Citrus limonoid nomilin inhibits osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways

Kimira, Yoshifumi; Taniuchi, Yuri; Nakatani, Sachie; Sekiguchi, Yuusuke; Kim, Hyoun Ju; Shimizu, Jun; Ebata, Midori; Wada, Masahiro; Matsumoto, Akiyo; Miyata, Hiroshi

doi:10.1016/j.phymed.2015.08.013

Cited by 21 publications

(11 citation statements)

References 21 publications

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“…Moreover, the non-toxic concentrations of the compound decreased bone resorption activity and down regulated osteoclast-specific genes (NFATc1 and TRAP mRNA levels), coupled with suppression of the MAPK signaling pathway. Studies have shown the therapeutic potential of nomilin for the prevention of bone metabolic diseases such as osteoporosis [66].…”

Section: Influence On Skeletal Systemmentioning

confidence: 99%

“…[68] Effects on the skeletal system -Increasing bone density; -Decreasing osteoclast activity; -Decreasing TRAP-positive multinucleated cell numbers (nomilin); -Decreasing bone resorption activity (nomilin); -Down regulation osteoclast-specific genes (NFATc1 and TRAP mRNA levels) (nomilin). [66,69] Treatment of menstrual disorders -Period induction in cases of irregular menstrual cycles.…”

Section: Mechanism Of Action Referencesmentioning

confidence: 99%

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Citrus limon (Lemon) Phenomenon—A Review of the Chemistry, Pharmacological Properties, Applications in the Modern Pharmaceutical, Food, and Cosmetics Industries, and Biotechnological Studies

Klimek-Szczykutowicz

Szopa

2020

Plants

287

153

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This review presents important botanical, chemical and pharmacological characteristics of Citrus limon (lemon)—a species with valuable pharmaceutical, cosmetic and culinary (healthy food) properties. A short description of the genus Citrus is followed by information on the chemical composition, metabolomic studies and biological activities of the main raw materials obtained from C. limon (fruit extract, juice, essential oil). The valuable biological activity of C. limon is determined by its high content of phenolic compounds, mainly flavonoids (e.g., diosmin, hesperidin, limocitrin) and phenolic acids (e.g., ferulic, synapic, p-hydroxybenzoic acids). The essential oil is rich in bioactive monoterpenoids such as D-limonene, β-pinene, γ-terpinene. Recently scientifically proven therapeutic activities of C. limon include anti-inflammatory, antimicrobial, anticancer and antiparasitic activities. The review pays particular attention, with references to published scientific research, to the use of C. limon in the food industry and cosmetology. It also addresses the safety of use and potential phototoxicity of the raw materials. Lastly, the review emphasizes the significance of biotechnological studies on C. limon.

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Section: Influence On Skeletal Systemmentioning

confidence: 99%

Section: Mechanism Of Action Referencesmentioning

confidence: 99%

Citrus limon (Lemon) Phenomenon—A Review of the Chemistry, Pharmacological Properties, Applications in the Modern Pharmaceutical, Food, and Cosmetics Industries, and Biotechnological Studies

Klimek-Szczykutowicz

Szopa

2020

Plants

287

153

View full text Add to dashboard Cite

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“…Kimira et al studied the potential use of nomilin (2) for the inhibition of osteoclastogenesis in vitro [72]. They measured cell viability of the mouse RAW 264.7 macrophage cell line and mouse primary bone marrow-derived macrophages (BMMs) with the Cell Counting Kit.…”

Section: Inhibition Of Osteoclastogenesismentioning

confidence: 99%

The Chemistry and Pharmacology of Citrus Limonoids

et al. 2016

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Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detail.

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“…13) Accumulating lines of evidence suggest that several natural compounds may have potential anabolic effects on bone. 14,15) Carvacrol (5-isopropyl-2-methylphenol), is a monoterpenic phenol found in oregano and thyme. 16) Essential oils containing carvacrol have been widely used in various traditional medicines.…”

mentioning

confidence: 99%

Carvacrol Inhibits Osteoclastogenesis and Negatively Regulates the Survival of Mature Osteoclasts

Deepak

Kasonga

Kruger

et al. 2016

Biological & Pharmaceutical Bulletin

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Bone is a dynamic tissue that undergoes continuous remodeling coupled with the action of osteoblasts and osteoclasts. Osteoclast activity is elevated during osteoporosis and periodontitis resulting in excessive loss of trabecular and alveolar bone. Osteoclasts are formed in an inflammatory response to cytokine production receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL) and bacterial challenge lipopolysaccharide (LPS). Carvacrol, a monoterpenic phenol present in Origanum vulgare and Thymus vulgaris, is a natural compound with known medicinal properties. We investigated the effects of carvacrol Key words osteoclast; osteoporosis; periodontitis; receptor activator of nuclear factor-κB ligand (RANKL); lipopolysaccharide (LPS) Bone homeostasis is tightly coupled to the bone-forming activity of osteoblasts and bone-resorbing activity of osteoclasts.1) Osteoclasts are multi-nucleated cells that arise from hematopoietic progenitors of monocyte/macrophage lineage and specialize in bone resorption.2) Bone-loss related diseases such as osteoporosis and periodontitis are associated with increased osteoclast formation and elevated osteoclast activity. [3][4][5] Binding of receptor activator of nuclear factor-κB ligand (RANKL) to its receptor RANK in osteoclast precursors triggers trimerization of the receptor and subsequent activation of downstream signaling pathways that includes inhibitor of kappaB (IκB)-a/b kinase (IKK), nuclear factor kappa-B (NF-κB), mitogen-activated protein kinases (MAPKs)-p38, extracellular-signal-regulated kinase (ERK) and c-Jun Nterminal kinase (JNK).6) Activation of these pathways leads to the formation of tartrate resistant acid phosphatase-positive (TRAP+) osteoclasts and bone resorption.Development of apical periodontitis is associated with the presence of microorganisms in the root canal system. 7) Gramnegative bacteria are the most common causative agents in endodontic infections. 8) Bacterial death causes release of lipopolysaccharide (LPS) in the necrotic pulp and dental wall of periapically affected teeth. 9) LPS elicits alveolar bone loss during periodontitis. 10) LPS stimulates the secretion of cytokines by osteoclast precursors such as monocytes and macrophages, resulting in osteoclast formation and bone resorption in vitro and in vivo.11) Earlier studies have also shown that injection of LPS into mouse gingiva induces alveolar bone resorption. 12)

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Citrus limonoid nomilin inhibits osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways

Abstract: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.

Cited by 21 publications

References 21 publications

Citrus limon (Lemon) Phenomenon—A Review of the Chemistry, Pharmacological Properties, Applications in the Modern Pharmaceutical, Food, and Cosmetics Industries, and Biotechnological Studies

Citrus limon (Lemon) Phenomenon—A Review of the Chemistry, Pharmacological Properties, Applications in the Modern Pharmaceutical, Food, and Cosmetics Industries, and Biotechnological Studies

The Chemistry and Pharmacology of Citrus Limonoids

Carvacrol Inhibits Osteoclastogenesis and Negatively Regulates the Survival of Mature Osteoclasts

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