Monomeric Proanthocyanidins Increase Intracellular NAD+Content by Enhancing NAMPT Transcription

10.6919/ICJE.202205_8(5).0104

Wenjing Wei；Jinhua Zhang；Yiting Fu；Hansen Chen

Proanthocyanidins ； NAMPT ； NAD+

International Core Journal of Engineering

8卷5期（2022 / 05 / 01）

811 - 816

英文

Proanthocyanidins (PCs), a group of polyphenolic compounds that have been studied for almost 80 years, have a high antioxidant capacity and considerable benefits to human health. These compounds are effective at scavenging free radicals in organisms and have anti-inflammatory and antiaging effects. The content of nicotinamide adenine dinucleotide (NAD+) decreases with age. Exogenous supplementation with NAD+ plays a vital role in impeding aging and prolonging lifespan; thus, NAD+ is a potential target for antiaging research. There is evidence that PCs can affect the content of NAD+, but the effects of monomeric proanthocyanidins (MPCs) and oligomeric proanthocyanidins (OPCs) on NAD+ levels are still unclear. In our study, normal human diploid skin fibroblast BJ cells were treated with MPCs and OPCs, and changes in intracellular NAD+ content were examined. Real-time qPCR was used to detect changes in the transcription of enzymes associated with NAD+ synthesis. The results showed that both MPCs and OPCs could increase NAD+ content. In low-passage BJ cells, the effects of MPCs were greater than those of OPCs. Moreover, the qPCR results showed that the mRNA expression levels of the rate-limiting enzyme NAMPT were significantly upregulated in PC-treated low-passage and senescent BJ cells, suggesting that the effect of PCs on NAD+ content may be achieved by regulating NAMPT transcription, which may provide a theoretical basis for the effect of PCs on intracellular NAD+ content.

1. She J, Sheng R, Qin Z-H J A, et al. Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors[J], 2021, 12(8): 1879.
   連結：
2. Hosseini L, Vafaee M S, Mahmoudi J, et al. Nicotinamide adenine dinucleotide emerges as a therapeutic target in aging and ischemic conditions[J], 2019, 20(4): 381-395.
   連結：
3. Covarrubias A J, Perrone R, Grozio A, et al. NAD+ metabolism and its roles in cellular processes during ageing[J], 2021, 22(2): 119-141.
   連結：
4. Pîrvu A S, Andrei A M, Stănciulescu E C, et al. NAD+ metabolism and retinal degeneration[J], 2021, 22(1): 1-6.
   連結：
5. Ji L L, Yeo D J C. Maintenance of NAD+ Homeostasis in Skeletal Muscle during Aging and Exercise[J], 2022, 11(4): 710.
   連結：
6. Sara A, Nisar S, Bhat A A, et al. Role of NAD+ in regulating cellular and metabolic signaling pathways[J], 2021.
   連結：
7. Wan W, Zhu W, Wu Y, et al. Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway[J]. J Inflamm Res, 2021, 14: 3129-3143.
   連結：
8. Rongvaux A, Shea R J, Mulks M H, et al. Pre‐B‐cell colony‐enhancing factor, whose expression is up‐regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis[J], 2002, 32(11): 3225-3234.
   連結：
9. Oszmianski J, Wolniak M, Wojdylo A, et al. Comparative study of polyphenolic content and antiradical activity of cloudy and clear apple juices[J], 2007, 87(4): 573-579.
   連結：
10. Rauf A, Imran M, Abu-Izneid T, et al. Proanthocyanidins: A comprehensive review[J], 2019, 116: 108999.
    連結：
11. Unusan N J J O F F. Proanthocyanidins in grape seeds: An updated review of their health benefits and potential uses in the food industry[J], 2020, 67: 103861.
    連結：
12. Rodríguez-Pérez C, García-Villanova B, Guerra-Hernández E, et al. Grape Seeds Proanthocyanidins: An Overview of In Vivo Bioactivity in Animal Models[J]. Nutrients, 2019, 11(10).
    連結：
13. Zheng W, Feng Y, Bai Y, et al. Proanthocyanidins extracted from grape seeds inhibit the growth of hepatocellular carcinoma cells and induce apoptosis through the MAPK/AKT pathway[J], 2022, 45: 101337.
    連結：
14. Zhong H, Xue Y, Lu X, et al. The effects of different degrees of procyanidin polymerization on the nutrient absorption and digestive enzyme activity in mice[J], 2018, 23(11): 2916.
    連結：
15. Chen Y, Wang J, Zou L, et al. Dietary proanthocyanidins on gastrointestinal health and the interactions with gut microbiota[J]. Crit Rev Food Sci Nutr, 2022: 1-24.
    連結：
16. Li S, Yang Y, Li J, et al. Increasing yield and antioxidative performance of Litchi pericarp procyanidins in baked food by ultrasound-assisted extraction coupled with enzymatic treatment[J], 2018, 23(9): 2089.
    連結：
17. Lu M-C, Yang M-D, Li P-C, et al. Effect of oligomeric proanthocyanidin on the antioxidant status and lung function of patients with chronic obstructive pulmonary disease[J], 2018, 32(4): 753-758.
    連結：
18. Mohammadi Y, Kamangar B B, Zarei M a J A. Effects of diets containing grape seed proanthocyanidin extract on the growth and oxidative capacity of common carp (Cyprinus carpio)[J], 2021, 540: 736689.
    連結：
19. Chu H, Tang Q, Huang H, et al. Grape-seed proanthocyanidins inhibit the lipopolysaccharide-induced inflammatory mediator expression in RAW264. 7 macrophages by suppressing MAPK and NF-κb signal pathways[J], 2016, 41: 159-166.
    連結：
20. Mousavi S, Sheikhzadeh N, Tayefi-Nasrabadi H, et al. Administration of grape (Vitis vinifera) seed extract to rainbow trout (Oncorhynchus mykiss) modulates growth performance, some biochemical parameters, and antioxidant-relevant gene expression[J], 2020, 46(3): 777-786.
    連結：
21. Yang L, Xian D, Xiong X, et al. Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications[J]. Biomed Res Int, 2018, 2018: 8584136.
    連結：
22. Praud D, Parpinel M, Guercio V, et al. Proanthocyanidins and the risk of prostate cancer in Italy[J]. Cancer Causes Control, 2018, 29(2): 261-268.
    連結：
23. Ribas-Latre A, Baselga-Escudero L, Casanova E, et al. Dietary proanthocyanidins modulate BMAL1 acetylation, Nampt expression and NAD levels in rat liver[J]. Sci Rep, 2015, 5: 10954.
    連結：
24. Aragonès G, Suárez M, Ardid-Ruiz A, et al. Dietary proanthocyanidins boost hepatic NAD(+) metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats[J]. Sci Rep, 2016, 6: 24977.
    連結：
25. Mekala N K, Kurdys J, Depuydt M M, et al. Apoptosis inducing factor deficiency causes retinal photoreceptor degeneration. The protective role of the redox compound methylene blue[J]. Redox Biol, 2019, 20: 107-117.
    連結：
26. Dong C J D R. Protective effect of proanthocyanidins in cadmium induced neurotoxicity in mice[J], 2015, 65(10): 555-560.
    連結：
27. Ahmad S R, Gokulakrishnan P, Giriprasad R, et al. Fruit-based Natural Antioxidants in Meat and Meat Products: A Review[J]. Crit Rev Food Sci Nutr, 2015, 55(11): 1503-13.
    連結：
28. Nie Y, Stürzenbaum S R. Proanthocyanidins of Natural Origin: Molecular Mechanisms and Implications for Lipid Disorder and Aging-Associated Diseases[J]. Adv Nutr, 2019, 10(3): 464-478.
    連結：
29. Masquelier J, Michaud J, Laparra J, et al. Flavonoids and pycnogenols[J], 1979, 49(3): 307-311.
30. Yun S J F, Industries F. Relationship between the degree of polymerization and antioxidant activities of grape seed procyanidins[J], 2006, 32(10): 41.