Osteogenic potential of zingerone, a phenolic compound in mouse mesenchymal stem cells

Srinaath, N.; Balagangadharan, K.; Pooja, V.S.; Paarkavi, Udhaykumar; Trishla, Adhikari; Selvamurugan, N.

doi:10.1002/biof.1515

Cited by 21 publications

(10 citation statements)

References 29 publications

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“…As an immunostimulant, ZG has various biological functions, including anti-inflammatory activity, antioxidant activity, antidiarrhoeic, phagocytic activity and anti-pathogenic activity [30][31][32][33]. Particularly, ZG is positive and has a stimulating effect on the differentiation of mMSCs into osteoblasts at the cellular and molecular levels [11]. Similarly, our research suggested that ZG contributed to osteoblast differentiation by stimulating the expression osteoblast differentiation markers, including RUNX2, ALP, OSX, and OC.…”

Section: Discussionmentioning

confidence: 99%

“…Osteogenesis was induced by ZG (Sigma-Aldrich, St. Louis, MO, USA) according to the previous description [11]. Briefly, hBMSCs were treated with ZG at concentrations of 50 μM, 100 μM, and 200 μM for 48 hours, and the untreated group was considered as control.…”

Section: Cell Culture and Cell Treatmentmentioning

confidence: 99%

“…However, the research on ZG on osteogenic differentiation is extremely limited. Srinaath et al reported that ZG had a stimulatory action on the differentiation of mouse mesenchymal stem cells (mMSCs) towards osteoblasts, suggesting its unique role in bone tissue regeneration [11].…”

Section: Introductionmentioning

confidence: 99%

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Zingerone Promotes Osteoblast Differentiation Via MiR-200c-3p/smad7 Regulatory Axis in Human Bone Mesenchymal Stem Cells

Song

Mou

et al. 2020

Med Sci Monit

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Departmental sources Background:Osteoblast differentiation is a critical process to maintain the stability of the bone homeostasis. Zingerone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone (ZG), isolated from ginger, performs a wide range of biological functions in human diseases. The objective of this paper was to clarify the role of ZG in human bone mesenchymal stem cells (hBMSCs) and associated mechanisms of ZG promoting osteoblast differentiation. Material/Methods:The cytotoxicity of ZG was detected by MTT assay. The expression levels of miR-200c-3p, smad7, and osteoblast differentiation markers (alkaline phosphatase [ALP], osteocalcin [OC], osterix [OSX] and runt-related transcription factor 2 [RUNX2]) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of smad7, ALP, OC, OSX, and RUNX2 were quantified by western blot analysis. The target mRNAs were predicted by bioinformatics tools TargetScan. The interaction between miR-200c-3p and smad7 was verified by luciferase reporter assay and RIP assay. Results:ZG was nontoxic to hBMSCs, and it accelerated osteoblast differentiation by inducing the expression of ALP, OC, OSX, and RUNX2. MiR-200c-3p was upregulated, but smad7 was downregulated in hBMSCs treated with ZG at different concentrations at different periods. Besides, miR-200c-3p positively regulated the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs. Moreover, miR-200c-3p targeted smad7 and strengthened the expression of ALP, OC, OSX, and RUNX2 in ZG-induced hBMSCs by downregulating smad7. Conclusions:ZG contributed to osteoblast differentiation via miR-200c-3p/smad7 regulatory axis by promoting the expression of ALP, OC, OSX, and RUNX2 in hBMSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Culture and Cell Treatmentmentioning

confidence: 99%

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Zingerone Promotes Osteoblast Differentiation Via MiR-200c-3p/smad7 Regulatory Axis in Human Bone Mesenchymal Stem Cells

Song

Mou

et al. 2020

Med Sci Monit

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“…mRNA Runx2, involved differentiation is enhanced by zingerone treatment. Zingerone may deposit calcium, which is responsible for osteogenesis (51).…”

Section: Other Biological Activitiesmentioning

confidence: 99%

Pharmacological activity and biochemical interaction of zingerone: a flavour additive in spice food

Sahoo¹,

Sahoo²,

Nayak³

et al. 2021

Plant Sci. Today

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Zingerone (4-(4-Hydroxy-3-methoxyphenyl)-2-butanone) is one of the non-volatile and nontoxic compounds of ginger. It is also called vanillylacetone with a crystalline solid form which is sparingly soluble in water and more soluble in ether. The contribution of this compound in ginger is about 9.25%. The chemical structure is made of a phenolic ring with methoxy group attached to benzene ring. Gingerol can be heated to form zingerone by retroaldol reaction. It has been reported that zingerone has multiple pharmacological activities. It is effective against diarrhoea causing enterotoxigenic bacteria that leads to infant death. It is also used against intestinal gastric, oxidative stress, weak immunity, obesity. During its activity against cancer, it governs the expression of different cell cycle protein and TGF-?1 expression. Antioxidant response is controlled by inducing the activity of ROS neutralising enzymes like superoxide dismutase, catalase and glutathione reductase. It can also reduce various inflammations by restricting the activity of interleukins. This review summarizes the multiple pharmacology activities of zingerone against various important diseases like cancers, tumors, inflammations, oxidative conditions, microbial infections, biofilm formations, thrombosis and other diseases. In addition, the molecular regulation of these pharmacological responses by zingerone is also critically discussed.

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“…In zingerone-induced mouse mesenchymal stem cells (mMSCs), microRNA-590 regulates osteoblast differentiation by protecting the Runx2 protein through targeting of Smad7. 29 However, it is not known if zingerone can induce osteoblast differentiation by regulating Smad1/5/9, a member of the receptorregulated Smad (R-Smad) family. In this study, we evaluated the effect of zingerone on bone differentiation and mineralization in MC3T3-E1 cells and primary mouse calvarial cells and showed that zingerone increased Smad1/5/9 and HO-1 expression.…”

Section: Introductionmentioning

confidence: 99%

Zingerone stimulates osteoblast differentiation by increasing Smad1/5/9‐mediated HO‐1 expression in MC3T3‐E1 cells and primary mouse calvarial cells

Kim

Lim

Jang

2022

Clin Exp Pharma Physio

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Zingerone is a non-volatile compound found mainly in dried ginger. Zingerone increases the expression of osteogenic markers and has antioxidant effects. A previous study showed that zingerone accelerated osteoblast differentiation by suppressing the expression of Smad7, a member of the inhibitory Smad (I-Smad) family. However, it is not known if zingerone can induce osteoblast differentiation by regulating Smad1/5/9, a member of the receptor-regulated Smad (R-Smad) family. In addition, osteoblast differentiation induced by Smad1/5/9 mediated increases in the expression of heme oxygenase 1 (HO-1) has not been reported. This study investigated the effects of zingerone on osteoblast differentiation and confirmed the relationship between Smad1/5/9 and HO-1. Zingerone increased the expression of osteogenic genes including runt-related transcription factor 2 (Runx2), distal-less homeobox (Dlx5) and osteocalcin (OC) and also promoted Smad1/5/9 phosphorylation. Interestingly, HO-1 expression was also elevated by zingerone, and an inhibitor of HO-1 (Sn[IV] protoporphyrin IX dichloride [SnPP]) suppressed the zingeroneinduced increase in HO-1 expression and expression of osteogenic marker genes such as Dlx5, Runx2 and OC. Protein phosphatase 2A Cα (PP2A Cα, an inhibitor of Smad1/5/9) suppressed the zingerone-induced increase in HO-1 expression and expression of osteogenic marker genes. The zingerone-induced increase in HO-1 luciferase activity was suppressed by PP2A Cα. Taken together; our data demonstrate that zingerone promotes osteoblast differentiation by increasing Smad1/5/9 mediated HO-1 expression.

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Osteogenic potential of zingerone, a phenolic compound in mouse mesenchymal stem cells

Cited by 21 publications

References 29 publications

Zingerone Promotes Osteoblast Differentiation Via MiR-200c-3p/smad7 Regulatory Axis in Human Bone Mesenchymal Stem Cells

Zingerone Promotes Osteoblast Differentiation Via MiR-200c-3p/smad7 Regulatory Axis in Human Bone Mesenchymal Stem Cells

Pharmacological activity and biochemical interaction of zingerone: a flavour additive in spice food

Zingerone stimulates osteoblast differentiation by increasing Smad1/5/9‐mediated HO‐1 expression in MC3T3‐E1 cells and primary mouse calvarial cells

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