We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

We previously found that daidzein decreased food intake in female rats. The present study aimed to elucidate the relationship between dynamics of appetite-mediated neuropeptides and the anorectic effect of daidzein. We examined appetite-mediated gene expression in the hypothalamus and small intestine during the 3 meals per day feeding method. Daidzein had an anorectic effect specifically at the second feeding. Neuropeptide-Y (NPY) and galanin mRNA levels in the hypothalamus were significantly higher after feeding in the control but not in the daidzein group, suggesting that daidzein attenuated the postprandial increase in NPY and galanin expression. The daidzein group had higher corticotrophin-releasing hormone (CRH) mRNA levels in the hypothalamus after feeding, and increased cholelcystokinin (CCK) mRNA levels in the small intestine, suggesting that CCK is involved in the hypothalamic regulation of this　anorectic effect. Therefore, daidzein may induce anorexia by suppressing expression of NPY and galanin and increasing expression of CRH in the hypothalamus.

We previously found that daidzein decreased food intake in female rats. To understand the mechanism of anorectic action of dietary daidzein, it is necessary to determine distributions of daidzein and S-equol, a metabolite of intestinal bacterial conversion from daidzein, in the body. In the present study, we measured the concentrations of daidzein and S-equol in serum and bile in sham-operated and ovariectomized female rats fed a diet containing 150 mg/kg daidzein for 7 days. Dietary daidzein increased serum and bile concentrations of S-equol to far higher levels than those of daidzein. S-equol concentration was more than several hundred fold-higher in bile than in serum, regardless of ovariectomy. Moreover, to investigate whether accumulation of S-equol is facilitated by efficient enterohepatic circulation during continuous intake of daidzein and S-equol, female rats were fed diet containing daidzein or S-equol (both 150 mg/kg), or control diet for 1, 2, 3, or 5 days. Dietary daidzein significantly increased serum and bile concentrations of S-equol in a time-dependent manner, but not those of daidzein. These results indicated that substantial proportion of dietary daidzein was converted to S-equol, which underwent efficient enterohepatic circulation and predominantly accumulated there.

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Searching the organic compound as anti-inflammatory agent is a fruitful effort to treat inflammatory disorders such as asthma, arthritis, psoriasis, and especially cancer. These disorders can be cured by lipoxygenase (LOX) inhibitors, which have the ability to stop the development and progression of inflammation. The present research described the synthesis of fifteen new N-alkyl/ aralkyl/aryl derivatives (7 a-o) of 2-(4-ethyl-5-(1-phenylcarbamoyl)piperidine-4H-1,2,4-triazol-3-ylthio)acetamide by the continuous conversions of ethyl piperidine-4-carboxylate (a) into phenylcarbamoyl derivative (1) hydrazide (2), semicarbazide (3) and finally the N-ethylated 5-(1-phenylcarbamoyl)piperidine-1,2,4-triazole (4). The target molecules (7 a-o) were formed by the reaction of 4 with various electrophiles (6 a-o), in methanolic potassium hydroxide. These synthetic analogues were characterized by FTIR, 1 H, 13 C NMR spectroscopy, EIMS, and HREIMS spectrometry. The compounds 7 a-o were screened for their inhibitory potential against 15-lipoxygenase. Compounds 7 b, 7 e, 7 c and 7 g displayed the potent inhibitory potential (IC 50 17.52 � 0.67, 35.61 � 0.81, 36.24 � 0.83 & 36.52 � 0.58 μM, respectively), whereas, moderate inhibition was shown by 7 h, 7 a, 7 d with IC 50 values between 42.95 � 0.73 to 45.67 � 0.75 μM, respectively. Some compounds exhibited drug-like characteristics due to their lower cytotoxic and good ADME profiles and supported by molecular modeling studies where one of the NH groups was found engaged through hydrogen bonding with Ala672. The carbonyl group amide and Asn554 were connected by a hydrogen bond, whereas the second NH group was also linked through hydrogen bonds with Gln363.

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Context: Streptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities.Objective: This study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed. Materials and methods: The compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay. Results: Ethyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 mg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12-KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C 14 H 16 N 2 O 3 as determined by the [M þ H] þ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC 50 , 2.16 ± 0.05 mg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC 50 , 4.8 ± 0.05 mg/mL). No toxicity was observed for maculosin (LD 50 , <128 mg/mL) in brine shrimp lethality assay (BSLA) up to the compound's antioxidant activity (IC 50 ) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD 50 value of 8.63 ± 0.15 mg/mL. Conclusions: Maculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.