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In the 1970s, Eucommia leaf tea, known as Tochu-cha in Japanese, was developed from roasted Eucommia leaves in Japan and is considered as a healthy tea. The antihypertensive, diuretic, anti-stress, insulin resistance improving, and anti-obesity effects of Eucommia leaf extract have been reported. However, the identification and properties of the active components as well as the underlying mechanism of action are largely unknown. In this review, we summarize studies involving the oral administration of geniposidic acid, a major iridoid component of Eucommia leaf extract which increases plasma atrial natriuretic peptide (ANP) on the atria of spontaneously hypertensive rats (SHR) by activating the glucagon-like peptide-1 receptor (GLP-1R). To achieve the antihypertensive effects of the Eucommia leaf extract through ANP secretion in humans, combining a potent cyclic adenosine monophosphate phosphodiesterase (cAMP-PDE) inhibitor, such as pinoresinol di-β-d-glucoside, with geniposidic acid may be necessary. Changes in the gut microbiota are an important aspect involved in the efficacy of asperuloside, another component of the Eucommia leaf extract, which improves obesity and related sequelae, such as insulin resistance and glucose intolerance. There are species differences of mechanisms associated with the antihypertensive and anti-obesity effects between rodents and humans, and not all animal test results are consistent with that of human studies. This review is focused on the mechanisms in antihypertensive and anti-obesity effects of the Eucommia leaf extract and summarizes the differences of mechanisms in their effects on rodents and humans based on our studies and those of others.

Serotonin (5-hydroxytryptamine; 5-HT) is known to be activated during ischemia-reperfusion and triggers contractile dysfunction and pathological apoptosis. Here, the beneficial effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine was demonstrated on ischemia-reperfusion injury in guinea-pig hearts perfused using the Langendorff technique. The recovery (%) of left ventricular developed pressure (LVDP) by fluvoxamine (5×10(-8) M) was 95.4% (control: 32%), which was consistent with the inhibition of mitochondrial Ca(2+)([Ca(2+)]m) uptake induced by changes in the Ca(2+) content and acidification of the perfusate, and similar to reperfusion following global ischemia in Langendorff-perfused hearts. Fluvoxamine inhibited the increase in [Ca(2+)]m induced by changes in the Ca(2+) content of the perfusate in perfused preparations of mitochondria, which was similar to the results obtained with the mitochondrial permeability transition pore (MPTP) opener atractyroside. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly less in fluvoxamine-treated hearts than in control hearts, with decreases in caspase-3 activity. These results suggest that SSRI inhibits opening of the MPTP by preventing [Ca(2+)]m overload-induced apoptosis related to the endogenous accumulation of 5-HT in ischemia-reperfusion hearts.

When treated with (diethylamino)sulfur trifluoride (DAST), 11α-hydroxygedunin gave 11β-fluorogedunin and 9,11-didehydrogedunin, whereas deacetylgedunin afforded two skeletal rearranged products 6 and 7, in which the Me-30 had shifted from position 8 to position 7. Of those products, 11β-fluorogedunin and 6 were shown to be more cytotoxic than gedunin on P-388 leukemia cells.

The protective effects of cyclic dipeptides in alcoholic beverages were investigated in the perfused guinea-pig hearts subjected to ischemia and reperfusion. Subsequently, in order to determine the importance of cyclic dipeptide structure, the effects of cyclo(L-Leu-L-Tyr) (cLY) were compared with those of the newly synthesized non-cyclic dipeptides, L-Leu-L-Tyr (LY) and L-Tyr-L-Leu (YL). After reperfusion, pressure recovery (%) in the left ventricle reached a peak of over 90% in the presence of cLY (10(-6) M and 10(-5) M) (control: 22.9%). The recovery by LY and YL was significantly lower than that by cLY, and ATP levels simultaneously monitored using (31)P-NMR were already lower during the ischemic end period than those observed with cLY treatment. In perfused mitochondrial preparations, cLY significantly inhibited mitochondrial Ca(2+) ([Ca(2+)](m)) elevation in a similar way to that of the mitochondrial permeability transition pore (MPTP) inhibitor cyclosporin A. In vitro electron paramagnetic resonance (EPR) revealed that the active oxygen radicals quenching activity of cLY was greater than those of non-cyclic dipeptides. cLY inhibited caspase-3-induced apoptosis. The cyclic dipeptide structure inhibits opening of the MPTP by preventing [Ca(2+)](m) overload-induced apoptosis related to mitochondrial active oxygen radical accumulation in ischemia-reperfusion hearts.

Nine new triterpenoids, 1-9, were isolated from the cortex of Cedrela sinensis (Meliaceae), together with six known compounds, sapelin E acetate, grandifoliolenone, azadirone, bourjotinolone A, piscidinol A, and hispidol B. The structures of 1-9 were determined by the 2D NMR experiments, chemical methods, and X-ray crystallography.

Four new limonoids, 11alpha-hydroxygedunin (1), 11beta-hydroxygedunin (2), 7-deacetoxy-7alpha,11alpha-dihydroxygedunin (3), and 7-deacetoxy-7alpha,11beta-dihydroxygedunin (4), were isolated from the cortex of Cedrela sinensis, together with three known compounds, gedunin (5), 7-deacetoxy-7alpha-hydroxygedunin (6), and 11-oxogedunin (7). The structures of 1-4 were determined by a combination of 2D NMR experiments and chemical methods and by X-ray crystallography of 1 and 2.

Twenty-three new triterpenoids ( 1–23 ), all having an apotirucallane skeleton, were isolated from the seeds, leaves, and stems of Cedrela sinensis (Meliaceae). Their structures were determined by 2D NMR experiments, X-ray crystallographic analysis, and chemical methods. These triterpenoids showed a moderate cytotoxic activity against P-388 murine leukemia cells (IC50 0.26–9.9 μg/mL).

We studied the effect of the selective serotonin reuptake inhibitor (SSRI) paroxetine on the immobility time in the forced swimming test using different strains of mice (ICR, ddY, C57BL/6, BALB/c and DBA/2). There was a difference between strains in the response to paroxetine (although it induced anti-immobility effects in all strains of mice used). The mouse strain most sensitive to paroxetine was DBA/2; the ICR strain showed the lowest sensitivity. We previously demonstrated variations in the responses to another SSRI, fluvoxamine, in different strains of mice, which was in agreement with the present findings. In DBA/2 and ICR mice, the anti-immobility effects of paroxetine were significantly antagonized by the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). The noradrenergic α(1)-adrenoceptor antagonist prazosin significantly reduced the anti-immobility effects elicited by a high dose (5mg/kg) of paroxetine in DBA/2 and ICR mice. However, prazosin did not affect the anti-immobility effects of a lower dose of paroxetine (1mg/kg) in DBA/2 mice. This suggests that the anti-immobility effects of a higher dose of paroxetine in mice are associated with serotonergic and noradrenergic neurons. Prazosin did not the affect anti-immobility effects of fluvoxamine. These results suggest that there are differences between mice strains in the antidepressant-like effects of paroxetine (which are similar to those elicited by fluvoxamine). Moreover, involvement of the noradrenergic system was partly related to the anti-immobility effects of paroxetine (which are different to those elicited by fluvoxamine).

Nine new triterpenoids, 1-9, were isolated from the cortex of Cedrela sinensis (Meliaceae), together with six known compounds, sapelin E acetate, grandifoliolenone, azadirone, bourjotinolone A, piscidinol A, and hispidol B. The structures of 1-9 were determined by the 2D NMR experiments, chemical methods, and X-ray crystallography.

Five limonoids were isolated from the leaves of Cedrela sinensis (Meliaceae) and their structures were determined to be 11beta-hydroxy-7alpha-obacunyl acetate, 11-oxo-7alpha-obacunyl acetate, 11-oxo-7alpha-obacunol, 11beta-hydroxycneorin G, and 11-oxocneorin G, by 2D NMR spectroscopic experiments, X-ray crystallographic analysis, and chemical methods.