Yasujiro Morimitsu

6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-α mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes

In this study, we demonstrated that the two ginger-derived components have a potent and unique pharmacological function in 3T3-L1 adipocytes via different mechanisms. Both pretreatment of 6-shogaol (6S) and 6-gingerol (6G) significantly inhibited the tumor necrosis factor-alpha (TNF-alpha) mediated downregulation of the adiponectin expression in 3T3-L1 adipocytes. Our study demonstrate that (1) 6S functions as a PPARgamma agonist with its inhibitory mechanism due to the PPARgamma transactivation, and (2) 6G is not a PPARgamma agonist, but it is an effective inhibitor of TNF-alpha induced c-Jun-NH(2)-terminal kinase signaling activation and thus, its inhibitory mechanism is due to this inhibitory effect.

A nonpungent component of steamed ginger--[10]-shogaol--increases adrenaline secretion via the activation of TRPV1.

Abstract We investigated the components of ginger that are involved in increasing body temperature. Gingerols ([6,8,10]-gingerols) and shogaols ([6,8,10]-shogaols) having different alkyl carbon chain lengths were targeted. All the gingerols and shogaols increased intracellular calcium concentration in rat transient receptor potential vanilloid subtype 1 (TRPV1)-expressing HEK293 cells via TRPV1. In this regard, the shogaols were more potent than the gingerols. Aversive responses were induced by [6]-, [10]-gingerol, and [6]-shogaol (5 mmol/l) in rats when these compounds were applied to the eye; however, no response was observed in response to [10]-shogaol (5 and 10 mmol/l). [10]-Shogaol induced nociceptive responses via TRPV1 in rats following its subcutaneous injection into the hindpaw; the pungent compound capsaicin (CAP) and [6]-shogaol were observed to have similar effects. Moreover, adrenal catecholamine secretion, which influences energy consumption, was promoted in rats in response to [6]- and [10]-gingerols and [6]- and [10]-shogaols (1.6 μmol/kg, i.v.). [10]-Shogaol-induced adrenaline secretion was inhibited by administration of capsazepine, a TRPV1 antagonist. In conclusion, gingerols and shogaols activated TRPV1 and increased adrenaline secretion. Interestingly, [10]-shogaol is the only nonpungent compound among the gingerols and shogaols, suggesting its usefulness as a functional ingredient in food.

Identification of medicinal Dendrobium species by phylogenetic analyses using matK and rbcL sequences.

Species identification of five Dendrobium plants was conducted using phylogenetic analysis and the validity of the method was verified. Some Dendrobium plants (Orchidaceae) have been used as herbal medicines but the difficulty in identifying their botanical origin by traditional methods prevented their full modern utilization. Based on the emerging field of molecular systematics as a powerful classification tool, a phylogenetic analysis was conducted using sequences of two plastid genes, the maturase-coding gene (matK) and the large subunit of ribulose 1,5-bisphosphate carboxylase-coding gene (rbcL), as DNA barcodes for species identification of Dendrobium plants. We investigated five medicinal Dendrobium species, Dendrobium fimbriatum, D. moniliforme, D. nobile, D. pulchellum, and D. tosaense. The phylogenetic trees constructed from matK data successfully distinguished each species from each other. On the other hand, rbcL, as a single-locus barcode, offered less species discriminating power than matK, possibly due to its being present with little variation. When results using matK sequences of D. officinale that was deposited in the DNA database were combined, D. officinale and D. tosaense showed a close genetic relationship, which brought us closer to resolving the question of their taxonomic identity. Identification of the plant source as well as the uniformity of the chemical components is critical for the quality control of herbal medicines and it is important that the processed materials be validated. The methods presented here could be applied to the analysis of processed Dendrobium plants and be a promising tool for the identification of botanical origins of crude drugs.

Pungent Qualities of Sanshool-Related Compounds Evaluated by a Sensory Test and Activation of Rat TRPV1

The detection threshold and taste characteristics of sanshools were examined by sensory evaluation, after isolating four sanshools (α-, β-, γ-, and δ-), and two hydroxy sanshools (α- and β-) from the pericarp of Japanese pepper. The Scoville unit (SU) values of the four sanshools were in the range of 80,000–110,000, while those of hydroxy sanshools were 3–5 fold lower than corresponding sanshools. The pungent qualities of each sanshool were different. Burning and tingling were predominantly perceived and lasted for the longest time with α-sanshool. Burning and fresh for γ-sanshool, and tingling and numbing for hydroxy α-sanshool were perceived. Tests on the activation of rat TRPV1 were also performed. All of them were weak agonists. Among them, γ-sanshool was the most potent agonist, although its EC50 value of 5.3 μM was 230 fold higher than that of capsaicin. These results indicate that it would be difficult to explain the pungent quality of each sanshool simply in terms of TRPV1 activation.

Isolation of Antioxidative Phenolic Glucosides from Lemon Juice and Their Suppressive Effect on the Expression of Blood Adhesion Molecules

Phenolic glucosides having radical scavenging activity were examined from the fraction eluted with 20% methanol on Amberlite XAD-2 resin applied to lemon (Citrus limon) juice by using reversed phase chromatography. Four phenolic glucosides were identified as 1-feruloyl-β-D-glucopyranoside, 1-sinapoyl-β-D-glucopyranoside, 6,8-di-C-glucosylapigenin and 6,8-di-C-glucosyldiosmetin by 1H-NMR, 13C-NMR, and MS analyses. They exhibited radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide, although the activity was low in comparison with eriocitrin, a potent antioxidant in lemon fruit, and the eriodictyol of its aglycone. The phenolic compounds in lemon juice were examined for their suppressive effect on the expression of blood adhesion molecules by measuring the expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) induced by necrosis factor-α (TNF-α). 6,8-Di-C-glucosylapigenin, apigenin, and diosmentin of the flavones were found to significantly suppress the expression of ICAM-1 at 10 μM (P<0.05). The phenolic glucosides isolated in this study were contained in comparative abundance in daidai (Citrus aurantium) and niihime (Citrus unshiu × Citrus tachibana) among the sour citrus juices.

Miogadial and miogatrial with α,β-unsaturated 1,4-dialdehyde moieties - novel and potent TRPA1 agonists.

AIMS Most of the terpenoids with an alpha,beta-unsaturated 1,4-dialdehyde moiety, which are found in plants, fungi, and insects, have a pungent taste. However, the neural receptors responsible for the pungency of these terpenoids have not been identified yet. The transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1), which are expressed in the nociceptive neurons, induce a sensation of heat on activation by some pungent ingredients in food. In this study, we selected miogadial (MD), miogatrial (MT), and polygodial (PG) from the terpenoids with an alpha,beta-unsaturated 1,4-dialdehyde moiety and examined the effects of these 3 terpenoids on TRPA1 or TRPV1. MAIN METHODS TRPV1 and TRPA1 activity by 3 terpenoids were evaluated using Ca(2+) imaging and patch-clamp methods in mammalian cells that express TRP heterologously and mouse sensory neurons. KEY FINDINGS The 3 terpenoids activated TRPA1 that was heterologously expressed in HEK293 or CHO cells. The potencies of activation by the 3 terpenoids were equal and almost 10 times stronger than that of allyl isothiocyanate (AITC), which is known as the most potent TRPA1 agonist among all natural products. Moreover, these 3 terpenoids exhibited increased intracellular Ca(2+) concentration in mouse sensory neuron cells compared to AITC. High concentrations of the 3 terpenoids also activated TRPV1 that was heterologously expressed in HEK293 cells. SIGNIFICANCE These results indicated that MD, MT, and PG were more potent in activating TRPA1 than TRPV1, and suggested that they primarily activate TRPA1 to induce pungency.

Protective effect of colored rice over white rice on fenton reaction-based renal lipid peroxidation in rats

Rice has been one of the most important grains. While polished white rice is favored, colored strains of rice, red, or black, have been maintained for religious purposes in Japan. We studied whether feeding of unpolished colored rice instead of white rice ameliorates oxidative renal tubular damage in rats induced by ferric nitrilotriacetate. Whereas renal lipid peroxidation was exacerbated in white rice-fed group in comparison with standard chow group, this exacerbation was not observed in red or black rice-fed groups. These changes were dependent on the proportion of colored rice to standard chow in the diet. Cyanidin 3- O - g - d -glucoside was detectable neither in the serum nor kidney after one week of colored rice diet, but serum protocatechuic acid was significantly increased after black rice diet. There was a generalized decrease in the renal glutathione peroxidase activity in rice diet groups. Renal enzymatic activities of superoxide dismutase, glutathione S -transferase and NAD(P)H quinone reductase were not associated with the levels of lipid peroxidation. However, renal catalase activity was significantly increased in black rice-fed groups. These may partly explain the antioxidative effect. Furthermore, colored strains of rice are rich in proteins. Thus, our data warrants further investigation of the antioxidative effect of colored rice.

Inhibitory effect of anthocyanins and colored rice on diabetic cataract formation in the rat lenses

Abstract In the course of our screening for diabetic cataract inhibitors from edible plants using a rat lens organ culture system under 15 mM xylose condition, five anthocyanin monomers isolated from the extract of grape skins showed the inhibitory activities for lens opacity. Malvidin 3-glucoside and delphinidin 3-glucoside showed stronger inhibitory activities than cyanidin 3-glucoside (C3G), petunidin 3-glucoside (P3G) and peonidin 3-glucoside in this assay system. Concerning a continuous intake of anthocyanins from daily foods, colored rice is one of the good candidates among the Asian countries. Red rice and black rice have been eaten traditionally in China, Japan, India, etc. Thus, we started to collect strains of colored rice from the Asian countries; finally, 48 stains were collected. After extended screening of the collected strains of colored rice, two excellent strains, asamurasaki-2 (AS2, Japanese black rice) and chikushi-akamochi-2 (CH2; Japanese red rice), were selected as potential inhibitory strains for the rat lens opacity. The content of anthocyanins (mainly C3G) and the other important polyphenols (ferulic acid (FA), caffeic acid (CA) and protocatechuic acid (PA)) of these strains were quantified.

The formation mechanism by yeast of 4-hydroxy-2(or 5)-ethyl-5(or 2 ) -methyl -3 (2H) -furanone in miso

The mechanism of the formation of 4-hydroxy-2(or 5)-ethyl-5-(or 2)-methyl-3(2H)-furanone (HEMF) with yeast under caltivation in a medium containing amino-carbonyl reactants of ribose and glycine was investigated using stable isotopes of the corresponding compounds. It was confirmed that the skeleton of the five-membered ring and the methyl group of the side chain of HEMF was formed from ribose, and that the ethyl group was derived from the glucose metabolite by yeast. The formation of HEMF was confirmed when acetaldehyde as the glucose metabolite and a cell-free extract from yeast were added to the medium containing amino-carbonyl reactants. These results suggest that the role of yeast in HEMF formation is not only to provide the glucose metabolite, but also in combining the amino-carbonyl reactants with the glucose metabolite.

Quantitative Analysis of Sanshool Compounds in Japanese Pepper (Xanthoxylum piperitum DC.) and Their Pungent Characteristics

The distributions of each sanshool in the Japanese pepper plant grown in various regions and the change in composition of sanshools during maturation of the fruit were investigated. The degree of pungency, defined as the amount of a sanshool/the threshold value, was calculated, and the pungent qualities of the products were evaluated and compared. The degree of pungency and amount of a sanshool showed a positive correlation. In young leaves and flowers, the degree of pungency was less than that in the fruits, the main compound being α-sanshool, while the two hydroxy sanshools were detected only in trace amounts. The main compound in fruits was hydroxy α-sanshool, whose threshold value was higher than that of α-sanshool. It is concluded that the pungency of Japanese pepper should be evaluated not only by the threshold values, but also by the pungent qualities, the composition of sanshools, and the usage of each product of Japanese pepper.