Oxoglaucine

Oxoglaucine (O-Methylatheroline) is a natural product with multiple activities including autophagy activation, anti-inflammation, antibacterial activity, and immunoregulation. Oxoglaucine inhibits the TRPV5/calmodulin/CAMK-II pathway, suppresses TGFβ-induced Smad2 phosphorylation by upregulating Smad7, blocks Ca²⁺ influx, activates autophagy, alleviates apoptosis and inflammation, inhibits ROS production and the expression of fibrosis markers in hepatocytes, and regulates immune cell populations and responses. Oxoglaucine protects against infections caused by Candida albicans and Klebsiella pneumoniae, and exerts effects on adjuvant-induced arthritis. Oxoglaucine can be used in studies related to arthritis, liver fibrosis, bacterial infections, and fungal infections^{[1][2][3][4][5]}. In Vitro:Oxoglaucine (1.25-40 ng/mL; 24 h) enhances the viability and proliferation of human osteoarthritic chondrocytes, while higher concentrations reduce their viability^[1].
Oxoglaucine (10-40 ng/mL; 24 h) exerts a protective effect on human osteoarthritic chondrocytes by enhancing cell viability; it promotes cartilage matrix maintenance in human osteoarthritic chondrocytes by increasing GAG secretion and upregulating the mRNA expression of cartilage-specific markers Sox-9, Aggrecan and Col 2A1^[1].
Oxoglaucine (10-40 ng/mL; 24 h) reduces Ca²⁺ influx in human osteoarthritic chondrocytes and downregulates the TRPV5/calmodulin/CAMK-II pathway in these cells^[1].
Oxoglaucine (10-15 μM; 24 h pretreatment, 6 h TGFβ stimulation) inhibits TGFβ-induced phosphorylation of Smad2 in Hepa1c1c7 cells and primary mouse hepatocytes, and additionally reduces TGFβ-induced phosphorylation of AKT in primary mouse hepatocytes. It suppresses the expression of fibrosis-related genes (collagen type I alpha 1 chain, α-SMA, fibronectin) and the corresponding protein (collagen type I alpha 1 chain), and inhibits the expression of IL6 and Ccl2^[2].
Oxoglaucine (10-15 μM; 24 h pretreatment, 6 h TGFβ stimulation) inhibits TGFβ-induced expression of fibrosis markers in human LX-2 hepatic stellate cells^[2].
Oxoglaucine (10-40 ng/mL; 24 h) alleviates inflammation and apoptosis in human osteoarthritic chondrocytes by downregulating the mRNA and protein expression of inflammatory, apoptotic and catabolic markers, as well as reducing the levels of NO, PGE2 and ADAMTS-5; it activates autophagy in human osteoarthritic chondrocytes by upregulating the mRNA and protein expression of autophagy-related markers LC3, Beclin-1, ATG5 and ATG7^[1].
Oxoglaucine (10 μM; pre-treatment for 24 h followed by TGFβ stimulation) inhibits TGFβ-induced ROS production and upregulates Smad7 expression in Hepa1c1c7 cells^[2].
Oxoglaucine (40 ng/mL; 24 h) activates autophagy in human osteoarthritic chondrocytes by increasing the formation of autolysosomes and promoting acidification^[1].
Oxoglaucine (2×10^-4 M; 72 h) inhibits mitogen-induced proliferation of mouse splenocytes^[4]. In Vivo:Oxoglaucine (40 ng/mL; intra-articular injection; twice a week for 4 weeks) alleviates surgically induced osteoarthritis in Sprague-Dawley rats, mitigates cartilage degeneration, reduces levels of inflammatory cytokines and TRPV5 pathway activity, and activates autophagy. Experimental results show that the gross score of rats decreases by approximately 50%, and the levels of TNF-α, IL-6, caspase-3 and BAX in the synovium also decrease^[1].
Oxoglaucine (0.02-5.0 mg/kg; i.p.; single administration; daily) regulates antibody-mediated immune responses in a dose-dependent and regimen-dependent manner. Among the tested regimens, the daily administration of 0.5 mg/kg for 3 consecutive days prior to immunization with sheep red blood cells (SRBC) exerts the strongest inhibitory effect on anti-SRBC IgM^[4].
Oxoglaucine (0.5 mg/kg; i.p.; administered on day 0 and day +2) significantly enhances SRBC-induced PLN responses^[4].
Oxoglaucine (0.5 mg/kg; i.p.; once daily for 5 consecutive days) enhances LPS-induced B cell activation and increases anti-LPS IgM levels^[4].
Oxoglaucine (1 mg/kg; i.p.; daily) modulates adjuvant-induced arthritis depending on the timing of treatment: it exacerbates paw swelling in the early stage of the disease and reduces swelling in the established disease stage^[4].
Oxoglaucine (1-20 mg/kg; i.p.; daily administration for 3 consecutive days before inoculation; single administration on day 0; single administration 24 h before inoculation) dose-dependently enhances resistance to Klebsiella pneumoniae infection^[4].
Oxoglaucine (10 mg/kg; i.p.; once daily; for 10 consecutive days) modulates splenic lymphocyte subsets in adult female ICR mice infected with Candida albicans, inhibits the accumulation of serum TNF-α, significantly reduces CD4⁺ cells, and prevents the infection-induced increase in CD8⁺ and Ig⁺ cells^[5].
Oxoglaucine (5 mg/kg; i.p.; once daily for 3 consecutive days) reduces the numbers of splenic CD4⁺, CD8⁺ and Ig⁺ cell populations when detected at 8 weeks post Candida albicans infection^[5].
Oxoglaucine (10 mg/kg, intraperitoneal injection, once daily for 10 consecutive days) suppresses late-stage serum TNF-α accumulation and elevates host resistance to Candida albicans infection in female ICR mice with adjuvant-induced arthritis^[5].