition of gluconeogenesis.…”

Section: Resultsmentioning

confidence: 97%

“…Decreased glycogen synthesis and increased hepatic gluconeogenesis, which are major manifestations of hepatic insulin resistance (Yan et al ., ), lead to increased blood glucose levels. The effect of glimepiride on hepatic glycogen was identified by PAS staining, which stains stored glycogen as purple particles.…”

Section: Resultsmentioning

confidence: 99%

“…Our results showed that glimepiride increased the phosphorylation of GSK3 and decreased that of GS. As the rate‐limiting step for glycogen synthesis, GS activation is manifested as a decrease in its phosphorylation through inhibition of GSK3 by increasing its phosphorylation and then finally results in increased glycogen synthesis (Montori‐Grau et al ., ; Yan et al ., ). In the present study, the glimepiride‐induced increase in hepatic glycogen storage was accompanied by the inhibition of GSK3 and the activation of GS.…”

Section: Discussionmentioning

confidence: 97%

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Hypoglycaemic effects of glimepiride in sulfonylurea receptor 1 deficient rat

Zhou

Zhang

Zou

et al. 2018

British J Pharmacology

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Background and Purpose Sulfonylureas (SUs) have been suggested to have an insulin‐independent blood glucose‐decreasing activity due to an extrapancreatic effect. However, a lack of adequate in vivo evidence makes this statement controversial. Here, we aimed to evaluate whether glimepiride has extrapancreatic blood glucose‐lowering activity in vivo. Experimental Approach Sulfonylurea receptor 1 deficient (SUR1−/−) rats were created by means of transcription activator‐like effector nucleases (TALEN)‐mediated gene targeting technology. Type 2 diabetic models were established by feeding a high‐fat diet and administering a low‐dose of streptozotocin. These rats were then randomly divided into four groups: glimepiride, gliclazide, metformin and saline. All rats were treated for 2 weeks. Key Results Glimepiride decreased blood glucose levels and increased insulin sensitivity without elevating insulin levels. Gliclazide showed similar effects as glimepiride. Both agents were weaker than metformin. Further mechanistic investigations revealed that glimepiride increased hepatic glycogen synthesis and decreased gluconeogenesis, which were accompanied by the activation of Akt in the liver. Moreover, glimepiride increased both total and membrane glucose transporter 4 (GLUT4) levels in muscle and fat, which might be attributed to insulin receptor‐independent IRS1/Akt activation. Conclusion and Implications Glimepiride possesses an extrapancreatic blood glucose‐lowering effect in vivo, which might be attributed to its direct effect on insulin‐sensitive tissues. Therefore, the combination of glimepiride with multiple insulin injections should not be excluded per se.

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Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway

Lei,

Li,

Liu

et al. 2024

BioFactors

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Despite the observation of diabetes‐induced brain tissue damage and impaired learning and memory, the underlying mechanism of damage remains elusive, and effective, targeted therapeutics are lacking. Notably, the NLRP3 inflammasome is highly expressed in the hippocampus of diabetic individuals. Nerolidol, a naturally occurring compound with anti‐inflammatory and antioxidant properties, has been identified as a potential therapeutic option for metabolic disorders. However, the ameliorative capacity of nerolidol on diabetic hippocampal injury and its underlying mechanism remain unclear. Network pharmacology and molecular docking was used to predict the signaling pathways and therapeutic targets of nerolidol for the treatment of diabetes. Then established a diabetic rat model using streptozotocin (STZ) combined with a high‐fat diet and nerolidol was administered. Morris water maze to assess spatial learning memory capacity. Hematoxylin and eosin and Nissl staining was used to detect neuronal damage in the diabetic hippocampus. Transmission electron microscopy was used to detect the extent of damage to mitochondria, endoplasmic reticulum (ER) and synapses. Immunofluorescence was used to detect GFAP, IBA1, and NLRP3 expression in the hippocampus. Western blot was used to detect apoptosis (Bcl‐2, BAX, and Cleaved‐Caspase‐3); synapses (postsynaptic densifying protein 95, SYN1, and Synaptophysin); mitochondria (DRP1, OPA1, MFN1, and MFN2); ER (GRP78, ATF6, CHOP, and caspase‐12); NLRP3 inflammasome (NLRP3, ASC, and caspase‐1); inflammatory cytokines (IL‐18, IL‐1β, and TNF‐α); AKT (P‐AKT); and mitogen‐activated protein kinase (MAPK) pathway (P‐ERK, P‐p38, and P‐JNK) related protein expression. Network pharmacology showed that nerolidol's possible mechanisms for treating diabetes are the MAPK/AKT pathway and anti‐inflammatory effects. Animal experiments demonstrated that nerolidol could improve blood glucose, blood lipids, and hippocampal neuronal damage in diabetic rats. Furthermore, nerolidol could improve synaptic, mitochondrial, and ER damage in the hippocampal ultrastructure of diabetic rats by potentially affecting synaptic, mitochondrial, and ER‐related proteins. Further studies revealed that nerolidol decreased neuroinflammation, NLRP3 and inflammatory factor expression in hippocampal tissue while also decreasing MAPK pathway expression and enhancing AKT pathway expression. However, nerolidol improves hippocampal damage in diabetic rats cannot be shown to improve cognitive function. In conclusion, our study reveals for the first time that nerolidol can ameliorate hippocampal damage, neuroinflammation, synaptic, ER, and mitochondrial damage in diabetic rats. Furthermore, we suggest that nerolidol may inhibit NLRP3 inflammasome and affected the expression of MAPK and AKT. These findings provide a new experimental basis for the use of nerolidol to ameliorate diabetes‐induced brain tissue damage and the associated disease.

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Catalpol ameliorates hepatic insulin resistance in type 2 diabetes through acting on AMPK/NOX4/PI3K/AKT pathway

Cited by 155 publications

References 65 publications

Chemical fingerprint and bioactivity evaluation of Globularia orientalis L. and Globularia trichosantha Fisch. & C. A. Mey. using non‐targeted HPLC‐ESI‐QTOF‐MS approach

Chemical fingerprint and bioactivity evaluation of Globularia orientalis L. and Globularia trichosantha Fisch. & C. A. Mey. using non‐targeted HPLC‐ESI‐QTOF‐MS approach

Hypoglycaemic effects of glimepiride in sulfonylurea receptor 1 deficient rat

Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway

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