(−)‐Epigallocatechin‐3‐ O ‐gallate ( EGCG ), present in green tea, exhibits antioxidant and antiallergy effects. EGCG 3″Me, a 3‐ O ‐methylated derivative of EGCG , has been reported to show similar biological functions; the inhibitory activity of EGCG 3″Me in a mouse allergy model was more potent than that of EGCG , probably due to the efficiency of absorption from the intestine. However, the functional potency of these EGCG s is controversial in each disease model. We previously observed that EGCG suppressed inflammatory bone resorption and prevented alveolar bone loss in a mouse model of periodontosis. In this study, we examined the role of EGCG 3″Me in bone resorption using a mouse model of periodontitis. Lipopolysaccharide ( LPS )‐induced osteoclast formation was suppressed by adding EGCG 3″Me to cocultures of osteoblasts and bone marrow cells, and LPS ‐induced bone resorption was also inhibited by EGCG 3″Me in calvarial organ cultures. EGCG 3″Me acted on osteoblasts and suppressed prostaglandin E ( PGE ) production, which is critical for inflammatory bone resorption, by inhibiting the expression of COX ‐2 and mPGES ‐1, key enzymes for PGE synthesis. In osteoclast precursor macrophages, EGCG 3″Me suppressed RANKL ‐dependent differentiation into mature osteoclasts. In a mouse model of periodontitis, LPS ‐induced bone resorption was suppressed by EGCG 3″Me in organ culture of mouse alveolar bone, and the alveolar bone loss was further attenuated by the treatment of EGCG 3″Me in the lower gingiva in vivo . EGCG 3″Me may be a potential natural compound for the protection of inflammatory bone loss in periodontitis.

Polymethoxyflavonoids (PMFs) are a family of the natural compounds that mainly compise nobiletin, tangeretin, heptamethoxyflavone (HMF), and tetramethoxyflavone (TMF) in citrus fruits. PMFs have shown various biological functions, including anti-oxidative effects. We previously showed that nobiletin, tangeretin, and HMF all inhibited interleukin (IL)-1-mediated osteoclast differentiation via the inhibition of prostaglandin E2 synthesis. In this study, we created an original mixture of PMFs (nobiletin, tangeretin, HMF, and TMF) and examined whether or not PMFs exhibit co-operative inhibitory effects on osteoclastogenesis and bone resorption. In a coculture of bone marrow cells and osteoblasts, PMFs dose-dependently inhibited IL-1-induced osteoclast differentiation and bone resorption. The optimum concentration of PMFs was lower than that of nobiletin alone in the suppression of osteoclast differentiation, suggesting that the potency of PMFs was stronger than that of nobiletin in vitro. The oral administration of PMFs recovered the femoral bone loss induced by estrogen deficiency in ovariectomized mice. We further tested the effects of PMFs on lipopolysaccharide-induced bone resorption in mouse alveolar bone. In an ex vivo experimental model for periodontitis, PMFs significantly suppressed the bone-resorbing activity in organ cultures of mouse alveolar bone. These results indicate that a mixture of purified nobiletin, tangeretin, HMF, and TMF exhibits a co-operative inhibitory effect for the protection against bone loss in a mouse model of bone disease, suggesting that PMFs may be potential candidates for the prevention of bone resorption diseases, such as osteoporosis and periodontitis.

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The pathologies and lethality of lung cancers are associated with smoking, lifestyle, and genomic factors. Several experimental mouse models of lung cancer, including those induced via intrapulmonary injection and intratracheal injection, have been reported for evaluating the pharmacological effect of drugs. However, these models are not sufficient for evaluating the efficacy of drugs during screening, as these direct injection models ignore the native processes of cancer progression in vivo, resulting in the inadequate pathological formation of lung cancer. In the present study, we developed a novel intranasal injection model of lung cancer simulating the native lung cancer pathology for anticancer drug screening. A mouse lung cancer cell line (Lewis lung carcinoma; LCC) was intranasally injected into mouse lungs, and injected cell number‐dependent cancer proliferation was apparent in both the left and right lungs. Human non‐small‐cell lung cancer (NCI‐H460) cells were also intranasally injected into nude mice and similarly showed injected cell number‐dependent cancer growth. For the pharmacological evaluation of cisplatin, two different treatment frequencies were tested four times per month and twice a month. The intranasal injection model confirmed that cisplatin suppressed lung cancer progression to a greater extent under the more frequent treatment condition. In conclusion, these results indicated that our intranasal injection model is a powerful tool for investigating lung cancer pathology and may aid in the development of new anti‐lung cancer agents.