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ObjectiveTo investigate the protective effect of salidroside against nonalcoholic fatty liver disease （NAFLD） and its mechanism of action. MethodsA total of 24 male KM mice were randomly divided into normal group， HFD group， HFD+blank control group， and HFD+salidroside group， with 6 mice in each group. The mice in the normal group were given normal diet， and those in the other groups were given high-fat diet. After 14 weeks of modeling， the mice were given salidroside 100 mg/kg/day by gavage， and related samples were collected at the end of week 22. Enzyme-linked immunosorbent assay was used to measure the serum levels of related biochemical parameters including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）； HE staining and NAFLD activity score （NAS） were used to observe the liver histopathology of mice； Western blot was used to measure the changes in the expression of NAMPT， Sirt1， AMPKα， and SREBP1 in liver tissue. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the HFD group had obvious steatosis and extensive large lipid droplets in liver tissue， with significant increases in NAS score （P<0.01） and the content of AST， ALT， TG， TC， and LDL-C in peripheral blood （all P<0.05） and a significant reduction in the content of HDL-C （P<0.05）， as well as significant reductions in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant increase in the expression level of SERBP1 （P<0.01）. Compared with the HFD group and the HFD+blank control group， the HFD+salidroside group had reductions in the distribution of vacuolar lipid droplets and intralobular inflammation in liver tissue， alleviation of the ballooning degeneration of hepatocytes， significant reductions in NAS score （P<0.01） and the content of AST， ALT， TG， and LDL-C in peripheral blood （all P<0.05）， and a significant increase in the content of HDL-C （P<0.05）， as well as significant increases in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant reduction in the expression level of SERBP1 （P<0.01）. ConclusionSalidroside can significantly improve the pathological state of mice with NAFLD induced by high-fat diet and exert a protective effect against NAFLD by increasing the expression of NAMPT， Sirt1， and AMPKα and reducing the expression of SERBP1.
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@#【Objective】 As the main active ingredient of Tibetan medicine Hongjingtian (Rhodiolae Crenulatae Radix et Rhizoma), salidroside (Sal) has a good anti-apoptotic potential. Currently, there are some conflicting results on the anti-apoptotic mechanisms of Sal. Here we conducted a systematic review and meta-analysis to provide the preclinical evidence of its anti-apoptotic properties in preventing and treating hypoxic-ischemic cerebral damage(HICD). 【Methods】 The literature on the anti-apoptotic potential of Sal in the treatment of HICD from January 1, 1980 to November 9, 2021 was searched online using Chinese databases including Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database, and English databases including PubMed and Web of Science. The quality of the included articles was evaluated by the Cochrane Collaboration network bias risk assessment criteria, and meta-analysis was performed using RevMan 5.3 software. 【Results】 A total of 40 articles were finally included. Among the 40 articles, 30 were about in vivo animal experiments and 17 about in vitro cell experiments, and 7 of them included both animal and cell experiments. After analysis, it was found that Sal had significant effects on disease-related indicators of HICD (P < 0.05), such as cerebral infarctsize and brain water content. As to in vivo studies, Sal mainly affects the expressions of apoptotic factors through antiinflammation, anti-oxidation, activation of complement pathway, and regulation of signal transduction and autophagy, thus exerting anti-apoptotic potential in treating HICD. While for in vitro studies, Sal plays the anti-apoptotic role in HICD models mainly through anti-oxidation, anti-inflammation, reduction of Ca2+ overload, regulation of mitochondrial function, signal transduction, and C3 complement. 【Conclusion】 Sal can take anti-apoptotic effects to prevent and treat HICD through mechanisms such as anti-inflammation, anti-oxidation, enhanced autophagy, complement and signal transduction, regulation of mitochondrial membrane potential, and reduction of Ca2 + overload.
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ObjectiveThe aim of this study is to investigate the role of salidroside in regulating the miR-1343-3p/MAP3K6 （mitogen-activated protein kinase kinase kinase 6）/MMP24 （membrane-type matrix metalloproteinase 24） signaling pathway to inhibit gastric cancer cell proliferation and migration. MethodsHuman gastric cancer cells （MGC-803） were divided into several groups based on different salidroside concentrations： a control group （0 μmol/mL）， a low-dose group （6 μmol/mL）， a medium-dose group （12 μmol/mL）， and a high-dose group （24 μmol/mL）. The anti proliferative effects of salidroside on human gastric cancer cells were evaluated by CCK-8 assay. Clonogenic assay was used to examine the effects of salidroside drugs on the clonogenic ability of human gastric cancer cells. Transwell assay was performed to detect the effect of salidroside on the invasive ability of human gastric cancer cells. Cell scratch assay was performed to detect the effect of salidroside on the migration ability of human gastric cancer cells. The miRNA expression profile was analyzed by using RNA-seq in cancer cells for 24 h after salidroside treatment. The differentially expressed miRNAs were clustered and their target genes were predicted. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） were used to analyze and predict the functions of these target genes， and the interaction networks were established. Immunocytofluorescence was used to detect the expression of target proteins， and the transcription of candidate genes was detected by q-PCR. ResultsCCK-8 cytotoxicity experiments showed that salidroside inhibited the proliferation of MGC-803 cells （P < 0.01）. Cell cloning experiments showed that salidroside reduced the clonal formation capacity of MGC-803 cells （P < 0.000 1）. Cell invasion experiments showed that salidroside reduced the MGC-803 cell invasion capacity （P < 0.000 1）. Cell scratch experiments showed that salidroside reduced the cell migration capacity （P < 0.000 1）. RNA-seq findings showed that the expression of 44 miRNAs changed significantly after salidroside treatment in cancer cells （P < 0.05）. Bioinformatic analysis showed that there were 1 384 target mRNAs corresponding to the differentially expressed miRNAs， and the expression of the tumor suppressor miR-1343-3p was significantly upregulated after salidroside treatment （P < 0.01），and resulted in down-regulated transcription of MAP3K6 and MMP24 genes which are related to the proliferation and migration of cancer cells （P < 0.05）. Immunofluorescence experiments demonstrated that salidroside reduced protein expression levels in MAP3K6 and MMP24 genes （P < 0.000 1）. q-PCR experiments showed that salidroside reduced the mRNA expression level of MAP3K6 and MMP24 genes （P < 0.000 1）， while miRNA expression in miR-1343-3p gene was upregulated （P < 0.000 1）. ConclusionSalidroside regulates the miRNA-1343-3p/MAP3K6/MMP24 signaling molecules to inhibit proliferation and invasion of gastric cancer cells.
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AIM: To examine the effects of salidroside on choroidal thickness, hypoxia-inducible factor-1α(HIF-1α), dopamine(DA)and its D1 receptor expression in guinea pigs with lens-induced myopia(LIM).METHODS: A total of 18 two-week-old guinea pigs were randomly divided into the normal control(NC)group, the LIM group, and the LIM + salidroside(LIM+SA)group, with 6 guinea pigs in each group. The guinea pigs in the NC group were fed normally and intragastrically administered with 2 mL/d saline; those in the LIM group wore a -5D lens in front of their right eyes to establish a myopia model, then they were intragastrically administered with 2 mL/d saline. Finally, those in the LIM+SA group wore glasses along with intragastric administration of 2 mL/d salidroside at a dose of 100 mg/kg. The refraction, axial length, and choroidal thickness of guinea pigs in each group were measured 4wk following the establishment of the model. In addition, the relative mRNA expression and protein content of HIF-1α in the choroid and retina of guinea pigs in each group were detected by real-time quantitative PCR(qPCR)and immunohistochemistry(IHC). Finally, the DA concentration and its D1 receptor expression were detected by enzyme-linked immunosorbent assay(ELISA)and Western blot.RESULTS: At 4wk after model establishment, guinea pigs of LIM group and LIM+SA group exhibited increased negative refraction of the right eye, prolonged axial length, and decreased choroidal thickness compared to the NC group. The relative mRNA expression and protein content of HIF-1α in the choroid and retina of the guinea pigs increased. The concentration of DA and the expression of its D1 receptor both decreased. Moreover, compared to the LIM group, the diopter of the right eye of guinea pigs in LIM+SA group significantly reduced, the axial length was shorter, the thickness of choroid increased, the relative mRNA expression and protein content of HIF-1α in the choroid and retina decreased and the concentration of DA and the expression of its D1 receptor both increased.CONCLUSION: Salidroside can delay myopia progression in myopic guinea pigs by affecting choroidal thickness and the expression of HIF-1α, DA and its D1 receptor.
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Ischemic stroke is caused by a variety of factors caused by intracerebral artery stenosis or obstruction， can lead to cerebral ischemia， hypoxia， neuronal necrosis and neurological dysfunction and other pathological injuries， with high morbidity， high disability rate， high mortality characteristics. Cerebral ischemia-reperfusion injury is the main secondary injury， which can lead to permanent disability or even death in severe cases. With the development of traditional Chinese medicine（TCM） modernization， the extraction and application of active components of TCM have been paid more and more attention. Salidroside， as the main active component of Rhodirosea， a rare Chinese medicinal herb， has been proved to fight cerebral ischemia injury by inhibiting cell apoptosis， anti-oxidative stress， reducing inflammatory response， protecting blood-brain barrier， regulating autophagy， promoting nerve remodeling and synaptic regeneration in preclinical trials. However， due to its multi-pathway， multi-pathway and multi-target action characteristics， the specific mechanism of salidroside to improve cerebral ischemia injury has not been fully elucidated. By reviewing relevant literature in the past decade， the author reviewed the mechanism of action of salidroside in the treatment of ischemic brain injury， and summarized the recent progress of its pharmacokinetic studies and safety evaluation， in order to provide theoretical basis and new research ideas for the development and clinical application of the active ingredients of traditional Chinese medicine.
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OBJECTIVE To investigate the effects of salidroside （Sal） on myocardial fibrosis and pyroptosis and its potential mechanism. METHODS The mice were randomly divided into control group， model group and Sal low-dose， medium-dose and high-dose groups， with 10 mice in each group. Except for the control group， the mice in other groups were injected subcutaneously with isoproterenol 5 mg/（kg·d）to prepare the myocardial fibrosis model. Since modeling， mice in the Sal low-dose， medium-dose and high-dose groups were given 10， 30 and 50 mg/kg of Sal by intragastric administration every day； control group and model group were given 10 mL/kg of normal saline by intragastric administration every day， for 14 consecutive days. After the last medication， the mice were sacrificed； hematoxylin-eosin staining was used to observe pathological change of myocardial tissue and calculate the diameter of myocardial cell； Masson and Sirius Red staining were used to observe the degree of myocardial fibrosis in mice and calculate the collagen volume fraction （CVF）； quantitative real-time PCR was performed to detect the mRNA expressions of collagen type Ⅰ （Col Ⅰ）， α-smooth muscle actin （α-SMA）， Toll-like receptor 4 （TLR4）， NOD-like receptor pyrin domain containing 3 （NLRP3）， caspase-1 andgasdermin D （GSDMD） in myocardial tissues. The total protein expressions of Col Ⅰ， α-SMA， TLR4， NLRP3，caspase-1 and GSDMD in myocardial tissues and protein-positive cell score were measured by Western blot assay and immunohistochemistry. RESULTS Compared with control group， the myocardial cells in the model group were enlarged， the arrangement of myocardial fibers was disordered， the matrix metabolism was significantly increased， the CVF in myocardial tissue was significantly increased， and the mRNA and protein expression levels of Col Ⅰ， α-SMA， TLR4， NLRP3， caspase-1 and GSDMD were elevated and protein-positive cell score was increased significantly （P＜0.01）. Compared with model group， the myocardial cell morphology was clearer， myocardial fibrosis was alleviated， and the levels of the above indicators in myocardial tissue of Sal medium-dose and high-dose groups had been reversed to varying degrees， especially in Sal high-dose group（P＜0.05 or P＜0.01）. In addition， the Sal low-dose group also reversed some fibrosis and pyroptosis-related indicators to some extent. CONCLUSIONS Sal can significantly prevent the occurrence and development of myocardial fibrosis， and the mechanism of action may be related to the inhibition of TLR4-mediated pyroptosis pathway in myocardial tissue.
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Objective:To investigate whether salidroside (SAL) improves lung tissue injury in rats with severe pneumonia (SP) through mediating toll-like receptor 4/nuclear transcription factor-κB/NOD-like receptor protein 3 (TLR4/NF-κB/NLRP3) signaling pathway.Methods:Seventy-five Wistar rats were used in this study. Fifteen of them were randomly selected as the sham operation group, and the others were induced by endotracheal infusion of Klebsiella pneumoniae ( Kp) suspension to construct a rat model of SP. After modeling, the rats were randomly divided into four groups with 15 rats in each group: model group, low-dose SAL group (30 mg/kg), high-dose SAL group (60 mg/kg) and dexamethasone (DXMS, 15 mg/kg) group. The sham operation group and the model group were given the same amount of normal saline for seven consecutive days. The wet-dry weight ratio (W/D) of lung tissues in each group was detected. HE and TUNEL staining methods were used to observe the morphology of lung tissues and cell apoptosis. The levels of TNF-α, IL-1β, IL-6, IL-18 and IL-10 in bronchoalveolar lavage fluid (BALF) were detected by ELISA. The expression of TLR4, myeloid differentiation factor (MyD88), NF-κBp65, phosphorylated NF-κBp65 (p-NF-κBp65) and NLRP3 at protein level in lung tissues was detected by Western blot. Results:The rat model of SP was successfully constructed by endotracheal infusion of Kp suspension. Compared with the sham operation group, the model group showed more severe edema of lung tissues, increased W/D value ( P<0.05), loose and incomplete alveolar structure, edema of alveolar wall and thickened alveolar wall, massive inflammatory cell infiltration, increased apoptosis rate as well as higher levels of TNF-α, IL-1β, IL-6 and IL-18 and lower lover of IL-10 in BALF. Moreover, the relative expression of TLR4, MyD88, NF-κBp65, p-NF-κBp65 and NLRP3 at protein level in lung tissues was increased in the model group ( P<0.05). Gradually improved pathological injury of lung tissues, decreased W/D value ( P<0.05), recovered alveolar structure, reduced alveolar wall edema and decreased cell apoptosis rate were observed in the low-dose and high-dose SAL groups as well as the DXMS group as compared with those of the model group. Besides, the three groups also showed decreased levels of TNF-α, IL-1β, IL-6 and IL-18 and increased level of IL-10 in BALF, and inhibited expression of TLR4, MyD88, NF-κBp65, p-NF-κBp65 and NLRP3 at protein level in lung tissues ( P<0.05). DXMS performed better in improving lung injury in rats with SP, followed by high and low doses of SAL ( P<0.05). Conclusions:SAL could reduce cell apoptosis and improve the Kp-induced lung injury in rats. The mechanism might be related to the blockage of TLR4/NF-κB/NLRP3 signaling pathway activation and inhibition of inflammatory factor expression.
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Abstract Salidroside (SAL) has been confirmed to have some protective effects against inflammatory injury. However, little information was established as to the mechanism of these protective effects. To this effect, we designed this study to explore the protective effects and mechanisms of SAL against myocardial infarction (MI). A rat MI model was established and divided into five groups (n = 6): sham, MI, MI+SAL, MI+ LY294002 (PI3K inhibitor), and MI+SAL+ LY294002. The cardiac function and histological pathology were analyzed with a color Doppler ultrasonic diagnostic instrument. Anti-oxidative enzyme activities and the production of inflammatory media were assayed by biochemical kits and ELISA. MI size and fibrosis were assayed by Masson's trichrome staining while Bax/Bcl-2 and PI3K/Akt/Nrf2/HO-1 were assayed by Western blotting and immunofluorescence. The results showed that SAL significantly improved the left ventricle ejection fraction and fractional shortening, decreased the MI size and fibrosis, inhibited apoptosis and promoted blood vessel formation. SAL promoted anti-oxidative and anti-inflammatory abilities. Moreover, SAL enhanced PI3K/ Akt/Nrf2/HO-1 expression. To this effect, we designed this study suggested that SAL induced repair of MI via PI3K/A kt/ Nrf2/HO-1.
Subject(s)
Animals , Male , Rats , Heart Ventricles/abnormalities , Myocardial Infarction/drug therapy , Fibrosis/classification , Enzyme-Linked Immunosorbent Assay/methods , ApoptosisABSTRACT
ObjectiveTo investigate the quality of Ligustri Lucidi Fructus in the market， and the moisture， extract， determination of Zhuyao and Douchi Ligustri Lucidi Fructus were compared to increase the utilization rate of Ligustri Lucidi Fructus. MethodThe properties， moisture， total ash， alcohol-soluble extract content and thin layer chromatography （TLC） identification were determined by the methods of Ligustri Lucidi Fructus included in the 2020 edition of Chinese Pharmacopoeia， and high performance liquid chromatography （HPLC） fingerprint and determination of specnuezhenide and salidroside were established with the mobile phase of 0.2% phosphoric acid aqueous solution （A）-acetonitrile （B） （0-70 min， 92%-65%A） for gradient elution， and the detection wavelength of 220 nm at 0-14 min and 225 nm at 14-70 min. The two different characters of Ligustri Lucidi Fructus were comprehensively compared by the above indicators. ResultExcept for one batch which did not meet the requirements due to the quality of harvesting， the other 12 batches of samples all met the requirements of the 2020 edition of Chinese Pharmacopoeia， but there were two different characters. Comparing the two different characters of Ligustri Lucidi Fructus， it is found that the moisture， total ash， extract， salidroside and specnuezhenide contents of Zhuyao samples were 2.22%-5.19%， 3.91%-4.49%， 32.56%-40.95%， 0.073%-0.170% and 1.45%-4.14%， and these values of Douchi samples were 3.57%-5.61%， 3.65%-4.44%， 41.31%-46.70%， 0.041%-0.067% and 3.01%-4.20%， respectively. ConclusionThe contents of extract and specnuezhenide of Douchi Ligustri Lucidi Fructus are mostly higher than those of Zhuyao Ligustri Lucidi Fructus， while the content of salidroside is lower than that of Zhuyao samples， and there are no significant differences in moisture， TLC identification and total ash content. Based on the above research， if the main purpose is to extract salidroside， it is recommended to choose Zhuyao Ligustri Lucidi Fructus. If the main purpose is to use Ligustri Lucidi Fructus as medicine， it is recommended to choose Douchi Ligustri Lucidi Fructus.
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ObjectiveSalidroside is the most abundant natural active compound in the famous Chinese herbal medicine Rhodiolae Crenulatae Radix et Rhizoma. This study aims to explore the effect of salidroside on the proliferation， migration， invasion， and apoptosis of human hepatoma （HepG2） cells. MethodThe HepG2 cells without any treatment were selected as the blank group， and the HepG2 cells in the salidroside groups were treated with salidroside at final concentrations of 20， 40， 80 μmol·L-1， respectively. A multifunctional cell analyzer， scratch assay， and Transwell assay were employed to determine the proliferation， migration， and invasion of HepG2 cells， respectively. An inverted microscope was used to observe the morphology， and a transmission electron microscope to observe the mitochondria of HepG2 cells. Flow cytometry was employed to determine the apoptosis and cycle distribution of HepG2 cells. Real-time fluorescent quantitative polymerase chain reaction ( Real-time PCR ) and Western blot were employed to determine the expression of apoptosis-associated genes and migration-， invasion-， and apoptosis-associated proteins， respectively， in HepG2 cells. ResultCompared with the blank group， salidroside （20， 40， 80 μmol·L-1） decreased the cell index and increased the healing area in a time- and dose-dependent manner （P<0.05）. Compared with that in the blank group， the HepG2 cells that could pass through Matrigel reduced in the salidroside （20， 80 μmol·L-1） groups. Compared with the blank group， salidroside （20， 40， 80 μmol·L-1） increased the total apoptosis rate in a dose dependence manner and blocked the cells in the G2/M phase （P<0.05）. Compared with the blank group， salidroside up-regulated the expression of epithelial-cadherin （E-cadherin） in a dose-dependent manner （P<0.05） and down-regulated that of nerve-cadherin （N-cadherin） in the 20 and 80 μmol·L-1 groups （P<0.05）. Compared with the blank group， salidroside （20， 40， 80 μmol·L-1） up-regulated the mRNA level of cysteine-containing aspartate-specific protease -3 （Caspase-3） and the protein levels of B-cell lymphoma-2 （Bcl-2） associated X protein （Bax）， Caspase-3， and cysteine-containing aspartate-specific protease-9 （Caspase-9） in a dose-dependent manner （P<0.05）， while it down-regulated the protein levels of the actin-binding protein Girdin and Bcl-2 in a dose-dependent manner （P<0.05）. ConclusionSalidroside inhibited the proliferation， migration， and invasion and induced the apoptosis of HepG2 cells through the mitochondrial pathway. The results suggest that salidroside can be used as a potential chemotherapy candidate for liver cancer.
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This study investigated the effect of salidroside on phenotypic transformation of rat pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia. Rat pulmonary arteries were isolated by tissue digestion and PASMCs were cultured. The OD values of cells treated with salidroside at different concentrations for 48 hours were measured by cell counting kit-8(CCK-8) to determine the appropriate concentration range of salidroside. The cells were divided into a normal(normoxia) group, a model(hypoxia) group, and three hypoxia + salidroside groups(40, 60, and 80 μg·mL~(-1)). Quantitative real-time PCR(qRT-PCR) was used to detect the mRNA expression of cell contractile markers in each group, such as α-smooth muscle actin(α-SMA), smooth muscle 22(SM22), and calcium-binding protein(calponin), and synthetic marker vimentin. The expression levels of cell phenotypic markers and proliferating cell nuclear antigen(PCNA) were detected by Western blot. The proliferation of cells in each group was detected by the 5-ethynyl-2'-deoxyuridine(EdU) assay. Cell migration was measured by Transwell assay. As revealed by results, compared with the normal group, the model group showed decreased mRNA and protein expression of contractile phenotypic markers of PASMCs and increased mRNA and protein expression of synthetic markers. Compared with the conditions in the model group, salidroside could down-regulate the mRNA and protein expression of synthetic markers in PASMCs and up-regulated the mRNA and protein expression of contractile phenotypic markers. Compared with the normal group, the model group showed potentiated proliferation and migration. Compared with the model group, the hypoxia + salidroside groups showed blunted proliferation and migration of cells after phenotypic transformation. The results suggest that salidroside can inhibit the expression of synthetic markers in PASMCs and promote the expression of contractile markers to inhibit the hypoxia-induced phenotypic transformation of PASMCs. The mechanism of salidroside in inhibiting the proliferation and migration of PASMCs is related to the inhibition of the phenotypic transformation of PASMCs.
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Animals , Rats , Cell Proliferation , Cells, Cultured , Glucosides , Hypoxia , Myocytes, Smooth Muscle , Phenols , Pulmonary ArteryABSTRACT
Objective To develop a HPLC-MS/MS method for the absolute bioavailability study of salidroside in Beagle dogs. Methods Gastrodin was used as internal standard. Plasma samples were treated by protein precipitation and separated by Symmetry RP18 column (100 mm×4.6 mm, 3.5 μm). 0.1% formic acid in water(A) and 0.1% formic acid in acetonitrile: methanol (20 : 80, V/V) (B) were used as the mobile phase for isocratic elution with 35% mobile phase B. The flow rate was 0.4 ml/min. Column temperature was 40 ℃. Injection volume was 2 μl. By electrospray ionization source (ESI) and multi-reaction monitoring (MRM) mode, the MRM ion pairs of salidroside and gastrodin were identified as m/z 299.1→118.9 and m/z 285.1→122.9, separately. Blood samples were collected at different time points after oral or intravenous administration of salidroside. The harvested plasma samples were analyzed by HPLC-MS/MS method to assess the pharmacokinetics and absolute bioavailability of salidroside. Results Excellent linearity(r>0.998 6) was found in the concentration range of 10−10 000 ng/ml for salidroside and the lowest quantitative concentration was 10 ng/ml. The recovery was 89.5%−91.8%. The intra-day precision (RSD) was less than 9.7%, and the inter-day precision (RSD) was less than 7.3%. After a single oral dose of 15 mg/kg or an intravenous injection of 1.5 mg/kg of salidroside, cmax was (9 680±3725) and (9 310±1 645) ng/ml; tmax was (1.25±0.67) and (0.011±0.017) h, AUC0−t was (20 535.4±5 200.0) and (4 646.7±720.5) ng·h/ml, AUC0−∞ was (20 607.9±5 266.2) and (4 691.6±715.2) ng·h/ml; t1/2 was (1.31±0.63) and (0.98±0.13) h, respectively. Conclusion The LC-MS/MS method established in this study was simple, rapid, sensitive and reliable. It meets the regulatory requirements of biological analysis for pharmacokinetic properties of salidroside in Beagle dogs. The absolute bioavailability of salidroside in Beagle dogs is (43.9±11.2)%.
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Objective To study the pharmacokinetic differences of pure salidroside and Kunfukang pills in rats and explore the pharmacokinetic changes of salidroside as a pure form or in the mixture. Methods The rats were divided into two groups. One group received pure salidroside and the other was administrated with kunfukang pills. Concentrations of salidroside in both groups were determined by LC/MS/MS method. The main pharmacokinetic parameters were calculated. Results AUC0−t of salidroside was (587.11±35.02) in pure salidroside group and (956.35±47.65)ng·h/ml in Kunfukang group. cmax was (85.81±15.66) and (143.86±46.91)ng/ml separately, with significant difference. Conclusion The results indicated that other components in kunfukang pills had influence on the absorption, distribution and elimination of salidroside.
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Introduction@#Rhodiola rosea L. (R.rosea) is a popular plant in traditional medicine of the Nordic countries, Eastern Europe, and Asia. R.rosea plants are successfully cultivated in Mongolia. The Botanical Garden of Medicinal Plants under the “Monos” Group started to cultivate R. rosea since May 2015. @*Objective@#The aim of this research was to study the salidroside contents of R.rosea collected from Zavkhan and Khuvsgul province, Mongolia, and cultivated in the Botanical Garden of Medicinal Plants, Drug research Institute, Monos group.@*Material and Methods@#The underground parts of wild roseroot plants were collected from April to May 2020 from Jargalant soum, Khuvsgul province, and Nomrog soum, Zavkhan province, 3-years and 4-years-old cultivated R.rosea gathered from the Botanical Garden of Medicinal Plants in April 2020. For comparison, 4-year-old Rhodiola grenulata (R. grenulata) was ordered from Shanxi Zhendong Genuine Medicinal Materials Development Co., Ltd, China, and used for the study. The quantity of the salidroside constituents of the underground parts were compared and the sourcing of roseroot raw material was evaluated. Chemical analysis of roots and rhizome of R. Rosea namely the appearance, identification, moisture, organic impurities, mineral impurities, residue on ignition, water-soluble extractives, fresh weight of roots, and salidroside content were determined according to the National Pharmacopoeia of Mongolia (NPhM) 2011. Microbiological analysis was performed in accordance with the requirements of grade 3b specified in Annex 1 of the Order No. A / 219 of the Minister of Health dated May 30, 2017 to determine the degree of microbiological purity in medicinal products of roots and rhizome raw materials.@*Result@#The content of salidroside, the main biologically active substance of R.rosea plant, was 1.57% in samples collected from Zavkhan province, 1.45% in samples collected from Khuvsgul province, 1.7% in samples grown in China and 0.25% for 3-years-old samples and 1.89% for 4-years-old samples grown in the Botanical Garden of Medicinal Plants, Monos group, Mongolia. In addition, these raw materials meet the general requirements for plant raw materials and microbiological parameters.@*Conclusion@#Samples of underground parts of R.rosea cultivated for 4 years in the Botanical Garden of Medicinal Plants have the highest content (1.89%) of the salidrosde. Therefore, it is suggested that the roots and rhizomes of R.rosea planted in the future can be standardized and used as a raw materials for medicines.
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In order to investigate the effect of salidroside on inhibiting liver fibrosis and its relationship with CXC chemokine ligand 16(CXCL16) in vivo and in vitro, totally 45 C57 BL/6 J male mice were randomly divided into normal group, model group and salidroside group, with 15 mice in each group. The mice in model group and salidroside group were injected intraperitoneally with 15% carbontetrachloride(CCl_4) olive oil solution to establish liver fibrosis model, and the mice in normal group were injected intraperitoneally with the same dose of olive oil. Salidroside group was given with 100 mg·kg~(-1 )salidroside by gavage, while the normal group and model group received the same amount of double distilled water by gavage. All mice were sacrificed after 5 weeks of intragastric administration. The pathological changes of mouse liver were observed by hematoxylin-eosin(HE) staining, and the degree of liver fibrosis was observed by sirius red staining. The protein expressions of collagen Ⅰ(ColⅠ), α-smooth muscle actin(α-SMA), fibronectin(FN), CXCL16, phosphorylated Akt(p-Akt), Akt in liver tissues were detected by Western blot. Hepatic stellate cell line JS 1 was cultured in vitro and divided into control group, model group(100 μg·L~(-1) CXCL16) and salidroside group(100 μg·L~(-1) CXCL16+1×10~(-5) mol·L~(-1) salidroside). Cell migration was detected by cell scratch, the mRNA expressions of ColⅠ and α-SMA were detected by RT-PCR, and the protein expressions of p-Akt and Akt were detected by Western blot. As compared with the normal group, the protein expressions of ColⅠ, α-SMA, FN, CXCL16, and p-Akt in the model group were significantly increased, and salidroside could reduce the expression of these indicators(P<0.05 or P<0.01). In vitro, CXCL16 could promote the migration of JS 1, increase the mRNA expressions of ColⅠ and α-SMA in JS 1, and enhance Akt phosphorylation in JS 1(P<0.05 or P<0.01). As compared with the model group, salidroside could inhibit the migration of JS 1 induced by CXCL16(P<0.05), and reduce the high expression of ColⅠ and α-SMA mRNA and the phosphorylation of Akt in JS 1 induced by CXCL16(P<0.05). In conclusion, salidroside might attenuate CCl_4-induced liver fibrosis in mice by inhibiting the migration, activation and Akt phosphorylation of hepatic stellate cells induced by CXCL16.
Subject(s)
Animals , Male , Mice , Carbon Tetrachloride , Chemokine CXCL16 , Glucosides , Hepatic Stellate Cells , Liver/pathology , Liver Cirrhosis/genetics , PhenolsABSTRACT
Objective To establish a LC-MS/MS method for the determination of salidroside in the capsule. Methods An electrospray ionization and multiple reaction detection were used to detect negative ion. Theophylline was used as standard. The detection ions of salidroside and theophylline used for quantitative analysis were m/z 299.0→119.0, and m/z 178.8→164.0, respectively. The Shim-pack XR-ODS (3.0 mm×75 mm, 2.0 μm) column was used for separation. The mobile phase was acetonitrile: 5 mmol/L ammonium acetate solution (90∶10, V/V). The flow rate was 0.40 ml/min. The column temperature was 25 ℃. Results The content of salidroside was analyzed within 3 minutes. The linear range was 10–2 000 ng/ml, and the minimum detection limit was 10 ng/ml. Conclusion The method has good repeatability, high sensitivity, fast analysis speed and simple operation. It can be used as a method for the determination of salidroside in the capsule. It is suitable for the quality inspection of drugs and convenient for safe use.
ABSTRACT
Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola, and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention. This review summarizes the progress of recent research on the antiproliferative activities of salidroside and its effects on breast, ovarian, cervical, colorectal, lung, liver, gastric, bladder, renal, and skin cancer as well as gliomas and fibrosarcomas. Thus, it provides a reference for the further development and utilization of salidroside.
ABSTRACT
Salidroside (SAL), a major bioactive compound of Rhodiola crenulata, has significant anti-hypoxia effect, however, its underlying molecular mechanism has not been elucidated. In order to explore the protective mechanism of SAL, the lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD) and hypoxia-induced factor 1α (HIF-1α) were measured to establish the PC12 cell hypoxic model. Cell staining and cell viability analyses were performed to evaluate the protective effects of SAL. The metabolomics and bioinformatics methods were used to explore the protective effects of salidroside under hypoxia condition. The metabolite-protein interaction networks were further established and the protein expression level was examined by Western blotting. The results showed that 59 endogenous metabolites changed and the expression of the hub proteins of CK2, p-PTEN/PTEN, PI3K, p-Akt/Akt, NF-κB p65 and Bcl-2 were increased, suggesting that SAL could increase the expression of CK2, which induced the phosphorylation and inactivation of PTEN, reduced the inhibitory effect on PI3K signaling pathways and activated the PI3K/Akt/NF-κB survival signaling pathway. Our study provided an important insight to reveal the protective molecular mechanism of SAL as a novel drug candidate.
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Salidroside (SAL) is a phenolic substance with high solubility and low permeability, which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora, resulting in lower bioavailability. The aim of this study was to develop and optimize a water-in-oil nanoemulsion of SAL (w/o SAL-N) to explore its suitability in oral drug delivery systems. In this work, SAL-N was successfully prepared by water titration method at K
ABSTRACT
BACKGROUND: It has been found that salidroside can improve diabetic retinopathy. However, it is not clear whether salidroside can protect retinal Müller cells (rMC-1) against damage induced by high glucose. OBJECTIVE: To investigate the effect and mechanism of salidroside on oxidative stress and apoptosis induced by high glucose in rat rMC-1 cells. METHODS: The rMC-1 cells were divided into four groups: normal control group, high glucose group (culture medium with a final glucose concentration of 35.5 mmol/L), salidroside group (treatment with salidroside for 4 hours followed by co-culture with high glucose) and PI3K inhibitor group (treatment with salidroside and PI3K inhibitor for 4 hours followed by co-culture with high glucose). The viability of the rMC-1 cells was measured by cell counting kit-8 assay. Reactive oxygen species production was detected by DCFH-DA. The superoxide dismutase and catalase activities were tested by specific kits. Cell apoptosis was detected by flow cytometry. Western blot was used to detect the expression levels of Cleaved caspase-3, PI3K, AKT and phosphorylated AKT. RESULTS AND CONCLUSION: Compared with the normal control group, the cell viability and the activities of antioxidant enzymes (superoxide dismutase, catalase) in the high glucose group were significantly decreased, the production of reactive oxygen species, apoptotic rate and the level of Cleaved caspase-3 were significantly increased, and the phosphorylated AKT/AKT ratio was down-regulated (P < 0.05). Compared with the high glucose group, salidroside significantly enhanced the cell viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase), decreased the production of reactive oxygen species, reduced the apoptotic rate of the cells and downregulated the expression level of Cleaved caspase-3 (P < 0.05). Salidroside also activated the phosphorylation of Akt (P < 0.05). Whereas, the addition of LY294002, a pharmacological inhibitor of PI3K, showed similar results in the high glucose group (P < 0.05). To conclude, salidroside can protect rMC-1 cells through inhibiting apoptosis and oxidative stress induced by high glucose. The main mechanism responsible for the inhibition of oxidative stress is the activation of the PI3K/Akt pathway.