Kazuyuki Ohara

The effects of hydroxycinnamic acid derivatives on adiponectin secretion

Adiponectin is positively correlated with insulin sensitivity. Hydroxycinnamic acid derivatives (HADs), observed ubiquitously in plants, have some physiological functions. In this study, we investigated the effect of HADs on serum adiponectin concentrations in mice and on adiponectin secretion of 3T3-L1 adipocytes. In mice, serum adiponectin concentrations were increased by gamma-oryzanol administration. CAPE, curcumin, and trans-ferulic acid markedly enhanced the adiponectin secretion of 3T3-L1 adipocytes, but not gamma-oryzanol. To clarify the effects of gamma-oryzanol in mice or the effects of HADs on the underlying mechanisms of adiponectin secretion, we further investigated the effect of HADs on adiponectin secretion in the NF-kappaB activation state. Although the adiponectin secretion was reduced in the presence of lipopolysaccharide plus TNF-alpha and IFN-gamma, only gamma-oryzanol supported the activity of adiponectin secretion under NF-kappaB activated condition. The results indicate that these HADs might regulate adiponectin secretion by the inhibition of NF-kappaB activation. HADs might be effective for ameliorating type 2 diabetes.

Biological abilities of rice bran-derived antioxidant phytochemicals for medical therapy.

Rice bran contains important bioactive phytochemicals. Among these phytochemicals, steryl ferulates including γ-oryzanol and its major components such as cycloartenyl ferulate (CAF), 24-methylenecycloartanyl ferulate (24-mCAF), β-sitosteryl ferulate (β-SF), and campesteryl ferulate have been intensively studied due to their crucial roles in pathological processes. On the basis of experimental studies published during the last decade in relation to antioxidant, anti-inflammatory, anti-ulcerogenic, hypolipidemic, anti-neoplastic, anti-diabetic, and anti-allergic phenomena, these bioactive phytochemicals are reviewed in this paper. Particularly, in vivo and in vitro studies have clarified that rice bran phytosteryl ferulates mediate anti-inflammatory effects by down-regulating the inflammatory transcription factor, nuclear factor κB (NF-κB), which in turn reduces expression of inflammatory enzymes such as COX-2 and iNOS, and proinflammatory cytokines such as IL-1β, IL-6 and TNF-α. Moreover, rice bran phytosteryl ferulates up-regulate blood adiponectin levels via indirect activation of peroxisomal proliferator-activated receptor γ (PPARγ) through NF-κB inhibition. In this review, we discuss potential pharmacological aspects of rice bran phytosteryl ferulates in the clinical setting.

γ-Oryzanol recovers mouse hypoadiponectinemia induced by animal fat ingestion

Adiponectin is an insulin-sensitizing adipocyte-derived adipokine. The decrease in plasma adiponectin level (hypoadiponectinemia) is involved in the development of insulin resistance and the resulting type 2 diabetes. Our previous studies have demonstrated that γ-oryzanol (ORZ) from rice bran suppressed NF-κB activation and increased adiponectin secretion from adipocyte. In this study, we have evaluated effects of oral administration of animal fat (beef tallow) and palmitate on mouse serum adiponectin level. Oral administrations of beef tallow and palmitate significantly suppressed serum adiponectin levels into around half of the initial level from 48 to 96 h after administration compared with the case of corn oil (P<0.05). Coadministration of ORZ successfully remedied mouse hypoadiponectinemia induced by ingestion of beef tallow and the relative adiponectin levels attained to 1.66±0.23 at 96 h after administration (mean value±s.e., P<0.05). Diverse physiological functions of ORZ in crop bran might be promising us to prevent chronic inflammations in the pathogeneses of the metabolic or insulin resistance syndromes.

Oral administration of γ-aminobutyric acid and γ-oryzanol prevents stress-induced hypoadiponectinemia.

Metabolic syndrome is a cluster of risk factors including insulin resistance and type 2 diabetes and is found to associate partly with chronic stress at work in human. Adiponectin circulates in mammal blood mainly as a low molecular weight (LMW) trimer, hexamer, and a high molecular weight (HMW) multimers. Low circulating levels of adiponectin are related to metabolic syndrome. We have then investigated the influence of immobilization stress on plasma adiponectin concentrations in mice. Relative LMW and HMW adiponectin levels were markedly reduced by immobilization stress (0.66±0.07 and 0.59±0.06 after 102 h, respectively), significantly different from the control values (p<0.01 and 0.05, respectively). γ-Aminobutyric acid (GABA) and γ-oryzanol abundantly contained in germinated brown rice have some physiological functions. We further investigated the effect of GABA, γ-oryzanol, GABA plus γ-oryzanol on adiponectin levels in mice subjected to immobilization stress. GABA and γ-oryzanol significantly increased the relative LMW and HMW adiponectin levels under immobilization stress (1.10±0.11 and 0.99±0.19 after 102 h, respectively, for GABA; 1.08±0.17 and 1.15±0.17 after 102 h, respectively, for γ-oryzanol). Additionally, the co-administration of GABA and γ-oryzanol also increased both relative LMW and HMW adiponectin levels (1.02±0.07 and 0.99±0.10 after 102 h, respectively) and was effective in an earlier phase from 30 to 54 h. The results indicate that the co-administration of GABA and γ-oryzanol might be effective in preventing stress-induced hypoadiponectinemia in mice and be also a promising tool for improving metabolic syndrome aggravated by chronic stress.

Linear chain aldehydes evoke calcium responses in B16 melanoma cells

Oxidative stress is involved in various physiological impairing stages, such as aging, diabetes, atherosclerosis, cirrhosis, and neurological disorders. Recent research indicates that aldehyde compounds derived from oxidized lipids increase in cancer patients compared to healthy individuals. Among of them, hexanal, a six-carbon liner chain aldehyde, is commonly found in cancer patients. Lipid oxidation products including aldehydes are in general chemically unstable and react with biological molecules such as proteins. The purpose of this study is to investigate effects of lipid-derived aldehydes and the related compounds on intracellular Ca2+ responses in B16 melanoma cells. Hexanal-induced [Ca2+]i elevation is observed in B16 cells in a dose dependent manner, but [Ca2+]i changes were observed neither in 3T3-L1 cells nor Caco-2 cells. Propanal, a chain length analogue of hexanal, elicited no change in [Ca2+]i, but nonanal initiated [Ca2+]i increases. Analogue compounds of hexanal failed to induce [Ca2+]i elevation. Furthermore, unsaturated aldehydes known as TRPA1 channel agonists also failed to alter [Ca2+]i levels in B16 melanoma cells. Pharmacological spectra using inhibitors against intracellular Ca2+ signaling suggest that hexanal-induced [Ca2+]i responses in B16 cells might be involved in TRP channels other than TRPA1. Our results suggest that saturated aliphatic chain aldehydes would be novel compounds for initiating [Ca2+]i increases through very strict recognitions of chain saturation, aldehydic base structures, and chain lengths in B16 melanoma cells. B16 cells would have sensing mechanisms for oxidative status and/or metabolic activities in their growth environment.

Rice Bran Antioxidants in Health and Wellness

Rice is one of the worlds most important food crops, and more than half the people in the world eat rice as the main part of their diet. Rice bran is a component of raw rice that is obtained when it is removed from the starchy endosperm in the rice milling process. Antioxidants in rice bran have professed health benefits, as well as antioxidant characteristics for improving the storage ability of food additives for further health benefits. These antioxidants possess promising health-related benefits in the prevention of various diseases, including cancer, inflammatory bowel disease, hyperlipidemia, fatty liver, hypercalciuria, kidney stones, gastrointestinal ulcers, rheumatism, and heart disease, and also in postmenopausal syndrome, etc. In addition, extract from rice bran increases adiponectin secretion, which indicates its potential use for treatment of atherosclerosis and type 2 diabetes. Moreover, γ-oryzanol is widely used as an anabolic drug by bodybuilding athletes.

Plant-Derived Hydroxycinnamate Derivatives, Insulin Sensitivity, and Adiponectin: Implications for Diabetes Control

Hydroxycinnamate derivatives, observed ubiquitously in plants, have some physiological functions. Curcumin, a major active hydroxycinnamate derivative of turmeric in curry, is an inhibitor of nuclear factor (NF)-κB and shows antioxidant activity. Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, derived from plant metabolites, also acts as an NF-κB inhibitor and antioxidant. In this chapter, plant-derived hydroxycinnamate derivatives, curcumin, CAPE, and crop bran-derived γ-oryzanol are discussed. γ-Oryzanol showed the activation of adiponectin secretion from 3T3-L1 adipocyte only in the inflammatory state, but curcumin and CAPE enhanced the secretion even in the steady state. The conclusion is that the inhibition of NF-κB activation by the hydroxycinnamate derivatives disinhibits peroxisome proliferator-activated receptor gamma in adipocyte, resulting in the amelioration of insulin resistance. The hydroxycinnamate derivatives are promising tools for therapeutic drugs against insulin resistance syndromes, including type 2 diabetes mellitus.