Quercetin inhibits angiotensin II-induced vascular smooth muscle cell proliferation and activation of JAK2/STAT3 pathway: A target based networking pharmacology approach

Wang, Di; Ali, Farman; Liu, Huixin; Cheng, Ying; Saleem, Muhammad Zubair; Zheng, Hang; Wei, Lihui; Chu, Jiangfeng; Xie, Qiurong; Shen, Aling; Peng, Jun

doi:10.3389/fphar.2022.1002363

Cited by 7 publications

(4 citation statements)

References 72 publications

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“…Quercetin can play a role in anti-hypertension by suppressing Ang II-stimulated VSMC proliferation (Wang et al, 2022). Quercetin may reduce oxidative stress, and minimize arterial endothelial cell dysfunction (Pereira et al, 2018).…”

Section: Bioactive Components and Targets Of Ur-ap In Hypertension Ma...mentioning

confidence: 99%

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach

Yin,

Zhang,

Liu

et al. 2024

Front. Chem.

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Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear.Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment.Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA’s roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP’s main bioactives, underscoring their therapeutic potential.Conclusion: This research delineates UR-AP’s pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP’s potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

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Section: Bioactive Components and Targets Of Ur-ap In Hypertension Ma...mentioning

confidence: 99%

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach

Yin,

Zhang,

Liu

et al. 2024

Front. Chem.

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“…Healthy VSMCs are characterized by quiescent contractile phenotype which are transformed into synthetic proliferative and migrative phenotype during progression of hypertension and cardiovascular diseases (Cao et al, 2022). Flavonoids protect against hypertension development by maintaining contractile function of vascular smooth muscle cells by decreasing their growth (Wang et al, 2022; Wu et al, 2018). Flavonoids inhibit the activity of ACE (Guerrero et al, 2012).…”

Section: Flavonoids: Potential Mechanisms Beyond Vascular Tone Regula...mentioning

confidence: 99%

Current insights and future perspectives of flavonoids: A promising antihypertensive approach

Harahap,

Syahputra,

Ahmed

et al. 2024

Phytotherapy Research

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Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L‐NG‐nitro arginine methyl ester (L‐NAME), an analog of L‐arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L‐NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L‐NAME‐induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L‐NAME‐induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin‐converting enzyme (ACE) and endothelin‐1. Moreover, they exhibit anti‐inflammatory effects, attenuating inflammation‐mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L‐NAME‐induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.

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“…In addition, quercetin has been shown to inhibit angiotensin II-induced vascular smooth muscle cell proliferation and activation of the JAK2/STAT3 pathway [4; 27]. The KEGG pathway assessment showed that quercetin affects various signalling pathways, including the PI3K-AKT signalling pathway, cytokine receptor-cytokine interaction, JAK-STAT signalling pathway, MAPK signalling pathway, and cancer pathways [27].…”

Section: біотехнології та біоінженеріяmentioning

confidence: 99%

Bionanotechnological strategies for the synthesis of quercetin conjugates with selenium nanoparticles for their targeting of the Wnt/Ca2+signaling pathway

Bityutskyy,

Tsekhmistrenko,

Demchenko

et al. 2023

Tehnologìâ virobnictva ì pererobki produktìv tvarinnictva

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One of the applications of nanotechnology is the synthesis of nanoparticles for targeted drug delivery and disease prevention. In the agricultural sector, nanotechnology holds great promise for improving animal health and productivity. The article discusses the advantages of «green» synthesis of selenium nanoparticles functionalized with the flavonoid quercetin and their potential in the prevention of bone diseases in broilers. Selenium is an important trace element that plays a crucial role in various physiological processes, including the regulation of bone metabolism. Its deficiency can lead to bone diseases such as osteoporosis and osteomalacia. On the other hand, quercetin, a naturally occurring plant compound, has been shown to have numerous health benefits, including anti-inflammatory, antioxidant, and anticancer properties. However, quercetin's bioavailability and stability are limited, making its therapeutic potential challenging to exploit. To overcome these limitations, we have developed bionanotechnological strategies for the synthesis of quercetin conjugates with selenium nanoparticles. This approach not only improves the stability and bioavailability of quercetin, but also allows for targeted delivery to specific tissues or cellular pathways. Functionalization of Selenium nanoparticles with the flavonoid quercetin promotes the effect of the nanoconjugate on the transcription factors Nrf2 and NF-kB, Wnt, key pathways that regulate the delicate balance of cellular redox status and responses to stress and inflammation, calcium and phosphorus metabolism. In this case, the target is the Wnt signaling pathway, a complex cascade of processes involved in bone metabolism. It has been found that the synthesized nanoselenium-quercetin bioconjugates modulate the Wnt signaling pathway in different ways. Firstly, they reduce the activity of the protein β-catenin, a key regulator of the Wnt signaling pathway, and help maintain a balance between bone formation and resorption, thus preventing bone disease. Secondly, these bioconjugates increase the activity of LRP6, a Wnt receptor protein, which further enhances the effectiveness of the signaling pathway. Finally, they affect the expression of genes activated by the Wnt signaling pathway, thus regulating the metabolism of calcium and phosphorus, important elements for bone health. The potential of these bionanotechnology strategies is enormous, especially in the agricultural sector. By preventing bone disease in broilers, disease prevention and poultry productivity can be significantly increased. The use of nanotechnology advances can serve as an environmentally friendly alternative to the use of antibiotics and other pharmaceuticals, contributing to the overall health and well-being of animals. Thus, the «green» synthesis of quercetin-functionalized selenium nanoparticles offers a promising solution for targeting the Wnt signaling pathway, regulating calcium and phosphorus metabolism, and preventing bone disease in broilers. This bionanotechnology approach not only improves the stability and bioavailability of quercetin, but also enhances its therapeutic potential. By harnessing the potential of nanotechnology in the agricultural sector, we can improve animal health, reduce disease and increase productivity, ultimately benefiting both animals and humans. Key words: bionanotechnology, «green» synthesis, Nrf2 factor, NFkB, Wnt, β-catenin, Selenium, Calcium, Phosphorus.

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Quercetin inhibits angiotensin II-induced vascular smooth muscle cell proliferation and activation of JAK2/STAT3 pathway: A target based networking pharmacology approach

Cited by 7 publications

References 72 publications

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach

Current insights and future perspectives of flavonoids: A promising antihypertensive approach

Bionanotechnological strategies for the synthesis of quercetin conjugates with selenium nanoparticles for their targeting of the Wnt/Ca2+signaling pathway

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