Chemical Constituents with Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression Inhibitory Activity from Dried Immature <i>Morus alba</i> Fruits

Pel, Pisey; Chae, Hee‐Sung; Nhoek, Piseth; Kim, Youngmi; Chin, Young‐Won

doi:10.1021/acs.jafc.7b02088

Cited by 41 publications

(25 citation statements)

References 31 publications

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“…Under our experimental condition, we have utilized 50 µg/mL of RYR containing 15 µg/mL of monacolin K and 40 µg/mK BCE containing 34 µg/mL of berberine, thus with a molar ratio of 1 to 2.3 in favor of berberine, very similar that predicted to be present in human plasma. These in vitro concentrations are similar to those utilized in previous study [15,17,32,53], and have been shown to be not cytotoxic. Regarding the final concentration utilized for water-soluble extracts of Morus alba leaves, the interval of 0.25 ÷ 1 mg/mL, is lower than the previously tested 1 ÷ 6 mg/mL of mulberry water extracts on HepG2 cells [39].…”

Section: Discussionsupporting

confidence: 84%

“…Moracin C was identified from a chloroform soluble extract of Morus alba fruits while in our study we have utilized water soluble extracts of Morus alba leaves. Interestingly, the water-soluble extracts of Morus alba fruits did not show any activity on PCSK9 expression [17]. Thus, although moracin C is present in Morus alba leaves [47], it is unlikely that was present in our water extract.…”

Section: Discussionmentioning

confidence: 72%

“…Regarding the active components of MLE, it has been recently reported that moracin C, present in dried immature Morus alba fruits, reduced both the mRNA and protein of PCSK9 [17]. Moracin C was identified from a chloroform soluble extract of Morus alba fruits while in our study we have utilized water soluble extracts of Morus alba leaves.…”

Section: Discussionmentioning

confidence: 99%

“…Many nutraceuticals have been shown to modulate PCSK9 expression, including berberine [15], curcumin [16], moracin C [17], and lignans [18]. In addition, statins induce PCSK9 in vitro [19,20], and in clinical trials [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK®, on PCSK9 in HepG2 Cells

Mg¹,

Macchi²,

Marchianò³

et al. 2018

Preprint

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the key regulator of low-density lipoprotein cholesterol (LDL-C) plasma levels. We previously observed that treatment of dyslipidemic subjects with nutraceutical combination containing red yeast rice (monacolin K 3.3 mg), Berberis aristata cortex extract (Berberine 531.25 mg) and Morus alba leaves extract (1-deoxynojirimycin 4 mg) (LopiGLIK®) did not alter the plasma PCSK9 levels. Thus, the aim of the present study was to investigate the effect of these three components on PCSK9 expression in HepG2 cell line in relationship to their effects on LDL-C cellular uptake. HepG2 cell line were incubated with Berberis aristata cortex extract (BCE), red yeast rice (RYR) and Morus alba leaves extract (MLE) alone or in combination for 24 h. RYR (50 µg/mL) increased PCSK9 protein expression (WB and ELISA assays), PCSK9 mRNA and its promoter activity. BCE (40 µg/mL) reduced PCSK9 expression, mRNA levels and promoter activity. MLE determined a concentration-dependent inhibition of PCSK9 at mRNA and protein levels, with a maximal reduction at 1 mg/mL; no significant changes in PCSK9 promoter activity were found. MLE also downregulates the expression of fatty acid synthase and HMG-CoA reductase mRNA levels. The combination of RYR, BCE and MLE reduced PCSK9 at mRNA, protein, and promoter activity. Finally, this combination induced the LDL receptor and LDL-C uptake by HepG2 cells. In conclusion, the positive effect of MLE on PCSK9 supports the rational of using this nutraceutical combination to control hyperlipidemic conditions.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK®, on PCSK9 in HepG2 Cells

Mg¹,

Macchi²,

Marchianò³

et al. 2018

Preprint

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“… 45 , 47 In addition, extracts from dried immature M. alba fruits have been recently shown to have an inhibitory activity on PCSK9. 48 …”

Section: Discussionmentioning

confidence: 99%

Effect of a novel nutraceutical combination on serum lipoprotein functional profile and circulating PCSK9

Adorni¹,

Ferri²,

Marchianò³

et al. 2017

TCRM

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BackgroundA beneficial effect on cardiovascular risk may be obtained by improving lipid-related serum lipoprotein functions such as high-density lipoproteins (HDLs) cholesterol efflux capacity (CEC) and serum cholesterol loading capacity (CLC) and by reducing proprotein convertase subtilisin kexin type 9 (PCSK9), independently of lipoprotein concentrations.AimWe aimed to evaluate the effect of an innovative nutraceutical (NUT) combination containing red yeast rice (monacolin K 3.3 mg), berberine 531.25 mg and leaf extract of Morus alba 200 mg (LopiGLIK®), on HDL-CEC, serum CLC and on circulating PCSK9 levels.Materials and methodsTwenty three dyslipidemic subjects were treated for 4 weeks with the above NUT combination. HDL-CEC was measured using specific cell-based radioisotopic assays; serum CLC and PCSK9 concentrations were measured fluorimetrically and by enzyme-linked immunosorbent assay, respectively.ResultsThe NUT combination significantly reduced plasma level of the total cholesterol and low-density lipoprotein cholesterol (−9.8% and −12.6%, respectively). Despite no changes in HDL-cholesterol, the NUT combination improved total HDL-CEC in 83% of the patients, by an average of 16%, as a consequence of the increase mainly of the ATP-binding cassette A1-mediated CEC (+28.5%). The NUT combination significantly reduced serum CLC (−11.4%) while it did not change PCSK9 plasma levels (312.9±69.4 ng/mL vs 334.8±103.5 mg/L, before and after treatment, respectively).ConclusionThe present NUT combination improves the serum lipoprotein functional profile providing complementary beneficial effects, without any detrimental increase of PCSK9 plasma levels.

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Introduction

Ozturk,

Kamili,

Altay

et al. 2023

Mulberry

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Chemical Constituents with Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression Inhibitory Activity from Dried Immature Morus alba Fruits

Cited by 41 publications

References 31 publications

Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK®, on PCSK9 in HepG2 Cells

Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK®, on PCSK9 in HepG2 Cells

Effect of a novel nutraceutical combination on serum lipoprotein functional profile and circulating PCSK9

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Chemical Constituents with Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression Inhibitory Activity from Dried Immature Morus alba Fruits

Cited by 41 publications

References 31 publications

Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK&reg;, on PCSK9 in HepG2 Cells

Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK&reg;, on PCSK9 in HepG2 Cells

Effect of a novel nutraceutical combination on serum lipoprotein functional profile and circulating PCSK9

Introduction

Contact Info

Product

Resources

About

Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK®, on PCSK9 in HepG2 Cells

Differential Effects of Red Yeast Rice, Berberis Aristata and Morus Alba Extracts, Active Components of LopiGLIK®, on PCSK9 in HepG2 Cells