Anti-arthritic properties of crude extract from Chenopodium ambrosioides L. leaves.

OBJECTIVES: To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. METHODS: Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. KEY FINDINGS: Treatment of CIA mice with HCE 5 mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. CONCLUSIONS: HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.

The orally active pterocarpanquinone LQB-118 exhibits cytotoxicity in prostate cancer cell and tumor models through cellular redox stress.

BACKGROUND: The targeted induction of reactive oxygen species (ROS) is a developing mechanism for cancer therapy. LQB-118 is a pterocarpanquinone and ROS-inducing agent with proven antineoplastic activity. Here, LQB-118 efficacy and mechanism of activity, were examined in Prostate Cancer (PCa) cell and tumor models. METHODS: PC3, LNCaP, and LAPC4 PCa cells were applied. Dicoumarol treatment was used to inhibit quinone reductase activity. N-acetylcysteine (NAC) was applied as a ROS scavenger. ROS production was quantified by H2 DCFDA flow cytometry. LQB-118 treated cells were evaluated for changes in lipid peroxidation, viability, and apoptosis. Treatment-induced gene expression was measured by RT-qPCR and Western Blot. SOD1 knockdown was achieved with siRNA or miRNA mimic transfection. MicroRNA specificity was determined by 3'UTR reporter assay. Oral LQB-118 treatment (10 mg/kg/day) efficacy was determined in athymic male nude mice bearing subcutaneous PC3 xenograft tumors. RESULTS: LQB-118 treatment triggered PCa cell death and apoptosis. Therapeutic activity was at least partially dependent upon quinone reduction and ROS generation. LQB-118 treatment caused an increase in cellular ROS and lipid peroxidation. Treated cells exhibited elevated levels of NQO1, Nrf2, and SOD1. The miRNAs miR-206, miR-1, and miR-101 targeted and reduced SOD1 expression. The knockdown of SOD1, by siRNA or miRNA, enhanced LQB-118 cytotoxicity. Orally administered LQB-118 treatment significantly reduced the growth of established PCa xenograft tumors. CONCLUSION: LQB-118 is a developing and orally active pterocarpanquinone agent that effectively kills PCa cells through quinone reduction and ROS generation. The inhibition SOD1 expression enhances LQB-118 activity, presumably by impairing the cellular antioxidant response.