Quercetin 3-O-malonylglucoside in the leaves of mulberry (Morus alba) is a functional analog of ghrelin.

Mulberry (Morus alba) leaf is traditionally consumed as a functional tea with remedial effects, such as preventing aging-related diseases. Two similar compounds, quercetin 3-O-malonylglucoside, and kaempferol 3-O-malonylglucoside, were detected in mulberry leaves and found to be structural recombinant composites of teaghrelin and emoghrelin, two classes of non-peptidyl compounds functionally identified as analogs of ghrelin. Molecular modeling showed that these two mulberry compounds were able to enter and interact with the ghrelin receptor and theoretical calculation revealed that they were similar to emoghrelin but slightly weaker than teaghrelin in terms of interaction with the receptor. The relatively abundant compound, quercetin 3-O-malonylglucoside was subjected to a bioactivity assay, and the result confirmed that it was able to increase the growth hormone secretion of rat anterior pituitary cells. It seems that quercetin 3-O-malonylglucoside is also a functional analog of ghrelin and presumably a key ingredient for the anti-aging activity of mulberry leaves. PRACTICAL APPLICATIONS: According to this study, quercetin 3-O-malonylglucoside and kaempferol 3-O-malonylglucoside are suggested to serve as active ingredients in tea products prepared from mulberry leaves. Contents of these two compounds might be used as key factors for breeding or screening mulberry varieties for commercial cultivation. Moreover, water extract of mulberry leaves containing these compounds can be used as an adequate supplement for functional food.

Identification of two teaghrelins in Shy-jih-chuen oolong tea.

Teaghrelins are unique acylated flavonoid tetraglycosides originally identified in Chin-shin oolong tea, and proposed to be potential oral analogs of ghrelin. Two acylated flavonoid tetraglycosides were isolated from Shy-jih-chuen oolong tea, and their chemical structures were determined to be quercetin and kaempferol 3-O-[α-L-arabinopyranosyl(1 â†’ 3)][2"-O-(E)-p-coumaroyl] [ß-D-glucopyranosyl(1 â†’ 3)-α-L-rhamnopyranosyl(1 â†’ 6)]-ß-D-glucoside. These two compounds were extremely similar to the two teaghrelins (teaghrelin-1 and teaghrelin-2) in Chin-shin oolong tea by simply replacing a glucopyranosyl group with an arabinopyranosyl group. Molecular modeling showed that the two putative teaghrelins identified in Shy-jih-chuen docked to and interacted with the ghrelin receptor as well as teaghrelin-1 and teaghrelin-2. Mixture of these two putative teaghrelins was shown to enhance the release of growth hormone from primary anterior pituitary cells of rats. The results suggest that two teaghrelins, named teaghrelin-3 and teaghrelin-4, are present in Shy-jih-chuen oolong tea and possess biological activities analogous to teaghrelins in Chin-shin oolong tea. PRACTICAL APPLICATIONS: According to this study, teaghrelin-3 and teaghrelin-4 may be regarded as active ingredients for the quality control of Shy-jih-chuen oolong tea. The content of teaghrelins may serve as a key factor for the farmers to select new tea plants in their next propagation of Shy-jih-chuen cultivar. Crude water extract of Shy-jih-chuen oolong tea containing teaghrelins is considered to be an adequate food supplement or additive in functional food products.

Echinacoside Isolated from Cistanche tubulosa Putatively Stimulates Growth Hormone Secretion via Activation of the Ghrelin Receptor.

Cistanche species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides-echinacoside, tubuloside A, and acteoside-were detected in the water extract of Cistanche tubulosa (Schenk) R. Wight and the major constituent, echinacoside, was further purified. Echinacoside of a concentration higher than 10-6 M displayed significant activity to stimulate growth hormone secretion of rat pituitary cells. Similar to growth hormone-releasing hormone-6, a synthetic analog of ghrelin, the stimulation of growth hormone secretion by echinacoside was inhibited by [D-Arg¹, D-Phe5, D-Trp7,9, Leu11]-substance P, an inverse agonist of the ghrelin receptor. Molecular modeling showed that all the three phenylethanoid glycosides adequately interacted with the binding pocket of the ghrelin receptor, and echinacoside displayed a slightly better interaction with the receptor than tubuloside A and acteoside. The results suggest that phenylethanoid glycosides, particularly echinacoside, are active constituents putatively responsible for the anti-aging effects of C. tubulosa and may be considered to develop as non-peptidyl analogues of ghrelin.

Image-guided study of inter-fraction and intra-fraction set-up variability and margins in reverse semi-decubitus breast radiotherapy.

BACKGROUND: This study aimed to evaluate the inter-fraction set-up error and intra-fraction motion during reverse semi-decubitus (RSD) breast radiotherapy, and to determine a planning target volume (PTV) margin. MATERIAL AND METHODS: Pre- and post-treatment cone-beam computed tomography (CBCT) scans were prospectively acquired at fractions 1, 4, 7, 8, 11, and 14 for 30 patients who underwent RSD breast radiotherapy. Online correction for initial set-up error greater than 5 mm or 2° was performed and post-correction CBCT was acquired. An off-line analysis was performed to quantify initial and residual inter-fraction set-up errors and intra-fraction motion in three-dimensions. Patient inter-fraction errors were analysed for time trends during the course of radiotherapy. PTV margins were calculated from the systematic and random errors. RESULTS: The initial inter-fraction population systematic errors were 1.8-3.3 mm (translation) and 0.5° (rotation); random errors were 1.8-2.1 mm (translation) and 0.3-0.5° (rotation). After online correction, the residual inter-fraction population systematic errors were 1.2-1.8 mm (translation) and 0.3-0.4° (rotation); random errors were 1.4-1.6 mm (translation) and 0.3-0.4° (rotation). Intra-fraction population systematic and random errors were ≤ 1.3 mm (translation) and ≤ 0.2° (rotation). The magnitude of inter-fraction set-up errors in the anterior-posterior direction, roll, and yaw were significantly correlated with higher body weight and body mass index (BMI). The inter-fraction set-up error did not change significantly as a function of time during the course of radiotherapy. The magnitude of intra-fraction motion was not correlated with patient characteristics and treatment time. The total PTV margins accounting for pre-correction and intra-fraction errors were 6.5-10.2 mm; those accounting for post-correction and intra-fraction errors were 4.7-6.3 mm. CONCLUSIONS: CBCT is an effective modality to evaluate and improve the inter-fraction set-up reproducibility in RSD breast radiotherapy, particularly for patients with higher BMI. Intra-fraction motion was minimal during RSD breast radiotherapy.

The Effect of Body Mass Index and Weight Change on Late Gastrointestinal Toxicity in Locally Advanced Cervical Cancer Treated With Intensity-modulated Radiotherapy.

OBJECTIVE: To evaluate the effects of body mass index (BMI) and weight change during radiotherapy on the development of toxicity in patients with locally advanced cervical cancer (LACC) treated with intensity-modulated radiotherapy (IMRT). METHODS: A total of 245 patients were analyzed after undergoing definitive IMRT treatment between 2004 and 2015 for stage IB2 to stage IVA LACC. The patients were divided into 3 groups: underweight (BMI <18.5 kg/m), normal weight (BMI 18.5-24.9 kg/m), and overweight (BMI ≥25.0 kg/m). The relationships between toxicity, clinical factors, and the bowel dose-volume histogram were analyzed. V45 indicated the bowel volume that received a radiation dose of 45 Gy. RESULTS: The median follow-up period was 63 months. The V45 was similar among the 3 groups. The 5-year rates of grade 3 or higher late gastrointestinal toxicities were 18.6%, 4.0%, and 4.2% for the underweight, normal weight, and overweight groups, respectively (P = 0.002). In the multivariable analysis, underweight (hazard ratio, 13.99; 95% confidence interval, 3.22-60.82; P < 0.001) and weight loss (> -5%) (hazard ratio, 5.91; 95% confidence interval, 1.75-19.98; P = 0.004) were significant predictors of grade 3 or higher-grade late gastrointestinal toxicities. CONCLUSION: A BMI of less than 18.5 kg/m and weight loss (> -5%) were associated with a higher risk of grade ≥3 or higher late gastrointestinal toxicity in patients with LACC treated with definitive IMRT. Future research on the development of a standardized and structured approach to improve the therapeutic ratio for the supportive care of patients with LACC is needed.