• Injecting luteolin into a brain region that modulates blood pressure (paraventricular nucleus of the hypothalamus [PVN]) mitigates hypertension in rats.
  • Luteolin injections reduce circulating adrenal hormones norepinephrine and epinephrine that can contribute to hypertension.
  • Luteolin diminishes the number of neurons with high levels of inflammatory proteins (interleukin-1ꞵ [IL-1ꞵ]) in the PVN brain region.

Nearly half of adults in the US have hypertension – elevated blood pressure – which can cause ailments like heart disease and stroke if left untreated. Drugs for hypertension include diuretics and beta-blockers with side effects like extra urination for diuretics and depression and insomnia for beta-blockers. Because antihypertensive drugs have significant side effects, researchers have searched for naturally-occurring, plant-based molecules that can reduce hypertension.

Published in Nutrients, Kang and colleagues from Xi’an Jiaotong University in China show that injecting luteolin into the PVN reduced hypertension in rats. They go on to show that luteolin alleviated hypertension, in part, by diminishing circulating adrenal hormones norepinephrine and epinephrine. Additionally, luteolin reduced levels of the inflammatory protein IL-1ꞵ in the PVN, suggesting reduced neuroinflammation that may improve the PVN’s function in regulating blood pressure. These findings support that luteolin may be used to alleviate hypertension in addition to or in lieu of current antihypertensive drugs.

Luteolin Alleviates Neuroinflammation in a Brain Region Regulating Blood Pressure

Kang and colleagues injected luteolin into the PVN of hypertensive rats for 28 days and then measured blood pressure in arteries – blood vessels carrying oxygen-rich blood from the heart. They found that the luteolin-treated hypertensive rats showed substantially diminished arterial blood pressure, starting at around day 16 of treatment and continuing through the 28-day experiment. These results support that injecting luteolin into the PVN significantly reduces blood pressure in hypertensive rats.

(Gao et al., 2022 | Nutrients) Luteolin suppresses hypertension. The average blood pressure across arteries (mean arterial pressure [MAP]) was high for hypertensive rats (SHR + PVN vehicle), yet luteolin reduced hypertensive blood pressure (SHR + PVN Luteolin). No blood pressure difference was found between healthy rats treated with luteolin (WKY + PVN Luteolin) and untreated healthy rats (WKY + PVN vehicle).

Because high levels of the adrenal hormones norepinephrine and epinephrine are linked to and may drive hypertension, Kang and colleagues measured their circulating concentrations. The China-based research team found that the concentrations of these two hormones more than doubled with hypertension but that luteolin curtailed the elevation of these hormones. These findings suggest that luteolin treatments can alleviate high adrenal hormone levels to counter hypertension.

(Gao et al., 2022 | Nutrients) Luteolin diminishes circulating adrenal hormones that contribute to hypertension. Hypertensive rats (SHR + PVN vehicle) displayed more than twice the concentrations (pg/ml) of epinephrine (Plasma EPI) and norepinephrine (Plasma NE) compared to healthy rats with luteolin treatment (WKY + PVN Luteolin) and without treatment (WKY + PVN vehicle). Treating hypertensive rats with luteolin (SHR + PVN Luteolin) significantly reduced their circulating adrenal hormone concentrations.

To find if luteolin reduces neuroinflammation, which may contribute to functional improvements for the PVN, Kang and colleagues measured inflammatory protein levels. They found that hypertensive rats had markedly elevated numbers of PVN neurons that exhibited the inflammatory protein IL-1ꞵ. Treating with luteolin reduced the number of neurons with abundant IL-1ꞵ, supporting that luteolin reduces neuroinflammation in this brain structure. Although the precise mechanism by which this may improve PVN function isn’t completely clear, the reduced inflammation could allow the PVN to better regulate blood pressure. This could partially explain how luteolin alleviates hypertension.

(Gao et al., 2022 | Nutrients) Luteolin reduces PVN neurons that exhibit the inflammatory protein IL-1ꞵ. Non-treated hypertensive rats (SHR + PVN vehicle) have about triple the numbers of neurons with the inflammatory protein IL-1ꞵ (red fluorescing cells) than healthy rats with luteolin treatment (WKY + PVN Luteolin) and non-treated healthy rats (WKY + PVN vehicle). Luteolin treatment (SHR + PVN Luteolin) substantially reduces the numbers of neurons exhibiting IL-1ꞵ in the PVN of hypertensive rats.

“We reported that centrally administered luteolin can lower blood pressure,” said Kang and colleagues.

Luteolin Crosses the Blood Brain Barrier to Potentially Improve Cognition

The PVN has been shown to modulate blood pressure, and this study provides evidence that by reducing inflammation in the PVN, luteolin enhances this brain structure’s ability to regulate blood pressure. In this way, luteolin can alleviate hypertension, along with its underlying contributors like high adrenal hormone levels.

Interestingly, because luteolin is a small molecule that is soluble in fats (lipophilic), it is capable of crossing the blood brain barrier – a semi-permeable membrane protecting the brain from harmful substances. This makes luteolin an attractive candidate molecule for not only alleviating neuroinflammation, as shown in this study, but also helping with brain function.

Luteolin is a flavonoid – a class of metabolites found in plants. Dietary sources of this plant metabolite can be found in celery, broccoli, artichoke, green pepper, carrots, parsley, and peppermint. It’s also available as a supplement with prices ranging from $10 to $35 for a month’s supply of 100 mg per day doses.

Research has linked age-related cardiovascular diseases like hypertension to neuroinflammation. By reducing neuroinflammation along with other physiological contributors to hypertension such as adrenal hormones, luteolin may be a key, newfound remedy for elevated blood pressure.