Loliolide from Artemisia princeps Suppresses Adipogenesis in Human Bone Marrow-Derived Mesenchymal Stromal Cells via Activation of AMPK and Wnt/β-catenin Pathways

Regulating the adipogenic differentiation mechanism is a valid and promising mechanism to battle obesity. Natural products, especially phytochemicals as nutraceuticals, are important lead molecules with significant activities against obesity. Loliolide is a monoterpenoid hydroxyl lactone found in many dietary plants. The effect of loliolide on adipogenic differentiation is yet to be determined. Therefore, the present study aimed to evaluate its anti-adipogenic potential using human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) and assess its mechanism of action. Adipo-induced hBM-MSCs were treated with or without loliolide and their adipogenic characteristics were examined. Loliolide treatment decreased the lipid accumulation and expression of adipogenic transcription factors, PPARγ, C/EBPα, and SREBP1c. Adipo-induced hBM-MSCs also displayed increased AMPK phosphorylation and suppressed MAPK activation following loliolide treatment according to immunoblotting results. Importantly, loliolide could stimulate Wnt10b expression and active β-catenin translocation to exert PPARγ-linked adipogenesis suppression. In conclusion, loliolide was suggested to be a potential anti-adipogenic agent which may be utilized as a lead compound for obesity treatment or prevention.

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6-Acetyl-2,2-Dimethylchroman-4-One Isolated from Artemisia princeps Suppresses Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells via Activation of AMPK

Journal of Medicinal Food ◽

10.1089/jmf.2019.4653 ◽

2020 ◽

Vol 23 (3) ◽

pp. 250-257

Author(s):

Fatih Karadeniz ◽

Jung Hwan Oh ◽

Jung Im Lee ◽

Hojun Kim ◽

Youngwan Seo ◽

...

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Human Bone ◽

Human Bone Marrow ◽

Artemisia Princeps

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Effect of Quercetin 3-O-β-D-Galactopyranoside on the Adipogenic and Osteoblastogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21218044 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8044

Author(s):

Jung Hwan Oh ◽

Fatih Karadeniz ◽

Youngwan Seo ◽

Chang-Suk Kong

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Therapeutic Potential ◽

Adipogenic Differentiation ◽

Bmp Signaling ◽

Human Bone ◽

Human Bone Marrow ◽

Differentiation Markers ◽

Beneficial Effects

Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of quercetin 3-O-β-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated β-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.

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Myricetin 3-O-β-D-Galactopyranoside Exhibits Potential Anti-Osteoporotic Properties in Human Bone Marrow-Derived Mesenchymal Stromal Cells via Stimulation of Osteoblastogenesis and Suppression of Adipogenesis

Cells ◽

10.3390/cells10102690 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2690

Author(s):

Fatih Karadeniz ◽

Jung Hwan Oh ◽

Hyun Jin Jo ◽

Youngwan Seo ◽

Chang-Suk Kong

Keyword(s):

Bone Marrow ◽

Transcription Factors ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Intracellular Signaling ◽

Therapeutic Potential ◽

Adipogenic Differentiation ◽

Human Bone ◽

Human Bone Marrow ◽

Differentiation Markers

Natural bioactive substances are promising lead compounds with beneficial effects on various health problems including osteoporosis. In this context, the goal of this study was to investigate the effect of myricetin 3-O-β-D-galactopyranoside (M3G), a glycoside of a known bioactive phytochemical myricetin, on bone formation via osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of M3G and the differentiation markers were analyzed. Osteoblastogenesis-induced cells treated with M3G exhibited stimulated differentiation markers: cell proliferation, alkaline phosphatase (ALP) activity, and extracellular mineralization. In terms of intracellular signaling behind the stimulatory effect of M3G, the expression of RUNX2 and osteopontin transcription factors were upregulated. It has been shown that M3G treatment increased the activation of Wnt and BMP as a suggested mechanism of action for its effect. On the other hand, M3G treatment during adipogenesis-inducement of hBM-MSCs hindered the adipogenic differentiation shown as decreased lipid accumulation and expression of PPARγ, SREBP1c, and C/EBPα, adipogenic transcription factors. In conclusion, M3G treatment stimulated osteoblast differentiation and inhibited adipocyte differentiation in induced hBM-MSCs. Osteoblast formation was stimulated via Wnt/BMP and adipogenesis was inhibited via the PPARγ pathway. This study provided necessary data for further studies to utilize the therapeutic potential of M3G against osteoporosis via regulation of bone marrow stromal cell differentiation.

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