Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation

Zhang, Ting; Zhang, Qing; Wang, Zheng; Tao, Ting; Li, Ruo-lan; Wang, Li-Yu; Peng, Wei; Wu, Chunjie

doi:10.1016/j.joim.2022.07.004

Cited by 7 publications

(6 citation statements)

References 88 publications

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“…In our study, we investigated the antidiabetic effects of HAS against T2DM and explored the potential related molecular mechanisms. Previous studies have reported that zanthoxylamides extracted from Z. bungeanum have potential antidiabetic effects in mice via activation of the AMPK/PI3K/Akt signaling pathway ( Xu et al, 2022 ; Zhang et al, 2022 ). In our study, we found that HAS, which is the most important zanthoxylamide in Z. bungeanum , has potential antidiabetic effects against T2DM based on investigation using a high-fat-fed and streptozotocin-induced T2DM mouse model.…”

Section: Discussionmentioning

confidence: 99%

Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum Maxim. has antidiabetic effects on high-fat-fed and streptozotocin-treated mice via increasing glycogen synthesis by regulation of PI3K/Akt/GSK-3β/GS signaling

Zhang

et al. 2022

Front. Pharmacol.

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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia. The fruits of Zanthoxylum bungeanum Maxim. is a common spice and herbal medicine in China, and hydroxy-α-sanshool (HAS) is the most abundant amide in Z. bungeanum and reported to have significant hypoglycemic effects. The purpose of this study was to evaluate the ameliorative effects of HAS on T2DM and the potential mechanisms responsible for those effects. An acute toxicity test revealed the median lethal dose (LD50) of HAS is 73 mg/kg. C57BL/6 J mice were fed a high-fat diet and given an intraperitoneal injection of streptozotocin (STZ) to induce T2DM in mice to evaluate the hypoglycemic effects of HAS. The results showed that HAS significantly reduced fasting blood glucose, reduced pathological changes in the liver and pancreas, and increased liver glycogen content. In addition, glucosamine (GlcN)-induced HepG2 cells were used to establish an insulin resistance cell model and explore the molecular mechanisms of HAS activity. The results demonstrated that HAS significantly increases glucose uptake and glycogen synthesis in HepG2 cells and activates the PI3K/Akt pathway in GlcN-induced cells, as well as increases GSK-3β phosphorylation, suppresses phosphorylation of glycogen synthase (GS) and increases glycogen synthesis in liver cells. Furthermore, these effects of HAS were blocked by the PI3K inhibitor LY294002. The results of our study suggest that HAS reduces hepatic insulin resistance and increases hepatic glycogen synthesis by activating the PI3K/Akt/GSK-3β/GS signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum Maxim. has antidiabetic effects on high-fat-fed and streptozotocin-treated mice via increasing glycogen synthesis by regulation of PI3K/Akt/GSK-3β/GS signaling

Zhang

et al. 2022

Front. Pharmacol.

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“…Zhang et al used network pharmacology in conjunction with experimental validation to investigate the potential mechanisms of freeze-dried ZBM powder's beneficial effects in the management of type 2 diabetes mellitus (T2DM). 71 The drug component-target network indicated that 39 differentially expressed overlapping genes were screened as the possible targets of ZBM in T2DM. In vitro experiments further confirmed that ZBM significantly inhibited palmitic acid-induced lipid formation in HepG2 cells, through promoting the phosphatidylinositol-3-kinase (PI3 K)/Akt and the adenosine monophosphate-activated protein kinase expressions in HepG2 cells.…”

Section: Biological Activities Of Zbmmentioning

confidence: 99%

Section: Antiobesity and Antidiabetic Effectmentioning

confidence: 99%

Zanthoxylum bungeanum Maxim: A Review of Its Phytochemistry, Pharmacology, and Pharmacokinetics

Yan,

Zhou,

Liu

et al. 2023

Natural Product Communications

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Zanthoxylum bungeanum Maxim (ZBM) belongs to Rutaceae family and has been used as traditional spice and herb for hundreds of years in China. Accumulating evidence suggests a series of pharmacological effects associated with ZBM. This review aims to provide a systematic analysis of the composition, structural properties, pharmacology, and pharmacokinetics of ZBM. Chemical composition analysis of ZBM showed that the main compositions were volatile oil, amide compounds, flavonoids, alkaloids, coumarins, lignans, and phenylpropanoids. Interestingly, ZBM exhibits a wide range of significant biological activities including anti-inflammatory and analgesic effect, anesthetic effect, neuroprotective effect, antiobesity activity, antineoplastic activity, antibacterial, and other activities. However, there is currently no comprehensive review available on ZBM. Therefore, an up-to-date research was accomplished through systematic searching of multiple electronic databases. In a word, this review summarizes the recent researches investigating the chemical composition and biological properties which will provide a better understanding about the health benefits and preclinical assessment of novel application of ZBM.

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“…Diabetes mellitus (DM) is a metabolic disorder caused by insufficient insulin secretion or insulin sensitivity, usually characterized by elevated blood glucose levels, [1,2] and is expected to affect 693 million adults by 2045, compared to the current prevalence of more than 400 million. [3] DM is the leading cause of chronic kidney disease (CKD).…”

Section: Introductionmentioning

confidence: 99%

The effects of Salvia miltiorrhiza and ligustrazine injection combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis

Zhang,

Luo,

et al. 2024

Medicine

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Background: In China, Salvia miltiorrhiza and ligustrazine (SML) injection are widely used as adjunctive therapy for patients with diabetic kidney disease (DKD). However, different studies have reported conflicting results. Therefore, a systematic review and meta-analysis are necessary to assess the efficacy and safety of SML injection for the treatment of DKD. Methods: We searched 6 electronic literature databases comparing randomized controlled trials (RCTs) of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), SML injection in combination with ACEIs/ARBs that were conducted from inception until September 5, 2023. Two reviewers extracted data and independently assessed the risk of bias. Using the Cochrane Risk of Bias Tool for Risk Assessment. Mean differences (MD) were combined with random-effects models and the corresponding 95% confidence intervals (CI) were reported. Review Manager 5.4 software was used for meta-analysis. Stata 17.0 software was used for sensitivity analysis and Egger test. Results: The combined results show that the use of SML injection along with ACEI/ARB led to better outcomes than the use of controls in terms of enhancing recovery: renal function: Serum creatinine (MD = −14.69, 95% CI (−19.38, −10.00)), Blood urea nitrogen (MD = −1.23, 95% CI (−1.72, −0.74)), Urinary β2-microglobulin (MD = −4.58, 95% CI (−7.72, −1.44)); urinary protein: Urinary albumin excretion rate (MD = −45.74, 95% CI (−58.92, −32.56)), Urine albumin-creatinine ratio (MD = −11.93, 95% CI (−13.89, −9.96)), 24-h urine proteinuria (MD = −0.59, 95% CI (−0.86, −0.32)), Urine microalbumin (MD = −13.50, 95% CI (−20.18, −6.83)). Additionally, adjuvant therapy with SML injection enhanced results in blood glucose, blood pressure, lipids, and inflammatory responses, and no significant variations in adverse events were discovered between the 2 groups. Conclusions: In patients with DKD, combining SML injection with ACEI/ARB improves renal function, renal proteinuria, hyperglycemia, blood pressure, dyslipidemia, and inflammatory response.

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Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation

Cited by 7 publications

References 88 publications

Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum Maxim. has antidiabetic effects on high-fat-fed and streptozotocin-treated mice via increasing glycogen synthesis by regulation of PI3K/Akt/GSK-3β/GS signaling

Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum Maxim. has antidiabetic effects on high-fat-fed and streptozotocin-treated mice via increasing glycogen synthesis by regulation of PI3K/Akt/GSK-3β/GS signaling

Zanthoxylum bungeanum Maxim: A Review of Its Phytochemistry, Pharmacology, and Pharmacokinetics

The effects of Salvia miltiorrhiza and ligustrazine injection combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis

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