Development of S-Methylmethionine Sulfonium Derivatives and Their Skin-Protective Effect against Ultraviolet Exposure

In a previous study, we have demonstrated that S-methylmethionine sulfonium (SMMS) confers wound-healing and photoprotective effects on the skin, suggesting that SMMS can be used as a cosmetic raw material. However, it has an unpleasant odor. Therefore, in the present study, we synthesized odor-free SMMS derivatives by eliminating dimethyl sulfide, which is the cause of the unpleasant odor and identified two derivatives that exhibited skin-protective effects: one derivative comprised (2S,4S)- and (2R,4S)-2-phenylthiazolidine-4-carboxylic acid and the other comprised (2S,4R)-, (2S,4S)-, (2R,4R)-, and (2R,4S)-2-phenyl-1,3-thiazinane-4-carboxylic acid. We performed in vitro proliferation assays using human dermal fibroblasts (hDFs) and an immortalized human keratinocyte cell line (HaCaT). The two SMMS derivatives were shown to increase hDF and HaCaT cell proliferation as well as improve their survival by protecting against ultraviolet exposure. Moreover, the derivatives regulated the expression of collagen type I and MMP mRNAs against ultraviolet exposure in hDFs, suggesting that these derivatives can be developed as cosmetic raw materials.

Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-(L)-Methionine

S-methyl-(L)-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of −3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

Inhibitory Effect of Vitamin U (S-Methylmethionine Sulfonium Chloride) on Differentiation in 3T3-L1 Pre-adipocyte Cell Lines

BACKGROUND: S-methylmethionine sulfonium chloride was originally called vitamin U because of its inhibition of ulceration in the digestive system. Vitamin U is ubiquitously expressed in the tissues of flowering plants, and while there have been reports on its hypolipidemic effect, its precise function remains unknown. OBJECTIVE: This study was designed to evaluate the anti-obesity effect of vitamin U in 3T3-L1 pre-adipocyte cell lines. METHODS: We cultured the pre-adipocyte cell line 3T3L1 to overconfluency and then added fat differentiation-inducing media (dexamethasone, IBMX [isobutylmethylxanthine], insulin, indomethacin) and different concentrations (10, 50, 70, 90, 100 mM) of vitamin U. Then, we evaluated changes in the levels of triglycerides (TGs), glycerol-3-phosphate dehydrogenase (G3PDH), AMP-activated protein kinase (AMPK), adipocyte-specific markers (peroxisome proliferator-activated receptor gamma [PPAR-gamma], CCAAT/enhancer-binding protein alpha [C/EBP-alpha], adipocyte differentiation and determination factor 1 [ADD-1], adipsin, fatty acid synthase, lipoprotein lipase) and apoptosis-related signals (Bcl-2, Bax). RESULTS: There was a gradual decrease in the level of TGs, C/EBP-alpha, PPAR-gamma, adipsin, ADD-1 and GPDH activity with increasing concentrations of vitamin U. In contrast, we observed a significant increase in AMPK activity with increasing levels of vitamin U. The decrease in bcl-2 and increase in Bax observed with increasing concentrations of vitamin U in the media were not statistically significant. CONCLUSION: This study suggests that vitamin U inhibits adipocyte differentiation via down-regulation of adipogenic factors and up-regulation of AMPK activity.

Úlceras en intestino delgado por glucosamina con MSM: Reporte de un caso / Case report: Ulcers in the small intestine due to glucosamine and methylsulfonylmethane (MSM) use

Reportamos el caso de una paciente con dolor abdominal, anemia por deficiencia de hierro y sangre oculta positiva en materia fecal. Sin sangrado evidente. Historia de osteoartritis en manejo con glucosamina con metilsulfonilmetano. Endoscopia superior y colonoscopia no explican sangrado. Cápsula endoscópica muestra múltiples úlceras circunferenciales algunas de ellas con sangrado activo. Se descarta uso de AINES y enfermedad de Crohn. Al mes de suspender suplemento nutricional hay resolución de síntomas y de anemia con sangre oculta negativa. No hubo recurrencia de síntomas.

We report on the case of a female patient with abdominal pain, iron deficiency anemia who tested positive for fecal occult blood but had no overt gastrointestinal bleeding. Patient had a known history of osteoarthritis and used Glucosamine - MSM. Both upper GI endoscopy and colonoscopy were negative. Capsule endoscopy showed multiple concentric ulcers, several of which were actively bleeding. Patient reported no use of NSAIDs, and there was no evidence of Crohn's disease. Nutritional supplements were stopped. After four weeks abdominal pain improved, patient had anemia and a fecal occult blood test was negative. Symptoms have not recurred.

Positron emission tomography with L-S-methyl-11C-methioine and its biodistribution / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the biodistribution of L-[S-methyl-(11)C]-methioine ((11)C-MET) and explore its clinical application in positron emission tomography (PET) for brain tumor detection.</p><p><b>METHODS</b>Twenty-four Wistar rats and divided into 6 equal groups and injected with (11)C-MET through the tail vein and killed by decollation at 5, 10, 20, 30 and 40 min after injection, respectively. The liver, brain, blood, heart, lung, kidney, and spleen were harvested to measure the radioactivity and calculate the biodistribution of (11)C-MET. PET imaging with (11)C-MET was performed in 6 normal volunteers and 30 patients with pathologically confirmed brain gliomas.</p><p><b>RESULTS AND CONCLUSION</b>(11)C-MET showed high blood uptake and a long retention in the tumor mass, therefore can be a valuable tracer for PET imaging of brain tumor and the hypophysis.</p>