Bergenin Activates SIRT1 as a Novel Therapeutic Agent for Osteogenesis of Bone Mesenchymal Stem Cells

Hou, Weiduo; Ye, Chenyi; Chen, Mo; Li, Weixu; Gao, Xiang; He, Rongxin; Zheng, Qiang; Zhang, Wei

doi:10.3389/fphar.2019.00618

Cited by 20 publications

(14 citation statements)

References 38 publications

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“…Bergenin is the C-glucoside of 4- O -methyl gallic acid and can be found in several medicinal plants, including Bergenia crassifolia and Corylopsis spicata ( Liang et al, 2017 ). Bergenin has been reported to have multiple biological activities, including antiarthritic ( Jain et al, 2014 ; Singh et al, 2017 ), immunomodulatory ( Wang et al, 2017 ; Kumar et al, 2019 ), antidiabetic ( Veerapur et al, 2012 ), osteogenic ( Hou et al, 2019 ), neuroprotective ( Barai et al, 2019 ; Ji et al, 2019 ), and wound-healing effects ( Mukherjee et al, 2013 ). Wang et al (2017) showed that bergenin attenuated colitis by activating the peroxisome proliferator-activated receptor (PPAR) γ.…”

Section: Introductionmentioning

confidence: 99%

Bergenin as a Novel Urate-Lowering Therapeutic Strategy for Hyperuricemia

Chen

Zhu

et al. 2020

Front. Cell Dev. Biol.

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Bergenin is a C-glucoside of 4-O-methyl gallic acid isolated from several medicinal plants and has multiple biological activities. The aim of this study was to assess the potential usefulness of bergenin in hyperuricemia. We found that bergenin reduced serum urate levels in hyperuricemia mice by promoting renal and gut uric acid excretion. Bergenin treatment increased Abcg2 expression both in the kidneys and intestine, while the expression of Slc2a9 was suppressed in the kidney and increased in the intestine. Moreover, bergenin induced ABCG2 expression in HK-2 and Caco-2 cells, as well as SLC2A9 in Caco-2 cells, via the activation of PPARγ. Nevertheless, bergenin suppressed SLC2A9 expression in HK-2 cells by inhibiting the nuclear translocation of p53. Furthermore, bergenin decreased the serum levels of IL-6, IL-1β, and TNF-α in hyperuricemia mice, and promoted a polarization shift from the M1 to M2 phenotype in RAW264.7 cells. In conclusion, these findings provide evidence supporting the further development of bergenin as a novel therapeutic strategy for hyperuricemia.

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Section: Introductionmentioning

confidence: 99%

Bergenin as a Novel Urate-Lowering Therapeutic Strategy for Hyperuricemia

Chen

Zhu

et al. 2020

Front. Cell Dev. Biol.

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“…mscMSCs, a resident cell population existing in the bone marrow, are involved in the catabolic-anabolic coupling of bone metabolism [ 7 , 23 ]. MSCs have multiple lineages of differentiation potential, including chondrogenesis, osteogenesis, adipogenesis, and stromal cells differentiation.…”

Section: Discussionmentioning

confidence: 99%

Shu-Di-Huang and Gan-Cao Herb Pair Restored the Differentiation Potentials of Mesenchymal Stem Progenitors in Treating Osteoporosis via Downregulation of NF-κB Signaling Pathway

Ling

Wang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Shu-Di-Huang (Radix Rehmanniae Praeparata, RR) and Gan-Cao (liquorice, L) are frequently used traditional Chinese herb pair in treating osteoporosis (OP). However, the exact mechanism of the RR and L herb pair (RR-L) remains unclear. To explore the efficacy and possible mechanisms of RR-L in treating OP, in silico, in vitro, and in vivo experiments were conducted in the current study. Methods. In silico, potential therapeutic target genes and active chemical compounds of RR-L herb pair were predicted and constructed into a network. In vivo, 30 Sprague Dawley rats were divided into 3 groups, including the sham group, the OP model group, and the RR-L-treated OP group. Micro-CT and pathological sections were conducted to validate the therapeutic effects of RR-L in treating OP. MSCs of rats were isolated and cultured in vitro to validate the mesenchymal stem cells (MSCs) related phenotype changes, including Alizarin red staining, Oil red staining, and immunofluorescence. In vitro, cell proliferation analysis, Alizarin red staining, Oil red staining, immunofluorescence of NF-κB, and protein expression of PPARγ, RUNX2, OCN, and p65 were conducted on MSCs to explore the RR-L containing serum in vitro. Also, activator and inhibitor of NF-κB signaling pathway were introduced to determine the possible mechanism of RR-L in the treatment of OP via enhancing MSCs proliferation and differentiation. Results. In silico, 168 chemical compounds with a property of oral bioavailability ≥30% and drug-likeness ≥0.18 were recognized as potentially active compounds in RR-L and 249 genes were found to be the targets of which. Among them, 120 genes were found to be therapeutic genes of RR-L in treating OP and KEGG and GO analysis of which demonstrated that RR-L involves in lipid metabolism and multiple inflammation-related signaling pathways. In vivo, ovariectomy- (OVX-) induced OP phenotypes in Sprague Dawley rats include bone mineral density and microarchitecture damaging, abnormal bone metabolism, upregulation of inflammation markers, and damaged differentiation potential of MSCs. Treatment of RR-L reversed the trend and restored the differentiation potential of MSCs. In vitro, RR-L containing serum promoted the osteogenic differentiation and suppressed adipogenic differentiation of MSCs via downregulation of the NF-κB signaling pathway. Also, RR-L containing serum inhibited the tumor necrosis factor-α (TNF-α) induced activation of the NF-κB signaling pathway. On the opposite, the addition of the NF-κB specific inhibitor significantly reduced the effect of RR-L on MSCs. Conclusions. In the current study, network pharmacology prediction and experimental validation elucidated that the RR-L herb pair restored damaged MSC differentiation potential via the NF-κB signaling pathway; this could be the possible mechanism of RR-L in treating OP. This finding provides an alternative option in OP therapy.

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“…Our study provides both in vitro and in vivo evidence to show that SIRT1 expression is upregulated in damaged tubular cells during cisplatin-induced AKI. Previous studies have demonstrated the beneficial effects of SIRT1 in many organs, including the liver (Zhu et al, 2014;Abd Elwahab et al, 2017), heart (Li et al, 2019), bone (Hou et al, 2019), and FIGURE 7 | SIRT1 mediates the beneficial effects of FGF21 on cisplatin-induced mouse AKI. (A,B) Representative immunoblotting analysis of SIRT1 in SIRT1 knockdown mice.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury

Chen

Yang

et al. 2020

Front. Pharmacol.

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Acute kidney injury (AKI) is a common complication in cancer patients. Kidney function is closely related to patients' quality of life and tumor prognosis. Cisplatin is a highly effective anti-tumor drug. However, the use of cisplatin is limited by its nephrotoxicity. It has been reported that FGF21 has a renal-protective function, but the mechanisms by which it does so remain unclear. In this study, we show that the expression of FGF21 is significantly upregulated in both in vitro and in vivo cisplatin-induced AKI models. Administration of recombinant FGF21 to cisplatin-induced AKI mice resulted in significantly decreased blood urea nitrogen (BUN) and serum creatinine levels, as well as significantly reduced protein levels of kidney injury molecule-1 (TIM-1), C-caspase 3, and Bax. H&E-stained kidney sections from cisplatin-induced AKI mice treated with recombinant FGF21 showed a relatively normal renal tissue structure, a reduced number of necrotic sites and vacuolar changes, and decreased casts, suggesting alleviated renal tubular injury. Experiments with an AKI cell model (cisplatin-treated HK-2 cells) yielded similar results as the mouse model; recombinant FGF21 significantly downregulated protein expression levels of TIM-1, C-caspase 3, and Bax. Furthermore, administration of recombinant FGF21 to cisplatin-treated AKI models significantly increased SIRT1 expression, and the beneficial effects of FGF21 on kidney injury were reversed by SIRT1 knockdown. Collectively, our results suggest that SIRT1 mediates the protective effect of FGF21 on cisplatin-induced kidney injury.

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Bergenin Activates SIRT1 as a Novel Therapeutic Agent for Osteogenesis of Bone Mesenchymal Stem Cells

Cited by 20 publications

References 38 publications

Bergenin as a Novel Urate-Lowering Therapeutic Strategy for Hyperuricemia

Bergenin as a Novel Urate-Lowering Therapeutic Strategy for Hyperuricemia

Shu-Di-Huang and Gan-Cao Herb Pair Restored the Differentiation Potentials of Mesenchymal Stem Progenitors in Treating Osteoporosis via Downregulation of NF-κB Signaling Pathway

SIRT1 Mediates Effects of FGF21 to Ameliorate Cisplatin-Induced Acute Kidney Injury

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