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. 2023 Oct 12;12(10):1849.
doi: 10.3390/antiox12101849.

Nicotinamide Riboside and Phycocyanin Oligopeptides Affect Stress Susceptibility in Chronic Corticosterone-Exposed Rats

Cemal Orhan  1 , Emre Sahin  2 , Mehmet Tuzcu  3 , Nurhan Sahin  1 , Abdullah Celik  1 , Sara Perez Ojalvo  4 , Sarah Sylla  4 , James R Komorowski  4 , Kazim Sahin  1
Affiliations

Nicotinamide Riboside and Phycocyanin Oligopeptides Affect Stress Susceptibility in Chronic Corticosterone-Exposed Rats

Cemal Orhan et al. Antioxidants (Basel). .

Abstract

Nicotinamide riboside (NR) is an NAD+ precursor capable of regulating mammalian cellular metabolism. Phycocyanin oligopeptide (PC), a phytonutrient found in blue-green algae, has antioxidant and anti-inflammatory properties. This study explored the effects of NR, PC, and their combination on the telomere length as well as inflammatory and antioxidant status of rats under chronic stress conditions (CS). Forty-nine rats were allocated into seven groups: control, chronic stress (CS), CS with NR (26.44 mg/kg), a low dose of 2.64 mg/kg of PC (PC-LD), or a high dose of 26.44 mg/kg PC (PC-HD), NR + PC-LD, and NR + PC-HF. The rats were given daily corticosterone injections (40 mg/kg) to induce stress conditions, or NR and PC were orally administered for 21 days. NR and PC supplementation, particularly NR plus PC, increased the serum antioxidant enzyme activities, hepatic nicotinamide adenine (NAD+) content, and telomere length (p < 0.001 for all) compared to the CS group. The levels of serum malondialdehyde (MDA), liver interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), IL-1β, and IL-8 were reduced under the CS condition (p < 0.001). In addition, CS decreased the levels of hepatic telomere-related proteins and sirtuins (SIRT1 and 3), whereas administration of NR and PC or their combination to CS-exposed rats increased the levels of telomere-related proteins (e.g., POT1b, TRF1 and TRF2), SIRT3 and NAMPT (p < 0.05). In conclusion, NR and PC, especially their combination, can alleviate metabolic abnormalities by enhancing hepatic cytokines, SIRT3, NAMPT, and NAD+ levels in CS-exposed rats. More research is needed to further elucidate the potential health effects of the combination of NR and PC in humans.

Keywords: NAD; corticosterone; hepatic metabolism; nicotinamide riboside; phycocyanin.

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Conflict of interest statement

James R. Komorowski, Sara Perez Ojalvo, and Sarah Sylla are employees of Nutrition 21 LLC (Harrison, NY, USA). The remaining authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The experimental design. CS: chronic stress induced with corticosterone; NR: nicotinamide riboside (26.44 mg/kg); PC-LD: Phycocyanin oligopeptide, low dose (2.64 mg/kg); PC-HD: Phycocyanin oligopeptide, high dose (26.44 mg/kg). Rats except those of the control group were given daily corticosterone injections (40 mg/kg) to induce stress conditions or NR and PC were orally administered for 21 days.
Figure 2
Figure 2
Effects of NR and PC oligopeptides on liver relative telomere length in rats subject to chronic corticosterone (CORT). Data are expressed as a relative fold change compared to the control. The error bars above the lines indicate the standard deviation of the mean. Different symbols (a–f) indicate significant differences among the groups (ANOVA and Tukey post hoc test; p < 0.05). CS: chronic stress; NR: Nicotinamide riboside (26.44 mg/kg); PC-LD: Phycocyanin oligopeptide, low dose (2.64 mg/kg); PC-HD: Phycocyanin oligopeptide, high dose (26.44 mg/kg). Rats except those of the control group were given daily corticosterone injections (40 mg/kg) to induce stress conditions, or NR and PC were orally administered for 21 days.
Figure 3
Figure 3
Effects of NR and PC oligopeptides on liver IL-6 (A), TNF-α (B), IL-1β (C), and IL-8 (D) levels in rats subject to chronic corticosterone (CORT). The densitometric analysis of the relative intensity according to the control group of the Western blotting bands was performed with β-actin normalization to ensure equal protein loading (E). Blots were repeated at least three times (n = 3), and a representative blot is shown. Data are expressed as a percent of the control set at 100%. The error bars above the lines indicate the standard deviation of the mean. Different symbols (a–f) indicate significant differences among the groups (ANOVA and Tukey post hoc test; p < 0.05). IL-6, interleukin-6; TNF-α, tumor necrosis factor α; IL-1β, interleukin-1β; IL-8, interleukin-8. CS: chronic stress; NR: Nicotinamide riboside (26.44 mg/kg); PC-LD: Phycocyanin oligopeptide, low dose (2.64 mg/kg); PC-HD: Phycocyanin oligopeptide, high dose (26.44 mg/kg). Rats except those of the control group were given daily corticosterone injections (40 mg/kg) to induce stress conditions, or NR and PC were orally administered for 21 days. Full immunoblots presented in Figure S1.
Figure 4
Figure 4
Effects of NR and PC oligopeptides on liver POT1a (A), POT1b (B), TRF1 (C), TRF2 (D), and Tin2 (E) levels in rats subject to chronic corticosterone (CORT). The densitometric analysis of the relative intensity according to the control group of the Western blotting bands was performed with β-actin normalization to ensure equal protein loading (F). Blots were repeated at least three times (n = 3), and a representative blot is shown. Data are expressed as a percent of the control set at 100%. The error bars above the lines indicate the standard deviation of the mean. Different symbols (a–f) indicate significant differences among the groups (ANOVA and Tukey post hoc test; p < 0.05). POT1a, protection of telomeres protein 1a; POT1b, protection of telomeres protein 1b; TRF1, telomeric repeat-binding factor 1; TRF2, telomeric repeat-binding factor 1; Tin2, TRF1-interacting protein 2. CS: chronic stress; NR: Nicotinamide riboside (26.44 mg/kg); PC-LD: Phycocyanin oligopeptide, low dose (2.64 mg/kg); PC-HD: Phycocyanin oligopeptide, high dose (26.44 mg/kg). Rats except those of the control group were given daily corticosterone injections (40 mg/kg) to induce stress conditions, or NR and PC were orally administered for 21 days. Full immunoblots presented in Figure S2.
Figure 5
Figure 5
Effects of NR and PC oligopeptides on liver SIRT1 (A), SIRT3 (B), and NAMPT (C) levels in rats subject to chronic corticosterone (CORT). The densitometric analysis of the relative intensity according to the control group of the Western blotting bands was performed with β-actin normalization to ensure equal protein loading (D). Blots were repeated at least three times (n = 3), and a representative blot is shown. Data are expressed as a percent of the control set at 100%. The error bars above the lines indicate the standard deviation of the mean. Different symbols (a–e) indicate significant differences among the groups (ANOVA and Tukey post hoc test; p < 0.05). SIRT1, sirtuin 1; SIRT3, sirtuin 3; NAMPT, nicotinamide phosphoribosyltransferase. CS: chronic stress; NR: Nicotinamide riboside (26.44 mg/kg); PC-LD: Phycocyanin oligopeptide, low dose (2.64 mg/kg); PC-HD: Phycocyanin oligopeptide, high dose (26.44 mg/kg). Rats except those of the control group were given daily corticosterone injections (40 mg/kg) to induce stress conditions, or NR and PC were orally administered for 21 days. Full immunoblots presented in Figure S3.
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