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Background During periodontitis, tooth‐supporting alveolar bone is resorbed when there is an increased expression of the pro‐osteolytic factor termed receptor activator of nuclear factor κB ligand (RANKL), which is responsible for osteoclast differentiation and activation. In periodontitis‐affected tissues, the imbalance between T‐helper type‐17 (Th17) and T‐regulatory (Treg) lymphocyte activity favors this RANKL overexpression. In this context, immunotherapeutic strategies aimed at modulating this Th17/Treg imbalance could eventually arrest the RANKL‐mediated alveolar bone loss. Boldine has been reported to protect from pathological bone loss during rheumatoid arthritis and osteoporosis, whose pathogenesis is associated with a Th17/Treg imbalance. However, the effect of boldine on alveolar bone resorption during periodontitis has not been elucidated yet. This study aimed to determine whether boldine inhibits alveolar bone resorption by modulating the Th17/Treg imbalance during periodontitis. Methods Mice with ligature‐induced periodontitis were orally treated with boldine (10/20/40 mg/kg) for 15 consecutive days. Non‐treated periodontitis‐affected mice and non‐ligated mice were used as controls. Alveolar bone loss was analyzed by micro‐computed tomography and scanning electron microscopy. Osteoclasts were quantified by histological identification of tartrate‐resistant acid phosphatase‐positive cells. Production of RANKL and its competitive antagonist osteoprotegerin (OPG) were analyzed by ELISA, quantitative polymerase chain reaction (qPCR), and immunohistochemistry. The Th17 and Treg responses were analyzed by quantifying the T‐cell frequency and number by flow cytometry. Also, the expression of their signature transcription factors and cytokines were quantified by qPCR. Results Boldine inhibited the alveolar bone resorption. Consistently, boldine caused a decrease in the osteoclast number and RANKL/OPG ratio in periodontal lesions. Besides, boldine reduced the Th17‐lymphocyte detection and response and increased the Treg‐lymphocyte detection and response in periodontitis‐affected tissues. Conclusion Boldine, administered orally, inhibited the alveolar bone resorption and modulated the Th17/Treg imbalance during experimental periodontitis.

A phytochemical study of the roots and aerial parts of Cryptocarya alba (Mol.) Looser (Lauraceae), an endemic Chilean tree and the southernmost Cryptocarya species, led for the first time to the isolation and unambiguous characterization of four known alkaloids by NMR techniques: boldine, laurolitsine, laurotetanine and norglaucine, in addition to the previously identified reticuline, and the identification via UHPLC-MS of seven more alkaloids, coclaurine, N-methylcoclaurine, norreticuline, isocorydine, N-methyllaurotetanine, predicentrine and glaucine. In spite of this fairly broad variety of benzyltetrahydroisoquinolines and aporphines, the concentrations of these alkaloids in the different organs of C. alba are quite low, which is in contrast with the sometimes generous yields of alkaloids in this genus.

Boldo leaves (Boldo folium, from Peumus boldus Mol.) are very frequently used as a medicinal herb in Chile and are exported to many countries to be used in teas or as extracts included in herbal remedies, primarily as an aid to digestion and as a mild sedative. Scientific support for these uses is scanty, and boldine, an alkaloid viewed as characteristic of the tree and present in high concentration in the bark, is extracted by specialized companies and sold as the supposed main active constituent. Consequently, boldine has been the subject of a considerable number of research papers, while some of the other alkaloids present to a greater extent in the leaves have been relatively neglected except when found in large amounts in other species. These studies range from assays of antioxidant activity to anti-inflammatory, antineoplastic and other medical applications. The essential oil, usually containing a large percentage of the toxic ascaridole, was once used as a vermifuge and is now regarded with caution, but is still of interest as a possible natural insecticide, fungicide, antiparasitic and herbicide. The last decade has seen an explosive increase in papers pointing to possible uses of boldo and its constituents. This review attempts to bring these publications together in a comprehensive way with the purpose of stimulating and orienting further research into the useful properties of this Chilean endemic tree.