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

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.

Apigenin Improves Hypertension and Cardiac Hypertrophy Through Modulating NADPH Oxidase-Dependent ROS Generation and Cytokines in Hypothalamic Paraventricular Nucleus.

Apigenin, identified as 4', 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 µg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1ß (IL-1ß), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN.

Phomopsols A and B from the Mangrove Endophytic Fungus Phomopsis sp. xy21: Structures, Neuroprotective Effects, and Biogenetic Relationships.

A polyketide-derived alkaloid featuring a unique 3,4-dihydro-2H-indeno[1,2-b]pyridine 1-oxide motif, named phomopsol A (1), and a highly oxidized polyketide containing a new 3,5-dihydro-2H-2,5-methanobenzo[e][1,4]dioxepine moiety, named phomopsol B (2), were isolated from the Thai mangrove endophytic fungus Phomopsis sp. xy21, together with the related biosynthetic polyketide 3. The structures of 1-3 were unambiguously established by single-crystal X-ray diffraction analysis (Cu Kα), and their neuroprotective effects in PC12 cells were evaluated. The biosynthetic origins of 1-3 are proposed.

Xanthone-derived polyketides from the Thai mangrove endophytic fungus Phomopsis sp. xy21.

Six new xanthone-derived polyketides, named phomoxanthones F-K (1-6), along with three known ones, were isolated from Phomopsis sp. xy21, which was isolated as an endophytic fungus from the Thai mangrove Xylocarpus granatum. Phomoxanthone F (1) represents the first xanthone-derived polyketide containing a 10a-decarboxylated benzopyranone nucleus that was substituted by a 4-methyldihydrofuran-2(3H)-one moiety at C10a. Phomoxanthones G (2) and H (3) are highly oxidized xanthone-derived polyketides containing a novel 5-methyl-6-oxabicyclo[3.2.1]octane motif. This is the first report of a C6-O-C12 bridge in xanthone-derived polyketides. Additionally, a plausible biogenetic pathway for these xanthone-derived polyketides is proposed.