Exploration of Foods and Foodomics

Table 3. Betacyanins and their effects on cardiometabolic diseases.

Source	Model: in vitro/in vivo	Dosage/Duration of treatment	Biological effects and mechanisms of action	References
Betacyanin (red beetroot, Beta vulgaris)	Human subjects	3 days, 14 days 114.5 mg/day betacyanins, 15.6 mg/day polyphenols, nitrate 228.5 mg/day	↑ Akkermansia muciniphila, Escherichia coli ↓ Bacteroides fragilis Positive correlations of betacyanins and Bifidobacterium and Coprococcusm Inverse correlation of betacyanins with Ruminococcus and Peptoniphilus ↑ SCFAs (butyric and isobutyric) Total excreted amount of betacyanins positively correlated with contents of (iso)butyric acid, (iso)valeric acid and total SCFAs; (iso)butyric acid and total SCFA contents showed a positive relationship with genera Blautia, Collinsella, Lachnobacterium, and Lactobacillus, but inverse association with Ruminococcus	Wang et al. [170], 2023
Betanin (fresh beetroot juice, Beta vulgaris)	In vivo Wistar rats, high-fat food	20 mg/kg 20 days	↓ Blood glucose levels, insulin and insulin resistance ↓ Liver damage (AST and ALT levels) and hepatic lipid accumulation ↓ Oxidative stress [decreased hepatic MDA, increased superoxidase dismutase, catalase (CAT) and glutathione peroxidase (GPx) activities] ↓ Plasma triglycerides	da Silva et al. [160], 2019
Betanin (pure compound)	In vivo Streptozotocin-induced diabetic animal Sprague-Dawley rats	10, 20 and 40 mg/kg body weight 28 days	↓ Fasting blood glucose concentration ↑ Serum insulin level Improved glucose tolerance test Improved lipid profile and liver enzymes concentrations Improved liver and pancreas histology ↑ AMPK and SIRT1 ↓ NF-κB mRNA expressions	Abedimanesh et al. [163], 2021
Betanin (pure compound)	In vivo Streptozotocin-induced diabetic animal Sprague-Dawley rats	10, 20 and 40 mg/kg body weight 28 days	↑ Total antioxidant capacity level, protein carbonyl and malondialdehyde (MDA) ↑ Activity of hepatic antioxidant enzymes, superoxide dismutase (SOD), CAT, and GPx ↑ Expression of Nrf2, SOD, GPx, and CAT genes	Mousavi et al. [161], 2022
Betanin and neobetanin (red beetroot and yellow prickly pear)	In vitro RAW 264.7 macrophages	10, 50, 100 μM	↓ Inflammatory cytokines mRNA expressions (IL-6, IL-1β, iNOS, and COX-2) ↓ ROS formation ↓ NOX-2 mRNA levels ↑ HO-1 and γGCS mRNA expression ↑ IL-10 mRNA expression	Fernando et al. [165], 2023
Hylocereus undatus peel (white pitaya)	In vivo C57BL/6 mice	50, 100 and 200 mg/kg 14 weeks	↓ High-fat diet induced body weight gain ↓ Adipose tissue hypertrophy ↓ Hepatosteatosis, insulin resistance Improved glucose tolerance ↑ Expression of lipid metabolism related genes (AdipoR2, Cpt1a, Cpt1b, Acox1, PPARγ, Insig1, and Insig2) ↑ Expression of FGF21-related genes (β-Klotho and FGFR1/2) Effects might be due to improved fatty acid oxidation, ↓ fatty acid biosynthesis, ↓ FGF21 resistance	Song et al. [8], 2016
Hylocereus polyrhizus (red pitaya)	In vivo C57BL/6 mice	200 mg/kg 14 weeks	↓ High-fat diet induced body weight gain ↓ Visceral adipose tissue weight ↓ Serum levels of blood lipids ↓ Hepatic steatosis ↓ Size of both white and brown adipocyte ↓ Glucose intolerance and insulin resistance ↓ Inflammatory cytokines (IL6, IL-1β, TNF-α) but ↑ anti-inflammatory cytokine (IL-10) ↓ Firmicutes proportion ↑ Bacteriodetes and Proteobacteria proportions	Song et al. [128], 2016
Hylocereus polyrhizus cv. Jindu (betacyanin and anthocyanins)	In vitro 3T3-L1 cells	0.0625–1.0 mg/mL 24 and 48 h	Both peel and pulp extract had similar total antioxidant activities against H₂O₂-induced oxidative stress on 3T3-L1 cell line Peel extract had inhibitory effects on 3T3-L1 cell lipid accumulation	Khoo et al. [27], 2022
Betanin	In vitro 3T3-L1 cells	10–50 μM of betanin for 72 h (lipid accumulation) 24 h for protein and 6 h for gene expressions	↓ Number of lipid droplets Betanin levels at 10, 25 and 50 μM ↓ lipid accumulation by 19.6%, 26.1% and 32.6%, respectively Betanin levels at 10, 25 and 50 μM ↓ intracellular triglyceride levels in 3T3-L1 adipocytes by 10.5%, 16.6% and 18.1% Suppressed expression of adipogenic genes PPARγ, C/EBPα and SREBP-1c ↓ PPARγ protein expression	Chen et al. [169], 2019
Hylocereus polyrhizus (betalains including betacyanins)	Human subjects (healthy men and women)	Double-blind, randomized controlled crossover trial 24 g of dragon fruit powder containing 33 mg of betalains, 14 days	Both acute and sustained consumption of dragon fruit improved flow-mediated dilation Acute consumption ↓ pulse-wave velocity but not sustained consumption ↓ Heart-rate augmentation index after 14 days No significant changes in blood pressure (central systolic and peripheral diastolic) Only two metabolites were significantly increased in the plasma after consumption of dragon fruit powder	Cheok et al. [167], 2022
Opuntia elatior Mill (red flower prickly pear) Betanin	In vivo Sprague-Dawley rats (STZ-induced)	25, 50, and 100 mg/kg/day 8 weeks	Inhibiting proteinuria ↓ Blood glucose and nephrotoxicity markers (serum creatinine and BUN levels) Restored antioxidant enzymes activities in kidney tissues (↓ TBARS, ↑ SOD, CAT) ↓ Glomerular surface area, glomerulosclerosis, tubulointerstitial fibrosis Modulated mRNA and protein expression of TGF-β, type IV collagen, α-SMA and E-cadherin	Sutariya and Saraf [168], 2017
Opuntia robusta Betacyanin/Betanin	In vivo Wistar rats [diclofenac (DF)-induced acute liver injury model]	Opuntia robusta (OR) fruit extract (800 mg/kg/5 days, orally) (4.45 mg of betanin equivalents) Betanin (25 mg/kg/5 days, orally)	Pretreatment with OR extract and betanin ↓ MDA levels and maintained GSH level OR extract increased Cat, Sod1 expression Betanin ↑ Cat expression OR extract or betanin only ↓ Sod2 expression but DF treatment ↑ Sod2 expression with corresponding treatments OR or betanin ↑ Nrf2 gene expression OR or betanin ↓ Hmox1, Gclc expressions OR or betanin ↓ active caspase-3-positive cells	Villa-Jaimes et al. [162], 2023
Opuntia stricta (Prickly pear cactus) Betalain/Betacyanin	Human subjects (men with coronary artery disease) Randomised, double-blind, crossover trial: 2 weeks each (total duration 10 weeks)	50 mg betacyanin/betalains per day (blood collection 12 h post fasting, 0, 14, 28, 42, 56 and 70 days)	↓ Homocysteine level ↓ Systolic blood pressure ↓ Fasting blood glucose ↓ Non-HDL cholesterol and LDL cholesterol	Rahimi et al. [166], 2019

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↑: increase; ↓: decrease; CAT: catalase; COX-2: cyclooxygenase-2; iNOS: inducible nitric oxide synthase; NF-κB: nuclear factor-kappa B; Nrf2: nuclear factor erythroid 2-related factor 2; ROS: reactive oxygen species; SCFAs: short-chain fatty acids; SIRT1: Sirtuin-1; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BUN: blood urea nitrogen; C/EBPα: CCAAT/enhancer-binding protein alpha; FGF21: fibroblast growth factor 21; FGFR1/2: FGF receptor 1/2; GSH: reduced glutathione; HO-1: heme oxygenase 1; PPARγ: peroxisome proliferator-activated receptor gamma; SREBP-1c: sterol regulatory element-binding protein 1c; TGF-β: transforming growth factor beta; TNF-α: tumor necrosis factor alpha; α-SMA: alpha-smooth muscle actin.

Declarations

Acknowledgments

The authors would like to thank Mr. James Wong Yung Khai and Mr. Luther Ku for their assistance in drawing some of the diagrams in this manuscript. English grammar was improved using the Grammarly application and proofread by Dr. Elvin M. Walemba.

Author contributions

ODJ: Supervision, Project administration, Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing. WGS: Investigation, Visualization, Writing—original draft. APGdS: Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing. SAT: Investigation, Writing—original draft, Writing—review & editing, Validation. CYB: Investigation, Writing—original draft, Writing—review & editing, Validation. RN: Investigation, Writing—original draft, Writing—review & editing, Validation. EMW: Investigation, Writing—original draft, Writing—review & editing, Validation. ATM: Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing, Validation. All authors have read and agreed to the published version of the manuscript.

Conflicts of interest

The authors declare that there are no conflicts of interest.

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