J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Review

Volume 29, March 2025, pages 1-12

Phytochemistry, biological function and metabolism of Seleno-flavonoids

Figure 1. Food sources of flavonoids. Flavonols: Primarily found in vegetables and fruits such as broccoli, onions, apples, grapes, and berries. Flavones: Concentrated in herbs, celery, and bell peppers. Flavanones: Characteristic of citrus fruits like oranges, lemons, and grapefruits. Flavanols: Abundant in tea. Anthocyanidins: Grape skins, peanut skins, and pine bark. Isoflavones: Primarily found in legumes.

Figure 3. Metabolic pathways of selenium compounds in biological systems. Abbreviations: SeCys (selenocysteine) - an organic selenium-containing amino acid released during selenoprotein catabolism; SeMet (selenomethionine) - an organic selenium compound that can follow multiple metabolic pathways; GGSMC (γ-glutamyl-Se-methylselenocysteine) - a dipeptide form of selenium that undergoes hydrolysis; SMC (Se-methylselenocysteine) - an organic selenium compound that can be directly converted to methylselenol; H₂Se (hydrogen selenide) - the central metabolic intermediate in selenium metabolism; β-lyase (beta-lyase) - an enzyme that catalyzes the conversion of selenium compounds to methylselenol; γ-glutamyl transpeptidase - an enzyme that hydrolyzes GGSMC to release SMC. The diagram depicts two primary metabolic fates: under normal selenium levels (indicated by red arrow), H₂Se is primarily directed toward selenocysteinyl-tRNA for selenoprotein synthesis; under excess selenium conditions (indicated by red arrow), detoxification pathways are activated, leading to the formation of methylated selenium compounds (methylselenol, dimethylselenide, and trimethylselonium) that are subsequently excreted. Blue arrows represent metabolic conversion pathways between compounds. The protein pool represents the non-specific incorporation of SeMet into proteins and its subsequent release through protein degradation, an important selenium recycling mechanism.

**Table 1.** Recommended daily intake of selenium (Kipp et al., 2015).
No.	Age	Selenium (μg/day)
1	0-4 months	10	10
2	4 months-4 years	15	15
3	4 years-7 years	20	20
4	7 years-10 years	30	30
5	10 years-13 years	45	45
6	13 years-15 years	60	60
7	15 years+	70	60
8	Pregnancy	–	60
9	Lactation	–	75

Table 1. Recommended daily intake of selenium (Kipp et al., 2015).

No.

Age

Selenium (μg/day)

Male

Female

0-4 months

4 months-4 years

4 years-7 years

7 years-10 years

10 years-13 years

13 years-15 years

15 years+

Pregnancy

–

Lactation

–

**Table 2.** Summary of SeFs mechanisms of action across different biological systems
Biological Activity	Representative SeFs	Key Mechanisms of Action
Anti-inflammatory and Antioxidant Activities	Se-enriched rice grass extract (flavone glycosides, tricin, swertisin); Selenoauraptene; Se-enriched mung bean fermentation broth	(1) Inhibition of NF-κβ pathway and subsequent reduction of iNOS and COX-2 expression; (2) GPx-mimetic activity enhancing cellular redox statu; (3) Direct radical scavenging properties; (4) Modulation of MAPK and PI3K-Akt signaling pathways; (5) Suppression of inflammatory mediator production
Neuroprotective Effects	Se-Rutin; Se-EGCG; Se-enriched tea extracts; Resveratrol-selenium nanoparticles (RSV-SeNPs)	(1) Upregulation of Nrf2/HO-1 pathway protecting against oxidative stress; (2) Prevention of β-amyloid aggregation and fibril formation; (3) Modulation of Sirt1/miRNA-134/GSK3β signaling axis; (4) Reduction of neuroinflammation; (5) Restoration of gut microbiota homeostasis; (6) Preservation of mitochondrial function
Regulation of Glucose and Lipid Metabolism	Mulberry-kudzu-Se nanoparticles (MPE-SeNPs); Luteolin-loaded Se nanoparticles (LT-SeNPs); Rutin-Se nanoparticles	(1) Enhancement of insulin sensitivity; (2) Improvement of intestinal permeability and nutrient transport.; (3) Modulation of Nrf2/ARE pathway and inhibition of NLRP3 inflammasome; (4) Upregulation of Nrf-2/HO-1 and downregulation of Jak-2/Stat3 signaling; (5) Protection against diabetes-induced organ damage
Antitumor Effects	SeNPs-quercetin; Se-enriched tea extract; SeNPs-apigenin; SePQue; SeChry; ACM-SSe-BE (Se-baicalein nanoparticles)	(1) Modulation of p53/β-catenin/cyclin D axis; (2) Induction of G2/M phase cell cycle arrest; (3) Regulation of apoptotic proteins (Bcl-2/Bax/Caspase-3); (4) TrxR inhibition; (5) Disruption of mitochondrial membrane potential; (6) Modulation of multiple metabolic pathways (glycolysis, TCA cycle); (7) Systematic reduction of SOD activity with concurrent increase in ROS levels
Impact on Bone Metabolism	Silibinin-selenium (SSe)	(1) Reduction of oxidative stress in bone microenvironment; (2) Upregulation of osteogenic proteins (SIRT1, SOD2, RUNX-2, OC); (3) Enhancement of bone mineralization; (4) Promotion of bone regeneration

Table 2. Summary of SeFs mechanisms of action across different biological systems

Biological Activity

Representative SeFs

Key Mechanisms of Action

Anti-inflammatory and Antioxidant Activities

Se-enriched rice grass extract (flavone glycosides, tricin, swertisin); Selenoauraptene; Se-enriched mung bean fermentation broth

(1) Inhibition of NF-κβ pathway and subsequent reduction of iNOS and COX-2 expression; (2) GPx-mimetic activity enhancing cellular redox statu; (3) Direct radical scavenging properties; (4) Modulation of MAPK and PI3K-Akt signaling pathways; (5) Suppression of inflammatory mediator production

Neuroprotective Effects

Se-Rutin; Se-EGCG; Se-enriched tea extracts; Resveratrol-selenium nanoparticles (RSV-SeNPs)

(1) Upregulation of Nrf2/HO-1 pathway protecting against oxidative stress; (2) Prevention of β-amyloid aggregation and fibril formation; (3) Modulation of Sirt1/miRNA-134/GSK3β signaling axis; (4) Reduction of neuroinflammation; (5) Restoration of gut microbiota homeostasis; (6) Preservation of mitochondrial function

Regulation of Glucose and Lipid Metabolism

Mulberry-kudzu-Se nanoparticles (MPE-SeNPs); Luteolin-loaded Se nanoparticles (LT-SeNPs); Rutin-Se nanoparticles

(1) Enhancement of insulin sensitivity; (2) Improvement of intestinal permeability and nutrient transport.; (3) Modulation of Nrf2/ARE pathway and inhibition of NLRP3 inflammasome; (4) Upregulation of Nrf-2/HO-1 and downregulation of Jak-2/Stat3 signaling; (5) Protection against diabetes-induced organ damage

Antitumor Effects

SeNPs-quercetin; Se-enriched tea extract; SeNPs-apigenin; SePQue; SeChry; ACM-SSe-BE (Se-baicalein nanoparticles)

(1) Modulation of p53/β-catenin/cyclin D axis; (2) Induction of G2/M phase cell cycle arrest; (3) Regulation of apoptotic proteins (Bcl-2/Bax/Caspase-3); (4) TrxR inhibition; (5) Disruption of mitochondrial membrane potential; (6) Modulation of multiple metabolic pathways (glycolysis, TCA cycle); (7) Systematic reduction of SOD activity with concurrent increase in ROS levels

Impact on Bone Metabolism

Silibinin-selenium (SSe)

(1) Reduction of oxidative stress in bone microenvironment; (2) Upregulation of osteogenic proteins (SIRT1, SOD2, RUNX-2, OC); (3) Enhancement of bone mineralization; (4) Promotion of bone regeneration