Highlights: 

  • Apigenin prevents heart enlargement and tissue scarring in a mouse model for cardiac injury. 
  • The effects of apigenin are mediated by countering oxidative stress — damage caused to cells by excess levels of reactive oxygen species (ROS).
  • By promoting an increase in NAD+, apigenin is implicated in extending lifespan.

According to estimates from the American Heart Association, nearly half of American adults will suffer from cardiovascular disease by 2030. While a healthy diet and regular exercise may very well prevent many cardiovascular complications, scientists are on the lookout for natural compounds that counter such complications. Hence, researchers from the Chinese Academy of Medical Sciences have turned to apigenin. 

Apigenin is a plant-based chemical classified as a flavonoid, abundant in foods such as parsley, celery, and oranges. As reported in the European Journal of Pharmacology, Xu and colleagues show that apigenin alleviates damage to the heart in mice. These new findings suggest that consuming apigenin could counter some of the cellular defects that underlie heart disease. 

“Based on our findings, and combined with the extensive literature that has been reported before, we know that apigenin is a natural compound that can prevent cardiovascular disease,” say the authors.

Apigenin Prevents Heart Damage 

Chronically overworking the heart, which occurs with chronic high blood pressure or clogged arteries (coronary heart disease), can lead to heart enlargement. To model heart enlargement, Xu and colleagues exposed mice to a high dose of a drug called isoprenaline (Iso), a prescription medication used for increasing heart rate. After 2 weeks of Iso exposure, the mice were shown to have enlarged hearts. However, feeding mice 50 mg/kg of apigenin prevented Iso-induced heart enlargement, suggesting that apigenin can counter this condition. 

(Xu et al., 2023 | Eur. J. Pharmacol.) Apigenin Prevents Heart Enlargement. Compared to normal mice (Sham), mice exposed to isoprenaline (Iso) have enlarged hearts as depicted and measured by heart weight to body weight ratio (HB/BW). However, treating Iso-exposed mice with apigenin (Iso+Api) prevents this enlargement.

Chronically overworking the heart can also cause damage to heart tissue. However, heart tissue cannot readily regenerate and damaged tissue is usually replaced by collagen protein, manifesting in scar tissue — a phenomenon known as fibrosis. Xu and colleagues showed that the hearts of Iso-exposed mice had high levels of fibrosis. However, apigenin treatment was shown to prevent this.

(Xu et al., 2023 | Eur. J. Pharmacol.) Apigenin Prevents Fibrosis. Compared to normal mice (Sham), mice exposed to isoprenaline (Iso) have high levels of fibrosis as depicted in red and quantified as “Fibrosis volume fraction”. However, treating Iso-exposed mice with apigenin (Iso+Api) prevents this increase in fibrosis.

Scientists propose that oxidative stress — damage caused to cells by excess levels of reactive oxygen species (ROS) — underlies cardiovascular disease. It follows that reducing ROS levels can counter the damaging effects of oxidative stress. Using a fluorescent dye, Xu and colleagues showed that ROS levels were dramatically increased in the heart tissue of Iso-exposed mice. However, apigenin largely prevented this increase in ROS, suggesting that apigenin can counter oxidative stress.

(Xu et al., 2023 | Eur. J. Pharmacol.) Apigenin Reduces ROS. Compared to normal mice (Sham), mice exposed to isoprenaline (Iso) have high ROS levels as depicted in red and quantified as “ROS fluorescence intensity”. However, treating Iso-exposed mice with apigenin (Iso+Api) markedly reduces ROS levels.

Apigenin for Cardiovascular Aging 

Overall, the findings of Xu and colleagues suggest that apigenin can prevent damage and remodeling (enlargement) of the heart by countering oxidative stress. Previous animal studies, including one that used gold particles covered in apigenin, corroborate the cardioprotective effects of apigenin. Furthermore, a human epidemiological study showed that a diet rich in apigenin is associated with a reduced risk of coronary heart disease.  Apigenin can be found in various foods as well as chamomile tea. It also comes in supplement form, although the authors mention that apigenin is not water-soluble, potentially making it less bioavailable. 

Apigenin Inhibits the Breakdown of NAD+: Implications for Longevity  

In many tissues, including heart tissue, nicotinamide adenine dinucleotide (NAD+) has been shown to decline with age. This decline is associated with reduced NAD+ synthesis and elevated NAD+ degradation, which is primarily attributed to an enzyme called CD38. Moreover, blocking CD38 with a small molecule called 78c has been shown to increase the lifespan of mice while improving exercise performance and raising NAD+ levels in multiple tissues. 

Furthermore, in 2013, it was discovered that apigenin inhibits CD38, similar to 78c. Therefore, assuming that apigenin and 78c have similar anti-CD38 effects, it is possible that apigenin could also increase the lifespan of mice by boosting NAD+ levels. In the future, a direct comparison of apigenin and 78c could inform the relative longevity effects of each CD38 inhibitor.