The extract, fractions, and compounds of the Bouvardia ternifolia root were evaluated as an antiarthritic using a complete Freund’s adjuvant (CFA) model in mice and NF-κB inhibition in RAW 264.7 macrophages. Four active compounds, including two new compounds, ternifoliol and ternifolial, were isolated by open column chromatography and identified by spectroscopic and spectrometric techniques, resulting in benzochromone-like structures with aromatic rings and hydroxyl groups, which could be responsible for the anti-inflammatory activity and inhibitory NF-κB. Changes in the joint cytokine profile monitored the antiarthritic effect. A decrement was observed in the local concentration of the following cytokines with different treatments: IL-17 by 64% and 70.3% with the aqueous extract (BtAq), ethyl acetate extract (BtAcOEt), and M3 fraction; interleukin-1 beta (IL-1β) by 10.2% and 15.7% with BtAq and the M4 fraction, respectively; IL-6 with M1, M2, M3, and M4 between 42% and 64%; necrosis factor-alpha (TNF-α) by 60.9% with M4. Conversely, the anti-inflammatory cytokine interleukin-10 (IL-10) increased between 94% and 99% with M1, M2, M3, and M4. Kidney IL-6 decreased with BtAq, M1, M2, M3, and M4 between 68.9% and 85.8%. TNF-α decreased with BtAcOEt, BtAq, M1, M2, and M4 between 34% and 80.2%. The NF-κB pathway was inhibited with BtAcOEt (90.1%), M1 (85%), M2 (93.5%), M3 (84.5%), M4 (90.3%), ternifoliol (75.6%), bouvardin (20.4%), and scopoletin (89%). We conclude that B. ternifolia modulated the inflammatory response at the joint and kidney levels and the NF-κB pathway.

Bouvardia ternifolia (Cav.) Schltdl. is a shrub that belongs to the Rubiaceae family and is distributed throughout México; it has been used for its antioxidant, neuroprotective, and anti-inflammatory properties. This work aimed to evaluate the protective effects of B. ternifolia root extracts on the blood-brain barrier and the positive regulation of cytokines IL-1β, IL-6, and TNF-α, and the characterization of compounds present in the dichloromethane (BtD) and hexane (BtH) extracts. Male ICR mice were orally administered with B. ternifolia extracts for 5 days before a single injection of LPS. Administration of BtH and BtD significantly decreased Evans blue leakage into brain tissue by 70% and 68%, respectively. Meloxicam (MX) decreased the concentration of IL-1β by 39.6%; BtM by 53.9%; BtAq by 48.4%; BtD by 31.9%, and BtH by 37.7%. BtH was the only treatment that significantly decreased the concentration of IL-6 by 32.2%. The concentration of TNF-α declined with each of the treatments. The chemical composition of BtD and BtH was characterized by GC–MS, and the cyclic hexapeptide was identified by 13C, 1H NMR, and two-dimension techniques. In the BtD extract, seven compounds were found and in BtH 13 compounds were found. The methanolic (BtM) and aqueous (BtAq) extracts were not subjected to chemical analysis, because they did not show a significant difference in the BBB protection activity. Therefore, the results suggested that the extracts BtD and BtH protect the blood-brain barrier, maintaining stable its selective permeability, thereby preventing LPS from entering the brain tissue. Simultaneously, they modulate the production of IL-1β, IL-6, and TNF-α. It is important to note that this research only evaluated the complete extracts.