Identification of a New Pyrrolyl Pyridoindole Alkaloid, Melpyrrole, and Flazin from Honey and Their Cough-Suppressing Effect in Guinea Pigs.

The cough-suppressing effect of honey was demonstrated for the first time using a guinea pig model whereby cough was induced by citric acid and capsaicin, and a new pyrrolyl pyridoindole, 1-(5-(hydroxymethyl)-1H-pyrrol-2-yl)-9H-pyrido[3,4-b]indole-3-carboxylic acid (1), named melpyrrole, and flazin (2) were identified as the active principle components. The structures of 1 and 2 were estimated using a combination approach of an activity-guided survey and LC-MS/MS multivariate analysis and were finally established by total synthesis of 1 and comparison with an authentic standard for 2. Both compounds showed antitussive activity comparable to that of dextromethorphan in guinea pigs. Their antitussive effects were unaffected by an opioid antagonist and reversed by a nitric oxide (NO) synthase inhibitor, indicating that these natural products do not act directly on opiate receptors but through the NO signaling pathway.

Effect of facial application of essence containing royal jelly extract on stratum corneum moisture content: A placebo-controlled, double-blind, parallel-group study.

OBJECTIVES: To evaluate the moisturizing function and other effects of royal jelly extract on the skin. The effects of applying an essence containing royal jelly extract on the skin of healthy Japanese males and females were examined. METHODS: Thirty-five healthy Japanese men and women who were aware of their skin dryness applied an essence containing royal jelly extract or placebo for 4 weeks using the split-face method in a placebo-controlled, double-blind, parallel comparative study. The stratum corneum water content, transepidermal water evaporation, pigmentation, pores, and redness were evaluated. RESULTS: The stratum corneum water content significantly increased by the application of essence containing royal jelly extract to the cheeks for 4 weeks compared with placebo. CONCLUSION: The application of an essence containing royal jelly extract significantly improved the moisture content of the stratum corneum of the cheeks, confirming the improvement in the moisturizing function of the royal jelly extract. Furthermore, no adverse events were observed at the application site during the application period, and the test products and royal jelly extract contained in the test product were considered highly safe.

Acetylcholine and Royal Jelly Fatty Acid Combinations as Potential Dry Eye Treatment Components in Mice.

Dry eye is a multifactorial disease characterized by ocular discomfort and visual impairment. Our previous studies have shown that royal jelly (RJ) has restored the capacity for tear secretion by modulating muscarinic calcium signaling. RJ contains acetylcholine, which is a major cholinergic neurotransmitter, and a unique set of fatty acids with C 8 to 12 chains, which are expected to be associated with health benefits. The purpose of the present study was to investigate the active components involved in tear secretion capacity, focusing on acetylcholine and fatty acids in RJ. Using the stress-induced dry-eye model mice, it was confirmed that acetylcholine with three fatty acids (10-hydroxydecanoic acid, 8-hydroxyoctanoic acid, and (R)-3,10-dihydroxydecanoic acid) was essential for tear secretion. In ex vivo Ca2+ imaging, these three fatty acids suppressed the decrease in intracellular modulation of Ca2+ in the lacrimal gland by acetylcholine when treated with acetylcholinesterase, indicating that the specific type of RJ fatty acids contributed to the stability of acetylcholine. To our knowledge, this study is the first to confirm that a specific compound combination is important for the pharmacological activities of RJ. Our results elucidate the active molecules and efficacy mechanisms of RJ.

Cognitive Improvement and Safety Assessment of a Dietary Supplement Containing Propolis Extract in Elderly Japanese: A Placebo-Controlled, Randomized, Parallel-Group, Double-Blind Human Clinical Study.

Objectives. This study aimed to evaluate the effect of propolis on cognitive function in elderly Japanese with a placebo-controlled design. Material and Methods. This study was performed on 79 elderly Japanese. Participants orally received either a placebo or dietary supplement containing propolis extract for 24 weeks. Cognitive function assessed by Cognitrax and various blood or urine markers were measured at pre- and postadministration. Results and Conclusion. Eligible data from 68 subjects (placebo: 33, propolis: 35) who completed the study were analyzed. Compared to the placebo group, the propolis group showed significant improvement in verbal memory in Cognitrax (P=0.028). Total cholesterol, LDL cholesterol, urea nitrogen, creatinine, and uric acid were significantly improved in the propolis group compared to the placebo group (P = 0.011, P = 0.004, P = 0.048, P = 0.045, and P = 0.005, respectively). However, urea nitrogen, creatinine, and uric acid fluctuated within the normal level. Furthermore, a subgroup analysis was performed on those with higher than 100 of the standardized score of the neurocognitive index indicated by the overall Cognitrax score. Significant improvements in the propolis group compared to placebo were confirmed in verbal memory (P = 0.007) and processing speed as indications for information processing ability, complex attention, and concentration (P = 0.029). No side effects were observed in any of the groups. This study demonstrates that propolis is effective in improving cognitive functions such as memory, information processing, complex attention, and concentration in elderly Japanese.

Metabolism and pharmacokinetics of medium chain fatty acids after oral administration of royal jelly to healthy subjects.

The unique fatty acids in royal jelly (RJ), 10-hydroxy-2-decenoic acid and 10-hydroxydecanoic acid are expected to be associated with many health benefits, but little is known on the pharmacokinetics and metabolism. The aim of this study is to confirm the metabolism and pharmacokinetics of RJ fatty acids in humans. Twelve volunteers received RJ capsules or enzyme treated RJ (ETRJ) capsules (800 mg). The other group received two doses of ETRJ tablets (800 mg and 1600 mg). Plasma samples were collected up to 12 h after the RJ intake and urine samples were collected within 24 h after ETRJ tablet consumption. The samples were analyzed by LC/MS/MS. A multivariate analysis of the RJ dose plasma samples detected 2-decenedioic acid (2-DA), sebacic acid (SA), and 3-hydroxysebacic acid (3-HSA) with significantly different intensities (P < 0.05) before and after RJ intake. The area under the concentration (AUC) of 2-DA, SA, and 3-HSA was 2500.05 ± 569.58, 322.57 ± 137.36, and 242.98 ± 58.36 ng h mL-1, respectively. By enzyme treatment, the AUC of 2-DA, SA, and 3-HSA was significantly increased (P < 0.05). The values of AUC and urinary excretion of these metabolites were dose-dependent. The major RJ fatty acids were metabolized to dicarboxylate, absorbed into the circulation and their absorption increased by enzyme treatment. This study provides useful information that will support studies aimed at clarifying the identity of bioactive RJ constituents and their biological effect, and further the development of RJ.