Effects of Hura crepitans and its active ingredient, daphne factor F3, on dihydrotestosterone-induced neurotrophin-4 activation and hair retardation.

Neurotrophin (NT)-4 is known to be an inducer of catagen in the hair cycle, but little is known of its role in the pathogenesis of androgenetic alopecia (AGA). We previously studied the gene expression of dermal papilla cells from AGA patients and controls and found that NT-4 was up-regulated in the AGA patients. In the present study, the etiological relationship between NT-4 and androgen, which is one of the causes of AGA, and the effect of an NT-4 inhibitor on hair growth were investigated. We established a NT-4 luciferase reporter assay system using a roughly 2-kb region upstream of the NT-4 transcriptional start site and investigated an accelerating effect of androgen on NT-4 transcription. We also screened for a NT-4 inhibitor by using the NT-4 reporter assay and evaluated the effects of NT-4 inhibitors on hair growth by using dihydrotestosterone (DHT)-implanted mice. The results show that transcriptional activity of NT-4 was accelerated by androgen, and extract of Hura crepitans L. inhibited the DHT-induced NT-4 transcriptional activation and ameliorated the retardation of hair regrowth by DHT-implanted mice. We also isolated the active ingredient in H. crepitans and found its structure to be that of 6,7-epoxy-5-hydroxyresiniferonol-14-(2,4-tetradecadienoate), i.e., daphne factor F3. These findings demonstrated that NT-4 activity accelerated by androgen might contribute to the pathogenesis of AGA and indicated that NT-4 inhibitors such as H. crepitans and daphne factor F3 might have a salutary effect on AGA.

Study of the pharmacokinetics of eriodictyol-6-C-ß-d-glucoside, a flavonoid of rooibos (Aspalathus linearis) extract, after its oral administration in mice.

Systemic dry syndrome affects quality of life, and various effective methods are being developed for its treatment. We recently found that rooibos (Aspalathus linearis) extract activates muscarinic M3 receptor and improves dryness in mice and humans. We identified eriodictyol-6-C-ß-D-glucoside (E6CG) as the active component affecting the secretory functions of exocrine glands; however, the pharmacokinetics and distribution of E6CG in exocrine glands have not been elucidated in mice receiving rooibos extract. We have developed a quantification method using LC-MS/MS to detect E6CG without an internal standard. Experiments on C57BL/6 mice administered rooibos extract showed that E6CG was transferred into blood plasma, with its concentration levels peaking 19.3 min after treatment. Substantial levels of E6CG were detected in the submandibular, sublingual, parotid, and lacrimal glands and in the sweat glands in palm skin. This study reports that rooibos extracts containing E6CG can be used as functional foods for improving systemic dryness.

A thin layer of sucrose octasulfate protects the oesophageal mucosal epithelium in reflux oesophagitis.

Sucralfate is effective for the treatment of gastric and duodenal ulcers owing to its protective gel-forming ability. However, the mechanism by which sucralfate protects the oesophageal mucosa against reflux oesophagitis has not been clarified. We aimed to investigate the mechanisms of action of sucralfate and sucrose octasulfate (SOS), a component of sucralfate. SOS and sucralfate were administered to oesophagitis-induced rats, and the ulcer lesion size was macroscopically examined and scored. Effective pepsin activity in the gastric juices obtained from the animal model was evaluated by a casein digestion test. Sucralfate and SOS improved the pathology scores in a dose-dependent manner, whereas gastric juice pepsin activity was not impaired by therapeutic doses of SOS. As SOS lacks the ability to form a thick gel layer by polymerisation, we examined the distribution of SOS in the mucosal lumen by imaging mass spectrometry (IMS) to determine whether SOS directly adheres to the mucosal surface. A clear homogeneous thin-layer SOS film (>100 µm thick) was visualized on the oesophageal mucosal surface. Moreover, this SOS film formation was enhanced at ulcer lesion sites. Taken together, SOS appears to protect oesophageal mucosa against reflux oesophagitis via thin-layer formation on the mucosal surface.