Cancer preventive agents. Part 8: Chemopreventive effects of stevioside and related compounds.

In a search for potential cancer chemopreventive agents from natural resources, stevioside (1), a sweetener, and six related compounds, including two aglycones steviol (6) and isosteviol (7), were screened in an in vitro assay for inhibitory effects on Epstein-Barr virus early antigen activation. Compounds 1, 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1, as well as 6 and 7, could be valuable as chemopreventive agents for chemical carcinogenesis.

[Effects of Piper longum L. on chills in Japanese young women: time-dependent changes in skin surface temperature and its recovery rate following the exposure to mild cold stress].

Chills can lead to problems such as insomnia, mental fatigue, and unstable emotions. Increasing evidence shows that young women, as well as menopausal women, suffer from chills. The present study investigated the effect of Piper longum L. on chills in young women. Participants with (n = 16) and without (n = 16) chills were sampled randomly from female university students using reported discriminative criteria (Yamada et al, 2007). Each participant was randomly assigned to low- (15 mg) and high-dose (30 mg) P. longum groups. We determined the severity of complaints related to chills, physical parameters (body mass index, body fat ratio, and blood pressure), the peripheral circulation dynamics using a laser tissue blood flow-meter, and the skin surface temperature in the fingers using a thermograph. Mild cold stress was applied 10 min after taking a capsule containing P. longum or a dextrin placebo. Then, a thermograph was recorded every minute for 11 min. Piper longum significantly facilitated the recovery of skin surface temperature at either low or high dosages in participants with chills. In subjects without chills, neither high- nor low-dosage of P. longum had an effect. Our findings have important implications for the utility of P. longum in women with chills.

Hepatoprotective effect of sesquiterpenes in turmeric.

Hepatoprotective effect of turmeric together with its sesquiterpenes and curcuminoids fractions were examined on D-galactosamine induced liver injury in rats. All the diets individually contained the turmeric extract, the curcuminoids fraction, and the sesquiterpenes fraction suppressed the increase of LDH, ALT, and AST levels caused by D-GalN treatment. Since few anti-oxidative activities are expected in the sesquiterpenes fraction, it is presumed that hepatoprotective mechanism of sesquiterpenes in turmeric is different from that of curuminoids.

Hepatoprotective activity of tocha, the stems and leaves of Ampelopsis grossedentata, and ampelopsin.

Hepatoprotective effect of the leaves and stems of Ampelopsis grossedentata together with its main constituent, ampelopsin, were examined on D-galactosamine induced liver injury in rats. The diet containing 50% ethanolic extract (1%) and ampelopsin (0.1%) markedly suppressed the increase of LDH, ALT, AST, alpha-tocopherol levels and GSG/GSSH caused by GalN treatment. These results suggested that ampelopsin from Tocha acted to prevent the oxidative stress in vivo that may have been due to active oxygen species formed by a macrophage by the action of GalN.

Blood pressure-depressing activity of a peptide derived from silkworm fibroin in spontaneously hypertensive rats.

Peptides showing inhibitory activity against the angiotensin I-converting enzyme (ACE) were investigated from the fibroin fraction of discarded silk fabric. Fibroin, which was hydrolyzed with alcalase after partial hydrolysis with hot aqueous 40% CaCl(2), released two major active peptides showing ACE-inhibitory activity. The two peptides were identified as glycyl-valyl-glycyl-tyrosine (GVGY) and glycyl-valyl-glycyl-alanyl-glycyl-tyrosine (GVGAGY) by analyses with a protein sequencer and LC/MS/MS. GVGY, whose ACE-inhibitory activity has not previously been reported, showed a blood pressure-depressing effect on spontaneously hypertensive rat (SHR).

Antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides from a sesame protein hydrolysate in spontaneously hypertensive rats.

Sesame peptide powder (SPP) exhibited angiotensin I-converting enzyme (ACE) inhibitory activity, and significantly and temporarily decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) by a single administration (1 and 10 mg/kg). Six peptide ACE inhibitors were isolated and identified from SPP. The representative peptides, Leu-Val-Tyr, Leu-Gln-Pro and Leu-Lys-Tyr, could competitively inhibit ACE activity at respective Ki values of 0.92 microM, 0.50 microM, and 0.48 microM. A reconstituted sesame peptide mixture of Leu-Ser-Ala, Leu-Gln-Pro, Leu-Lys-Tyr, Ile-Val-Tyr, Val-Ile-Tyr, Leu-Val-Tyr, and Met-Leu-Pro-Ala-Tyr according to their content ratio in SPP showed a strong antihypertensive effect on SHR at doses of 3.63 and 36.3 microg/kg, which accounted for more than 70% of the corresponding dosage for the SPP-induced hypotensive effect. Repeated oral administration of SPP also lowered both SBP and the aortic ACE activity in SHR. These results demonstrate that SPP would be a beneficial ingredient for preventing and providing therapy against hypertension and its related diseases.