Dehydroabietic acid, a diterpene, improves diabetes and hyperlipidemia in obese diabetic KK-Ay mice.

Kang, Min-Sook,Hirai, Shizuka,Goto, Tsuyoshi,Kuroyanagi, Kayo,Kim, Young-Il,Ohyama, Kana,Uemura, Taku,Lee, Joo-Young,Sakamoto, Tomoya,Ezaki, Yoichiro,Yu, Rina,Takahashi, Nobuyuki,Kawada, Teruo Published for International Union of Biochemistry 2009 Biofactors Vol.35 No.5

<P>Terpenoids, which are contained in a large number of dietary and herbal plants, have many biological effects. In this study, the effects of dehydroabietic acid (DAA), a diterpene, on glucose and lipid metabolism were examined using obese diabetic KK-Ay mice. We showed here that DAA treatment decreased not only plasma glucose and insulin levels but also plasma triglyceride (TG) and hepatic TG levels. To examine the mechanism underlying the effects of DAA, the production of inflammatory cytokines was measured. It was shown that the DAA treatment suppressed the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNFalpha) (proinflammatory cytokines) and increased that of adiponectin (an anti-inflammatory cytokine). As a result of the changes in the production of inflammatory cytokines caused by the DAA treatment, the accumulation of macrophages in adipose tissues was reduced. These results indicate that treatment with DAA improves the levels of plasma glucose, plasma insulin, plasma TG, and hepatic TG through the decrease in the macrophage infiltration into adipose tissues, suggesting that DAA is a useful food-derived compound for treating obesity-related diseases.</P>

Curcumin in various cancers.

Shehzad, Adeeb,Lee, Jaetae,Lee, Young Sup Published for International Union of Biochemistry 2013 Biofactors Vol.39 No.1

<P>Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers.</P>

Inhibitory effect of luteolin on the odorant-induced cAMP level in HEK293 cells expressing the olfactory receptor.

Yoon, Yeo Cho,Hwang, Jin-Teak,Sung, Mi-Jeong,Wang, Shuaiyu,Munkhtugs, Davaatseren,Rhyu, Mee-Ra,Park, Jae-Ho Published for International Union of Biochemistry 2012 Biofactors Vol.38 No.5

<P>Luteolin is a flavonoid in many fruits and vegetables. Although luteolin has important biological functions, including antioxidant, anti-inflammatory, antimicrobial, and neuroprotective activities, little is known about the functions of luteolin in the olfactory system. Various odorants can be detected and distinguished by using several molecular processes, including the binding of odorants to odorant receptors, activation of adenylyl cyclase (AC), changes of cyclic adenosine monophosphate (cAMP) and Ca(2+) levels in olfactory sensory neurons, as well as changes in membrane potentials and the transmission of electric signals to the brain. Because AC-cAMP signal transduction plays a pivotal role in the olfactory system, we evaluated the effects of luteolin on the AC-cAMP pathway that had been stimulated by the odorant eugenol. We demonstrated that eugenol caused an upregulation of the cAMP level and the phosphorylation of phosphokinase A (PKA, a downstream target of cAMP) in human embryonic kidney 293 (HEK293) cells expressing the murine eugenol receptor. This upregulation significantly decreased in the presence of luteolin, suggesting that luteolin inhibited the odorant-induced production of cAMP and affected the downstream phosphorylation of PKA.</P>

Novel cell-based assay reveals associations of circulating serum AhR-ligands with metabolic syndrome and mitochondrial dysfunction.

Park, Wook-Ha,Jun, Dae Won,Kim, Jin Taek,Jeong, Jae Hoon,Park, Hyokeun,Chang, Yoon-Seok,Park, Kyong Soo,Lee, Hong Kyu,Pak, Youngmi Kim Published for International Union of Biochemistry 2013 Biofactors Vol.39 No.4

<P>Serum concentrations of environmental pollutants have been positively correlated with diabetes and metabolic syndrome in epidemiologic studies. In turn, abnormal mitochondrial function has been associated with the diseases. The relationships between these variables, however, have not been studied. We developed novel cell-based aryl hydrocarbon receptor (AhR) agonist bioassay system without solvent extraction process and analyzed whether low-dose circulating AhR ligands in human serum are associated with parameters of metabolic syndrome and mitochondrial function. Serum AhR ligand activities were measured as serum 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (sTCDDeq) in pM using 10 μL human sera from 97 Korean participants (47 with glucose intolerance and 50 matched controls, average age of 46.6 9.9 years, 53 male and 45 female). sTCDDeq were higher in participants with glucose intolerance than normal controls and were positively associated (P < 0.01) with obesity, blood pressure, serum triglyceride, and fasting glucose, but not with HDL-cholesterol. Body mass index was in a positive linear relationship with serum AhR ligands in healthy participants. When myoblast cells were incubated with human sera, ATP generating power of mitochondria became impaired in an AhR ligand concentration-dependent manner. Our results support that circulating AhR ligands may directly reduce mitochondrial function in tissues, leading to weight gain, glucose intolerance, and metabolic syndrome. Our rapid cell-based assay using minute volume of human serum may provide one of the best monitoring systems for circulating AhR ligands, good clinical biomarkers for the progress of disease and therapeutic efficacy.</P>

In vivo protective effects of dietary curcumin and capsaicin against alcohol-induced oxidative stress.

Pyun, Chang-Won,Kim, Ji-Han,Han, Kyu-Ho,Hong, Go-Eun,Lee, Chi-Ho Published for International Union of Biochemistry 2014 Biofactors Vol.40 No.5

<P>BALB/c mice were exposed to chronic alcohol-induced oxidative stress by intragastric administration of excessive ethanol (5 g/kg body weight) during the 24-week period. Curcumin (0.016%) or capsaicin (0.014%) containing diets were fed with or without ethanol treatment in four groups. There was no statistically significant difference in the behavioral test between all groups during the experimental period. Only one alcohol-treated mouse fed a normal diet showed a behavioral disorder and died before the raising period was completed. There were no effects on the activity of catalase and superoxide dismutase in the brain. However, curcumin or capsaicin treatment prevented alcohol-induced decline in brain weight. Furthermore, the levels of malondialdehyde and phosphatidylcholine hydroperoxide were significantly reduced in the brain tissue extract. The findings of this study demonstrated and confirmed the antioxidant effect of curcumin and capsaicin against alcohol-induced oxidative stress, and they suggest a direction for further studies.</P>