Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp). However, purpurogallin did not affect the bone resorbing function of mature osteoclasts evident by the resorption pit assay. Activation of mitogen-activated protein kinases, Akt and IkB pathways in RANK signaling were not altered by purpurogallin, whereas the expression of c-Fos and NFATc1, key transcriptional regulators in osteoclastogenesis, was dramatically inhibited by purpurogallin. Purpurogallin also significantly reduced the expression level of B lymphocyte-induced maturation protein-1 (Blimp1) gene (Prdm1). Further, downregulation of Blimp1 led to forced expression of anti-osteoclastogenic genes, including interferon regulatory factor-8 (Irf8) and B-cell lymphoma 6 (Bcl6) genes. Taken together, our data suggested that purpurogallin inhibits osteoclast differentiation via downregulation of c-Fos and NFATc1.

In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n-hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and β-santalol as the active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9 ppm) of α-santalol was comparable with that of a positive control, inulavosin (TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were also found to show a significant antifungal effect against a dermatophytic fungus, Trichophyton rubrum. Based on a similarity of the morphological change of the immobilized Trichophyton hyphae in scanning electron micrographs between treatments with α-santalol and griseofulvin (used as the positive control), inhibitory effect of α-santalol on mitosis (the antifungal mechanism proposed for griseofulvin) was assessed using sea urchin embryos. As a result, α-santalol was revealed to be a potent antimitotic agent induced by interference with microtubule assembly. These data suggested that α-santalol or sandalwood oil would be promising to further practically investigate as therapeutic agent for cancers as well as fungal skin infections.

Annual wormwood (AW) (Artemisia annua L.) has anti-malarial, anti-bacterial, anti-oxidant, anti-tumour, and anti-inflammatory activities. In the present study, we evaluated the effects of annual wormwood leaves (AWL) on adipocyte differentiation in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. 3T3-L1 adipocytes and HFD-induced obese rats were treated with AWL, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Treatment with AWL effectively prevented triglyceride accumulation during adipogenesis in a dose-dependent manner. Consistently, AWL suppressed the differentiation of 3T3-L1 preadipocytes into adipocytes through the downregulation of dexamethasone, 3-isobutyl-1- methylxanthine, and insulin (DMI)-induced serine/threonine kinase protein kinase B (PKB/Akt) activation and the expression of adipogenic genes, including the CCAAT/enhancer binding protein-α (C/EBPα) and peroximal proliferator-activated receptor-γ (PPARγ). Moreover, the expression of adipocyte fatty acid-binding protein 4 (aP2), which is a known PPARγ-target gene, was downregulated by AWL treatment. Oral administration of AWL extracts significantly decreased the body weight gain, adipose tissue mass, adipocyte cell size, serum triglyceride (TG), and total cholesterol (TC) levels in HFD-induced obese rats. These results provide novel insight into the molecular mechanisms underlying the anti-obesity effects of AWL that are mediated by the downregulation of the expression of major adipogenic transcription factors, C/EBPα and PPARγ and Akt signalling.

Rotenone, isolated from roots of derris plant, has been shown to possess various biological activities, which lead to attempting to develop a potent drug against several diseases. However, recent studies have demonstrated that rotenone has the potential to induce several adverse effects such as a neurodegenerative disease. Radiolytic transformation of the rotenone with gamma-irradiation created a new product, named rotenoisin B. The present work was designed to investigate the anticancer activity of rotenoisin B with low toxicity and its molecular mechanism in hepatic cancer cells compared to a parent compound, rotenone. Our results showed rotenoisin B inhibited hepatic cancer cells’ proliferation in a dose dependent manner and increased in apoptotic cells. Interestingly, rotenoisin B showed low toxic effects on normal cells compared to rotenone. Mitochondrial transmembrane potential has been decreased, which leads to cytochrome c release. Down regulation of anti-apoptotic Bcl-2 levels as well as the up regulation of proapoptotic Bax levels were observed. The cleaved PARP (poly ADP-ribose polymerase) level increased as well. Moreover, phosphorylation of extracellular signal regulated kinase (ERK) and p38 slightly up regulated and intracellular reactive oxygen species (ROS) increased as well as cell cycle arrest predominantly at the G₂/M phase observed. These results suggest that rotenoisin B might be a potent anticancer candidate similar to rotenone in hepatic cancer cells with low toxicity to normal cells even at high concentrations compared to rotenone.