Guhong Injection promotes fracture healing by activating Wnt/beta-catenin signaling pathway in vivo and in vitro

Sun, Zhizhen; Jin, Hongting; Zhou, Huifen; Yu, Li; Wan, Haitong

doi:10.1016/j.biopha.2019.109436

Cited by 10 publications

(4 citation statements)

References 24 publications

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“…BMP-2, a member of the BMP family is fundamental for osteoblast differentiation ( Wu et al, 2016 ). A recent study showed that Guhong injection (GHI), a traditional compound preparation with 2 as one of its effective components, significantly increased BMP-2 and TGF-β expression levels ( Sun et al, 2019 ). In parallel with that finding, we also showed that 2 and 3 enhanced expressions of BMP-2-associated proteins at both the mRNA ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Compounds isolated from Euonymus spraguei Hayata induce ossification through multiple pathways

Imtiyaz

Lin

Cheong

et al. 2020

Saudi Journal of Biological Sciences

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The process of bone metabolism includes catabolism of old or mature bone and anabolism of new bone, carried out by osteoclasts and osteoblasts respectively. Any imbalance in this process results in loss of bone mass or osteoporosis. Drugs available to combat osteoporosis have certain adverse effects and are unable to improve bone formation, hence identifying new agents to fulfil these therapeutic gaps is required. To expand the scope of potential agents that enhance bone formation, we identified Euonymus spraguei Hayata as a plant material that possesses robust osteogenic potential using human osteoblast cells. We isolated three compounds, syringaresinol ( 1 ), syringin ( 2 ), and (−)-epicatechin ( 3 ), from E. spraguei. Results demonstrated that syringin ( 2 ), and (−)-epicatechin ( 3 ), increased alkaline phosphatase activity significantly up to 131.01% and 130.67%, respectively; they also elevated mineral deposition with respective values of up to 139.39% and 138.33%. In addition, 2 and 3 modulated autophagy and the bone morphogenetic protein (BMP)-2 signaling pathway. Our findings demonstrated that 2 and 3 induced osteogenesis by targeting multiple pathways and therefore can be considered as potent multi-targeted drugs for bone formation against osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Compounds isolated from Euonymus spraguei Hayata induce ossification through multiple pathways

Imtiyaz

Lin

Cheong

et al. 2020

Saudi Journal of Biological Sciences

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“…Intravenous parathyroid hormone (PTH) significantly increased β -catenin expression and TCF/LEF transcriptional activity in osteoblasts [ 156 ]. Guhong injection (GHI) can also promote osteoblast proliferation, increase the expression of Wnt3a, β -catenin, and LEF-1, and accelerate fracture healing, which indicates that the Wnt/ β -catenin signaling pathway plays positive roles in regulating osteogenic differentiation in vivo and in vitro [ 157 ].…”

Section: Wnt Signaling Pathway and Bone-related Cellsmentioning

confidence: 99%

Progress of Wnt Signaling Pathway in Osteoporosis

Gao

Chen

et al. 2023

Biomolecules

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Osteoporosis, one of the serious health diseases, involves bone mass loss, bone density diminishing, and degeneration of bone microstructure, which is accompanied by a tendency toward bone fragility and a predisposition to fracture. More than 200 million people worldwide suffer from osteoporosis, and the cost of treating osteoporotic fractures is expected to reach at least $25 billion by 2025. The generation and development of osteoporosis are regulated by genetic factors and regulatory factors such as TGF-β, BMP, and FGF through multiple pathways, including the Wnt signaling pathway, the Notch signaling pathway, and the MAPK signaling pathway. Among them, the Wnt signaling pathway is one of the most important pathways. It is not only involved in bone development and metabolism but also in the differentiation and proliferation of chondrocytes, mesenchymal stem cells, osteoclasts, and osteoblasts. Dkk-1 and SOST are Wnt inhibitory proteins that can inhibit the activation of the canonical Wnt signaling pathway and block the proliferation and differentiation of osteoblasts. Therefore, they may serve as potential targets for the treatment of osteoporosis. In this review, we analyzed the mechanisms of Wnt proteins, β-catenin, and signaling molecules in the process of signal transduction and summarized the relationship between the Wnt signaling pathway and bone-related cells. We hope to attract attention to the role of the Wnt signaling pathway in osteoporosis and offer new perspectives and approaches to making a diagnosis and giving treatment for osteoporosis.

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“…Guhong injection, a sterilized aqueous solution mixed with Acetylglutamide and Carthami Flos extract, is clinically used to treat cerebrovascular diseases [18] and orthopedic diseases [19] including cerebral insufficiency, cerebral thrombosis, coronary heart disease, fracture healing, etc. Carthami Flos, widely known as "Hong-Hua" in China, is the dried flower of Carthamus tinctorius L. It is a representative medicine for promoting blood circulation and removing blood stasis.…”

Section: Introductionmentioning

confidence: 99%

Design Space Calculation and Continuous Improvement Considering a Noise Parameter: A Case Study of Ethanol Precipitation Process Optimization for Carthami Flos Extract

Tai

Gong

2021

Separations

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The optimization of process parameters in the pharmaceutical industry is often carried out according to the Quality by Design (QbD) concept. QbD also emphasizes that continuous improvement should be performed in life cycle management. Process parameters that are difficult to control in actual production can be regarded as noise parameters. In this study, based on the QbD concept, the ethanol precipitation process of Carthami Flos extract was optimized, considering a noise parameter. The density of the concentrated extract, ethanol concentration, the volume ratio of ethanol to concentrated extract, stirring time after ethanol addition, and refrigeration temperature were selected as critical process parameters (CPPs), using a definitive screening design. The mathematical models among CPPs and evaluation indicators were established. Considering that the refrigeration temperature of industrial ethanol precipitation is often difficult to control with seasonal changes, refrigeration temperature was treated as a noise parameter. A calculation method for the design space in the presence of the noise parameter was proposed. The design space was calculated according to the probability of reaching the standards of evaluation indicators. Controlling parameters within the design space was expected to reduce the influence of noise parameter fluctuations on the quality of the ethanol precipitation supernatant. With more data obtained, the design space was updated. In industry, it is also recommended to adopt a similar idea: that is, continuing to collect industrial data and regularly updating mathematical models, which can further update the design space and make it more stable and reliable.

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Guhong Injection promotes fracture healing by activating Wnt/beta-catenin signaling pathway in vivo and in vitro

Cited by 10 publications

References 24 publications

Compounds isolated from Euonymus spraguei Hayata induce ossification through multiple pathways

Compounds isolated from Euonymus spraguei Hayata induce ossification through multiple pathways

Progress of Wnt Signaling Pathway in Osteoporosis

Design Space Calculation and Continuous Improvement Considering a Noise Parameter: A Case Study of Ethanol Precipitation Process Optimization for Carthami Flos Extract

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