Neuroprotective Effects of Rhodiola Sacra on Transient Global Cerebral Ischemia Through Activating AMPK/Nrf2 Pathway in Rats.

Aims: Rhodiola sacra is a widely used pharmaceutical component with multiple functions, including anti-oxidation and anti-inflammation. However, the exact mechanisms involved in neuroprotection against transient global cerebral ischemia (tGCI) remain to be elucidated. Herein, we aim at closing the gap in understanding on whether rhodiola sacra reduces neuronal death in hippocampal CA1 and at demonstrating how rhodiola sacra offers neuroprotection after tGCI. Results: The results show that rhodiola sacra (2.4 g/kg/d by feeding) pretreatment or/and postreatment significantly alleviated neuronal injury, inhibited glial activation, and improved cognitive function in male rats subjected to tGCI. The neuroprotection of prophylaxis with rhodiola sacra is equivalent to that of therapeutics. The binding mode of adenosine monophosphate-activated protein kinase (AMPK) α2-subunit with rhodiola sacra was predicted by molecular docking. Further, rhodiola sacra upregulates phosphorylated AMPK and promotes nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2). In addition, rhodiola sacra increases heme oxygenase-1 (HO-1) expression and activity and reduces malondialdehyde (MDA) content in CA1 after tGCI. However, the neuroprotection of rhodiola sacra is abolished by Nrf2 knockdown with small interfering RNA (siRNA) after tGCI. Similarly, the inhibition of AMPK with Compound C or siRNA against AMPK α2 aggravates neuronal death after tGCI through decreasing nuclear Nrf2 and the expression and activity of HO-1, and by increasing the release of MDA. Innovation and Conclusion: For the first time, this study demonstrates that as a prophylactic or therapeutic agent rhodiola sacra prevents oxidant stress, protects neurons, and improves cognitive function through activating the AMPK/Nrf2 pathway in tGCI rats. Antioxid. Redox Signal. 36, 567-591.

The complete chloroplast genome sequence of Rhodiola sacra (Prain ex Hamet) S. H. Fu.

Rhodiola sacra (Prain ex Hamet) S. H. Fu is a traditional natural plant pharmaceutical with anti-hypoxia effect and mainly distributed in Yunnan and Tibet (China). The complete chloroplast sequence of R. sacra was determined in our study. The cpDNA was 150,941 bp in length, containing a pair of inverted repeats (IRs) of 25,873 bp each separated by a large and small single copy (LSC and SSC) regions of 82,161 bp and 17,034 bp, respectively. The genome contained 84 protein coding genes, eight rRNA genes and 36 tRNA genes. Phylogenetic tree revealed that R. sacra closely related to Rhodiola kirilowii and Rhodiola crenulata.

Therapeutic effect of Rhodiola grandiflora combined alprostadil on acute coronary syndrome and its in‐fluence on blood lipid levels／ / 心血管康复医学杂志

Objective :To study therapeutic effect of Rhodiola grandiflora combined alprostadil on acute coronary syn‐drome (ACS) and its influence on blood lipid levels .Methods : A total of 104 ACS patients ,who were treated in our hospital from Jul 2016 to Sep 2017 ,were selected ,randomly and equally divided into alprostadil group (received al‐prostadil injection based on routine treatment ) and combined treatment group (received Rhodiola grandiflora injec‐tion based on alprostadil group ) ,both groups were treated for two weeks .LVEDd ,LVEF ,levels of blood lipid :TC ,TG ,HDL‐C ,LDL‐C ,serum high sensitive C reactive protein (hsCRP ) ,interleukin 6 (IL‐6) and monocyte chemoattractant protein‐1 (MCP‐1) before and after treatment ,total effective rate and incidence of adverse reac‐tions were observed and compared between two groups .Results : After two‐week treatment ,total effective rate of combined treatment group was significantly higher than that of alprostadil group (94.23% vs .78. 85%) , P＝0.022. Compared with before treatment ,after two‐week treatment ,there were significant reductions in LVEDd , levels of TC ,TG ,LDL‐C ,serum hsCRP ,IL‐6 and MCP‐1 ,and significant rise in LVEF and HDL‐C level in two groups , P＜0.05 or ＜0. 01. Compared with alprostadil group after two‐week treatment ,there were significant re‐ductions in LVEDd [ (58.07 ± 6. 14) mm vs.(55.12 ± 5. 06) mm] ,levels of TC [ (5.63 ± 0.94) mmol／L vs.(4. 75 ± 0.81) mmol／L] , TG [ (2. 78 ± 0.54) mmol／L vs.(2. 16 ± 0.47) mmol／L] , LDL‐C [ (3. 28 ± 0.57) mmol／L vs.(2.56 ± 0. 42) mmol／L] ,serum hsCRP [ (6.27 ± 1. 14) mg／L vs .(5. 39 ± 0. 96) mg／L] , IL‐6 [ (7.85 ± 1. 47) ng／L vs .(6. 82 ± 1. 30) ng／L] and MCP‐1 [ (113.74 ± 19.62) ng／L vs.(94.36 ± 16.58) ng／L] ,and significant rise in LVEF [(45.74 ± 8.48)% vs.(50.78 ± 8.34)%] and HDL‐Clevel [(2.36 ± 0. 52) mmol／L vs.(2. 93 ± 0. 57) mmol／L] in combined treatment group , P＜0.01 all.During treatment ,there was no significant difference in inci‐dence rate of adverse reactions between two groups , P＝0. 539. Conclusion :Rhodiola grandiflora combined alpros‐tadil possesses significant therapeutic effect on ACS .It can significantly improve cardiac function ,regulate blood lipid metabolism and reduce inflammation with low incidence of adverse reactions ,which is worth extending .

Effect of Rhodiola on the levels of inflammatory mediators and vascular endothelial function in rats with cerebral vasospasm after subarachnoid hemorrhage / 中国医师杂志

Objective To investigate the effect of Rhodiola on levels of inflammatory mediators and vascular endothelial function in rats with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH).Methods Forty adult male SD rats were randomly divided into the sham operation group, model group, low-dose Rhodiola group, and high-dose Rhodiola group, with 10 rats in each group.Except for the sham operation group, rat models of CVS after SAH were established by cisterna magna twice method.1-5 d after modeling, the model group were treated with intraperitoneal injection of normal saline.The low-dose and high-dose Rhodiola groups were injected with 5mg/kg and 10mg/kg of Rhodiola respectively.5 days later, docking was performed and blood was collected to determine the levels of serum endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and cyclic guanosine monophosphate (cGMP).Then the rats were killed, and HE staining was performed to measure the diameter of basilar artery.The expression levels of basilar artery interleukin-6 (IL-6) mRNA, interleukin-1 β (IL-1 β) mRNA, vascular endothelial growth factor (VEGF) mRNA, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by real-time fluorescence quantitative polymerase chain reaction (RT-q-PCR).Results (1) The diameters of basilar arteries showed model group ＜ low-dose and high-dose groups ＜ the sham operation group (P ＜ 0.05).(2) The levels of ET-1, IL-6, TNF-α, IL-6 mR-NA, IL-1β mRNA and iNOS mRNA showed model group ＞ low-dose and high-dose Rhodiola groups ＞ the sham operation group while levels of cGMP, VEGF mRNA and eNOS mRNA showed model group ＜ low dose and high-dose Rhodiola groups ＜ the sham operation group (P ＜ 0.05).Conclusions Rhodiola can reduce the expressions of inflammatory reactions, improve the vascular endothelial function, and promote the expressions of vascular endothelial growth factor in rats with CVS after SAH.

Improved TLC Bioautographic Assay for Qualitative and Quantitative Estimation of Tyrosinase Inhibitors in Natural Products.

INTRODUCTION: TLC bioautography for tyrosinase inhibitors has made recent progress; however, an assay with a relative low consumption of enzyme and quantitative capability would greatly advance the efficacy of related TLC bioautographic assays. OBJECTIVE: An improved TLC bioautographic assay for detecting tyrosinase inhibitors was developed and validated in this study. METHODS: L-DOPA (better water-solubility than L-tyrosine) was used as the substrate instead of reported L-tyrosine. The effects of enzyme and substrate concentrations, reaction temperatures and times, and pH values of the reaction system as well as different plate types on the TLC bioautographic assay were optimised. The quantitative analysis was conducted by densitometric scanning of spot areas, and expressed as the relative tyrosinase inhibitory capacity (RTIC) using a positive control (kojic acid) equivalent. RESULTS: The limit of detection (LOD) of this assay was 1.0 ng for kojic acid. This assay has acceptable accuracy (101.73-102.90%), intra- and inter-day, and intra- and inter-plate precisions [relative standard deviation (RSD), less than 7.0%], and ruggedness (RSD, less than 3.5%). The consumption of enzyme (75 U/mL) is relatively low. Two tyrosinase inhibitory compounds including naringenin and 1-O-ß-D-glucopyranosyl-4-allylbenzene have been isolated from Rhodiola sacra guided by this TLC bioautographic assay. CONCLUSION: Our improved assay is a relatively low-cost, sensitive, and quantitative method compared to the reported TLC bioautographic assays. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of sofren injection on acute lung injury in septic mice / 中华麻醉学杂志

Objective To evaluate the effect of sofren injection on acute lung injury (ALI) in septic mice.Methods Ninety-six pathogen-free made Kunming mice,aged 8-10 weeks,weighing 30-35 g,were divided into 4 groups (n =24 each) using a randon number table:sham operation group (group Sham),ALI group,vehicle group (group Vehicle) and sofren injection group (group Sofren).Sepsis was induced by cecal ligation and puncture.In Vehicle and Sofren groups,double distilled water and sofren injection 4 ml/kg were intraperitoneally injected,respectively,after the model was established,followed by repeated admninistration once every 12 h.At 12,24 and 48 h after operation,the animals were sacrificed and lungs were removed for mnicroscopic examination and for determination of wet to dry weight ratio (W/D ratio),malondialdehyde (MDA) content,superoxide dismutase (SOD) activity,and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in lung tissues (by enzyme-linked immunosorbent assay).The lung injury score (LIS) was calculated after haematoxylin and eosin staining.Results Compared with group Sham,the LIS,W/D ratio and contents of MDA,TNF-α and IL-6 were significantly increased,and the SOD activity was decreased at each time point in ALI and Vehicle groups (P＜0.05).Compared with group ALI,the LIS,W/D ratio and contents of MDA,TNF-α and IL-6 were significantly decreased,and the SOD activity was increased at each time point in group Sofren (P＜0.05),and no significant change was found in each parameter mentioned above in group Vehicle (P＞0.05).Conclusion Sofren injection can attenuate ALI in septic mice.

The protective effects of Rhodiola rosea combined with vitamin E on the skeletalmuscle through hypoxia combined with exercise training in mice / 重庆医学

Objective To study the protective effects of vitamin E combined with Rhodiola rosea on the injury in mice skeletal muscle through hypoxia with exercise training and research the mechanism of action.Methods Forty ICR mice were randomly divided into control group and observation group,20 mice in each group.The control group was given Vitamin E (40 mg·kg-1·d-1),and the observation group was given Vitamin E (40 mg·kg-1·d-1)combined with Rhodiola rosea (20 g·kg-1·d-1);the rats in the two groups were treated with hypoxia (11.3%) for 4 weeks (5 ℃,15 m/min,60 min/d) after 15-day drug using.After the last training,all the mice were euthanized and then detected the gene of Bax and Bcl-2 mRNA through the RT-PCR in the skeletal muscle and the activity of GSH-PX,SOD,ROS,the concentration of MDA in the skeletal muscle.During the period (pretrain and 1,2,4 weeks) of hypoxia combined with exercise training,the CK,LDH in the serum were detected.Results The expression of CK and LDH in the observation group were lower than those of the control group (P<0.05).The activity of GSH-PX and SOD in the skeletal muscle of the observation group was significantly higher than that of the control group (P<0.05),while the ROS and MDA were lower than those of the control group(P<0.05);the expression of Bax mRNA and Bax/Bcl-2 of the observation group was significantly lower than that of the control group(P<0.05).While the expression of Bcl-2 mRNA was significantly higher than that of the control group(P<0.05).Conclusion Rhodiola rosea combined with Vitamin E can inhibit the expression of apoptotic genes by correcting the oxidation and hypoxia imbalance under hypoxia.

Effect of Rhodioloside on PI3-K/AKT signaling pathway on cerebral ischemia-reperfusion injury in rats / 中国医师杂志

Objective To explore the mechanism of protective effect of Rhodioloside in cerebral ischemia-reperfusion rats and its relevance to phosphatidylinositol 3-kinases ( PI3-K)/protein serine-threonine kinases ( AKT) signaling pathway .Methods Forty eight Sprague-Dawley rats were randomly divided into four groups: sham-operation group , ischemia-reperfusion group , and Rhodiolo-side treatment groups (5 and 10 mg/kg).The model of right middle cerebral artery occlusion was established with thread ligation meth -od.The score of the neurological deficit was estimated 2 h followed by 24 h reperfusion.Histopathological changes were observed by hematoxylin-eosin(HE) staining.The infarct volume was measured with triphenyltetrazolium chloride (TTC) staining.Apoptotic cells were assessed with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method.The expressions of PI3-K and p-AKT were evaluated with immunohistochemistry .Results The score of the neurological deficit was decreased more ob-viously, the number of apoptotic were decreased more significantly , the expressions of PI3-K and p-AKT were increased more signifi-cantly in the Rhodioloside treatment groups (5 and 10 mg/kg) than in the ischemia-reperfusion group ( P <0.05).The score of the neurological deficit was decreased , the number of apoptotic was decreased , and the expressions of PI 3-K and p-AKT were increased in the Rhodioloside treatment group (10 mg/kg) than the Rhodioloside treatment group (5 mg/kg) ( P <0.05).Conclusions The protective mechanism of Rhodioloside therapy against cerebral ischemia r-eperfusion injury might be associated with activating the PI 3-K/AKT signaling pathway and then inhibiting neuronal apoptosis .

Microsatellite markers in Rhodiola (Crassulaceae), a medicinal herb genus widely used in traditional Chinese medicine.

PREMISE OF THE STUDY: Microsatellite loci are described for Rhodiola, a medicinal herb genus widely used in traditional Chinese medicine. • METHODS AND RESULTS: A total of 17 polymorphic microsatellite primer pairs were developed using the combined biotin capture method. The number of alleles per locus ranged from one to 12 across 192 individuals from R. bupleuroides, R. crenulata, R. fastigiata, and R. sacra, and the mean observed and expected heterozygosities ranged from 0.177 to 0.412 and from 0.363 to 0.578, respectively. • CONCLUSIONS: The results demonstrate the potential use of this new set of microsatellite markers for genotyping individuals and estimating genetic diversity in Rhodiola.