Caspase/AIF/apoptosis pathway: a new target of puerarin for diabetes mellitus therapy

Tao, Liang; Xu, Xiaogang; Ye, Dongmei; Chen, Wenxia; Gao, Biyun; Huang, Yanjun

doi:10.1007/s11033-019-04925-1

Cited by 27 publications

(20 citation statements)

References 25 publications

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“…Once the AIF enters the nucleus, the DNA is cleaved into 50-kb fragments and then caspase family-independent apoptosis is triggered (21). After Res treatment of H446 cells, the cytoplasmic expression of AIF decreased while its nuclear expression increased, which is consistent with a study of AIF involvement in apoptosis (22). After NAC treatment, the inductive effect of Res on the release of cyto-c and expression of Bax in H446 cells was alleviated.…”

Section: Discussionsupporting

confidence: 87%

Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway

Li¹,

Li²,

Ma³

et al. 2020

Oncol Rep

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There have been no major breakthroughs in the treatment of small-cell lung cancer (SCLC) in recent decades. It is thus essential to explore new or adjuvant treatment options for SCLC. Resveratrol (Res) is a natural antioxidant revealed to influence the entire process of cancer development. Accordingly, the present study used the SCLC cell line H446 to explore the antitumor mechanism of Res. Cells were treated with 40 µg/ml Res with or without pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). H446 cell viability and apoptosis were assessed with MTT and flow cytometry, and the expression of cytochrome c and the PI3K/Akt/c-Myc pathway and the nuclear translocation of apoptosis inducing factor (AIF) were assessed by western blotting. In addition, the changes in ROS content and mitochondrial membrane potential were determined. The results revealed that Res inhibited H446 cell viability and induced apoptosis, increased cytochrome c expression, inhibited the expression of PI3K/Akt/c-Myc signaling pathway components, and promoted the translocation of AIF from the cytoplasm to the nucleus in H446 cells. However, NAC pretreatment reversed these changes to various extents. The results of the present study indicated that Res may inhibit the viability and promote the apoptosis of human SCLC H446 cells through the PI3K/Akt/c-Myc pathway and that oxidative stress and mitochondrial membrane potential depolarization may be involved in the aforementioned processes.

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Section: Discussionsupporting

confidence: 87%

Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway

Li¹,

Li²,

Ma³

et al. 2020

Oncol Rep

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“…Evidence from our previous studies revealed a hypoglycemic effect of puerarin on DM. 12,13 In this study, the FBG levels at weeks 4 and 8 in the DN mice treated with puerarin were decreased compared with the FBG levels in DN control mice. Moreover, puerarin intervention also reduced the abnormally high levels of BUN, Scr, Ucr, and 24-hour urine protein in DN mice.…”

Section: Discussionmentioning

confidence: 47%

“…Electron microscopy studies were performed on kidney tissues, as previously described. 12 Kidney samples were removed, cut into small pieces (about 2 mm × 2 mm × 2 mm), and immediately fixed in 2.5% pre-cooled glutaraldehyde for 2 hours at 0°C. After rinsing in buffer, kidney tissues were post-fixed in 1% osmium tetroxide for 2 hours at room temperature and dehydrated in a graded series of ethanol.…”

Section: Transmission Electron Microscopy Evaluationmentioning

confidence: 99%

“…[9][10][11] In our previous studies, puerarin not only attenuates the oxidative stress in DN, but also meliorates the glucolipid metabolism. 12 Additionally, renal function and podocyte fusion were improved by puerarin intervention. 13 Most importantly, autophagy activity was enhanced by the presence of puerarin through the activation of PERK activity.…”

Section: Introductionmentioning

confidence: 99%

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<p>The Effects of Puerarin on Autophagy Through Regulating of the PERK/eIF2α/ATF4 Signaling Pathway Influences Renal Function in Diabetic Nephropathy</p>

Xu¹,

Chen²,

QiChun³

et al. 2020

DMSO

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Background and Purpose: Autophagy is the main protective mechanism against aging in podocytes, which are terminally differentiated cells that have a very limited capacity for mitosis and self-renewal. Here, a streptozotocin-induced DN C57BL/6 mouse model was used to investigate the effects of puerarin on the modulation of autophagy under conditions associated with endoplasmic reticulum stress (ERS). In addition, this study aimed to identify the potential underlying molecular mechanisms. Methods and Results: DN C57BL/6 mouse model was induced by streptozotocin (150 mg/ kg) injection. The mice were administered rapamycin and puerarin, respectively, daily for up to 8 weeks. After the serum and kidney samples were collected, the fasting blood glucose (FBG), parameters of renal function, histomorphology, and the podocyte functional proteins were analyzed. Moreover, the autophagy markers and the expressions of PERK/ATF4 pathway were studied in kidney. Results found that the FBG level in DN mice was significantly higher than in normal mice. Compared with DN model mice, puerarin-treated mice showed an increased expression of podocyte functional proteins, including nephrin, podocin, and podocalyxin. Furthermore, the pathology and structure alterations were improved by treatment with rapamycin and puerarin compared with the DN control. The results indicated an elevated level of autophagy in rapamycin and puerarin groups compared with the DN model, as demonstrated by the upregulated expression of autophagy markers Beclin-1, LC3II, and Atg5, and downregulated p62 expression. In addition, the levels of PERK, eIF2α, and ATF4 were reduced in the DN model, which was partially, but significantly, prevented by rapamycin and puerarin. Conclusion: This study emphasizes the renal-protective effects of puerarin in DN mice, particularly in the modulation of autophagy under ERS conditions, which may be associated with activation of the PERK/eIF2α/ATF4 signaling pathway. Therefore, PERK may be a potential target for DN treatment.

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“…Foxo1 acts as a transcription factor to inhibit pancreatic duodenum homeobox-1 (PDX-1) activity and mediate-cell dysfunction and apoptosis ( Yang et al, 2016a ). The caspase family of proteins is involved in inducing apoptosis ( Liang et al, 2019 ). ( Figure 1 )…”

Section: Hypoglycemic Mechanism Of Puerarinmentioning

confidence: 99%

Molecular Mechanism of Puerarin Against Diabetes and its Complications

et al. 2022

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Puerarin is a predominant component of Radix Puerarin. Despite its anti-tumor and anti-virus effects and efficacy in improving cardiovascular or cerebrovascular diseases and preventing osteoporosis, it has been shown to protect against diabetes and its complications. This review summarizes the current knowledge on Puerarin in diabetes and related complications, aiming to provide an overview of antidiabetic mechanisms of Puerarin and new targets for treatment.

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Caspase/AIF/apoptosis pathway: a new target of puerarin for diabetes mellitus therapy

Cited by 27 publications

References 25 publications

Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway

Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway

<p>The Effects of Puerarin on Autophagy Through Regulating of the PERK/eIF2α/ATF4 Signaling Pathway Influences Renal Function in Diabetic Nephropathy</p>

Molecular Mechanism of Puerarin Against Diabetes and its Complications

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