Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/β-catenin signaling pathway and analysis of active ingredients by molecular docking

Yuan, Yifeng; Wang, Shen; Zhou, Hang; Tang, Binbin; Liu, Yang; Huang, Hai; He, Caijian; Chen, Tianpeng; Fang, Mouhao; Liang, Bo; Mao, Yingdelong; Qie, Feng-Qin; Liu, Kang; Shi, Xiaolin

doi:10.3389/fphar.2022.994995

Cited by 6 publications

(1 citation statement)

References 42 publications

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“…47 However, QR and ALN decreased PINP, and CTX-1. The combination of QR and MCC950 or CQ resulted in an even more significant reduction in PINP and CTX-1, similar to the results of previous studies, 48 suggesting that QR may play a dual role in inhibiting bone resorption and promoting bone formation. However, the exact underlying mechanisms require further investigation.…”

Section: Discussionsupporting

confidence: 88%

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

Xiong,

Huang,

Shi

et al. 2023

Exp Biol Med (Maywood)

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With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1β (IL-1β) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.

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Section: Discussionsupporting

confidence: 88%

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

Xiong,

Huang,

Shi

et al. 2023

Exp Biol Med (Maywood)

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New‐QiangGuYin‐Containing Serum Inhibits Osteoclast‐Derived Exosome Secretion and Down‐Regulates Notum to Promote Osteoblast Differentiation

Meng,

Zhang,

et al. 2024

Advanced Biology

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New‐QiangGuYin (N‐QGY), the addition of sea buckthorn on the basis of QGY formula, is herbal formula widely used clinically in China for the treatment of osteoporosis (OP), but its mechanism warrants further exploration. The mechanisms of QGY and N‐QGY in the treatment of OP are probed from the perspective of osteoclast‐osteoblast balance. Thirty Sprague‐Dawley rats are randomly divided into N‐QGY group, QGY group, and Control group. Beyond control rats that orally took normal saline, other rats are orally administered with isometric N‐QGY or QGY twice every day for 3 days. The drug‐containing serum and control serum are prepared and their effects on osteoclast‐derived exosome secretion are determined by bicinchoninic acid assay (BCA), nanoparticle tracking analysis, and Western blot. GW4869 and Interleukin‐1β (IL‐1β) are adopted as the exosome inhibitor and inducer, respectively. Exosome uptake, cell counting kit‐8, alkaline phosphatase (ALP) staining, alizarin red staining, enzyme‐linked immunosorbent assay, quantitative real‐time polymerase chain reaction, and Western blot are performed to examine the effects of altered osteoclast exosome content on osteogenic differentiation of mesenchymal stem cells (MSCs). N‐QGY, QGY, and GW4869 inhibit osteoclast‐derived exosome secretion and exosome uptake by MSCs, whereas IL‐1β exerted the opposite effects (p < 0.05). Different from IL‐1β, N‐QGY, QGY, and GW4869 partially elevated MSC viability, osteocalcin secretion, ALP, RUNX Family Transcription Factor 2 (RUNX2) and Osteopontin (OPN) expressions, and calcium deposition in the osteoclast‐MSCs coculture system (p < 0.05). Mechanically, osteoclasts increased Notum protein level but decreased β‐catenin level, which is enhanced by IL‐1β but is reversed by GW4869, QGY, and N‐QGY (p < 0.05). And the effect of N‐QGY is more conspicuous than that of QGY (P<0.05). N‐QGY‐containing serum inhibits exosome levels in osteoclasts, thereby enhancing osteogenic differentiation of MSCs via inhibition of Notum protein and promotion of β‐catenin protein.

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Aqueous Extract of Wolfberry Alleviates Aging‐Related Skeletal Muscle Dysfunction by Modulating PRRs Signaling Pathways and Enhancing DNA Repair

Zheng,

Chen,

AL‐Ansi

et al. 2024

Molecular Nutrition Food Res

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Aging can lead to a series of degenerative changes in skeletal muscle, which would negatively impact physical activity and the quality of life of the elderly. Wolfberry contains numerous bioactive substances. It's vital to further explore the mechanisms underlying its healthy effects on skeletal muscle function during aging progress. This study discusses the benefits and mechanisms of aqueous extract of wolfberry (AEW) to protect skeletal muscle from aging‐related persistent DNA damage based on its anti‐inflammatory activity. It is found that AEW improves muscle mass, strength, and endurance, modulates the expression of Atrogin‐1, MyH, and MuRF‐1, and decreases oxidative stress and inflammation levels in aging mice, which is consistent with the in vitro results. Mechanistically, AEW inhibits the pattern recognition receptors (PRRs) pathway induced by inflammatory gene activation, suggesting its potential in response to DNA damage. AEW is also observed to mitigate chromatin decompaction. Network pharmacology is conducted to analyze the potential targets of AEW in promoting DNA repair. In conclusion, the study shows the anti‐aging effects of AEW on skeletal muscle by promoting DNA repair and reducing the transcriptional activity of inflammatory factors. AEW intake may become a potential strategy for strengthening skeletal muscle function in the elderly.

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Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/β-catenin signaling pathway and analysis of active ingredients by molecular docking

Cited by 6 publications

References 42 publications

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway

New‐QiangGuYin‐Containing Serum Inhibits Osteoclast‐Derived Exosome Secretion and Down‐Regulates Notum to Promote Osteoblast Differentiation

Aqueous Extract of Wolfberry Alleviates Aging‐Related Skeletal Muscle Dysfunction by Modulating PRRs Signaling Pathways and Enhancing DNA Repair

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