Standardized Arrabidaea chica Extract Shows Cytoprotective Effects in Zoledronic Acid-Treated Fibroblasts and Osteoblasts.

INTRODUCTION: Osteonecrosis of the jaw is a condition associated with intraoral ulceration and bone necrosis induced by antiresorptive medications, such as zoledronic acid, a bisphosphonate. Previous data on Arrabidaea chica (H&B.) Verlot wound healing activity prompted the study reported herein on A. chica standardized hydro alcoholic extract in vitro cytoprotective activity data on epithelial and osteoblastic cells exposed to zoledronic acid (ZA). METHODS: Primary human gingival fibroblasts and murine pre-osteoblasts were treated with ZA 10 µM together with 5 or 10 µg.mL-1 A. chica extract for 24h and 48 h. At both times, cells were submitted to viability assay and caspase 3/7 activation evaluation. Statistical analysis used one-way ANOVA and p=0.05. RESULTS: In cell viability assay, a drastic damage effect of ZA appeared after 48 h in both epithelial (55.8%) and pre-osteoblastic cells (39.7%). When treated with ZA in combination with A. chica extract, cells showed higher viability values: 74.1%-82.3% for fibroblasts and 66% for pre-osteoblasts. Furthermore, the combined treatment presented lower caspase 3/7 activation in fibroblasts and pre-osteoblasts. CONCLUSION: At low concentrations, A. chica extract showed promising cytoprotective effects against ZA-induced damage actions; however, further in vitro and in vivo studies are required to establish the mechanism of action.

Chitosan-tripolyphosphate nanoparticles as Arrabidaea chica standardized extract carrier: synthesis, characterization, biocompatibility, and antiulcerogenic activity.

Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan-sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract's composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems.