No abstract

Four new carbazole alkaloids, claurailas A-D (1-4), as well as 12 known carbazoles and three known coumarins were isolated from the roots of Clausena harmandiana. Heptaphylline (6) and 7-methoxyheptaphylline (7) showed strong cytotoxicity against NCI-H187 and KB cell lines with IC(50) values ranging from 1.3 to 2.7 μM. Compound 7 showed no cytotoxicity against Vero cells.

Thai traditional herbal formula ‘’Kleeb Bua Daeng (KBD)’’consists of a 1:1:1 ratio (dry weight) of three medicinal plants: Piper nigrum fruit, the aerial part of Centella asiatica and the petals of Nelumbo nucifera. Oral administration of KBD to unpredictable chronic mild stress (UCMS) mice significantly improved their cognitive function caused by chronic mild stress. Daily administration of KBD significantly decreased the serum corticosterone (CORT) and malondialdehyde (MDA) levels but increased the catalase and superoxide dismutase activities in both frontal cortex and hippocampus. The effects of KBD were similar to those caused by oral administration of vitamin E. HPLC analysis of the KBD extract revealed the presence of piperine, madecassoside, asiaticoside, luteolin-7-O-glucoside, rutin, kaempferol-3-glucoside, quercetin, kaempferol and ferulic acid as major constituents.

Background and Purpose: Itching is the most frequent pathology in dermatology that has significant impacts on people's mental health and social life. Transient receptor potential vanilloid 3 (TRPV3) channel is a promising target for treating pruritus. However, few selecetive and potent antagonists have been reported. This study was designed to identify selective TRPV3 antagonist and elucidate its anti-pruritus pharmacology. Experimental Approach: FlexStation and calcium fluorescence imaging were conducted to track the functional compounds. Whole-cell patch clamp was used to record itch-related ion channel currents. Homologous recombination and site-directed mutagenesis were employed to construct TRPV3 channel chimeras and point mutations for exploring pharmacological mechanism. Mouse models were used for in vivo anti-pruritus assay. Key Results: An acridone alkaloid (citrusinine-II) was purified and characterized from Atalantia monophylla. It directly interacts with Y564 within S4 helix of TRPV3 to selectively inhibit the channel with a half maximal inhibitory concentration (IC 50) of 12.43 μM. Citrusinine-II showed potential efficacy to attenuate both chronic and acute itch. Intradermal administration of citrusinine-II (143 ng/skin site) nearly completely inhibited itch behaviours. It also shows significant analgesic effects. Little side effects of the compound are observed. Conclusion and Implications: By acting as a selective and potent inhibitor of TRPV3 channel, citrusinine-II shows valuable therapeutic effects in pruritus animal models Abbreviations: 2-APB, 2-aminoethoxydiphenyl borate; ASIC3, acid-sensing (proton-gated) ion channel 3; CCK8, cell counting kit-8; Nav, voltage-gated sodium channel; TRP, transient receptor potential; TRPA1, transient receptor potential ankyrin 1; TRPM8, transient receptor potential melastatin 8; TRPV1, transient receptor potential vanilloid 1; TRPV2, transient receptor potential vanilloid 2; TRPV3, transient receptor potential vanilloid 3; TRPV4, transient receptor potential vanilloid 4.

Nine carbazoles and three coumarins were isolated from C. harmandiana. Crude extracts and all isolates were evaluated for antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and lipid peroxidation assay and cytotoxicity against cholangiocarcinoma, KKU-OCA17 and KKU-214 cell lines. 7-Hydroxyheptaphylline and nordentatin showed strong antioxidant activity on lipid peroxidation with IC50 values of 2.95 and 2.90 µM respectively, while the activity on a DPPH assay showed IC50 values of 56.82 and 29.3 µM, respectively. The two compounds exhibited strong cytotoxicity against KKU-OCA17 (IC50=88.7 and 46.1 µM, respectively) and KKU-214 (IC50=43.7 and 39.1 µM, respectively) cell lines. The results show convincingly that these compounds may be the promising leads for the development of cytotoxic agents.