Aim of the study Caesalpinia sappan is a common remedy in Traditional Chinese Medicine and possesses diverse biological activities including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. In order to provide a scientific basis for the applicability of Caesalpinia sappan in arthritic diseases, the present study aimed to assess the effects of an ethanolic Caesalpinia sappan extract (CSE) on human chondrocytes and macrophages. Materials and Methods Primary human chondrocytes were isolated from cartilage specimens of OA patients. Primary cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved and pretreated with different concentrations of CSE prior to stimulation with 10 ng/ml of interleukin-1beta (IL-1ß) or lipopolysaccharide (LPS). Following viability tests, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated by Griess assay and ELISA, respectively. Using validated real-time PCR assays, mRNA levels of IL-1ß, TNF-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified. SW1353 cells were cotransfected with a COX-2 luciferase reporter plasmid and nuclear factor-kappa-B (NF-κB) p50 and p65 expression vectors in the presence or absence of CSE. Results CSE dose-dependently inhibited the expression of pro-inflammatory cytokines IL-1ß and TNF-α in IL-1ß-stimulated chondrocytes and LPS-stimulated THP-1 macrophages. CSE further suppressed the synthesis of NO in primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2 transcription was found to be related with the CSE inhibition of the p65/p50-driven transactivation of the COX-2 promoter. Conclusions The present report is first to demonstrate the anti-inflammatory activity of CSE in an in vitro cell model of joint inflammation. CSE can effectively abrogate the IL-1ß-induced over-expression of inflammatory mediators at the transcriptional level in human chondrocytes and macrophages, most likely by inhibiting NF-κB (p65/p50) signaling. Blockade of IL-1ß-induced NF-κB signaling and its downstream pro-inflammatory targets by CSE may be beneficial for reducing cartilage breakdown in arthritis.

Human pancreatic cancer cells have an extreme tolerance to nutrition starvation, enabling them to survive in a hypovascular tumor microenvironment. Searching for agents that preferentially inhibit cancer cell viability under nutrition starvation conditions is a novel antiausterity strategy in anticancer drug discovery. In the present study, a hexane extract of the peels of Citrus hystrix fruits showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells using a nutrient-deprived medium. Phytochemical investigation of this bioactive extract led to the isolation of 10 coumarins (1-10) including a new furanocoumarin (1). The isolated compounds were tested for their preferential cytotoxic activity against three different human pancreatic cancer cell lines [PANC-1, MIA PaCa-2, and PSN-1]. Among these, bergamottin (7) was identified as the most active constituent. In real-time live imaging, 7 was found to induce cell shrinkage, membrane blebbing, and disintegration of organelles in PANC-1 cells. Bergamottin (7) was also found to inhibit PANC-1 cell migration and colony formation. Mechanistically, 7 inhibited key survival proteins in the Akt/mTOR signaling pathway. Bergamottin (7) and related compounds are potential antiausterity candidates for drug development against pancreatic cancer.

An ethanolic extract of Anneslea f ragrans leaves showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under a nutrient-deprived condition, with a PC 50 value of 9.6 μg/mL. Phytochemical investigation of this active extract led to the isolation of two new secondary metabolites, fragranones A (1) and B (2), along with 15 previously reported compounds. The structure elucidation of the new compounds was achieved by HRFABMS, acid hydrolysis, NMR, and ECD spectroscopic analysis. Fragranone A (1) is the first example of a rare natural product bearing an acetonide glucose moiety. Fragranone B ( 2) is representative of a rare class of natural products with a threonolactone unit linked to a chalcone through an ether linkage. The isolated compounds exhibited antiausterity activity against PANC-1 cells under nutrient-deprived conditions, and betulin ( 14) was found to be the most potent compound tested, with a PC 50 value of 8.4 μM. In addition, fragranone A (1) was found to suppress PANC-1 cancer cell migration in real time.

The genus Millettia WEIGHT et ARN. (Leguminosae) consists of ca. 100 old world species of climbers and trees, and their seeds and other parts are in some cases known to show insecticidal and piscicidal properties.1) In previous studies 2) flavonoids, isoflavonoids and alkaloids were isolated as chemical components. M. leucantha KURZ is a lofty tree, with pinnate leaves and white flowers, growing throughout Thailand 3); however, its medicinal use is unknown. The present investigation deals with the isolation of chalcone derivatives (1, 2, 4, 6, 7, 10) including four new ones (1, 4, 7, 10) and flavones (3, 5, 8, 9, 11) from the stem bark, and their cytotoxic, antiviral and anti-inflammatory activities. Isolation of Chemical ConstituentsRepeated column chromatography (CC) of the ethanolic extract of the stem bark of M. leucantha afforded eleven products (1-11) in the order of polarity.Among them, seven compounds were identified to be known chalcones, 2Ј-hydroxy-3,4,4Ј,6Ј-tetramethoxychalcone 4,5) (2) and dihydromilletenone methyl ether 6) (6), known furanoflavones, karanjin 7,8) (3) and lanceolatin B 4-6,9) (5), and known simple flavones, desmethoxykanugin 10) (8), 3Ј,4Ј-methylenedioxy-7-methoxyflavone 6) (9), and 3Ј,4Ј-methylenedioxy-5,7-dimethoxyflavone 11) (11), by comparison with reported data. Other chalcone derivatives (1, 4, 7, 10) were found to be new ones. (Chart 1).A new chalcone 1 with molecular formula C 18 H 16 O 5 , was obtained as yellow needles. The 1 H-NMR spectrum (Table 1) showed a set of trans-olefinic protons at d 7.35 and 7.60, a methylenedioxy group at d 6.01 and two methoxy substituents at d 3.87 and 3.91, in addition to two ABX aromatic systems. In electron impact mass spectrum (EI-MS) a relatively abundant fragment peak observed at m/z 165 [2,4-(MeO) 2 C 6 H 3 -CO ϩ , 43%] indicated that two methoxy groups were located on the A ring connected to the ketonic function in a chalcone system. 12) Thus, 1 was determined to be 2Ј,4Ј-dimethoxy-3,4-methylenedioxychalcone, which has been Compound 7, b-methoxychalcone, obtained as pale yellow needles, had molecular formula C 20 H 20 O 7 . The 1 H-NMR spectrum (Table 1) showed an olefinic proton as a singlet at d 6.33 assigned to H-a. Substitution of the ketonic A ring by a methylenedioxy group was deduced by the appearance of peaks at m/z 149 (3,4-OCH 2 O-C 6 H 3 -CO ϩ , 27%) and 121 (3,4-OCH 2 O-C 6 H 3 ϩ , 20%) in EI-MS. Furthermore, a base peak (m/z 341) was reasonably assigned to be a benzopyrilium cation 13,14) produced by the loss of a methoxy group Engineering and Biotechnology; 73/1 Rama VI Road, Rajathevee, Bangkok 10400, Thailand: c Drug Research Department, R&D Division, Nippon Kayaku Co., Ltd.; 3-31-12 Shimo, Kita-ku, Tokyo 115-8588, Japan: and d Graduate School of Pharmaceutical Sciences, Chiba University; 1-33 Yayoi, Inage-ku, Chiba 263-8522, Japan. Received August 16, 2002; accepted November 19, 2002 Four new chalcone derivatives (1, 4, 7, 10) were isolated from the stem bark of Millettia leucantha KURZ (Leguminosae) along wit...

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