Salidroside Suppresses IL-1β-Induced Apoptosis in Chondrocytes via Phosphatidylinositol 3-Kinases (PI3K)/Akt Signaling Inhibition

Wu, Mingzheng; Hu, Rui; Wang, Junwen; An, Yu; Lu, Lin; Chao, Long; Li, Yan

doi:10.12659/msm.917851

Cited by 18 publications

(15 citation statements)

References 24 publications

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“…Rats were divided into five groups (n=10): Control group (Healthy rats were given saline treatment); ACLT, ACLT model; ACLT + Sal (12.5 mg/kg), OA rats were treated with 12.5 mg/kg Sal; ACLT + Sal (25 mg/kg), OA rats were treated with chondrocytes. 40 Similarly, this study found that Sal promoted the proliferation of chondrocytes in OA rats and inhibited the expression of apoptotic proteins (cleaved caspase 3 and cleaved caspase 9). The main factors for the progression of OA are chronic inflammation and progressive structural changes in joint tissues.…”

Section: Discussionmentioning

confidence: 53%

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

Gao¹,

Lü

Li³

et al. 2020

DDDT

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Introduction: Osteoarthritis (OA) is the most common disease, which seriously affects the daily life of the elderly. Currently, no traditional or drug therapy has been shown to explicitly block the progression of OA. Salidroside (Sal) is a bioactive component of Rhodiola rosea, which has many beneficial effects on human health. However, the role and mechanism of Sal in OA have not been reported. Methods: We established an anterior cruciate ligament transection (ACLT)-induced OA Rat model. The rats were divided into five groups (n = 10): Control group; ACLT group; ACLT + Sal (12.5 mg/kg) group; ACLT + Sal (25 mg/kg) group; ACLT + Sal (50 mg/kg) group. Results: The study showed that Sal could significantly promote the proliferation of chondrocytes in OA rats induced by ACLT and restore the histological alteration of cartilage. Besides, Sal upregulated the levels of Collagen II and Aggrecan, and downregulated the level of MMP-13. Furthermore, Sal could reduce the number of CD4+IL-17 + cells and decrease the levels of IL-17, IKBα and p65, while elevating the number of CD4+IL-10 + cells and the level of IL-10. The decrease of IL-17 further inhibited the dissociation of IKBα to p65, thus reducing the release of TNF-α and VCAM-1. Taken together, Sal alleviates cartilage degeneration through promoting chondrocytes proliferation, inhibiting collagen fibrosis, and regulating inflammation and immune responses via NF-κB pathway in ACLT-induced OA Rats. Discussion: Collectively, our study investigates the role and mechanism of Sal in OA, which lays a foundation for the application of Sal in OA.

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Section: Discussionmentioning

confidence: 53%

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

Gao¹,

Lü

Li³

et al. 2020

DDDT

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“…Salidroside is a natural antioxidant originally extracted from medicinal food plant Rhodiola rosea 137 and possesses potential anti-inflammatory 138 , anti-viral 139 , and anti-cancer 140 properties. Salidroside was previously shown to exhibit tumor-suppressive activity by modulating multiple pathways including, Notch1 141 , STAT3 138 , and PI3K/AKT 142 . However, these direct tumor cytotoxic effects mediated by salidroside required relatively high dose both in vitro and in vivo 140 .…”

Section: Discussionmentioning

confidence: 99%

Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung

et al. 2021

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Smoking has a profound impact on tumor immunity, and nicotine, which is the major addictive component of smoke, is known to promote tumor progression despite being a non-carcinogen. In this study, we demonstrate that chronic exposure of nicotine plays a critical role in the formation of pre-metastatic niche within the lungs by recruiting pro-tumor N2-neutrophils. This pre-metastatic niche promotes the release of STAT3-activated lipocalin 2 (LCN2), a secretory glycoprotein from the N2-neutrophils, and induces mesenchymal-epithelial transition of tumor cells thereby facilitating colonization and metastatic outgrowth. Elevated levels of serum and urine LCN2 is elevated in early-stage breast cancer patients and cancer-free females with smoking history, suggesting that LCN2 serve as a promising prognostic biomarker for predicting increased risk of metastatic disease in female smoker(s). Moreover, natural compound, salidroside effectively abrogates nicotine-induced neutrophil polarization and consequently reduced lung metastasis of hormone receptor-negative breast cancer cells. Our findings suggest a pro-metastatic role of nicotine-induced N2-neutrophils for cancer cell colonization in the lungs and illuminate the therapeutic use of salidroside to enhance the anti-tumor activity of neutrophils in breast cancer patients.

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“…Thus, a variety of natural products have emerged as milder options for the treatment of OA in recent years [44,45]. Recent studies showed that salidroside (Sal) could protects against apoptosis and inflammatory response in chondrocytes via inhibition of NF-κB activation and Phosphatidylinositol 3-Kinases (PI3K)/Akt Signaling [46], [47], [48]. However, the effect of Sal on osteoarthritis in vivo and the underlying mechanisms remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological blockade of PCAF ameliorates osteoarthritis development via dual inhibition of TNF-α-driven inflammation and ER stress

Chen

Liu

et al. 2019

EBioMedicine

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Background: Epigenetic mechanisms have been reported to play key roles in osteoarthritis (OA) development. P300/CBP-associated factor (PCAF) is a member of the histone acetyltransferases, which exhibits a strong relationship with endoplasmic reticulum (ER) stress and transcription factor nuclear factor kappa B (NF-κB) signals. Salidroside, a natural histone acetylation inhibitor, showed its anti-inflammatory and anti-apoptotic effects in lipopolysaccharide (LPS)-stimulated microglia cells in our previous study. However, whether Sal has a protective effect against OA remains unknown, and its relationships to PCAF, NF-κB, and the ER stress pathway should be explored further. Methods: We identified the role of PCAF in the pathogenesis of OA and determined the chondroprotective effect of Sal on both tumor necrosis factor alpha (TNF-α)-treated human chondrocytes and a destabilized medial meniscus (DMM) mouse OA model. Findings: We found increased PCAF expression in human OA cartilage and TNF-α-driven chondrocytes. Meanwhile, silencing of PCAF attenuated nuclear p65 and C/EBP homologous protein levels in chondrocytes upon TNF-α stimulation. Furthermore, Sal was found to specifically bind to the inhibitory site of the PCAF protein structure, which subsequently reversed the TNF-α-induced activation of NF-κB signal and ER stress-related apoptosis in chondrocytes. In addition, the protective effect of Sal and its inhibitory effects on PCAF as well as inflammatory-and ER stress-related markers were also observed in the mouse DMM model. Interpretation: Pharmacological blockade of PCAF by Sal ameliorates OA development via inhibition of inflammation and ER stress, which makes Sal a promising therapeutic agents for the treatment of OA.

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Salidroside Suppresses IL-1β-Induced Apoptosis in Chondrocytes via Phosphatidylinositol 3-Kinases (PI3K)/Akt Signaling Inhibition

Cited by 18 publications

References 24 publications

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

Nicotine promotes breast cancer metastasis by stimulating N2 neutrophils and generating pre-metastatic niche in lung

Pharmacological blockade of PCAF ameliorates osteoarthritis development via dual inhibition of TNF-α-driven inflammation and ER stress

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