Osteoporosis is a systemic skeletal disorder where osteoclasts are prevalent among osteoblasts. Oxidative stress is one of the main causes of osteoporosis, and nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses. Phytol, a diterpene isolated from Stevia rebaudiana leaves, has many biological effects, including antimicrobial, antioxidant, and anti-inflammatory effects. This study investigated the crosstalk between Nrf2 and osteoclast differentiation in the presence of phytol. Phytol inhibited osteoclast differentiation through TRAP-positive and F-actin formation. The expression of anti-nuclear factor of activated T cells-c1 (NFATc1) and c-Fos was suppressed by phytol, as shown using Western blot and RT-PCR analysis. Phytol inhibited oxidative stress by suppressing reactive oxidant species (ROS) accumulation while recovering antioxidant enzymes, including superoxide dismutase and catalase. Additionally, phytol ameliorated osteoclast-specific differentiation, function, and oxidative stress through Nrf2 regulation by siRNA transfection. In conclusion, these data demonstrate the inhibitory effect of phytol on osteoclast differentiation through Nrf2 regulation, suggesting its potential use in oxidative stress-related osteoporosis and bone diseases.

Vernonia cinerea (L.) Less. is a perennial herbaceous plant found mainly in tropical areas, particularly in Southeast Asia, South America, and India. Various parts of V. cinerea have traditionally been used in folk medicine to treat several diseases, such as malaria, fever, and liver diseases. V. cinerea has so far yielded about 92 secondary metabolites. The majority of these are sesquiterpene lactones, but triterpenes, flavonoids, steroids, phenolics, and other compounds are present as well. V. cinerea crude extracts reportedly exhibit anti-inflammatory, antiprotozoal, antidiabetic, anticancer, antimicrobial, antioxidant, and renoprotective activities. This study aims to provide the latest up-to-date information on the botanical characterization, distribution, traditional uses, phytochemistry, and pharmacological activity of V. cinerea. Information on V. cinerea was thoroughly reviewed. The literature published between 1950 and 2024 was compiled through online bibliographic databases, including SciFinder, Web of Science, Google Scholar, PubMed, ScienceDirect, Springer Link, Wiley, and the MDPI online library. The keywords used for the literature search included Vernonia cinerea (L.) Less. and the synonyms Cyanthillium cinereum (L.) H.Rob., Conyza cinerea L., and various others.

Bone diseases such as osteoporosis are the result of osteoclast over-activation. There are many therapeutic agents from natural compounds inhibiting the formation of osteoclast that have been reported and are continuously being interested. Amygdalin (AD) is isolated from seeds of Prunus armeniaca L. which has many pharmaceutical effects; however, the effect of AD on osteoclast formation and function remains unknown. Therefore, the underlying mechanism of AD on RANKL-induced osteoclast in RAW 264.7 cells was investigated. Molecular docking simulation revealed that AD can bind to the active sites of RANKL with negative binding affinities. Through TRAP activity, bone resorption, and migration, AD effectively inhibited osteoclast differentiation and function. Expression of transcription factors, such as NFATc1, c-fos, and osteospecific genes (including dcstamp, acp5, ATP6v0d2, and ctsk results) showed an osteoclast differentiated inhibitory effect by AD treatment. In addition, RANKL-induced activation of MAPK, ER stress, and ROS levels in RANKL-induced osteoclast was significantly inhibited while antioxidant enzymes were recovered in the presence of AD. These results suggest that AD may be a potential candidate derived from natural sources for the treatment of osteoclast bone-related diseases.

Periodontal disease is a chronic disease with a high prevalence, and in order to secure natural materials to prevent oral diseases, new materials that protect periodontal tissue from inflammation are being sought. Genes were identified using real-time quantitative polymerase chain reaction (RT-qPCR), and proteins were confirmed using Western blot. Dichlorodihydrofluorescein diacetate (DCF-DA) analysis was used, and the antibacterial effects were confirmed through Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) analysis. To confirm this effect in vivo, Sprague–Dawley rats, in which periodontitis was induced using ligation or Lipopolysaccharide of Porphyromonas gingivalis (PG-LPS), were used. In vitro experiments using human periodontal ligament (HPDL) cells stimulated with PG-LPS showed that Ginsenoside Rg6 (G-Rg6) had anti-inflammatory, antibacterial, antioxidant, and osteoblast differentiation properties. In vivo, G-Rg6 was effective in Sprague–Dawley rats in which periodontitis was induced using ligation or PG-LPS. Therefore, Ginsenoside Rg6 shows potential effectiveness in alleviating periodontitis.

A new 4-hydroxyisoflavan, named lyratin D (1), was isolated from the whole plant of Solanum lyratum Thunb. Its structure and absolute configuration were elucidated through comprehensive analysis of its HR-ESI-MS, 1D and 2D NMR, and circular dichroism spectroscopy data. Compound 1 was then assessed for its cytotoxic effects on RAW264.7 murine macrophage cells, and its antioxidant activity was evaluated through DPPH assay.