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. 2026 Feb 27;57(2):95. doi: 10.1007/s10735-026-10749-8

Salidroside attenuates the osteoblastic differentiation of vascular smooth muscle cells via AMPK/AKT signaling pathway

Ying Lu 1, Yi Feng 1,✉
PMCID: PMC12948816  PMID: 41758410

Abstract

Salidroside (SAL), a major bioactive compound derived from Rhodiola rosea L., exhibits diverse pharmacological activities, including anti-tumor, anti-inflammatory and cardiovascular protective effects. Arterial calcification is a prevalent vascular pathology characterized by the osteogenic differentiation of vascular smooth muscle cells (VSMCs). However, the potential role of SAL in arterial calcification and its underlying molecular mechanisms remain to be elucidated. An in vitro arterial calcification model was established by stimulating VSMCs with β-glycerophosphate (β-GP). This model was utilized to investigate the effect of SAL on osteogenic differentiation, using alkaline phosphatase activity and Runx2 expression as key markers. To detemine the specific signaling mechanisms, the AMPK inhibitor Compound C and the AKT inhibitor LY294002 were employed. Furthermore, the in vivo efficacy of SAL in mitigating arterial calcification was evaluated using a vitamin D3-induced arterial calcification model in C57BL/6 J mice. Our study demonstrates that SAL effectively attenuates β-GP-induced osteogenic differentiation of VSMCs in vitro and suppresses arterial calcification in vivo. Mechanistically, SAL treatment resulted in the activation of both AMPK and AKT signaling pathways. Notably, pharmacological inhibition of either AMPK or AKT significantly abolished the protective effects of SAL against osteogenic differentiation of VSMCs, indicating that the anti-calcific activity of SAL in VSMCs is mediated via the AMPK/AKT axis. Collectively, our findings suggest that SAL ameliorates arterial calcification by suppressing the osteogenic differentiation of VSMCs via activation of the AMPK/AKT signaling pathway.

Keywords: Salidroside, Arterial calcification, Vascular smooth muslce cells, AMPK, AKT

Introduction

Arterial calcification is a hallmark pathological feature intimately associated with numerous conditions, including type 2 diabetes, aging, end-stage renal disease, and ageing (Onnis et al. 2024; Shan et al. 2024; Bell et al. 2022). As the global aging population continues to expand, the prevalence of arterial calcification has risen markedly. Substantial evidence has consistently demonstrated arterial calcification as a significant risk factor for cardiovascular events and mortality (Durham et al. 2018; Lanzer et al. 2021; Wu et al. 2023). While previously regarded as a passive deposition of calcium and phosphate, arterial calcification is now recognized as a complex, actively regulated process. A central mechanism in its pathophysiology is the trans-differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells, leading to hydroxyapatite deposition within the medial layer of the vascular wall (Lin et al. 2024; Guo et al. 2024; Zheng et al. 2023). Furthermore, the ectopic expression of key osteogenic molecules—such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2)—within calcified vascular walls underscores the fundamental role of VSMCs calcification in this pathogenic process (Jiang et al. 2022; Bergstrom et al. 2021).

Salidroside (p-hydroxyphenethyl-β-D-glucoside, SAL) is a bioactive compound derived from the traditional Chinese medicine Rhodiola rosea L. and is renowned for its diverse pharmacological properties. Recent studies have revealed the protective effects of SAL in various organ and cellular systems, showcasing neuroprotective, cardiovascular protective, anti-aging, and anti-tumor activities (Hu et al. 2021; Li et al. 2025). For instense, one recent study reported that SAL effectively inhibits metabolic stress-induced nonalcoholic steatohepatitis in both in vitro and in vivo models (Hu et al. 2021). Furthermore, SAL has been shown to exert anti-osteoporotic effects by reducing oxidative stress and promoting osteogenesis via Nrf2 activation (Wang et al. 2022). Additionally, SAL can mitigate high glucose-induced proliferation of VSMCs by preserving mitochondrial dynamics and reducing oxidative stress (Zhuang et al. 2017). Despite these significant findings and its known relevance to vascular health, the influence of SAL on VSMCs calcification remains to be elucidated.

Herein, we investigated the therapeutic potential of SAL in VSMCs calcification by modulating their osteogenic differentiation, and we aimed to elucidate the specific underlying signaling pathways involved in this process. Our findings provide novel insights into the pharmacological potential of SAL in vascular pathology and the regulatory mechanisms governing VSMCs calcification.

Materials and methods

Ethics statement

This study was approved by the Ethics Committee of Zhongshan People’s Hospital. All experimental procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Publication, 8th edition, 2011).

Cell culture and treatment

Primary human aortic smooth muscle cells were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA; Cat. No. CRL-1999). Cells at passages 4–6 were used for all experiments. VSMCs were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) and maintained under standard conditions (37 °C, 5% CO2). To induce osteogenic differentiation, cells were treated with 10 mM β-glycerophosphate (β-GP). For pharmacological intervention, VSMCs were incubated with 25 μM Salidroside (Sigma-Aldrich, St. Louis, MO, USA; Cat. No. 43866). To elucidate the underlying signaling pathways, VSMCs were pretreated with either 10 μM Compound C (Calbiochem, San Diego, CA, USA; Cat. No. 866405-64-3) or 10 μM LY294002 (Cat. No. 154447-36-6) for 30 min prior to SAL treatment.

Measurement of alkaline phosphatase (ALP) activity

Following the respective treatments, VSMCs were rinsed with phosphate-buffered saline (PBS) and lysed. ALP activity in the lysates was determined by measuring the release of p-nitrophenol at 37 °C using a commercial kit (Nanjing Jiancheng Bioengineering Institute, Nanjing, China; Cat. No. A059-2) according to the manufacturer’s instructions. Absorbance was measured spectrophotometrically, and ALP activity was normalized to the total protein content, which was quantified using Bradford assay.

Assessment of calcification

Calcification was evaluated by Alizarin Red S staining, Von Kossa staining and quantitative measurement of celluar calcium content. For Alizarin Red S staining, cells were washed with PBS, fixed with 4% paraformaldehyde for 20 min at room temperature, and stained with 2% Alizarin Red S solution (Sigma-Aldrich, St. Louis, MO, USA; pH 4.2) After thorough washing to remove unbound dye, mineralization nodules were visualizedand imaged using a digital microscope.

For Von Kossa staining, tissue sections were first rinsed with double-distilled water and then exposed to Von Kossa staining solution (G1043, Servicebio, Wuhan, China) under ultraviolet light for 2 h. Following thorough rinsing with double-distilled water, nuclei were counterstained with hematoxylin and cytoplasmic structures with eosin. The sections were subsequently dehydrated through a graded ethanol series and mounted with neutral balsam. Images were captured using a light microscope, and the areas showing positive calcification signals were quantified using ImageJ software.

For quantitative analysis, cellular calcium content was measured using the QuantiChrom Calcium Assay Kit (Biosino Bio-Technology and Science, Beijing, China) according to the manufacturer’s protocol. Calcium levels were normalized to the total protein content.

Western blot analysis

Protein expression was analyzed by Western blotting as previously described (Lei et al. 2024; Xu et al. 2019; Wu et al. 2019). Briefly, 30 μg of total protein lysates were separated by SDS-PAGE and transferred onto polyvinylidene fluoride (PVDF) membranes. The membranes were blocked and then incubated with primary antibodies against Runx2 (ab23981, 1:1000, Abcam), p-AMPK (ab92701, 1:1000, Abcam), AMPK (ab271188, 1:1000, Abcam), p-AKT (ab38449, 1:500, Abcam), and AKT (ab18785, 1:1000, Abcam). After incubation with appropriate secondary antibodies for 1 h at room temperature, immunoreactive bands were visualized using an enhanced chemiluminescence (ECL) detection kit.

Animal experiments

Eight-week-old male C57BL/6 J wild-type mice were obtained from Guangdong Yaokang Biotechnology Co., Ltd (Guangzhou, China). Mice were housed under specific pathogen-free (SPF) conditions at 20–24 °C with 50–60% relative humidity and a 12-h light/dark cycle, with ad libitum access to food and water. After one week of acclimation, sixteen mice were randomly assigned to two groups (n = 8 per group): vitamin D3 + vehicle group and vitamin D3 + SAL group. Arterial calcification was induced by subcutaneous injection of vitamin D3 (500,000 IU/kg body weight) for three consecutive days. Mice in vitamin D3 + SAL group additionally received salidroside (purity > 98%, National Institute for Food and Drug Control, Beijing, China) at 90 mg/kg /day via oral gavage, administered daily for 8 weeks starting on the day of the first vitamin D₃ injection. At the end of 8-week treatment period, mice were euthanized by intraperitoneal injection of sodium pentobarbital (150 mg/kg). Thoracic aortas were harvested for subsequent analysis.

Statistical analysis

Data are presented as mean ± standard deviation (SD). Statistical comparisons among multiple groups were performed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test for pairwise comparisons. A p-value < 0.05 was considered statistically significant. All experiments were independently repeated at least three times, and representative results are shown.

Results

Salidroside attenuates β-GP-induced osteogenic differentiation of VSMCs

To investigate the effect of SAL on osteogenic differentiation, VSMCs were treated with β-glycerophosphate (β-GP). As shown in Fig. 1A, B, β-GP treatment significantly induced osteogenic differentiation of VSMCs, as evidenced by increased Runx2 protein expression (Fig. 1A), elevated alkaline phosphatase (ALP) activity (Fig. 1B), enhanced matrix calcification (Fig. 1D), while concomitant downregulation of SM22α (Fig. 1C), a contractile marker of VSMCs. Treatment with SAL alone did not significantly alter these parameters; however, it effectively reversed the β-GP-induced upregulation of Runx2 and ALP activity (Fig. 1A, B) as well as the β-GP-mediated downregulation of SM22α (Fig. 1C). Similarly, SAL markedly attenuated the β-GP-stimulated calcification of VSMCs, as demonstrated by Alizarin Red S staining and quantitative calcium analysis (Fig. 1D). Collectively, These results indicate that SAL attenuates β-GP-induced osteogenic differentiation and calcification in VSMCs.

Fig. 1.

Fig. 1

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Salidroside (SAL) attenuates β-glycerophosphate (β-GP)-induced osteogenic differentiation and calcification in vascular smooth muscle cells (VSMCs). Effect of SAL on Runx2 protein expression. VSMCs were treated with or without 10 mM β-GP and/or 25 μM SAL for the indicated duration. Representative western blot bands are shown on the left. The right panel shows the quantitative densitometric analysis of Runx2 protein levels, normalized to a loading control. B Effect of SAL on alkaline phosphatase (ALP) activity. Cells were treated as described in (A). ALP activity was measured using a commercial kit and normalized to the total cellular protein content. Representative western blot bands are shown on the upper. The lower panel shows the quantitative densitometric analysis of SM22α protein levels, normalized to a loading control. C Effect of SAL on SM22α protein expression. Cells were treated as described in (A). D Representative images of Alizarin Red S staining. VSMCs were cultured under control conditions or with 25 μM SAL for 12 days to assess matrix mineralization (scale bar = 200 μm). Calcium content in the cell layers was quantified using the QuantiChrom Calcium Assay Kit and normalized to the total protein content. Data are presented as mean ± SD (n = 3). **p < 0.01 vs. control group; ## p < 0.01 vs. β-GP-treated group

Salidroside activates the AMPK/AKT signaling pathway in VSMCs

We next investigate whether the AMPK/AKT signaling pathway conributes to the protective effects of SAL. As shown in Fig. 2A, β-GP significantly suppressed the phosphorylation of both AMPK and AKT. Notably, co-treatment with SAL markedly reversed this suppression and restored phosphorylation levels to near-basal states. To further validate the involvement of this pathway, VSMCs were co-treated with SAL and specific pharmacological inhibitors: Compound C (an AMPK inhibitor) or LY294002 (a PI3K/AKT pathway inhibitor). As illustrated in Fig. 2B and C, the increase in AMPK and AKT phosphorylation induced by SAL was blocked by Compound C and LY294002, respectively. These findings demonstrates that SAL activates the AMPK/AKT signaling pathway in VSMCs under calcifying conditions.

Fig. 2.

Fig. 2

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Salidroside (SAL) activates the AMPK/AKT signaling pathway in vascular smooth muscle cells (VSMCs). A VSMCs were treated with 10 mM β-glycerophosphate (β-GP) in the presence or absence of 25 μM SAL for 30 min to assess pathway activation. Whole-cell lysates were analyzed by western blotting using antibodies specific for phosphorylated AMPK (p-AMPK), total AMPK, phosphorylated AKT (p-AKT), and total AKT. GAPDH or β-actin was used as a loading control. Representative blots from three independent experiments are shown. B VSMCs were pretreated with the AMPK inhibitor Compound C (10 μM) for 2 h, followed by co-treatment with 25 μM SAL and 10 mM β-GP for 30 min. Phosphorylation and total levels of AMPK were detected by western blotting. A representative blot is shown. C VSMCs were pretreated with the AKT inhibitor LY294002 (10 μM) for 2 h, followed by co-treatment with 25 μM SAL and 10 mM β-GP for 30 min. Phosphorylation and total levels of AKT were detected by western blotting. A representative blot is shown

The anti-calcification effect of Salidroside is mediated by AMPK/AKT signaling pathway

To determine whether the AMPK/AKT signaling pathway mediates the anti-calcification effect of SAL, we employed pharmacological inhibitors in β-GP-treated VSMCs. As shown in Fig. 3, the SAL-induced suppression of Runx2 expression and ALP activity was significantly attenuated by co-treatment with either Compound C or LY294002. These results demonstrate that pharmacological inhibition of either AMPK or AKT signaling pathway abolishes the protective effects of SAL against β-GP–induced osteogenic differentiation of VSMCs, indicating that SAL exerts its anti-calcification action in VSMCs primarily through activation of the AMPK/AKT signaling pathway.

Fig. 3.

Fig. 3

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The AMPK/AKT signaling pathway mediates the inhibitory effect of salidroside (SAL) on the osteogenic differentiation of vascular smooth muscle cells (VSMCs). A, B VSMCs were pretreated with the AMPK inhibitor Compound C (10 μM) or the AKT inhibitor LY294002 (10 μM) for 2 h, followed by co-treatment with 25 μM SAL and 10 mM β-glycerophosphate (β-GP) for 72 h. (A) Representative western blots showing Runx2 protein expression levels. (B) Quantitative analysis of Runx2 protein expression from three independent experiments. C ALP activity under the same treatment conditions as in (A, B). ALP activity was measured spectrophotometrically and normalized to the total cellular protein content. Data are presented as mean ± SD (n = 3). **p < 0.01 vs. control group; ## p < 0.01 vs. β-GP + SAL group

Salidroside suppresses arterial calcification in vivo

We further evaluated the effect of SAL on arterial calcification in a vitamin D3-induced mouse model (Li et al. 2023). Alizarin Red S staining and Von Kossa staining revealed pronounced medial calcification in the thoracic aortas of vitamin D3-treated mice, which was markedly attenuated by SAL administration (Fig. 4A). Consistent with this, quantitative analysis showed a significant decrease in aortic calcium content in the SAL-treated group compared to the vehicle control (Fig. 4B). Immunohistochemical analysis further demonstrated that vitamin D3-induced upregulation of Runx2 was suppressed by SAL treatment (Fig. 4C and D). Taken together, these results confirm that SAL attenuates arterial calcification and Runx2 expression in vivo.

Fig. 4.

Fig. 4

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Salidroside (SAL) attenuates arterial calcification in a vitamin D3-induced mouse model. A Representative images of Alizarin Red S (ARS) staining and Von Kossa staining in the medial layer of the thoracic aorta. Scale bar = 500 μm. B Quantitative analysis of calcium content and Von Kossa staining positive area in aortic tissues. C Immunohistochemical analysis of Runx2 expression (brown staining) in the thoracic aorta. Scale bar = 200 μm. D The quantitative analysis of the Runx2-positive area. Data are presented as mean ± SD (n = 8 per group). **p < 0.01 vs. Vitamin D3 + Vehicle group

Discussion

Arterial calcification was historically regarded as a passive, dystrophic process resulting from the unregulated deposition of calcium–phosphate crystals in the vessel wall. However, accumulating evidence now establishes it as an active, cell-mediated process driven by the osteogenic transdifferentiation of VSMCs into osteoblast-like cells. Despite this paradigm shift, the precise molecular mechanisms governing this phenotypic switch remain incompletely understood. In the present study, we demonstrate that SAL significantly attenuates both β-GP induced osteogenic differentiation of VSMCs in vitro and vitamin D₃–triggered arterial calcification in vivo. Moreover, we identify the activiation of the AMPK/AKT signaling pathway as a key mechanism underlying SAL’s protective effects, thereby providing novel mechanism insight arterial calcification.

Salidroside, a key bioactive compound derived from Rhodiola rosea L., exhibits a broad spectrum of pharmacological activities. Previous studies have highlighted its beneficial effects on cardiovascular and cerebrovascular health, including protection against myocardial ischemia–reperfusion injury, attenuation of cardiac fibrosis, and improvement of cardiac function (Chen et al. 2022). SAL has also been shown to exert hypoglycemic and vasoprotective effects in experimental models of diabetes (Ma et al. 2016, 2017). Notably, recent evidence indicates that SAL enhances vasodilation in cerebrovascular smooth muscle cells and reduces blood pressure in diabetic rats (Ma et al. 2017). Given these well-documented modulatory effects on vascular tone and smooth muscle cell homeostasis, we hypothesized that SAL might also interfere with the osteogenic differentiation and matrix mineralization of VSMCs—key processes underlying arterial calcification.

The early phase of osteogenic differentiation is characterized by the upregulation of ALP and the key transcription factor Runx2. In our experimental model, β-GP—a well-established inducer of VSMCs calcification—enhanced both ALP activity and Runx2 protein expression, confirming the successful induction of osteogenic differentiation. Notably, SAL treatment markedly suppressed these β-GP–induced changes, as evidenced by reduced ALP activity and downregulated Runx2 levels. These findings demonstrate that SAL inhibits the initiation of osteogenic transdifferentiation in VSMCs.

To further explore the signaling mechanisms underlying SAL protective effects, we focused on the AMPK and AKT signaling pathways, which have been implicated in regulating VSMCs calcification. Previous studies reported that adiponectin inhibits VSMCs osteogenic differentiation via AMPK activiation (Zhan et al. 2014), whereas liraglutide exerts anti-arterial calcification effects through the PI3K/AKT signaling cascade (Zhan et al. 2015). More recently, omentin-1 was shown to attenuate arterial calcification via the AMPK/AKT axis (Xu et al. 2019). Consistent with these reports, our study demonstrates that SAL enhances the phosphorylation of AMPK and AKT in VSMCs. Critically, the anti-calcification effects of SAL—evidenced by reduced Runx2 expression, ALP activity, and matrix mineralization—were abrogated upon co-treatment with either Compound C (an AMPK inhibitor) or LY294002 (a PI3K inhibitor that blocks AKT activation). These findings establish that SAL suppresses osteogenic transdifferentiation of VSMCs through dual activation of the AMPK/AKT signaling pathway.

Having established the efficacy of SAL in inhibiting VSMCs calcification in vitro, we further validated its protective role in vivo using a vitamin D3-induced murine model of arterial calcification. As expected, vitamin D3 treatment induced pronounced aortic calcification, accompanied by elevated ALP activity, calcium deposition, and Runx2 expression. Critically, SAL treatment markedly attenuated both the calcified lesion area and total aortic calcium content, concomitantly downregulating key osteogenic markers including Runx2 and ALP. Collectively, these findings demonstrate that SAL functions as a potent inhibitor of arterial calcification.

This study has several limitations. First, our findings are based solely on in vitro and in vivo models of arterial calcification. While these models are informative, there remains a significant gap between experimental models and clinical application, which should be explored in future work. Furthermore, while we have identified key pathways, additional molecular mechanisms likely contribute to the bioactivity of SAL, warranting further investigation.

In summary, our findings demonstrate that SAL attenuates osteogenic transdifferentiation of VSMCs and suppresses arterial calcification through activation of the AMPK/AKT signaling pathway. These results elucidate a novel molecular mechanism underlying SAL’s protective effects on arterial calcification.

Acknowledgements

Not applicable.

Author contributions

Y.L. and F.Y. designed the study, Y.L. and F.Y. wrote the manuscript. performed the experiment, collected the data, and conducted statistical analysis. All authors reviewed and approved the final version for submission.

Funding

This study received the support of 2026 Guangdong Provincial Administration of Traditional Chinese Medicine Scientific Research Project in Traditional Chinese Medicine (20261451). Social Welfare Science and Technology Research Project of Zhongshan City (2018B1065). The social public welfare and basic research projects in Zhongshan in 2021 (2021B1022).

Data availability

The datasets used during the present study are available from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Consent for publication

Not applicable.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. Bell KJL, White S, Hassan O, Zhu L, Scott AM, Clark J, Glasziou P (2022) Evaluation of the incremental value of a Coronary Artery calcium score beyond traditional cardiovascular risk assessment: a systematic review and meta-analysis. JAMA Intern Med 182(6):634–642 [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bergstrom G, Persson M, Adiels M, Bjornson E, Bonander C, Ahlstrom H, Alfredsson J, Angeras O, Berglund G, Blomberg A, Brandberg J, Borjesson M, Cederlund K, de Faire U, Duvernoy O, Ekblom O, Engstrom G, Engvall JE, Fagman E, Eriksson M, Erlinge D, Fagerberg B, Flinck A, Goncalves I, Hagstrom E, Hjelmgren O, Lind L, Lindberg E, Lindqvist P, Ljungberg J, Magnusson M, Mannila M, Markstad H, Mohammad MA, Nystrom FH, Ostenfeld E, Persson A, Rosengren A, Sandstrom A, Sjalander A, Skold MC, Sundstrom J, Swahn E, Soderberg S, Toren K, Ostgren CJ, Jernberg T (2021) Prevalence of subclinical Coronary Artery atherosclerosis in the general population. Circulation 144(12):916–929 [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen Y, Tang M, Yuan S, Fu S, Li Y, Li Y, Wang Q, Cao Y, Liu L, Zhang Q (2022) Rhodiola rosea: a therapeutic candidate on cardiovascular diseases. Oxid Med Cell Longev 2022:1348795 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM (2018) Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness. Cardiovasc Res 114(4):590–600 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Guo B, Zhuang TT, Li CC, Li F, Shan SK, Zheng MH, Xu QS, Wang Y, Lei LM, Tang KX, Ouyang W, Duan JY, Wu YY, Cao YC, Ullah MHE, Zhou ZA, Lin X, Wu F, Xu F, Liao XB, Yuan LQ (2024) MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression. Cardiovasc Diabetol 23(1):331 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hu M, Zhang D, Xu H, Zhang Y, Shi H, Huang X, Wang X, Wu Y, Qi Z (2021) Salidroside activates the AMP-activated protein kinase pathway to suppress nonalcoholic steatohepatitis in mice. Hepatology 74(6):3056–3073 [DOI] [PubMed] [Google Scholar]
  7. Jiang Y, Li Y, Shi K, Wang J, Qian WL, Yan WF, Pang T, Yang ZG (2022) The additive effect of essential hypertension on coronary artery plaques in type 2 diabetes mellitus patients: a coronary computed tomography angiography study. Cardiovasc Diabetol 21(1):1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lanzer P, Hannan FM, Lanzer JD, Janzen J, Raggi P, Furniss D, Schuchardt M, Thakker R, Fok PW, Saez-Rodriguez J, Millan A, Sato Y, Ferraresi R, Virmani R, St HC (2021) Medial arterial calcification: JACC state-of-the-art review. J Am Coll Cardiol 78(11):1145–1165 [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lei LM, Li FX, Lin X, Xu F, Shan SK, Guo B, Zheng MH, Tang KX, Wang Y, Xu QS, Ouyang WL, Duan JY, Wu YY, Cao YC, Zhou ZA, He SY, Wu YL, Chen X, Lin ZJ, Pan Y, Yuan LQ, Li ZH (2024) Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy. J Nanobiotechnol 22(1):361 [Google Scholar]
  10. Li FX, Liu JJ, Xu F, Shan SK, Zheng MH, Lei LM, Lin X, Guo B, Li CC, Wu F, Tang KX, Cao YC, Wu YY, Duan JY, Wu YL, He SY, Chen X, Yuan LQ (2023) Cold exposure protects against medial arterial calcification development via autophagy. J Nanobiotechnol 21(1):226 [Google Scholar]
  11. Li Q, Chen Q, Xiao S, Wang S, Ge X, Wang Q, Zheng L, Wei Q, Du W, Shen W, Wu Y, Song J (2025) A salidroside-based radiosensitizer regulates the Nrf2/ROS pathway for X-ray activated synergistic cancer precise therapy. Adv Mater 37(24):e2413226 [DOI] [PubMed] [Google Scholar]
  12. Lin X, He SQ, Shan SK, Xu F, Wu F, Li FX, Zheng MH, Lei LM, Duan JY, Wu YY, Wu YL, Tang KX, Cui RR, Huang B, Yang JJ, Liao XB, Liu J, Yuan LQ (2024) Endothelial cells derived extracellular vesicles promote diabetic arterial calcification via circ_0008362/miR-1251-5p/Runx2 axial. Cardiovasc Diabetol 23:369 [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ma YG, Zhang YB, Bai YG, Dai ZJ, Liang L, Liu M, Xie MJ, Guan HT (2016) Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca(2)(+) handling in smooth muscle cells. Cardiovasc Diabetol 12(15):63 [Google Scholar]
  14. Ma YG, Wang JW, Zhang YB, Wang BF, Dai ZJ, Xie MJ, Kang HF (2017) Salidroside improved cerebrovascular vasodilation in streptozotocin-induced diabetic rats through restoring the function of BKCa channel in smooth muscle cells. Cell Tissue Res 370(3):365–377 [DOI] [PubMed] [Google Scholar]
  15. Ma YG, Wang JW, Bai YG, Liu M, Xie MJ, Dai ZJ (2017) Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells. BMC Pharmacol Toxicol 18(1):30 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Onnis C, Virmani R, Kawai K, Nardi V, Lerman A, Cademartiri F, Scicolone R, Boi A, Congiu T, Faa G, Libby P, Saba L (2024) Coronary artery calcification: current concepts and clinical implications. Circulation 149(3):251–266 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shan SK, Lin X, Wu F, Li CC, Guo B, Li FX, Zheng MH, Wang Y, Xu QS, Lei LM, Tang KX, Wu YY, Duan JY, Cao YC, Wu YL, Tan CM, Liu ZH, Zhou ZA, Liao XB, Xu F, Yuan LQ (2024) Vascular wall microenvironment: endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner. Bioact Mater 42:52–67 [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wang YF, Chang YY, Zhang XM, Gao MT, Zhang QL, Li X, Zhang L, Yao WF (2022) Salidroside protects against osteoporosis in ovariectomized rats by inhibiting oxidative stress and promoting osteogenesis via Nrf2 activation. Phytomedicine 27(99):154020 [Google Scholar]
  19. Wu F, Li F, Lin X, Xu F, Cui RR, Zhong JY, Zhu T, Shan SK, Liao XB, Yuan LQ, Mo ZH (2019) Exosomes increased angiogenesis in papillary thyroid cancer microenvironment. Endocr Relat Cancer 26(5):525–538 [DOI] [PubMed] [Google Scholar]
  20. Wu YL, Lin ZJ, Li CC, Lin X, Shan SK, Guo B, Zheng MH, Li F, Yuan LQ, Li ZH (2023) Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study. Signal Transduct Target Ther 8(1):98 [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Xu F, Li FX, Lin X, Zhong JY, Wu F, Shan SK, Tan CM, Yuan LQ, Liao XB (2019) Adipose tissue-derived omentin-1 attenuates arterial calcification via AMPK/Akt signaling pathway. Aging (Albany NY) 11(20):8760–8776 [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zhan JK, Wang YJ, Wang Y, Tang ZY, Tan P, Huang W, Liu YS (2014) Adiponectin attenuates the osteoblastic differentiation of vascular smooth muscle cells through the AMPK/mTOR pathway. Exp Cell Res 323(2):352–358 [DOI] [PubMed] [Google Scholar]
  23. Zhan JK, Wang YJ, Wang Y, Tang ZY, Tan P, Huang W, Liu YS (2015) The protective effect of GLP-1 analogue in arterial calcification through attenuating osteoblastic differentiation of human VSMCs. Int J Cardiol 15(189):188–193 [Google Scholar]
  24. Zheng MH, Shan SK, Lin X, Xu F, Wu F, Guo B, Li FX, Zhou ZA, Wang Y, Lei LM, Tang KX, Duan JY, Wu YY, Cao YC, Liao XB*, Yuan LQ*. Vascular wall microenvironment: exosomes secreted by adventitial fibroblasts induced vascular calcification. J Nanobiotechnology. 21(1): 315
  25. Zhuang X, Maimaitijiang A, Li Y, Shi H, Jiang X (2017) Salidroside inhibits high-glucose induced proliferation of vascular smooth muscle cells via inhibiting mitochondrial fission and oxidative stress. Exp Ther Med 14(1):515–524 [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets used during the present study are available from the corresponding author upon reasonable request.

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