Antimelanogenesis Effect of Methyl Gallate through the Regulation of PI3K/Akt and MEK/ERK in B16F10 Melanoma Cells.

Methyl gallate is a polyphenolic compound found in many plants, and its antioxidant, antitumor, antibacterial, and anti-inflammatory effects have been extensively studied. More recently, antidepressant-like effects of methyl gallate have been demonstrated in some studies. In the present study, we examined the effects of methyl gallate on melanogenesis, including the tyrosinase inhibitory effect, the melanin content, and the molecular signaling pathways involved in this inhibition. The results showed that methyl gallate inhibited tyrosinase activity and significantly downregulated the expressions of melanin synthesis-associated proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase, dopachrome tautomerase (Dct), and tyrosinase-related protein-1 (TRP1). In conclusion, our findings indicated that activation of MEK/ERK and PI3K/Akt promoted by methyl gallate caused downregulation of MITF and triggered its downstream signaling pathway, thereby inhibiting the production of melanin. In summary, methyl gallate showed significant inhibitory activity against melanin formation, implying that it may be a potential ingredient for application in skin-whitening cosmetics.

A Norsesterterpene Peroxide from a Marine Sponge Hippospongia sp.

One new norsesterterpene peroxide, rhopaloic acid H (1), along with two known related metabolites 2 and 3, were isolated from a marine sponge Hippospongia sp. The structures of compounds were elucidated by means of IR, MS, and NMR techniques and comparison of the NMR data with those of known analogues. Evaluation of the cytotoxicities revealed that compound 2 exhibited significant cytotoxicity against DLD-1, Molt 4, T47D and K-562 cell lines, with IC50 values of 3.18, 0.69, 2.22 and 1.06 µg/mL, respectively. Moreover, compound 3 also showed significant K562 inhibitory activity, with IC50 value of 3.65 µg/mL.

Trocheliolide B, a New Cembranoidal Diterpene from the Octocoral Sarcophyton trocheliophorum.

A new cembranoidal diterpene, trocheliolide B (1), was isolated from the octocoral Sarcophyton trocheliophorum. The structure of 1 was elucidated on the basis of spectroscopic methods.

The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker.

The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation) and reduce the tetanic fade (20 Hz stimulations) observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug) has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia.

A sensitive enzyme-linked immunosorbent assay for detecting carcinogenic aristolochic acid in herbal remedies.

Aristolochic acid, a naturally occurring nephrotoxin and rodent carcinogen, has been associated with the development of various nephropathies in humans. Developing a sensitive and rapid method to screen the aristolochic acid levels in herbal remedies is urgent for protecting public health. Polyclonal antibodies for aristolochic acid were generated from rabbits after the animals had been immunized with either aristolochic acid-ovalbumin (OVA) or aristolochic acid-keyhole limpet hemocyanin (KLH). A competitive indirect enzyme-linked immunosorbent assay (ciELISA) and a competitive direct enzyme-linked immunosorbent assay (cdELISA) were used for the characterization of the antibodies and for analysis of aristolochic acid contaminated in herbal medicine and diet pills. The antibody titers in the serum of rabbits immunized with aristolochic acid-OVA were considerably higher than those from aristolochic acid-KLH-immunized rabbits. The antibodies from the aristolochic acid-OVA-immunized rabbits were further characterized. In the ciELISA with aristolochic acid-KLH as the plate-coating antigen, the concentrations of the aristolochic acid mixture, aristolochic acid I, and aristolochic acid II that caused 50% inhibition (IC50) of binding of antibodies to aristolochic acid-KLH were found to be 1.2, 0.7, and 18 ng/mL, respectively. When 0.25-5 microg/g of standard aristolochic acid was spiked to ground lotus seeds and then extracted with 0.01 M phosphate-buffered saline, the recovery rate was found to be 86.5% in the ciELISA. Analysis of aristolochic acid in herbal medicine and diet pills with ciELISA showed that 10 of the 12 examined samples were contaminated at levels from 0.6 to 655 microg/g. The presence of aristolochic acid was also confirmed by the high-performance liquid chromatography method.

Acute poisonings with Breynia officinalis--an outbreak of hepatotoxicity.

BACKGROUND: In combination with other traditional Chinese medicines, Breynia officinalis, a species of Euphorbiaceae, has long been used to treat contusions, heart failure, venereal diseases, growth retardation, and conjunctivitis. B. officinalis, regarded as a poison, was mistaken for a similar plant, Securinega suffruticosa, and cooked in a soup used for the treatment of muscle soreness, lumbago, and as a tonic in this outbreak. CASE SERIES: Nineteen patients, 11 males and 8 females (average age 49.2 +/- 9.1 years) consumed an average of 130 mL (30-900 mL) of soup containing B. officinalis stems. Fourteen patients developed diarrhea, 10 experienced nausea and chilly sensations, 9 had sensations of abdominal fullness, and 7 suffered from vomiting. The results of liver function tests (LFTs) indicated that the observed maximum median level of alanine aminotransferase (ALT) was 647U/L (range 89-9440 U/L), aspartate aminotransferase (AST) 314 U/L (range 47-7756 U/L), alkaline phosphatase 251 U/L (range 224-278 U/L), and gamma glutamyl transpeptidase 106 U/L (range 84-313 U/L). The median time to the observed median peak levels was 3 days for ALT, 2 days for AST, 5 days for alkaline phosphatase, and 12 days for gamma glutamyl transpeptidase. With supportive treatment, the majority of abnormalities in 14 of the cases resolved within 6 months of exposure. CONCLUSIONS: The consumption of a soup containing B. officinalis Hemsley resulted in dose-related toxic effects. Clinical toxicity consisted primarily of gastrointestinal symptoms and signs and hepatotoxicity. Hepatocellular liver injury rather than cholestatic liver injury was observed. Marked jaundice did not develop.