Alzheimer’s disease (AD) is a common and severe neurodegenerative disorder related to aging, marked by cognitive decline and synaptic dysfunction. Currently, about 50 million people aged 65 and older have Alzheimer’s disease (AD) worldwide, and this number is expected to triple by 2050 (37). Human studies have shown that consuming 200 milliliters of cherry juice daily for 12 weeks significantly enhances language fluency, short-term memory, and long-term memory in older adults aged 70 and above with mild to moderate dementia (38). Supplementation with anthocyanin-rich blueberry concentrate (30 mL/day for 12 weeks) may not only improve brain perfusion and activation in brain areas associated with cognitive function in healthy older adults (39), but also enhance neural activation in patients with mild cognitive impairment and strength neural responses during working memory challenges in older adults with cognitive decline (40). Animal studies have also shown that anthocyanin-rich blackcurrant extract (3% anthocyanin for 9 weeks) also improves long-term recognition memory and normalized anxiety levels in senescence-accelerated mouse prone 8 (SAMP 8) mice (41). Additionally, mulberry extract (0.18 and 0.9% mulberry extract for 12 weeks) reduces brain β-amyloid levels and improves learning and memory in SAMP 8 mice (42). These studies indicate that anthocyanins can effectively address age-related cognitive decline and may serve as a promising compound for preventing and treating Alzheimer’s disease.

The brain is particularly vulnerable to oxidative stress, as previous studies indicate that reactive oxygen species (ROS) levels are significantly elevated in the brains of Alzheimer’s disease (AD) patients and animal models (43). Mechanistic studies on the neuroprotective effects of anthocyanins indicate that Korean black bean anthocyanin (12 mg/kg/day for 30 days) regulates the phosphorylated phosphatidylinositol 3-kinase (p-PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) pathway, thereby reducing ROS levels and oxidative stress in the brains of APP/PS1 transgenic mice, which improves cognitive function in these AD models. In vitro experiments have also shown that anthocyanins mitigate neurotoxicity induced by amyloid β oligomers (AβO) through the PI3K/Akt/Nrf2 signaling pathway (44). In addition, anthocyanins-containing PEG-AuNPs (12 μg/g/day for 14 days) also modulated the p-PI3K/p-Akt/p-GSK3β pathway, thereby inhibiting the hyperphosphorylation of tau at serine 413 and 404 and apoptosis of neurons in the brains of mice injected with Aβ_1-42 (45). Excessive neuroinflammation is directly related to the development of AD, and microglia are the main effectors of neuroinflammation (46). Supplementing with bilberry anthocyanins (20 mg/kg/day for 3 months) can activate astrocytes and microglia, and improve their phagocytic function of beta amyloid plaques in APP/PSEN1 mice (47). Activation of c-Jun N-terminal kinase (JNK) in the brain can stimulate microglia and increase the expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) (48), anthocyanin supplementation in LPS treated mice inhibited JNK activation and reduced the expression of nuclear factor kappa-B (NF-κB), TNF-α and interleukin-1beta (IL-1β). In addition, anthocyanins also reduced neuroinflammatory markers in Aβ_1-42-induced mouse model by inhibiting the p-JNK/NF-κB/p-GSK3β pathway (49). High-fat diet is an important risk factor for inducing neurodegenerative diseases (50). Anthocyanin supplementation (4% blueberry diet for 5 months) was able to reverse some of the behavioral deficits in high-fat diet-induced mice, particularly object recognition memory (51). The neuroprotective effects of anthocyanins may be related to attenuated microglial activation and increased neuroplasticity (52). Anthocyanin supplementation (100 mg/kg/day for 20 weeks) could also further block oxidative stress by improving AMPK-mediated autophagy, restore brain-derived neurotrophic factor protein levels in the hippocampus of mice on a high-fat diet, and ultimately inhibit hippocampal cell apoptosis and ameliorate cognitive deficits (53). Anthocyanins (700 mg/kg/day for 20 weeks) can also alleviate high-fat diet-induced neuroinflammation by inhibiting extracellular signal-regulated kinases, JNK, p38, and NF-κB activation (54). In summary, both animal studies and randomized clinical trials demonstrate that anthocyanins enhance cognition and neuroprotection. The mechanisms underlying these neuroprotective benefits are linked to anthocyanins’ ability to reduce oxidative stress, inflammation, and apoptosis in the brain. To fully realize the neuroprotective effects, further research should determine the best dose and frequency of anthocyanins for human use (Table 2).

Aging significantly increases the risk of developing Parkinson’s disease (PD), with prevalence rising from age 50 to 80. The pathogenesis of PD is diverse, including α-synuclein misfolding and aggregation, oxidative stress, mitochondrial dysfunction, and neuroinflammation (55). Current treatments for PD are limited; common medications provide only symptom relief and often come with significant side effects. Human studies have shown that dietary anthocyanins can effectively reduce mortality risk and have a positive impact on the mood of patients with PD (56, 57). The main lesions in Parkinson’s disease are the midbrain substantia nigra (SN) and the striatum, accompanied by degeneration and death of dopaminergic neurons. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces the death of specific dopaminergic neurons. Mulberry (Morus alba L.) extract (500 mg/kg/day for 15 days) can mitigate this cell death, reduce pro-apoptotic protein levels, and alleviate symptoms of Parkinson’s disease (58). A similar study also suggests that the mulberry (Morus alba L.) extract (250 mg/kg/day for 38 days) significantly inhibited the expression of Lewy body α-synuclein and ubiquitin, which are induced by MPTP (59). The injection of 6-hydroxydopamine (6-OHDA) leads to oxidative damage in neurons, which is associated with the death of neurons in Parkinson’s disease (60). Pelargonidin supplementation (20 mg/kg 1 day before and on the day of surgery) significantly increased the number of dopaminergic neurons in the substantia nigra, reduced lipid peroxidation levels, and improved motor function in rats that were injected with 6-OHDA (61). Some studies indicate that neurodegeneration in Parkinson’s disease (PD) is linked to gastrointestinal dysregulation. Additionally, anthocyanin supplementation exhibits neuroprotective effects in PD mice (10, 20, 40 mg/kg/day for 4 weeks) (62) and high-fat diet-induced obese rats (25 mg/kg/day for 17 weeks) (63) by modulation the composition and metabolism of gut microbiota. Moreover, other foods rich in anthocyanins, including sweet cherries (64), black carrot (65), blueberries and grape seed (66), may alleviate PD symptoms by providing antioxidant benefits, preventing cell death, and improving mitochondrial function. These studies indicate that anthocyanins could be a promising new element of treatment strategy for PD, requiring further investigation in clinical trials (Table 2).

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease characterized by the progressive degeneration and death of motor neurons. While current research on anthocyanins in ALS remains limited, preliminary evidence from animal models suggests potential protective effects on ALS. For instance, anthocyanin-derived metabolites such as protocatechuic acid (100 mg/kg after onset until death, 1 time/day, 5 times/week) (67) and anthocyanin-enriched strawberry extract (2 mg/kg/day after 60 days of age until death) (68), were shown to attenuate spinal cord astrogliosis, inhibit motor neuron apoptosis, and preserve neuromuscular junction integrity in SOD1 mutant mice—a widely used ALS model. These interventions reportedly delayed disease progression, improved motor performance, and extended survival in preclinical settings. However, no recent studies have further explored anthocyanins’ therapeutic mechanisms or translational potential in ALS, nor have clinical trials investigated their efficacy in human patients. The scarcity of research highlights a critical gap in understanding how dietary polyphenols might intersect with ALS pathophysiology. Future studies should prioritize (1) validating these findings in additional ALS models (e.g., TDP-43 or C9orf72-related models), (2) elucidating gut-brain axis interactions, and (3) assessing bioavailability and dosing regimens for clinical translation (Table 2).

Osteoarthritis (OA) is a chronic disease primarily affecting the elderly. A global study showed that there were about 300 million cases of hip and knee OA in 2017 (69). As the elderly population increases, osteoarthritis has emerged as a serious disease that affects their quality of life. The main pathological mechanism of OA is the degradation of the articular cartilage matrix, whose formation is related to cellular senescence, aging-related mitochondrial dysfunction, and oxidative stress (70). Additionally, both malvidin and pelargonidin can alleviate inflammation, cartilage degradation, and pain in OA by inhibiting the NF-κB pathway (71). Drugs for osteoarthritis (OA) can have several side effects, while nutritional health products are seen as an effective alternative for protecting and enhancing bone health (72). Studies have shown that anthocyanins improve OA symptoms by inhibiting inflammatory responses and the degradation of articular cartilage. For example, the anthocyanin in purple rice (6.25–50 μg/mL for 35 days) can reduce articular chondrocyte damage by inhibiting IL-1β-induced matrix metalloproteinase expression, which is closely related to the NF-κB and ERK/MAPK signaling pathways (73). Additionally, malvidin (74) and pelargonidin (75) can enhance the inflammatory response, reduce cartilage degradation, and alleviate pain in OA by inhibiting the NF-κB pathway. Research indicates that Sirtuin 6 improves chondrocyte aging and slows the progression of osteoarthritis (OA) (76). Cyanidin administration (50 mg/kg/day for 8 weeks), both in vivo and in vitro, enhances Sirt6 activity and inhibits the NF-κB signaling pathway. It also prevents IL-1β-induced degradation of the extracellular matrix (ECM) and reduces the inflammatory response in human OA chondrocytes. Additionally, it mitigates proteoglycan loss and cartilage damage caused by destabilization of the medial meniscus (DMM) in OA mice (77). Clinical studies indicate that consuming foods rich in anthocyanins can help balance immune markers in patients with osteoarthritis, thereby reinforcing the potential of anthocyanins as an additional therapeutic strategy (78). Therefore, anthocyanins can reduce OA symptoms and improve patients’ quality of life (Table 2).

Osteoporosis is a disease marked by low bone mass and changes in bone microstructure, leading to increased fragility and susceptibility to fractures, which adversely impacts patients’ quality of life (79). Advanced age is a major risk factor for chronic diseases. Hormonal imbalances that occur with age lead to dysfunction of osteoclasts and osteoblasts, oxidative stress, and chronic inflammation, all of which significantly contribute to the development of osteoporosis (80, 81). Anthocyanins are known for their anti-inflammatory, anti-oxidative, and anti-apoptotic effects. Studies suggest that anthocyanin-rich foods can improve bone remodeling biomarkers in middle-aged and elderly people, indicating their potential role in osteoporosis management (82). Sakaki et al. found that blackcurrant diet (a standard chow diet with 1% (w/w) anthocyanin for 4 months) improved cancellous bone mass loss in young mice by increasing glutathione peroxidase (GPX) activity in the humerus. However, this diet only modestly reduced TNF-α expression in older mice, with no significant effect on cancellous bone mass. This suggests that early administration of anthocyanins may help prevent age-related bone loss (83). Osteoporosis involves a gradual decline in osteoblasts and increased bone resorption by osteoclasts. Cyandin-3-glucoside plays a role in regulating osteoblast differentiation via the ERK1/2 signaling pathway (84). Osteoporosis related to diabetes is a systemic endocrine metabolic bone disease characterized by reduced bone density and destruction of bone microstructure. Studies show that anthocyanins in black rice extract (0.5, 1.0 and 2.0 g/kg/day for 8 weeks) can improve bone loss in diabetes rats by inhibiting bone turnover and bone marrow fat production, and up regulating the ratio of RUNX2 and OPG/RANKL in bone tissue of diabetes rats (85). Decreased estrogen levels are the primary cause of bone loss in postmenopausal women, with more than 30% of them affected by osteoporosis (86). Studies have demonstrated that supplements containing anthocyanins from blueberries, blackcurrants, or maqui berries can reduce bone loss induced by ovariectomy (87–90). This finding suggests that anthocyanins may help alleviate osteoporosis in postmenopausal women; however, the exact mechanism of action remains unclear and requires further investigation. Thus, anthocyanins, as natural bioactive compounds, may offer innovative strategies for preventing and treating osteoporosis (Table 2).

Aging is a complex biological process, and epidemiological studies prove that aging is an independent risk factor leading to the occurrence of cardiovascular diseases. As people age, the heart transitions from compensatory adaptation to maladaptation, resulting in cardiac hypertrophy, changes in left ventricular diastolic function and contractile reserve, increased arterial stiffness, and impaired endothelial function (1). Cardiac dysfunction due to aging can lead to various cardiovascular diseases, including atherosclerosis, hypertension, and dyslipidemia. Atherosclerosis is a chronic and progressive vascular disease that is a precursor of an ischemic heart attack. The initial stage of atherosclerotic lesion development involves the activation of endothelial cells. Activated endothelial cells release the inflammatory mediator MCP-1 into the bloodstream and express adhesion molecules (ICAM-1 and VCAM-1) to attract circulating monocytes and other immune cells to the site of oxidized low-density lipoprotein accumulation (91, 92). Oral administration of anthocyanins has been recognized as a therapeutic option for managing cardiovascular disease. Research indicates that purple sweet potato, red Chinese cabbage (93, 94), and protocatechuic acid (95) can reduce plasma VCAM-1 levels and inhibit the expression of adhesion molecules on arterial endothelial surfaces. Furthermore, daily intake of an extract high in Chinese cabbage anthocyanins (150 and 300 mg/kg/day for 12 weeks) can lower inflammatory cytokines and adhesion molecule levels, thus preventing plaque buildup in the arteries of hyperlipidemic mice (94). This suggests that anthocyanins suppress inflammation and alleviate the progression of atherosclerosis. Furthermore, Cyanidin-3-O-β-glucoside (100, 200 and 300 mg/kg for 8 weeks) enhances endothelial nitric oxide synthase phosphorylation and preserves nitric oxide availability, promoting endothelial cell migration and survival (96, 97). Cyanidin-3-O-β-glucoside (0.2% C3G for 6 weeks) also enhances the function of endothelial progenitor cells and promotes endothelial repair, thereby slowing atherosclerosis in apolipoprotein E-deficient mice (98). More importantly, anthocyanin metabolites enhance endothelial function by influencing the gut microbiota (99). These studies suggest that anthocyanins slow atherosclerosis progression by regulating vascular endothelial function. In conclusion, anthocyanins are crucial for cardiovascular health due to their antioxidant and anti-inflammatory properties, as well as their role in regulating endothelial cell function (Table 2).

Hypertension is a significant risk factor for cardiovascular diseases. Chronic hypertension increases the heart’s workload, requiring it to pump blood more forcefully. Over time, this can lead to cardiac hypertrophy and ultimately result in heart failure. In addition, hypertension damages vascular endothelial cells and promotes the formation of atherosclerosis, which can lead to coronary heart disease, strokes, and other serious conditions. Clinical pilot studies indicate that healthy elderly individuals aged 65 to 80, who consume 26 grams of freeze-dried wild blueberry powder (containing 302 mg of anthocyanins) daily for 12 weeks, experience significant increases in blood flow-mediated vasodilation and decreases in 24 h dynamic systolic blood pressure compared to the placebo group (100). Studies have also found that 5-week low-dose wild blueberry extract (222 mg of anthocyanins) significantly reduced systolic blood pressure in healthy elderly people (68–75 years old) (101). Moreover, a 6-week regimen of 85 mg of cranberry extract (25% anthocyanins) per day significantly lowered both systolic and diastolic blood pressure in patients with myocardial infarction (102). Short-term (28 days) ingestion of 300 mg New Zealand blackcurrant extract capsules (35% blackcurrant extract) reduced arterial stiffness and blood pressure in elderly individuals with an average age of 73.3 years (103). These studies indicate that anthocyanins can lower blood pressure. Growing evidence suggests that anthocyanin’s anti-hypertensive effects primarily stem from its antioxidant, anti-inflammatory, and ACE inhibitory properties, along with its ability to inhibit the growth of vascular endothelial cells. However, the intake of anthocyanin-rich blood orange juice (50 mg/500 mL) for 4 weeks also had no effect on blood pressure in healthy people (25–84 years old) (104), but it could significantly reduce blood pressure in patients with dementia (104). Therefore, the antihypertensive effects of anthocyanins depend on both the dosage and the duration of administration, and additional clinical trials are needed to determine the ideal nutritional intake and specific mechanisms, which will help create a stronger scientific basis for the prevention and treatment of cardiovascular diseases (Table 2).