Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products
Abstract
:1. Introduction
- (i)
- Niacinamide effectively penetrates the stratum corneum, reaching its intended target in sufficient amounts;
- (ii)
- It exerts its effects via specific biochemical mechanisms of action within cutaneous cells and on human skin;
- (iii)
- Peer-reviewed, double-blinded, placebo-controlled clinical trials with statistically significant results substantiating the efficacy claims have been published.
2. Mechanistic Insights into the Functions and Activities of Niacinamide
2.1. NAD+-Dependent Enzyme Regulation by Niacinamide
2.2. Antioxidant Activity of Niacinamide
2.3. Anti-Inflammatory Activity of Niacinamide
2.4. Antimicrobial Activity of Niacinamide
2.5. Sebum Production Reduction Activity of Niacinamide
2.6. Skin Anti-Yellowing Activity of Niacinamide
2.7. Skin Lightening Activity of Niacinamide
2.8. Cutaneous Extracellular Matrix and Skin Barrier Enhancement by Niacinamide
2.9. Cutaneous Anti-Aging Activity of Niacinamide
3. Niacinamide Formulation Challenges and Opportunities
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AGE | Advanced glycation end products |
AMP | Antimicrobial peptide |
BCL6 | B-cell lymphoma-6 protein |
DNA | Deoxyribonucleic acid |
ECM | Extracellular matrix |
EMA | European Medicines Agency |
FDA | US Food and Drug Administration |
GRAS | Generally recognized as safe |
HA | Hyaluronic acid |
HCA2 | Hydroxycarboxylic acid receptor 2 |
IL | Interleukins |
MHC | Major histocompatibility complex |
MMP | Matrix metalloproteinases |
MRC-1 | Mannose receptor C-1 |
mRNA | Messenger ribonucleic acid |
NAD+ | Nicotinamide adenine dinucleotide (oxidized) |
NADH | Nicotinamide adenine dinucleotide (reduced) |
NADPH | Nicotinamide adenine dinucleotide phosphate |
NO | Nitric oxide |
NOS | Nitric oxide synthase |
PARP | Poly-(ADP-ribose) polymerase |
PGE2 | Prostaglandin E2 |
ROS | Reactive oxygen species |
SASP | Senescence-associated secretory phenotype |
SIRT | Sirtuin |
TNF-α Tumour necrosis factor alpha | |
US | United States of America |
UV | Ultraviolet |
References
- Aguilera-Méndez, A. The Chemistry and Biochemistry of Niacin (B3); Royal Society of Chemistry: London, UK, 2012; pp. 108–124. [Google Scholar]
- Mattiussi, A.J.; Blais, D. Niacin versus niacinamide. CMAJ 1992, 147, 990–991. [Google Scholar] [PubMed]
- Bissett, D.L.; Miyamoto, K.; Sun, P.; Li, J.; Berge, C.A. Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin. Int. J. Cosmet. Sci. 2004, 26, 231–238. [Google Scholar] [CrossRef] [PubMed]
- Niacin—Health Professional Fact Sheet. Available online: https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/ (accessed on 4 December 2023).
- Jia, H.; Li, X.; Gao, H.; Feng, Z.; Li, X.; Zhao, L.; Jia, X.; Zhang, H.; Liu, J. High doses of nicotinamide prevent oxidative mitochondrial dysfunction in a cellular model and improve motor deficit in a drosophila model of Parkinson’s disease. J. Neurosci. Res. 2008, 86, 2083–2090. [Google Scholar] [CrossRef] [PubMed]
- Boo, Y.C. Mechanistic basis and clinical evidence for the applications of nicotinamide (niacinamide) to control skin aging and pigmentation. Antioxidants 2021, 10, 1315. [Google Scholar] [CrossRef] [PubMed]
- Poljsak, B.; Milisav, I. Vitamin B3 forms as precursors to NAD+: Are they safe? Trends Food Sci. Technol. 2018, 79, 198–203. [Google Scholar] [CrossRef]
- Sabbagh, F.; Kim, B.-S. Ex vivo transdermal delivery of nicotinamide mononucleotide using polyvinyl alcohol microneedles. Polymers 2023, 15, 2031. [Google Scholar] [CrossRef] [PubMed]
- Green, R.G. Subclinical pellagra: Its diagnosis and treatment. Schizophrenia 1970, 2, 70–79. [Google Scholar]
- Kamal, M.; Abbasy, A.A.; Muslemani, A.A.; Bener, A. Effect of nicotinamide on newly diagnosed Type 1 diabetic children. Acta Pharmacol. Sin. 2006, 27, 724–727. [Google Scholar] [CrossRef] [PubMed]
- Jonas, W.B.; Rapoza, C.P.; Blair, W.F. The effect of niacinamide on osteoarthritis: A pilot study. Inflamm. Res. 1996, 45, 330–334. [Google Scholar] [CrossRef]
- Cosmetic Ingredient Review Expert Panel. Final report of the safety assessment of niacinamide and niacin. Int. J. Toxicol. 2005, 24, 1–31. [Google Scholar] [CrossRef]
- Kamat, J.P.; Devasagayam, T.P.A. Nicotinamide (Vitamin B3) as an effective antioxidant against oxidative damage in rat brain mitochondria. Redox Rep. 1999, 4, 179–184. [Google Scholar] [CrossRef] [PubMed]
- Levin, J.; Momin, S.B. How much do we really know about our favorite cosmeceutical ingredients? J. Clin. Aesthet. Dermatol. 2010, 3, 22–41. [Google Scholar] [PubMed]
- Kligman, D. Cosmeceuticals. Dermatol. Clin. 2000, 18, 609–615. [Google Scholar] [CrossRef] [PubMed]
- Rolfe, H.M. A review of nicotinamide: Treatment of skin diseases and potential side effects. J. Cosmet. Dermatol. 2014, 13, 324–328. [Google Scholar] [CrossRef] [PubMed]
- Qian, H.; Shan, Y.; Gong, R.; Lin, D.; Zhang, M.; Wang, C.; Wang, L. Mechanism of action and therapeutic effects of oxidative stress and stem cell-based materials in skin aging: Current evidence and future perspectives. Front. Bioeng. Biotechnol. 2023, 10, 1082403. [Google Scholar] [CrossRef]
- Silva, S.; Ferreira, M.; Oliveira, A.S.; Magalhães, C.; Sousa, M.E.; Pinto, M.; Sousa Lobo, J.M.; Almeida, I.F. Evolution of the use of antioxidants in anti-ageing cosmetics. Int. J. Cosmet. Sci. 2019, 41, 378–386. [Google Scholar] [CrossRef] [PubMed]
- Wątroba, M.; Szukiewicz, D. The role of sirtuins in aging and age-related diseases. Adv. Med. Sci. 2016, 61, 52–62. [Google Scholar] [CrossRef]
- Guan, X.; Lin, P.; Knoll, E.; Chakrabarti, R. Mechanism of inhibition of the human sirtuin enzyme SIRT3 by nicotinamide: Computational and experimental studies. PLoS ONE 2014, 9, e107729. [Google Scholar] [CrossRef] [PubMed]
- Lin, L.; Wen, S.; Guo, S.; Su, X.; Wu, H.; Chong, L.; Zhang, H.; Zhang, W.; Li, C. Role of SIRT1 in Streptococcus pneumoniae-induced human β-defensin-2 and interleukin-8 expression in A549 cell. Mol. Cell. Biochem. 2014, 394, 199–208. [Google Scholar] [CrossRef]
- Bitterman, K.J.; Anderson, R.M.; Cohen, H.Y.; Latorre-Esteves, M.; Sinclair, D.A. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1. J. Biol. Chem. 2002, 277, 45099–45107. [Google Scholar] [CrossRef]
- Scatozza, F.; Moschella, F.; D’Arcangelo, D.; Rossi, S.; Tabolacci, C.; Giampietri, C.; Proietti, E.; Facchiano, F.; Facchiano, A. Nicotinamide inhibits melanoma in vitro and in vivo. J. Exp. Clin. Cancer Res. 2020, 39, 211. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Peterson, L.M.; Wilking-Busch, M.J.; Ndiaye, M.A.; Philippe, C.G.A.; Setaluri, V.; Ahmad, N. Sirtuins in skin and skin cancers. Skin Pharmacol. Physiol. 2017, 30, 216–224. [Google Scholar] [CrossRef]
- Kammeyer, A.; Luiten, R.M. Oxidation events and skin aging. Ageing Res. Rev. 2015, 21, 16–29. [Google Scholar] [CrossRef]
- Chen, A.C.; Martin, A.J.; Choy, B.; Fernández-Peñas, P.; Dalziell, R.A.; McKenzie, C.A.; Scolyer, R.A.; Dhillon, H.M.; Vardy, J.L.; Kricker, A.; et al. A Phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N. Engl. J. Med. 2015, 373, 1618–1626. [Google Scholar] [CrossRef]
- Imai, S.; Guarente, L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech. Dis. 2016, 2, 16017. [Google Scholar] [CrossRef]
- Yanez, M.; Jhanji, M.; Murphy, K.; Gower, R.M.; Sajish, M.; Jabbarzadeh, E. Nicotinamide augments the anti-inflammatory properties of resveratrol through PARP1 activation. Sci. Rep. 2019, 9, 10219. [Google Scholar] [CrossRef] [PubMed]
- Surjana, D.; Halliday, G.M.; Damian, D.L. Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. J. Nucl. Acids 2010, 2010, e157591. [Google Scholar] [CrossRef] [PubMed]
- Benavente, C.A.; Jacobson, E.L. Niacin restriction upregulates NADPH oxidase and reactive oxygen species (ROS) in human keratinocytes. Free Radic. Biol. Med. 2008, 44, 527–537. [Google Scholar] [CrossRef]
- Burkart, V.; Koike, T.; Brenner, H.-H.; Kolb, H. Oxygen radicals generated by the enzyme xanthine oxidase lyse rat pancreatic islet cells in vitro. Diabetologia 1992, 35, 1028–1034. [Google Scholar] [CrossRef]
- Tan, C.Y.R.; Tan, C.L.; Chin, T.; Morenc, M.; Ho, C.Y.; Rovito, H.A.; Quek, L.S.; Soon, A.L.; Lim, J.S.Y.; Dreesen, O.; et al. Nicotinamide prevents UVB- and oxidative stress–induced photoaging in human primary keratinocytes. J. Investig. Dermatol. 2022, 142, 1670–1681. [Google Scholar] [CrossRef]
- Wang, Y.; Pleasure, D.; Deng, W.; Guo, F. Therapeutic potentials of poly (ADP-Ribose) polymerase 1 (PARP1) inhibition in multiple sclerosis and animal models: Concept revisiting. Adv. Sci. 2022, 9, 2102853. [Google Scholar] [CrossRef] [PubMed]
- Zhen, A.X.; Piao, M.J.; Kang, K.A.; Fernando, P.D.S.M.; Kang, H.K.; Koh, Y.S.; Yi, J.M.; Hyun, J.W. Niacinamide protects skin cells from oxidative stress induced by particulate matter. Biomol. Ther. 2019, 27, 562–569. [Google Scholar] [CrossRef] [PubMed]
- Sousa, F.G.; Matuo, R.; Soares, D.G.; Escargueil, A.E.; Henriques, J.A.P.; Larsen, A.K.; Saffi, J. PARPs and the DNA damage response. Carcinogenesis 2012, 33, 1433–1440. [Google Scholar] [CrossRef] [PubMed]
- Surjana, D.; Halliday, G.M.; Damian, D.L. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis 2013, 34, 1144–1149. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.E.; Cho, D.; Park, H.J. Air pollution and skin diseases: Adverse effects of airborne particulate matter on various skin diseases. Life Sci. 2016, 152, 126–134. [Google Scholar] [CrossRef] [PubMed]
- Magnani, N.D.; Muresan, X.M.; Belmonte, G.; Cervellati, F.; Sticozzi, C.; Pecorelli, A.; Miracco, C.; Marchini, T.; Evelson, P.; Valacchi, G. Skin damage mechanisms related to airborne particulate matter exposure. Toxicol. Sci. 2016, 149, 227–236. [Google Scholar] [CrossRef] [PubMed]
- Nakai, K.; Tsuruta, D. What are reactive oxygen species, free radicals, and oxidative stress in skin diseases? Int. J. Mol. Sci. 2021, 22, 10799. [Google Scholar] [CrossRef] [PubMed]
- Papaccio, G.; Ammendola, E.; Pisanti, F.A. Nicotinamide decreases MHC class II but not MHC class I expression and increases intercellular adhesion molecule-1 structures in non-obese diabetic mouse pancreas. J. Endocrinol. 1999, 160, 389–400. [Google Scholar] [CrossRef]
- Andrade, J.; Ramírez, R.; Conde, M.; Sobrino, F.; Bedoya, F.J. Nicotinamide inhibits inducible nitric oxide synthase enzyme activity in macrophages by allowing nitric oxide to inhibit its own formation. Life Sci. 1997, 61, 1843–1850. [Google Scholar] [CrossRef]
- Su, C.-F.; Liu, D.D.; Kao, S.J.; Chen, H.I. Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion. Eur. Respir. J. 2007, 30, 199–204. [Google Scholar] [CrossRef]
- Fujimura, M.; Tominaga, T.; Yoshimoto, T. Nicotinamide inhibits inducible nitric oxide synthase mRNA in primary rat glial cells. Neurosci. Lett. 1997, 228, 107–110. [Google Scholar] [CrossRef]
- Duan, D.; Yang, S.; Shao, Z.; Wang, H.; Xiong, X. Protective effect of niacinamide on interleukin-1β-induced annulus fibrosus type II collagen degeneration in vitro. J. Huazhong Univ. Sci. Technol. 2007, 27, 68–71. [Google Scholar] [CrossRef] [PubMed]
- Nadzhimutdinov, K.N.; Mavlianov, I.R.; Umarov, E.F.; Mutalov, N.K. The effect of alpha-tocopherol and nicotinamide on lipid peroxidation and the activity of the antioxidant system in the lung tissue of premature rat pups. Eksperimental Naia Klin. Farmakol. 1993, 56, 28–30. [Google Scholar]
- Shin, M.H.; Rhie, G.; Kim, Y.K.; Park, C.-H.; Cho, K.H.; Kim, K.H.; Eun, H.C.; Chung, J.H. H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged human skin in vivo. J. Gen. Int. Med. 2005, 20, 221–229. [Google Scholar] [CrossRef] [PubMed]
- Ogata, S.; Takeuchi, M.; Teradaira, S.; Yamamoto, N.; Iwata, K.; Okumura, K.; Taguchi, H. Radical scavenging activities of niacin-related compounds. Biosci. Biotechnol. Biochem. 2002, 66, 641–645. [Google Scholar] [CrossRef] [PubMed]
- Velykyĭ, M.M.; Burda, V.A.; Biront, N.V.; Oliiarnyk, O.D.; Velykyĭ, A.M. The effect of nicotinamide on the enzymatic activity of the antioxidant defense in experimental diabetes. Ukr. Biokhimicheskii Zhurnal 1996, 68, 109–114. [Google Scholar]
- Rehman, I.U.; Ahmad, R.; Khan, I.; Lee, H.J.; Park, J.; Ullah, R.; Choi, M.J.; Kang, H.Y.; Kim, M.O. Nicotinamide ameliorates amyloid beta-induced oxidative stress-mediated neuroinflammation and neurodegeneration in adult mouse brain. Biomedicines 2021, 9, 408. [Google Scholar] [CrossRef] [PubMed]
- Khodaeiani, E.; Fouladi, R.F.; Amirnia, M.; Saeidi, M.; Karimi, E.R. Topical 4% nicotinamide vs. 1% clindamycin in moderate inflammatory acne vulgaris. Int. J. Dermatol. 2013, 52, 999–1004. [Google Scholar] [CrossRef]
- Shalita, A.R.; Smith, J.G.; Parish, L.C.; Sofman, M.S.; Chalker, D.K. Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. Int. J. Dermatol. 1995, 34, 434–437. [Google Scholar] [CrossRef]
- Emanuele, E.; Bertona, M.; Altabas, K.; Altabas, V.; Alessandrini, G. Anti-inflammatory effects of a topical preparation containing nicotinamide, retinol, and 7-dehydrocholesterol in patients with acne: A gene expression study. Clin. Cosmet. Investig. Dermatol. 2012, 5, 33–37. [Google Scholar] [CrossRef]
- Villeda-González, J.D.; Gómez-Olivares, J.L.; Baiza-Gutman, L.A.; Manuel-Apolinar, L.; Damasio-Santana, L.; Millán-Pacheco, C.; Ángeles-Mejía, S.; Cortés-Ginez, M.C.; Cruz-López, M.; Vidal-Moreno, C.J.; et al. Nicotinamide reduces inflammation and oxidative stress via the cholinergic system in fructose-induced metabolic syndrome in rats. Life Sci. 2020, 250, 117585. [Google Scholar] [CrossRef] [PubMed]
- Kang, K.; Sun, Y.; Pan, D.; Chang, B.; Sang, L.-X. Nicotinamide ameliorates dextran sulfate sodium-induced chronic colitis in mice through its anti-inflammatory properties and modulates the gut microbiota. J. Immunol. Res. 2021, 2021, e5084713. [Google Scholar] [CrossRef] [PubMed]
- Godin, A.M.; Ferreira, W.C.; Rocha, L.T.S.; Seniuk, J.G.T.; Paiva, A.L.L.; Merlo, L.A.; Nascimento, E.B.; Bastos, L.F.S.; Coelho, M.M. Antinociceptive and anti-inflammatory activities of nicotinamide and its isomers in different experimental models. Pharmacol. Biochem. Behav. 2011, 99, 782–788. [Google Scholar] [CrossRef] [PubMed]
- Biedroń, R.; Ciszek, M.; Tokarczyk, M.; Bobek, M.; Kurnyta, M.; Słominska, E.M.; Smoleński, R.T.; Marcinkiewicz, J. 1-Methylnicotinamide and nicotinamide: Two related anti-inflammatory agents that differentially affect the functions of activated macrophages. Arch. Immunol. Ther. Exp. 2008, 56, 127–134. [Google Scholar] [CrossRef] [PubMed]
- Sánchez-Fidalgo, S.; Villegas, I.; Martín, A.; Sánchez-Hidalgo, M.; Alarcón de la Lastra, C. PARP inhibition reduces acute colonic inflammation in rats. Eur. J. Pharmacol. 2007, 563, 216–223. [Google Scholar] [CrossRef] [PubMed]
- Ungerstedt, J.S.; Blombäck, M.; Söderström, T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin. Exp. Immunol. 2003, 131, 48–52. [Google Scholar] [CrossRef] [PubMed]
- Pero, R.W.; Axelsson, B.; Siemann, D.; Chaplin, D.; Dougherty, G. Newly discovered anti-inflammatory properties of the benzamides and nicotinamides. Mol. Cell. Biochem. 1999, 193, 119–125. [Google Scholar] [CrossRef] [PubMed]
- Otsuka, A.; Hanafusa, T.; Miyagawa, J.-I.; Kono, N.; Tarui, S. Nicotinamide and 3-aminobenzamide reduce interferon-γ -induced class II MHC (HLA-DR and -DP) molecule expression on cultured human endothelial cells and fibroblasts. Immunopharmacol. Immunotoxicol. 1991, 13, 263–280. [Google Scholar] [CrossRef]
- Coppé, J.-P.; Desprez, P.-Y.; Krtolica, A.; Campisi, J. The senescence-associated secretory phenotype: The dark side of tumor suppression. Ann. Rev. Pathol. Mech. Dis. 2010, 5, 99–118. [Google Scholar] [CrossRef]
- Bierman, J.C.; Laughlin, T.; Tamura, M.; Hulette, B.C.; Mack, C.E.; Sherrill, J.D.; Tan, C.Y.R.; Morenc, M.; Bellanger, S.; Oblong, J.E. Niacinamide mitigates SASP-related inflammation induced by environmental stressors in human epidermal keratinocytes and skin. Int. J. Cosmet. Sci. 2020, 42, 501–511. [Google Scholar] [CrossRef]
- Bains, P.; Kaur, M.; Kaur, J.; Sharma, S. Nicotinamide: Mechanism of action and indications in dermatology. Indian J. Dermatol. Venereol. Leprol. 2018, 84, 234. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.-W.; Ryoo, G.-H.; Jang, H.-Y.; Rah, S.-Y.; Lee, D.H.; Kim, D.-K.; Bae, E.J.; Park, B.-H. NAD+-boosting molecules suppress mast cell degranulation and anaphylactic responses in mice. Theranostics 2022, 12, 3316–3328. [Google Scholar] [CrossRef]
- Chang, T.-M.; Yang, T.-Y.; Huang, H.-C. Nicotinamide mononucleotide and coenzyme Q10 protects fibroblast senescence induced by particulate matter preconditioned mast cells. Int. J. Mol. Sci. 2022, 23, 7539. [Google Scholar] [CrossRef] [PubMed]
- Namazi, M.R.; Fallahzadeh, M.K.; Roozbeh, J. Nicotinamide as a potential novel addition to the anti-uremic pruritus weaponry. Saudi J. Kidney Dis. Transplant. 2009, 20, 291–292. [Google Scholar] [PubMed]
- Smith, I.; Burmeister, L. Biochemically assisted antibiotic treatment of lethal murine Staphylococcus aureus septic shock. Am. J. Clin. Nutr. 1977, 30, 1364–1368. [Google Scholar] [CrossRef]
- Mathapathi, M.S.; Mallemalla, P.; Vora, S.; Iyer, V.; Tiwari, J.K.; Chakrabortty, A.; Majumdar, A. Niacinamide leave-on formulation provides long-lasting protection against bacteria in vivo. Exp. Dermatol. 2017, 26, 827–829. [Google Scholar] [CrossRef] [PubMed]
- Yan, Y.; Liao, Z.; Shen, J.; Zhu, Z.; Cao, Y. Nicotinamide potentiates amphotericin B activity against Candida albicans. Virulence 2022, 13, 1533–1542. [Google Scholar] [CrossRef] [PubMed]
- Lin, Y.; Gong, T.; Ma, Q.; Jing, M.; Zheng, T.; Yan, J.; Chen, J.; Pan, Y.; Sun, Q.; Zhou, X.; et al. Nicotinamide could reduce growth and cariogenic virulence of Streptococcus mutans. J. Oral Microbiol. 2022, 14, 2056291. [Google Scholar] [CrossRef] [PubMed]
- Shih, Y.-H.; Liu, D.; Chen, Y.-C.; Liao, M.-H.; Lee, W.-R.; Shen, S.-C. Activation of deoxyribonuclease I by nicotinamide as a new strategy to attenuate tetracycline-resistant biofilms of Cutibacterium acnes. Pharmaceutics 2021, 13, 819. [Google Scholar] [CrossRef]
- Dos, S.K.; Barbhuiya, J.N.; Jana, S.; Dey, S.K. Comparative evaluation of clindamycin phosphate 1% and clindamycin phosphate 1% with nicotinamide gel 4% in the treatment of acne vulgaris. Indian J. Dermatol. Venereol. Leprol. 2003, 69, 8. [Google Scholar]
- Sardesai, V.R.; Kambli, V.M. Comparison of efficacy of topical clindamycin and nicotinamide combination with plain clindamycin for the treatment of acne vulgaris and acne resistant to topical antibiotics. Indian J. Dermatol. Venereol. Leprol. 2003, 69, 138. [Google Scholar] [PubMed]
- Draelos, Z.D.; Matsubara, A.; Smiles, K. The effect of 2% niacinamide on facial sebum production. J. Cosmet. Laser Ther. 2006, 8, 96–101. [Google Scholar] [CrossRef] [PubMed]
- Bettenworth, D.; Nowacki, T.M.; Ross, M.; Kyme, P.; Schwammbach, D.; Kerstiens, L.; Thoennissen, G.B.; Bokemeyer, C.; Hengst, K.; Berdel, W.E.; et al. Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance. Mol. Nutr. Food Res. 2014, 58, 1474–1490. [Google Scholar] [CrossRef] [PubMed]
- Kenshi, Y.; Richard, L.G. Antimicrobial peptides in human skin disease. Eur. J. Dermatol. 2008, 18, 11–21. [Google Scholar] [CrossRef]
- Losasso, V.; Agarwal, K.; Waskar, M.; Majumdar, A.; Crain, J.; Winn, M.; Hoptroff, M. Small molecules enhance the potency of natural antimicrobial peptides. Biophys. J. 2022, 121, 491–501. [Google Scholar] [CrossRef]
- Hashimoto, T.; Perlot, T.; Rehman, A.; Trichereau, J.; Ishiguro, H.; Paolino, M.; Sigl, V.; Hanada, T.; Hanada, R.; Lipinski, S.; et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012, 487, 477–481. [Google Scholar] [CrossRef]
- Bhatt, T.; Dam, B.; Khedkar, S.U.; Lall, S.; Pandey, S.; Kataria, S.; Ajnabi, J.; Gulzar, S.-E.-J.; Dias, P.M.; Waskar, M.; et al. Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption. Front. Immunol. 2023, 14, 1255478. [Google Scholar] [CrossRef] [PubMed]
- Kyme, P.; Thoennissen, N.H.; Tseng, C.W.; Thoennissen, G.B.; Wolf, A.J.; Shimada, K.; Krug, U.O.; Lee, K.; Müller-Tidow, C.; Berdel, W.E.; et al. C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice. J. Clin. Investig. 2012, 122, 3316–3329. [Google Scholar] [CrossRef] [PubMed]
- Rosales, C. Neutrophil: A cell with many roles in inflammation or several cell types? Front. Physiol. 2018, 9, 113. [Google Scholar] [CrossRef]
- Nakagome, K.; Matsushita, S.; Nagata, M. Neutrophilic inflammation in severe asthma. Int. Arch. Allergy Immunol. 2012, 158, 96–102. [Google Scholar] [CrossRef]
- Suh, D.H.; Kwon, H.H. What’s new in the physiopathology of acne? Br. J. Dermatol. 2015, 172, 13–19. [Google Scholar] [CrossRef] [PubMed]
- Araviiskaia, E.; Dréno, B. The role of topical dermocosmetics in acne vulgaris. J. Eur. Acad. Dermatol. Venereol. 2016, 30, 926–935. [Google Scholar] [CrossRef] [PubMed]
- Gabarra Almeida Leite, M.; Berardo Gonçalves Maia Campos, P.M. Clinical efficacy of a cosmetic formulation with vitamin B3 for the treatment of oily skin. Biomed. Biopharm. Res. 2022, 18, 126. [Google Scholar] [CrossRef]
- Kaewsanit, T.; Chakkavittumrong, P.; Waranuch, N. Clinical comparison of topical 2.5% benzoyl peroxide plus 5% niacinamide to 2.5% benzoyl peroxide alone in the treatment of mild to moderate facial acne vulgaris. J. Clin. Aesthet. Dermatol. 2021, 14, 35–41. [Google Scholar] [PubMed]
- Kozlowska, J.; Kaczmarkiewicz, A.; Stachowiak, N.; Sionkowska, A. Evaluation of sebostatic activity of Juniperus communis fruit oil and Pelargonium graveolens oil compared to niacinamide. Cosmetics 2017, 4, 36. [Google Scholar] [CrossRef]
- Shahmoradi, Z.; Iraji, F.; Siadat, A.H.; Ghorbaini, A. Comparison of topical 5% nicotinamid gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris: A double-blinded randomized clinical trial. J. Res. Med. Sci. 2013, 18, 115–117. [Google Scholar] [PubMed]
- Markovics, A.; Tóth, K.F.; Sós, K.E.; Magi, J.; Gyöngyösi, A.; Benyó, Z.; Zouboulis, C.C.; Bíró, T.; Oláh, A. Nicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA2). J. Cell. Mol. Med. 2019, 23, 6203–6214. [Google Scholar] [CrossRef] [PubMed]
- Wise, A.; Foord, S.M.; Fraser, N.J.; Barnes, A.A.; Elshourbagy, N.; Eilert, M.; Ignar, D.M.; Murdock, P.R.; Steplewski, K.; Green, A.; et al. Molecular identification of high and low affinity receptors for nicotinic acid. J. Biol. Chem. 2003, 278, 9869–9874. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.; Zhang, J.-Q.; Li, L.; Guo, M.; He, Y.; Dong, Y.; Meng, H.; Yi, F. Advanced glycation end products in the skin: Molecular mechanisms, methods of measurement, and inhibitory pathways. Front. Med. 2022, 9, 837222. [Google Scholar] [CrossRef]
- Zheng, W.; Li, H.; Go, Y.; Chan, X.H.; Huang, Q.; Wu, J. Research advances on the damage mechanism of skin glycation and related inhibitors. Nutrients 2022, 14, 4588. [Google Scholar] [CrossRef]
- Sourris, K.C.; Watson, A.; Jandeleit-Dahm, K. Inhibitors of advanced glycation end product (AGE) formation and accumulation. Handb. Exp. Pharmacol. 2021, 264, 395–423. [Google Scholar] [CrossRef] [PubMed]
- Bissett, D.L.; Oblong, J.E.; Berge, C.A. Niacinamide: A B Vitamin that improves aging facial skin appearance. Dermatol. Surg. 2005, 31, 860–866. [Google Scholar] [CrossRef]
- Kim, H.J.; Kazi, J.U.; Lee, Y.-R.; Nguyen, D.H.; Lee, H.-B.; Shin, J.-H.; Soh, J.-W.; Kim, E.-K. Visualization of the melanosome transfer-inhibition in a mouse epidermal cell co-culture model. Int. J. Mol. Med. 2010, 25, 249–253. [Google Scholar] [CrossRef] [PubMed]
- Navarrete-Solís, J.; Castanedo-Cázares, J.P.; Torres-Álvarez, B.; Oros-Ovalle, C.; Fuentes-Ahumada, C.; González, F.J.; Martínez-Ramírez, J.D.; Moncada, B. A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. Dermatol. Res. Pract. 2011, 2011, e379173. [Google Scholar] [CrossRef]
- Resende, D.I.S.P.; Ferreira, M.S.; Lobo, J.M.S.; Sousa, E.; Almeida, I.F. Skin depigmenting agents in anti-aging cosmetics: A medicinal perspective on emerging ingredients. Appl. Sci. 2022, 12, 775. [Google Scholar] [CrossRef]
- Castanedo-Cazares, J.P.; Lárraga-Piñones, G.; Ehnis-Pérez, A.; Fuentes-Ahumada, C.; Oros-Ovalle, C.; Smoller, B.R.; Torres-Álvarez, B. Topical niacinamide 4% and desonide 0.05% for treatment of axillary hyperpigmentation: A randomized, double-blind, placebo-controlled study. Clin. Cosmet. Investig. Dermatol. 2013, 6, 29–36. [Google Scholar] [CrossRef]
- Hakozaki, T.; Minwalla, L.; Zhuang, J.; Chhoa, M.; Matsubara, A.; Miyamoto, K.; Greatens, A.; Hillebrand, G.G.; Bissett, D.L.; Boissy, R.E. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br. J. Dermatol. 2002, 147, 20–31. [Google Scholar] [CrossRef] [PubMed]
- Virador, V.M.; Kobayashi, N.; Matsunaga, J.; Hearing, V.J. A standardized protocol for assessing regulators of pigmentation. Anal. Biochem. 1999, 270, 207–219. [Google Scholar] [CrossRef]
- Greatens, A.; Hakozaki, T.; Koshoffer, A.; Epstein, H.; Schwemberger, S.; Babcock, G.; Bissett, D.; Takiwaki, H.; Arase, S.; Wickett, R.R.; et al. Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversible. Exp. Dermatol. 2005, 14, 498–508. [Google Scholar] [CrossRef]
- Upadhyay, P.R.; Ho, T.; Abdel-Malek, Z.A. Participation of keratinocyte- and fibroblast-derived factors in melanocyte homeostasis, the response to UV, and pigmentary disorders. Pigment Cell Melanoma Res. 2021, 34, 762–776. [Google Scholar] [CrossRef]
- Ahn, K.S.; Moon, K.-Y.; Lee, J.; Kim, Y.S. Downregulation of NF-κB activation in human keratinocytes by melanogenic inhibitors. J. Dermatol. Sci. 2003, 31, 193–201. [Google Scholar] [CrossRef] [PubMed]
- Tzaphlidou, M. The role of collagen and elastin in aged skin: An image processing approach. Micron 2004, 35, 173–177. [Google Scholar] [CrossRef] [PubMed]
- Ansel, J.; Perry, P.; Brown, J.; Damm, D.; Phan, T.; Hart, C.; Luger, T.; Hefeneider, S. Cytokine modulation of keratinocyte cytokines. J. Investig. Dermatol. 1990, 94, s101–s107. [Google Scholar] [CrossRef] [PubMed]
- Osborne, R.; Carver, R.S.; Mullins, L.A.; Finlay, D.R. Practical application of cellular bioenergetics to the care of aged skin. Br. J. Dermatol. 2013, 169, 32–38. [Google Scholar] [CrossRef]
- Philips, N.; Chalensouk-Khaosaat, J.; Gonzalez, S. Stimulation of the fibrillar collagen and heat shock proteins by nicotinamide or its derivatives in non-irradiated or UVA radiated fibroblasts, and direct anti-oxidant activity of nicotinamide derivatives. Cosmetics 2015, 2, 146–161. [Google Scholar] [CrossRef]
- Bansode, S.; Bashtanova, U.; Li, R.; Clark, J.; Müller, K.H.; Puszkarska, A.; Goldberga, I.; Chetwood, H.H.; Reid, D.G.; Colwell, L.J.; et al. Glycation changes molecular organization and charge distribution in type I collagen fibrils. Sci. Rep. 2020, 10, 3397. [Google Scholar] [CrossRef] [PubMed]
- Tanno, O.; Ota, Y.; Kitamura, N.; Katsube, T.; Inoue, S. Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. Br. J. Dermatol. 2000, 143, 524–531. [Google Scholar] [CrossRef] [PubMed]
- Tanno, O.; Ota, Y.; Kitamura, N.; Inoue, S. Effects of niacinamide on ceramide biosynthesis and differentiation of cultured human keratinocytes. J. Investig. Dermatol. 1997, 4, 643. [Google Scholar]
- Rittié, L.; Fisher, G.J. Natural and sun-induced aging of human skin. Cold Spring Harb. Perspect. Med. 2015, 5, a015370. [Google Scholar] [CrossRef]
- Fisher, G.J.; Kang, S.; Varani, J.; Bata-Csorgo, Z.; Wan, Y.; Datta, S.; Voorhees, J.J. Mechanisms of photoaging and chronological skin aging. Arch. Dermatol. 2002, 138, 1462–1470. [Google Scholar] [CrossRef]
- Sivapirabu, G.; Yiasemides, E.; Halliday, G.M.; Park, J.; Damian, D.L. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans. Br. J. Dermatol. 2009, 161, 1357–1364. [Google Scholar] [CrossRef] [PubMed]
- Wertz, P.W. Epidermal lipids and formation of the barrier of the skin. In Dry Skin and Moisturizers; CRC Press: Boca Raton, FL, USA, 2006. [Google Scholar]
- Sohn, J.S.; Choi, J.-S. Development and evaluation of niacinamide transdermal formulation by artificial membrane permeability. Saudi Pharm. J. 2023, 31, 1229–1236. [Google Scholar] [CrossRef] [PubMed]
- Haque, T.; Lane, M.E.; Sil, B.C.; Crowther, J.M.; Moore, D.J. In vitro permeation and disposition of niacinamide in silicone and porcine skin of skin barrier-mimetic formulations. Int. J. Pharm. 2017, 520, 158–162. [Google Scholar] [CrossRef]
- Zhang, Y.; Lane, M.E.; Hadgraft, J.; Heinrich, M.; Chen, T.; Lian, G.; Sinko, B. A comparison of the in vitro permeation of niacinamide in mammalian skin and in the parallel artificial membrane permeation assay (PAMPA) model. Int. J. Pharm. 2019, 556, 142–149. [Google Scholar] [CrossRef]
- Basto, R.; Andrade, R.; Nunes, C.; Lima, S.A.C.; Reis, S. Topical delivery of niacinamide to skin using hybrid nanogels enhances photoprotection effect. Pharmaceutics 2021, 13, 1968. [Google Scholar] [CrossRef] [PubMed]
- Alyoussef, A.; Nasr, M.; Ahmed, R.F.; Ahmed Farid, O.A.H.; Bakeer, R.; Karandikar, H.; Paradkar, A. Nicotinamide extrudates as novel anti-aging and collagen promoting platform: A comparative cosmeceutical study versus the gel form. Pharm. Dev. Technol. 2020, 25, 1139–1149. [Google Scholar] [CrossRef] [PubMed]
- Park, Y.; Kim, K.S.; Chung, M.; Sung, J.H.; Kim, B. Fabrication and characterization of dissolving microneedle arrays for improving skin permeability of cosmetic ingredients. J. Industr. Eng. Chem. 2016, 39, 121–126. [Google Scholar] [CrossRef]
- Lee, S.-Y.; Yun, Y.-H.; Ahn, G.; Yoon, S.-D. Preparation of niacinamide imprinted starch-based biomaterials for treating of hyperpigmentation. Int. J. Biol. Macromol. 2023, 232, 123382. [Google Scholar] [CrossRef]
- Grand-Vincent, A.; Boisnic, S.; Salomon, C.; Prinderre, P.; Piccerelle, P. Clinical assessment of a mesotherapy formulation for skin rejuvenation in healthy volunteers. J. Cosm. Dermatol. Sci. Appl. 2017, 7, 291–305. [Google Scholar] [CrossRef]
- Sivagnanam, G. Mesotherapy—The French connection. J. Pharmacol. Pharmacother. 2010, 1, 4–8. [Google Scholar] [CrossRef]
- Kildegaard, J.; Buckley, S.T.; Nielsen, R.H.; Povlsen, G.K.; Seested, T.; Ribel, U.; Olsen, H.B.; Ludvigsen, S.; Jeppesen, C.B.; Refsgaard, H.H.F.; et al. Elucidating the mechanism of absorption of fast-acting insulin aspart: The role of niacinamide. Pharm. Res. 2019, 36, 49. [Google Scholar] [CrossRef] [PubMed]
- Porcello, A.; Hadjab, F.; Ajouaou, M.; Philippe, V.; Martin, R.; Abdel-Sayed, P.; Hirt-Burri, N.; Scaletta, C.; Raffoul, W.; Applegate, L.A.; et al. Ex vivo functional benchmarking of hyaluronan-based osteoarthritis viscosupplement products: Comprehensive assessment of rheological, lubricative, adhesive, and stability attributes. Gels 2023, 9, 808. [Google Scholar] [CrossRef] [PubMed]
- Micheels, P.; Porcello, A.; Bezzola, T.; Perrenoud, D.; Quinodoz, P.; Kalia, Y.; Allémann, E.; Laurent, A.; Jordan, O. Clinical perspectives on the injectability of cross-linked hyaluronic acid dermal fillers: A standardized methodology for commercial product benchmarking with inter-injector assessments. Gels 2024, 10, 101. [Google Scholar] [CrossRef] [PubMed]
- Zerbinati, N.; Capillo, M.C.; Sommatis, S.; Maccario, C.; Alonci, G.; Rauso, R.; Galadari, H.; Guida, S.; Mocchi, R. Rheological investigation as tool to assess physicochemical stability of a hyaluronic acid dermal filler cross-linked with polyethylene glycol diglycidyl ether and containing calcium hydroxyapatite, glycine and L-proline. Gels 2022, 8, 264. [Google Scholar] [CrossRef]
- Rashid, F.; Albayati, M.; Dodou, K. Novel crosslinked HA hydrogel films for the immediate release of active ingredients. Cosmetics 2023, 10, 6. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Marques, C.; Hadjab, F.; Porcello, A.; Lourenço, K.; Scaletta, C.; Abdel-Sayed, P.; Hirt-Burri, N.; Applegate, L.A.; Laurent, A. Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products. Antioxidants 2024, 13, 425. https://doi.org/10.3390/antiox13040425
Marques C, Hadjab F, Porcello A, Lourenço K, Scaletta C, Abdel-Sayed P, Hirt-Burri N, Applegate LA, Laurent A. Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products. Antioxidants. 2024; 13(4):425. https://doi.org/10.3390/antiox13040425
Chicago/Turabian StyleMarques, Cíntia, Farid Hadjab, Alexandre Porcello, Kelly Lourenço, Corinne Scaletta, Philippe Abdel-Sayed, Nathalie Hirt-Burri, Lee Ann Applegate, and Alexis Laurent. 2024. "Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products" Antioxidants 13, no. 4: 425. https://doi.org/10.3390/antiox13040425