Inhibitory Effects Of Salidroside Research Articles

Study on Inhibitory Effect of Salidroside on Diabetic Cataract in Rats

Study on Inhibitory Effect of Salidroside on Diabetic Cataract in Rats

Salidroside Inhibits Reactive Astrogliosis and Glial Scar Formation in Late Cerebral Ischemia via the Akt/GSK-3β Pathway.

Cerebral ischemia leads to reactive astrogliosis and glial scar formation. Glial scarring can impede functional restoration during the recovery phase of stroke. Salidroside has been shown to have neuroprotective effects after ischemic stroke, but its impact on long-term neurological recovery, especially whether it regulates reactive astrogliosis and glial scar formation, is unclear. In this study, male adult C57/BL6 mice were subjected to transient cerebral ischemia injury followed by intravenous salidroside treatment. Primary astrocytes were treated with lipopolysaccharide (LPS) or conditioned medium from cultured primary neurons subjected to oxygen-glucose deprivation (CM-OGD). Salidroside significantly improved long-term functional outcomes following ischemic stroke in the rotarod and corner tests. It also reduced brain glial scar volume and decreased expression of the glial scar marker, glial fibrillary acidic protein (GFAP) and inhibited astrocyte proliferation. In primary astrocyte cultures, salidroside protected astrocytes from CM-OGD injury-induced reactive astroglial proliferation, increasing the percentage of cells in G0/G1 phase and reducing the S populations. The inhibitory effect of salidroside on the cell cycle was related to downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA expression and increased p27Kip1 mRNA expression. Similar results were found in the LPS-stimulated injury model in astroglial cultures. Western blot analysis demonstrated that salidroside attenuated the CM-OGD-induced upregulation of phosphorylated Akt and glycogen synthase kinase 3β (GSK-3β). Taken together, these results suggested that salidroside can inhibit reactive astrocyte proliferation, ameliorate glial scar formation and improve long-term recovery, probably through its effects on the Akt/GSK-3β pathway.

Inhibitory effects of salidroside on MCF-7 breast cancer cells in vivo.

ObjectiveWe investigated the antitumor effects of salidroside and preliminarily examined its underlying mechanisms by establishing a nude mouse model bearing MCF-7 breast cancer cell xenografts.MethodsThe mice were grouped and intraperitoneally injected with salidroside, paclitaxel, or physiological saline. Tumor samples were weighed, and immunohistochemical staining with hematoxylin and eosin and anti-CD34 antibody was performed. Tumor cell apoptosis was observed using the terminal deoxynucleotidyl transferase deoxyuridine dUTP nick end labeling assay. Bcl-1, p53, Bax, and caspase 3 expression in tumor tissues was determined via western blotting.ResultsThe tumor inhibition rate of high-dose salidroside was 75.16%, which was significantly higher than the rates for paclitaxel and saline. A tumor tissue pathology analysis revealed that high-dose salidroside inhibited tumor cell proliferation and promoted tumor cell apoptosis. Western blotting revealed that Bcl-2 and p53 expression were significantly lower in the salidroside group than in the other groups, whereas Bax and caspase 3 (17 kDa) expression were increased.ConclusionsSalidroside was more effective than paclitaxel in inhibiting tumor growth in MCF-7 breast cancer cell-bearing nude mice. The mechanism of action may involve Bcl-2 and p53 downregulation and Bax and caspase 3 upregulation, thereby increasing proapoptotic factor expression and inducing tumor cell apoptosis.

Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2.

Herein, we found that salidroside suppressed hypoxia‐inducible factor 1 alpha (HIF‐1α) and lysyl oxidase‐like protein 2 (LOXL2) within human pancreatic cancer BxPC‐3 cells cultured both under normoxia and hypoxia condition. To investigate the effect of salidroside on tumorigenesis of BxPC‐3 cells and whether HIF‐1α and LXCL2 were involved in this process, cells transfected with or without LOXL2 overexpression vector, were treated with 50 μg/mL of salidroside or 50 μM of KC7F2 (a HIF‐1α inhibitor) under hypoxia. Cell viability and invasion were assessed using CCK‐8 and Transwell chamber assay, respectively. Expression of E‐cadherin and matrix metalloproteinase 2/9 (MMP 2/9) was determined, by Western blot analysis, to assess cell mobility at molecular levels. We confirmed that hypoxia increased LOXL2 and induced tumorigenesis of BxPC‐3 cells, as evidenced by promoted cell proliferation and invasion, enhanced MMP2/9 while reduced E‐cadherin. Interestingly, hypoxia‐induced carcinogenesis was significantly retarded by both salidroside and KC7F2, however, enhanced with LOXL2 overexpression. Besides, salidroside and KC7F2 reduced LOXL2, and reversed the tumorigenesis of BxPC‐3 cells induced by LOXL2 overexpression. Given the inhibitory effect of salidroside on HIF‐1α expression, our data suggested that: (1) LOXL2 was the mechanism, whereby salidroside and KC7F2 showed inhibitory effect on cancer progression of BxPC‐3 cells; (2) salidroside exerted its anticancer effect, most likely, by a HIF‐1α/LOXL2 pathway. In conclusion, salidroside was a novel therapeutic drug in pancreatic cancer, and downregulation of HIF‐1α and LXCL2 was the underlying mechanism.

Inhibitory Effects of Salidroside on Nitric Oxide and Prostaglandin E2Production in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

The aim of this study was to evaluate the effect of salidroside on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in RAW 264.7 macrophages and related anti-inflammatory mechanism. PGE₂ production was measured by enzyme-linked immunosorbent assay (ELISA); NO production was tested by Griess reagent. Inducible nitric oxidesynthase (iNOS) and COX-2 were determined by RT-PCR and Western blot analysis; IκB and P-IκB protein express were detected by Western blot analysis; cytosolic free Ca²⁺ ([Ca²⁺](i)) was measured by a fluorescent microscope. The data showed salidroside inhibited LPS-induced NO and PGE₂ production and reduced iNOS and COX-2 protein expression in RAW 264.7 macrophages. Consistent with these observations, salidroside inhibited LPS-induced cytosolic free Ca²⁺ concentration ([Ca²⁺](i)) elevation. In addition, we further investigated signal transduction mechanisms and found that the activation of NF-κB was suppressed by salidroside in a dose-dependent manner. These results suggest that salidroside suppresses NO and PGE₂ production by inhibiting iNOS and COX-2 protein expression, level of [Ca²⁺](i), and activation of NF-κB signal transduction pathway.

Inhibitory effects of salidroside and paeonol on tyrosinase activity and melanin synthesis in mouse B16F10 melanoma cells and ultraviolet B-induced pigmentation in guinea pig skin

Salidroside, the major active component of Rhodiola rosea, a herb with antioxidant, free radical scavenging and tyrosinase inhibitory effects, has been recently reported in protecting the kerationcytes from the UV radiation, suggesting the potential of this component in depigmentation. Paeonol is isolated from Moutan Cortex Radicis with anti-inflammation/microbial activities, was reported to induce the down-regulation of microphthalmia-associated transcription factor and subsequently tyrosinase. To testify the potential of these compounds as melanin formation inhibitors for hyperpigmentation therapy, the influence of salidroside and paeonol on pigmentation was investigated. With arbutin as a positive control, salidroside and paeonol were evaluated for their inhibitory effect on the cell viability, tyrosinase activity and melanin synthesis in B16F10 melanoma cells, as well as their effects in UVB-induced hyperpigmentation in brown guinea pig skins. It was demonstrated that the significant inhibition of salidroside (33.0%) and paeonol (22.2–30.9%) on the tyrosinase activity is slightly lower than that of arbutin (18.4–44.7%). However, salidroside exhibited the dose-dependent inhibition (30.6–42.0%) in melanin synthesis at a low concentration of 100μM, paeonol and arbutin expressed inhibition rates of 27.4–37.2% and 25.8–45.6% within 500–1000μM. The in vivo topical application of these compounds was demonstrated to obviously decrease the hyperpigmentation on UVB stimulated guinea pig skin. This study provided the original evidence for the salidroside and paeonol as therapeutic agents for pigmentation disorder and skin lightening, with further clinical investigation of these compounds in the field of depigmentation was suggested.