A possible new activator of PI3K‐Huayu Qutan Recipe alleviates mitochondrial apoptosis in obesity rats with acute myocardial infarction

Tai, He; Tong, Yu-Jing; Yu, Rui; Yu, You; Yao, Si-Cheng; Li, Ling-Bing; Liu, Ye; Cui, Xiao-Zheng; Kuang, Jin-song; Meng, Xin-He; Jiang, Xiaolin

doi:10.1111/jcmm.17353

Cited by 6 publications

(5 citation statements)

References 69 publications

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“…The downregulation of PI3K and Akt results in decreased NO production by eNOS, contributing to hypertension and an increased risk of atherosclerosis [144]. Obesity aggravates myocardial mitochondrial dysfunction following AMI by increasing the mRNA expression of caspase 9/3, Cyt-c, and PARP and decreasing the mRNA expression of PI3K, Bad, and Akt [145]. In a study investigating the cardioprotective properties of roselle in a diet-induced obesity rat model with MI, there was a significant deterioration in cardiac systolic function (LVDP and LVdP/dtmax), diastolic function (LVdP/dtmin and Tau), coronary flow, and cardiac output (RPP) in the obese (OB) and obese with MI (OB + MI) groups compared to the control group.…”

Section: Obesitymentioning

confidence: 99%

The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes

Gumede,

Khathi

2024

Biomedicines

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Myocardial infarction is a major contributor to CVD-related mortality. T2DM is a risk factor for MI. Stress activates the HPA axis, SNS, and endogenous OPS. These POMC derivatives increase the blood glucose and cardiovascular response by inhibiting the PI3K/AkT insulin signaling pathway and increasing cardiac contraction. Opioids regulate the effect of the HPA axis and SNS and they are cardioprotective. The chronic activation of the stress response may lead to insulin resistance, cardiac dysfunction, and MI. Stress and T2DM, therefore, increase the risk of MI. T2DM is preceded by prediabetes. Studies have shown that prediabetes is associated with an increased risk of MI because of inflammation, hyperlipidemia, endothelial dysfunction, and hypertension. The HPA axis is reported to be dysregulated in prediabetes. However, the SNS and the OPS have not been explored during prediabetes. The effect of prediabetes on POMC derivatives has yet to be fully explored and understood. The impact of stress and prediabetes on the cardiovascular response needs to be investigated. This study sought to review the potential impact of prediabetes on the POMC derivatives and pathways that could lead to MI.

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Section: Obesitymentioning

confidence: 99%

The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes

Gumede,

Khathi

2024

Biomedicines

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“…We took out the renal tissues from abdominal cavity immediately following anesthesia, and then sliced the renal tissues into snippets (1 mm 3 ). The specific process was conducted based on previous studies [23].…”

Section: Observing Mitochondria With Transmission Electron Microscopementioning

confidence: 99%

“…Then, PBS was used to incubate the sections for 2 h at room temperature followed by incubation overnight (4° C) via the following two antibodies: rabbit anti-Bax (1: 50) and rabbit anti-Bcl-2 (1: 100). Finally, we used the secondary antibodies (Servicebio, Wuhan, China) to incubate the thin sections for 2 h at 4° C, and used a fluorescence microscope (Leica) to observe the results [23].…”

Section: Apoptosis Protein Assessment Of the Renal Tissues With Immun...mentioning

confidence: 99%

“…Bicinchoninic acid (BCA) test kit (Beyotime, Shanghai, China) was used to detect the concentration of protein in the renal mitochondrial suspension for ensuring a stable protein level (100-1000 μg/ml). We used mitochondria suspension to measure MMP [25], the opening of mPTP [26], damaged mtDNA, ROS [27], mitochondrial oxygen consumption rate [28], RCR [28], mitochondrial respiratory chain complex enzymes (I, II, III, IV, and V) [23], and ATP.…”

Section: Preparation Of Mitochondria Suspensionmentioning

confidence: 99%

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Renoprotective effect of Tanshinone IIA against kidney injury induced by ischemia-reperfusion in obese rats

Tai

Cui

et al. 2022

Aging

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Objective: Obesity enhances the frequency and severity of acute kidney injury (AKI) induced by renal ischemiareperfusion (IR). Tanshinone IIA (TIIA) pre-treatment was used to alleviate renal injury induced by renal IR, and whether TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats was examined. Methods: Male rates were fed a high-fat diet for 8 weeks to generate obesity, followed by 30 min of kidney ischemia and 24 h reperfusion induced AKI. The male obese rates were given TIIA ( 5mg/kg.d, 10 mg/kg.d, and 20 mg/kg.d) for 2 weeks before renal IR. Results: TIIA alleviated the pathohistological injury and apoptosis induced by IR. In addition, TIIA improved renal function, inflammatory factor, and balance of oxidation and antioxidation in obese rats after renal IR. At the same time, TIIA can inhibit cell apoptosis by improving mitochondrial function through the PI3K/Akt/Bad pathway. Mitochondrial dysfunction was supported by decreasing intracellular ATP, respiration controlling rate (RCR), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex enzymes, and by increasing ROS, the opening of mitochondrial permeability transition pore (mPTP), and the mtDNA damage. The injury to mitochondrial dynamic function was assessed by decreasing Drp1, and increasing Mfn1/2; and the injury of mitochondrial biogenesis was assessed by decreasing PGC-1, Nrf1, and TFam.

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“…However, there is currently no research available on the impact of TCM in terms of invigorating qi, invigorating the spleen, removing stasis and removing phlegm on macrophage lipophagy. HYQT, a modified formula that integrates Chinese and Western medical theories, has been found to possess anti‐hyperlipidaemic 15 and atherosclerotic effects in previous studies. Moreover, HYQT plays a significant role in the regulation of autophagy 16–19 …”

Section: Introductionmentioning

confidence: 99%

Huayu Qutan Recipe promotes lipophagy and cholesterol efflux through the mTORC1/TFEB/ABCA1‐SCARB1 signal axis

Li,

Pan,

et al. 2024

J Cellular Molecular Medi

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This study aims to investigate the mechanism of the anti‐atherosclerosis effect of Huayu Qutan Recipe (HYQT) on the inhibition of foam cell formation. In vivo, the mice were randomly divided into three groups: CTRL group, MOD group and HYQT group. The HYQT group received HYQT oral administration twice a day (20.54 g/kg/d), and the plaque formation in ApoE−/− mice was observed using haematoxylin–eosin (HE) staining and oil red O (ORO) staining. The co‐localization of aortic macrophages and lipid droplets (LDs) was examined using fluorescent labelling of CD11b and BODIPY fluorescence probe. In vitro, RAW 264.7 cells were exposed to 50 μg/mL ox‐LDL for 48 h and then treated with HYQT for 24 h. The accumulation of LDs was evaluated using ORO and BODIPY. Cell viability was assessed using the CCK‐8 assay. The co‐localization of LC3b and BODIPY was detected via immunofluorescence and fluorescence probe. LysoTracker Red and BODIPY 493/503 were used as markers for lysosomes and LDs, respectively. Autophagosome formation were observed via transmission electron microscopy. The levels of LC3A/B II/LC3A/B I, p‐mTOR/mTOR, p‐4EBP1/4EBP1, p‐P70S6K/P70S6K and TFEB protein level were examined via western blotting, while SQSTM1/p62, Beclin1, ABCA1, ABCG1 and SCARB1 were examined via qRT‐PCR and western blotting. The nuclear translocation of TFEB was detected using immunofluorescence. The components of HYQT medicated serum were determined using Q‐Orbitrap high‐resolution MS analysis. Molecular docking was employed to identify the components of HYQT medicated serum responsible for the mTOR signalling pathway. The mechanism of taurine was illustrated. HYQT has a remarkable effect on atherosclerotic plaque formation and blood lipid level in ApoE−/− mice. HYQT decreased the co‐localization of CD11b and BODIPY. HYQT (10% medicated serum) reduced the LDs accumulation in RAW 264.7 cells. HYQT and RAPA (rapamycin, a mTOR inhibitor) could promote cholesterol efflux, while chloroquine (CQ, an autophagy inhibitor) weakened the effect of HYQT. Moreover, MHY1485 (a mTOR agonist) also mitigated the effects of HYQT by reduced cholesterol efflux. qRT‐PCR and WB results suggested that HYQT improved the expression of the proteins ABCA1, ABCG1 and SCARB1.HYQT regulates ABCA1 and SCARB1 protein depending on the mTORC1/TFEB signalling pathway. However, the activation of ABCG1 does not depend on this pathway. Q‐Orbitrap high‐resolution MS analysis results demonstrated that seven core compounds have good binding ability to the mTOR protein. Taurine may play an important role in the mechanism regulation. HYQT may reduce cardiovascular risk by promoting cholesterol efflux and degrading macrophage‐derived foam cell formation. It has been observed that HYQT and ox‐LDL regulate lipophagy through the mTOR/TFEB signalling pathway, rather than the mTOR/4EBP1/P70S6K pathway. Additionally, HYQT is found to regulate cholesterol efflux through the mTORC1/TFEB/ABCA1‐SCARB1 signal axis, while taurine plays a significant role in lipophagy.

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A possible new activator of PI3K‐Huayu Qutan Recipe alleviates mitochondrial apoptosis in obesity rats with acute myocardial infarction

Cited by 6 publications

References 69 publications

The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes

The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes

Renoprotective effect of Tanshinone IIA against kidney injury induced by ischemia-reperfusion in obese rats

Huayu Qutan Recipe promotes lipophagy and cholesterol efflux through the mTORC1/TFEB/ABCA1‐SCARB1 signal axis

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