Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway

Zhang, Yongfeng; Liu, Xin; Li, Yangyang; Song, Minkai; Li, Yutong; Yang, Anhui; Zhang, Yaqin; Wang, Di; Hu, Min

doi:10.1080/13880209.2021.1996614

Cited by 12 publications

(6 citation statements)

References 54 publications

(57 reference statements)

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“…Wnt/ β -catenin signaling is a well-known transduction pathway and it plays critical role in bone formation [ 26 ]. H19 was reported to stimulate Wnt/ β -catenin signaling and facilitated osteogenic differentiation in our previous study [ 27 ]. We therefore wondered whether this Wnt/ β -catenin signaling participated in the Aucubin-induced osteoblast differentiation.…”

Section: Resultsmentioning

confidence: 99%

“…Further studies have demonstrated that Aucubin plays a protective role in bone metabolism via various mechanisms [ 10 – 12 ]. For instance, Aucubin promoted autophagy via AMPK activation and thus prevented steroid-induced osteoblast apoptosis [ 11 ]; it also inhibited osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway and thus alleviated osteoporosis [ 27 ]. The beneficial impacts of Aucubin on osteogenic differentiation are well established.…”

Section: Discussionmentioning

confidence: 99%

“…It is well-established that Wnt/ β -catenin signaling plays a pivotal role in the differentiation of cells and the formation of the skeletal matrix during skeletal development [ 27 – 29 ]. In the present study, our results showed that Aucubin increased the expression of β -catenin and downstream genes of Wnt signaling, indicating that it may activate the Wnt/ β -catenin pathway.…”

Section: Discussionmentioning

confidence: 99%

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Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA‐H19 Driven Wnt/β‐Catenin Signaling Regulatory Axis

Mai,

Li,

Pang

et al. 2024

Stem Cells International

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Objectives. Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. Materials and Methods. The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/β-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results. In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/β-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/β-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/β-catenin signaling through promoting H19 expression. Conclusion. Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/β-catenin regulatory axis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA‐H19 Driven Wnt/β‐Catenin Signaling Regulatory Axis

Mai,

Li,

Pang

et al. 2024

Stem Cells International

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“…In hepatocytes, an HF diet can down-regulate the expression of the SIRT6/PGC-1α/ENDOG signaling pathway, inducing oxidative stress [ 36 ]. Recently, NRF2 has been regarded as a transcription factor for bone balance, participating in the regulation of OP development [ 37 ]. Sham-operated or OVX NRF2 −/− mice have reported a decreased value of BMD [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway

Xiao,

Zhang,

et al. 2023

J Orthop Surg Res

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Background Osteoporosis (OP), due to microarchitectural alterations, is associated with decreased bone mass, declined strength, and increased fracture risk. Increased osteoblast apoptosis contributes to the progression of OP. Natural compounds from herbs provide a rich resource for drug screening. Our previous investigation showed that geniposide (GEN), an effective compound from Eucommia ulmoides, could protect against the pathological development of OP induced by cholesterol accumulation. Methods The rat OP models were duplicated. Dual-energy X-ray absorptiometry, hematoxylin and eosin staining, and immunohistochemistry were used to evaluate bone changes. TUNEL/DAPI staining assays were used for cell apoptosis detection. Protein expression was determined by western blotting assays. Results A high-fat diet promoted OP development in vivo, and OX-LDL stimulated osteoblast apoptosis in vitro. GEN exhibited protective activities against OX-LDL-induced osteoblast apoptosis by increasing the NRF2 pathway and decreasing the NF-κB pathway. PDTC, an NF-κB inhibitor, could further promote the biological functions of GEN. In contrast, ML385, an NRF2 inhibitor, might eliminate GEN’s protection. Conclusion GEN suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway.

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“…Te majority of TCM in this formula have similar and synergistic kidney-yin-tonifying functions and thus have the potential to beneft bone health [11,12]. Many bioactive ingredients in Zuogui Pill, including aucubin, loganin, chlorogenic acid, and morroniside can promote osteoblast diferentiation, reduce calcitonin levels, and inhibit osteoblast apoptosis and osteoclast proliferation [13][14][15][16][17]. Meanwhile, protocatechuic aldehyde has been shown to be efective in the prevention and treatment of osteoporosis [18,19].…”

Section: Introductionmentioning

confidence: 99%

Comparative Pharmacokinetic Study of 5 Active Ingredients after Oral Administration of Zuogui Pill in Osteoporotic Rats with Different Syndrome Types

Qiu

Zhu

Xing

et al. 2023

International Journal of Analytical Chemistry

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Zuogui Pill is a kidney-yin-tonifying formula in traditional Chinese medicine that is widely used to manage osteoporosis with kidney-yin-deficiency in China. Herein, an efficient and accurate high-performance liquid chromatography-tandem mass spectrometry method was developed to determine the concentrations of 5 bioactive compounds in rat plasma following oral administration of Zuogui Pill. Because drug absorption and distribution differ under physiological and pathological conditions, the established method was used to quantify blood components and dynamic change in osteoporotic rats with different syndrome types. Moreover, integrated pharmacokinetic study was conducted to describe the overall pharmacokinetic characteristics of traditional Chinese medicine. The results showed that the absorption, distribution, and metabolism of Zuogui Pill varied widely under different states. The bioavailability of most active components showed significant advantages in osteoporotic rats with kidney-yin-deficiency, which corresponds to the opinion that Zuogui Pill has the effect of nourishing kidney-yin. It is hoped that this finding could interpret the pharmacodynamic substances and mechanism of Zuogui Pill in the treatment of osteoporosis with kidney-yin-deficiency.

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Aucubin slows the development of osteoporosis by inhibiting osteoclast differentiation via the nuclear factor erythroid 2-related factor 2-mediated antioxidation pathway

Cited by 12 publications

References 54 publications

Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA‐H19 Driven Wnt/β‐Catenin Signaling Regulatory Axis

Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA‐H19 Driven Wnt/β‐Catenin Signaling Regulatory Axis

Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway

Comparative Pharmacokinetic Study of 5 Active Ingredients after Oral Administration of Zuogui Pill in Osteoporotic Rats with Different Syndrome Types

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