Potential dual inhibitors of PCSK-9 and HMG-R from natural sources in cardiovascular risk management

Waiz, Mohd; Alvi, Sahir Sultan; Khan, Mohd Salman

doi:10.17179/excli2021-4453

Cited by 11 publications

(10 citation statements)

References 185 publications

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“…Oxidative stress induced by ROS damages proteins, lipids, and DNA and is one of the major causes of several chronic diseases, such as DM [ 29 , 32 ]. The prevalence of DM is rising globally and this trend is predicted to continue in the coming decades [ 8 ]. Oxidative stress and DM are independent risk factors for several complications, including cardiovascular diseases, diabetic encephalopathy, and AD [ 2 , 32 , 33 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Because phenolic compounds are believed to be responsible for the majority of antioxidant properties of plant extracts, the antioxidant potential of the MeOH extract might be attributable to polyphenolic compounds [ 32 , 41 ]. Compounds with the ability to reduce oxidative stress via quenching of free radicals can delay or stop the progression of several chronic diseases [ 1 , 8 , 42 , 43 ]. The MeOH extract of C. nocturnum leaves exhibited strong DPPH and ABTS radical quenching ability ( Figure 1 , Table 3 ), indicating its potent antioxidant activity.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of diabetes is increasing globally—approximately 537 million adults lived with diabetes in 2021 and the disease accounted for more than 6.0 million fatalities, half of which were in cases that were still undiagnosed. These numbers are predicted to increase to ~645 and ~785 million by 2030 and 2045, respectively [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Secondary Metabolite Profiling, Antioxidant, Antidiabetic and Neuroprotective Activity of Cestrum nocturnum (Night Scented-Jasmine): Use of In Vitro and In Silico Approach in Determining the Potential Bioactive Compound

Ahmad

Alrouji

Alhajlah

et al. 2023

Plants

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This study aims to describe the therapeutic potential of C. nocturnum leaf extracts against diabetes and neurological disorders via the targeting of α-amylase and acetylcholinesterase (AChE) activities, followed by computational molecular docking studies to establish a strong rationale behind the α-amylase and AChE inhibitory potential of C. nocturnum leaves-derived secondary metabolites. In our study, the antioxidant activity of the sequentially extracted C. nocturnum leaves extract was also investigated, in which the methanolic fraction exhibited the strongest antioxidant potential against DPPH (IC50 39.12 ± 0.53 µg/mL) and ABTS (IC50 20.94 ± 0.82 µg/mL) radicals. This extract strongly inhibited the α-amylase (IC50188.77 ± 1.67 µg/mL) and AChE (IC50 239.44 ± 0.93 µg/mL) in a non-competitive and competitive manner, respectively. Furthermore, in silico analysis of compounds identified in the methanolic extract of the leaves of C. nocturnum using GC-MS revealed high-affinity binding of these compounds with the catalytic sites of α-amylase and AChE, with binding energy ranging from −3.10 to −6.23 kcal/mol and from −3.32 to −8.76 kcal/mol, respectively. Conclusively, the antioxidant, antidiabetic, and anti-Alzheimer activity of this extract might be driven by the synergistic effect of these bioactive phytoconstituents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Secondary Metabolite Profiling, Antioxidant, Antidiabetic and Neuroprotective Activity of Cestrum nocturnum (Night Scented-Jasmine): Use of In Vitro and In Silico Approach in Determining the Potential Bioactive Compound

Ahmad

Alrouji

Alhajlah

et al. 2023

Plants

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“…Of note, accumulating evidence have demonstrated that natural products are an important resource for discovery of PCSK9i. These natural products include berberine, lupin, quercetin, resveratrol, and others as reviewed by several groups ( Ahamad et al, 2022 ; Waiz et al, 2022 ). Mechanistically, these small molecules may directly inhibit PCSK9-LDLR interactions, PCSK9 production, transcription, and secretion ( Ahamad et al, 2022 ).…”

Section: Therapies Targeting Ldl-pmentioning

confidence: 99%

Low-density lipoprotein particles in atherosclerosis

2022

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Among the diseases causing human death, cardiovascular disease (CVD) remains number one according to the World Health Organization report in 2021. It is known that atherosclerosis is the pathological basis of CVD. Low-density lipoprotein (LDL) plays a pivotal role in the initiation and progression of atherosclerotic CVD (ASCVD). LDL cholesterol (LDL-C) is the traditional biological marker of LDL. However, large numbers of patients who have achieved the recommended LDL-C goals still have ASCVD risk. In multiple prospective studies, LDL particle (LDL-P) is reported to be more accurate in predicting CVD risk than LDL-C. LDL-Ps differ in size, density and chemical composition. Numerous clinical studies have proved that the atherogenic mechanisms of LDL-Ps are determined not only by LDL number and size but also by LDL modifications. Of note, small dense LDL (sdLDL) particles possess stronger atherogenic ability compared with large and intermediate LDL subfractions. Besides, oxidized LDL (ox-LDL) is another risk factor in atherosclerosis. Among the traditional lipid-lowering drugs, statins induce dramatic reductions in LDL-C and LDL-P to a lesser extend. Recently, proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) have been demonstrated to be effective in lowering the levels of LDL-C, LDL-P, as well as CVD events. In this article, we will make a short review of LDL metabolism, discuss the discordance between LDL-C and LDL-P, outline the atherogenic mechanisms of action of LDL by focusing on sdLDL and ox-LDL, summarize the methods used for measurement of LDL subclasses, and conclude the advances in LDL-lowering therapies using statins and PCSK9i.

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“…The currently available HMG-CoA reductase inhibitors (statins) and PCSK-9 inhibitors have shown great promise in achieving LDL-C therapeutic target. Since their lifelong prescriptions prompt various side effects, nutraceuticals with dual HMG-R and PCSK-9 inhibitory activities have been extensively studied these days [41] [42] . In addition to HMG-CoA inhibitory activity, it has been also shown that policosanol may reduce circulating levels of PCSK9 in the animal model [43] as well as in healthy participants [27] .…”

Section: Discussionmentioning

confidence: 99%

Association of octacosanol supplementation with redox status in patients on chronic statin therapy

Ciric¹,

Kotur-Stevuljevic²,

Stanković³

et al. 2023

J Med Biochemistry

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Background: The uneven lipid-lowering statin effects and statin intolerance raise interest regarding the involvement of coadministration of statins and dietary supplements. This study aimed to evaluate the effects of octacosanol supplementation on markers of redox status in cardiovascular patients on chronic atorvastatin therapy. Methods: A double-blind, randomized, placebo-controlled, single-centre study was conducted. Redox status homeostasis parameters [i.e., advanced oxidation protein products (AOPP), pro-oxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase activity (SOD), total protein sulfhydryl (SHgroups), and paraoxonase 1 (PON1) activity] were assessed in 81 patients. According to favorable changes in lipid profile, patients were classified into two groups: responders (n = 35) and non-responders (n = 46), and followed for 13 weeks. A principal component analysis (PCA) was applied to explore the effect of octacosanol supplementation and the relationship between investigated parameters as predictors of responders' and non-responders' status. Results: Significant decrease in Oxy-score value was found at the endpoint compared to baseline in responders' group Kratak sadr`ajUvod: Neujedna~eni hipolipemijski efekti primene statina kao i intolerancija na statine dovode do porasta inte re sovanja u vezi sa zajedni~kom primenom statina i dijetetskih suplemenata. Ova studija je imala za cilj da proceni efekte suplementacije oktakozanolom na markere redoks statusa kod kardiovaskularnih pacijenata na hroni~noj terapiji atorvastatinom. Metode: Sprovedena je dvostruko slepa, randomizovana, placebo kontrolisana studija. U serumu 81 pacijenta odre -|ivani su parametri redoks statusa [produkti uznapredovale oksidacije proteina (AOPP), prooksidativno-antioksidativni balans (PAB), totalni oksidativni status (TOS), totalni antioksidativni status (TAS), aktivnost superoksid dismutaze (SOD), sulfihidrilne grupe (SH-grupe) i aktivnost paraoksonaze 1 (PON1)]. U odnosu na povoljne promene lipidnog profila, pacijenti su klasifikovani u dve grupe: responderi (n = 35) i neresponderi (n = 46), i pra}eni su 13 nedelja. Rezultati: Zna~ajno smanjenje vrednosti oksi-skora pri me -}eno je kod respondera na kraju studije u pore|enju sa vrednostima na po~etku studije (21,0 (13,4-25,5) vs. 15,1 (12,4-18,0); P < 0,01). Principal component analiza (PCA) je primenjena da bi se procenio efekat suple -

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Potential dual inhibitors of PCSK-9 and HMG-R from natural sources in cardiovascular risk management

Cited by 11 publications

References 185 publications

Secondary Metabolite Profiling, Antioxidant, Antidiabetic and Neuroprotective Activity of Cestrum nocturnum (Night Scented-Jasmine): Use of In Vitro and In Silico Approach in Determining the Potential Bioactive Compound

Secondary Metabolite Profiling, Antioxidant, Antidiabetic and Neuroprotective Activity of Cestrum nocturnum (Night Scented-Jasmine): Use of In Vitro and In Silico Approach in Determining the Potential Bioactive Compound

Low-density lipoprotein particles in atherosclerosis

Association of octacosanol supplementation with redox status in patients on chronic statin therapy

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