Underlying mechanisms and molecular targets of genistein in the management of type 2 diabetes mellitus and related complications

Jin-hua, Tao; Dong, Yuhe; Zhu, Wei; Wu, Tong; Chen, Linyan; Cao, Yanna; Yu, Xi; Ye, Peng; Xiao, Ying; Zhong, Tian

doi:10.1080/10408398.2023.2240886

Cited by 7 publications

(5 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, many studies have been focused on the remedial roles of genistein for diabetes mellitus, renal, reproductive disorders, neurodegenerative dysfunctions, and malignancy [26][27][28][29]. As a strong antioxidative agent, genistein has been shown to inhibit oxidative stress and postpone the progression of diabetes-associated complication [32][33][34][35][36][37]. Several mechanisms have been proposed for MG in stimulating ROS production and promoting oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Genistein exhibits estrogen effects, neuroprotective action against ischemic injury, antilipogenic and hypolipidemic properties, as well as chemoprevention in cancer treatment [28,30,31]. Moreover, genistein is suitable in playing a protective role in diabetes and its vascular complication as result of its antioxidant, anti-inflammatory and hypoglycemic activity [32][33][34][35][36][37]. Genistein also plays a protective role in MG-induced immune dysfunction in diabetic patients, reducing the oxidative stress and DNA damage as well as ROS generation and apoptosis in mononuclear cells [38].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genistein Prevents Apoptosis and Oxidative Stress Induced by Methylglyoxal in Endothelial Cells

Liccardo,

Sapio,

Perrella

et al. 2024

Molecules

View full text Add to dashboard Cite

Glycolytic overload promotes accumulation of the highly reactive dicarbonyl compounds, resulting in harmful conditions called dicarbonyl stress. Methylglyoxal (MG) is a highly reactive dicarbonyl species and its accumulation plays a crucial pathophysiological role in diabetes and its vascular complications. MG cytotoxicity is mediated by reactive oxygen species (ROS) generation, a key event underlying the intracellular signaling pathways leading to inflammation and apoptosis. The identification of compounds able to inhibit ROS signaling pathways and counteract the MG-induced toxicity is a crucial step for developing new therapeutic strategies in the treatment of diabetic vascular complications. In this study, the effect of genistein, a natural soybean isoflavone, has been evaluated on MG-induced cytotoxicity in human endothelial cells. Our results show that genistein is able to counteract the MG-induced apoptosis by restraining ROS production, thus inhibiting the MAPK signaling pathways and caspase-3 activation. These findings identify a beneficial role for genistein, providing new insights for its potential clinical applications in preserving endothelial function in diabetic vascular complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genistein Prevents Apoptosis and Oxidative Stress Induced by Methylglyoxal in Endothelial Cells

Liccardo,

Sapio,

Perrella

et al. 2024

Molecules

View full text Add to dashboard Cite

show abstract

“…They achieve this by counteracting oxidative stress through the neutralization of free radicals and the inhibition of lipid peroxidation. Genistein, in particular, stands out for its effectiveness in protecting pancreatic beta cells, which are crucial for insulin production [54].…”

Section: Roles Of Phytoestrogen's Antioxidant Activity In Metabolic D...mentioning

confidence: 99%

From Plant to Patient: The Metabolic Benefits of Phytoestrogens

Kumar Verma,

Kumar Singh,

Tripathi

2024

Herbs and Spices - New Perspectives in Human Health and Food Industry

View full text Add to dashboard Cite

In recent years, there has been a growing interest in the potential health benefits of phytoestrogens, a diverse group of naturally occurring compounds found in plants. These compounds, with structural similarities to estrogen, are found in foods such as soybeans, flaxseeds and sesame seeds, and are studied for their roles in modulating hormonal activity and antioxidant properties. Their estrogen-like functions make them particularly interesting in managing conditions exacerbated by hormonal imbalances, such as type 2 diabetes, obesity, cardiovascular diseases, and osteoporosis. Phytoestrogens enhance insulin sensitivity and glucose metabolism, while their anti-oxidant properties neutralize free radicals and inhibit lipid peroxidation. They also influence fat metabolism and reduce adipogenesis, addressing oxidative stress and inflammation. Their estrogenic effects improve bone mineral density and reduce fracture risks, particularly in postmenopausal women, highlighting their broad potential in metabolic disease management. This growing body of research suggests that phytoestrogens, due to their unique properties and diverse mechanisms of action, could be a valuable addition to dietary and therapeutic strategies in the prevention and management of various metabolic diseases. This chapter delves into the multifaceted roles of phytoestrogens in metabolic disorders, with a special focus on their antioxidant properties.

show abstract

“…The International Diabetes Federation (IDF) reported in 2022 that approximately 537 million adults worldwide are affected by diabetes. DR patients are expected to increase to 643 million by 2030 and 783 million by 2045 ( Jiang et al, 2023a ). Due to its insidious onset, many patients are only diagnosed at advanced, often proliferative stages, highlighting the urgency of developing more effective treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment

Zhang,

Wu,

Wang

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

Objective:Diabetic retinopathy (DR) is a severe diabetic complication that leads to severe visual impairment or blindness. He-Ying-Qing-Re formula (HF), a traditional Chinese medicinal concoction, has been identified as an efficient therapy for DR with retinal vascular dysfunction for decades and has been experimentally reported to ameliorate retinal conditions in diabetic mice. This study endeavors to explore the therapeutic potential of HF with key ingredients in DR and its underlying novel mechanisms.Methods:Co-expression gene modules and hub genes were calculated by weighted gene co-expression network analysis (WGCNA) based on transcriptome sequencing data from high-glucose-treated adult retinal pigment epithelial cell line-19 (ARPE-19). The chromatographic fingerprint of HF was established by ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-Q-TOF-MS). The molecular affinity of the herbal compound was measured by molecular docking. Reactive oxygen species (ROS) was measured by a DCFDA/H2DCFDA assay. Apoptosis was detected using the TUNEL Assay Kit, while ELISA, Western blot, and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used for detecting the cytokine, protein, and mRNA expressions, respectively.Results:Key compounds in HF were identified as luteolin, paeoniflorin, and nobiletin. For WGCNA, ME-salmon (“protein deacetylation”) was negatively correlated with ME-purple (“oxidative impairment”) in high-glucose-treated ARPE-19. Luteolin has a high affinity for SIRT1 and P53, as indicated by molecular docking. Luteolin has a hypoglycemic effect on type I diabetic mice. Moreover, HF and luteolin suppress oxidative stress production (ROS and MDA), inflammatory factor expression (IL-6, TNF-α, IL1-β, and MCP-1), and apoptosis, as shown in the in vivo and in vitro experiments. Concurrently, treatment with HF and luteolin led to an upregulation of SIRT1 and a corresponding downregulation of P53.Conclusion:Using HF and its active compound luteolin as therapeutic agents offers a promising approach to diabetic retinopathy treatment. It primarily suppressed protein acetylation and oxidative stress via the SIRT1/P53 pathway in retinal pigment epithelial cells.

show abstract

Underlying mechanisms and molecular targets of genistein in the management of type 2 diabetes mellitus and related complications

Cited by 7 publications

References 112 publications

Genistein Prevents Apoptosis and Oxidative Stress Induced by Methylglyoxal in Endothelial Cells

Genistein Prevents Apoptosis and Oxidative Stress Induced by Methylglyoxal in Endothelial Cells

From Plant to Patient: The Metabolic Benefits of Phytoestrogens

SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment

Contact Info

Product

Resources

About