Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus

Abstract

Background: Luteolin is widely distributed among a number of vegetal species worldwide. The pharmacological effects of luteolin are diverse and amongst antioxidant, free radical scavenging, and anti-inflammatory activities. Preliminary study showed that luteolin can ameliorate hypertension. However, the precise mechanism needs further investigation. There is no evidence that luteolin affects the paraventricular nucleus of the hypothalamus (PVN), a brain nucleus associated with a critical neural regulator of blood pressure. Our main aim was to explore the effect of luteolin on the PI3K/Akt/NF-κB signaling pathway within the PVN of hypertensive rats. Methods: spontaneously hypertensive rats (SHRs) and corresponding normotensive control rats, the Wistar Kyoto (WKY) rats were divided into four groups and subsequently treated for 4 weeks with bilateral PVN injections of either luteolin (20 µg/0.11 µL, volume: 0.11 µL/h) or vehicle (artificial cerebrospinal fluid). Results: luteolin infusion to the PVN significantly decreased some hemodynamic parameters including the mean arterial pressure (MAP), heart rate (HR), circulating plasma norepinephrine (NE) and epinephrine (EPI). Additionally, there was a decrease in the expressions of the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT), levels of reactive oxygen species (ROS), NAD(P)H oxidase subunit (NOX2, NOX4) in the PVN of SHRs. Meanwhile, the expression of inflammatory cytokines and the activity of nuclear factor κB (NF-κB) p65 in the PVN of SHRs were lowered. Furthermore, immunofluorescence results showed that injection of luteolin in the PVN reduced the expression of tyrosine hydroxylase (TH), and increased that of superoxide dismutase (SOD1) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN of SHRs. Conclusion: Our novel findings revealed that luteolin lowered hypertension via inhibiting NF-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN.

Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus

“…The animal study protocol was approved by the Animal Care and Use Committee of Xi’an Jiaotong University (protocol code No. 2020–62 and date of approval 25 March 2020) ( Gao et al, 2023 ).…”

“…After 1 week of acclimatization, Dahl S rats were divided into four groups according to diet type: (1) NSD + PVN vehicle group ( n = 7): rats were fed with food containing 0.3% NaCl and PVN infusion with vehicle; (2) NSD + capsaicin group ( n = 7): rats were fed with food containing 0.3% NaCl and PVN infusion with capsaicin; (3) HSD + PVN vehicle group ( n = 7): rats were fed with food containing 8% NaCl and PVN infusion with vehicle; (4) HSD + capsaicin group ( n = 7): rats were fed with food containing 8% NaCl and PVN infusion with capsaicin. The determination of the effective dose of capsaicin is based on our pilot study combined with previous studies ( Qi et al, 2022 ; Gao et al, 2023 ).…”

Aptamers for the Delivery of Plant-Based Compounds: A Review

“…Luteolin, a flavone abundant in fruits, vegetables, and flowers, possesses anti-inflammatory, antihypertensive [ 161 ], and anticancer properties, which are related to its ability to induce apoptosis, inhibit proliferation, and prevent angiogenesis [ 162 ]. Notably, it modulates the JNK protein in cancer cells [ 163 ], suppresses anti-apoptotic proteins like Bcl-2 and Bcl-xL, activates caspases, and triggers DNA damage through ROS, thereby activating p53 [ 164 ].…”

Identification and Quantitation of the Bioactive Components in Wasted Aralia elata Leaves Extract with Endothelial Protective Activity

“…The ability of LAE extract to reduce VCAM-1 and ICAM-1 expression may be an essential mechanism for the extract's anti-inflammatory effects. Several studies have reported the activation of the PI3K/Akt pathway and its contribution to the upregulated production of inflammatory cytokines in activated endothelial cells [28,29]. Consequently, the effects of LAE extract on LPS-induced PI3K/Akt activation in HUVECs were analyzed.…”