Enhanced inhibition of protein disulfide isomerase and anti-thrombotic activity of a rutin derivative: rutin:Zn complex

Liao, Xinyuan; Ji, Panpan; Chi, Kunxiang; Chen, Xueying; Zhou, Yang; Chen, Shanli; Cheng, Yuan; Flaumenhaft, Robert; Yuan, Cai; Huang, Mingdong

doi:10.1039/d3ra01135f

Cited by 2 publications

(4 citation statements)

References 24 publications

(41 reference statements)

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“…The functional tests used in our study also showed that PDIA1 activity is modified in the presence of zinc. Interestingly, it has been recently demonstrated that zinc-loaded flavonoids (e.g., rutin and quercetin) are significantly more effective in PDI inhibition than their respective apo-forms [63]. Although the observed effect was initially attributed to the complex of the flavonoid molecule with zinc, our findings suggest that the formation of the Zn 2+ -PDIA1 complex is also a viable factor and should not be overlooked.…”

Section: Zinc Impact On Pdia1 Activitymentioning

confidence: 45%

Exploring the Influence of Zinc Ions on the Conformational Stability and Activity of Protein Disulfide Isomerase

Moretti,

Baksheeva,

Roman

et al. 2024

IJMS

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The interplay between metal ion binding and the activity of thiol proteins, particularly within the protein disulfide isomerase family, remains an area of active investigation due to the critical role that these proteins play in many vital processes. This research investigates the interaction between recombinant human PDIA1 and zinc ions, focusing on the subsequent implications for PDIA1’s conformational stability and enzymatic activity. Employing isothermal titration calorimetry and differential scanning calorimetry, we systematically compared the zinc binding capabilities of both oxidized and reduced forms of PDIA1 and assessed the structural consequences of this interaction. Our results demonstrate that PDIA1 can bind zinc both in reduced and oxidized states, but with significantly different stoichiometry and more pronounced conformational effects in the reduced form of PDIA1. Furthermore, zinc binding was observed to inhibit the catalytic activity of reduced-PDIA1, likely due to induced alterations in its conformation. These findings unveil a potential regulatory mechanism in PDIA1, wherein metal ion binding under reductive conditions modulates its activity. Our study highlights the potential role of zinc in regulating the catalytic function of PDIA1 through conformational modulation, suggesting a nuanced interplay between metal binding and protein stability in the broader context of cellular redox regulation.

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Section: Zinc Impact On Pdia1 Activitymentioning

confidence: 45%

Exploring the Influence of Zinc Ions on the Conformational Stability and Activity of Protein Disulfide Isomerase

Moretti,

Baksheeva,

Roman

et al. 2024

IJMS

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“…Rutin is another characteristic bioactive flavonoid found in many plant organisms, even in frequently consumed foods (Figure 9) [11]. In fact, recent studies have highlighted the antithrombotic activity of rutin, as it is able to inhibit protein disulfide isomerase (PDI).…”

Section: Metal-based Complexes Containing Well-established Natural An...mentioning

confidence: 99%

“…In other words, the antiplatelet potency, better expressed as anti-PAF activity, of any substance can be exerted by inhibiting the PAFinduced aggregation in washed rabbit/human platelets (WRPs and hWPs respectively), and rabbit/human platelet reach plasma (rPRP and hPRP, respectively) [8]. Towards this goal, several compounds with antiplatelet potencies and a more general anti-PAF activity have been studied [10][11][12][13], among which some metal-based compounds bear natural bioactive properties as ligands, while others bear some porphyrin derivatives that also pose as attractive bioactive alternative ligand metal complexes [14]. Thus, apart from the classic organic compounds against inflammation and thrombosis, several "metal-based inflammatory mediators," have also been developed that are able to successfully encounter all of these thrombo-inflammatory pathways [15].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, there is another class of metal-based complexes which act as ligands in several natural phenolic bioactive compounds, such as rutin, curcumin, chrysin or vanillin and several of their derivatives. These phenolics of natural origin possess, on their own, antithrombotic and anti-inflammatory properties, but their complexation as ligands in metalbased compounds results in improved biological properties (such as anti-inflammatory or antimicrobial) when compared with the original natural compound in the absence of the metal center [10][11][12]20]. This suggests that the bioactive properties of any of these natural phenolic compounds are improved by their coupling as ligands in metal-based complexes.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Inflammatory and Antithrombotic Potential of Metal-Based Complexes and Porphyrins

Tsoupras,

Pafli,

Stylianoudakis

et al. 2024

Compounds

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Inflammation and thrombosis are implicated in several chronic disorders. Recent studies have outlined the way in which several compounds can offer protection against inflammation. Within this comprehensive review the so-far reported anti-inflammatory health-promoting effects of several metal-based complexes, both in vitro and in vivo, are thoroughly presented. These metal-based compounds usually interfere with various biochemical processes associated with the inflammatory response and thrombus formation and become capable of inhibiting these biochemical pathways with proposed health benefits. Emphasis is given to the multifaceted actions of metal-based complexes that have exhibited potent anti-inflammatory and antithrombotic activities against the inflammatory mediator, platelet-activating factor (PAF), and its thrombo-inflammatory signaling, as well as on their anti-platelet and antitumor health promoting properties. Furthermore, the enhancement of the anti-inflammatory potency of well-established bioactive compounds by their incorporation as ligands in several metal-based complexes is discussed. Metal-based complexes bearing natural anti-inflammatory bioactives are also outlined. Characteristic examples of both free and metal-based porphyrins are explored. These compounds are recognized to have anti-inflammatory and antithrombotic assets, in addition to other pleiotropic advantages including antibacterial or anticancer actions. Additionally, applications of metal complexes in various models of inflammatory and thrombotic complications are demonstrated. The combined results of this study show that further research is required towards the preparation of several metal-based complexes with improved pharmacological profiles. Finally, restrictions on the application of these metal-based compounds are also covered, along with their prospects for the future and the need for additional study in order to improve their efficacy and safety.

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Enhanced inhibition of protein disulfide isomerase and anti-thrombotic activity of a rutin derivative: rutin:Zn complex

Abstract: The chelation of zinc to adjacent keto and phenoxy position was critical for enhancing rutin and flavonoids' inhibition to PDI, which provides a new strategy for the clinical translation of flavonoids.

Cited by 2 publications

References 24 publications

Exploring the Influence of Zinc Ions on the Conformational Stability and Activity of Protein Disulfide Isomerase

Exploring the Influence of Zinc Ions on the Conformational Stability and Activity of Protein Disulfide Isomerase

Anti-Inflammatory and Antithrombotic Potential of Metal-Based Complexes and Porphyrins

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