Mechanism of Ginseng-Rhodiola rosea in treatment of myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking / 中国药理学通报

Aim To investigate the sites and mechanisms of action of Ginseng-Rhodiola rosea in the treat ment of myocardial ischemia-reperfusion injury ( MI-RI) via using network pharmacology approach, molecu¬lar docking techniques and experimental studies. Methods The active ingredients and targets of Gin¬seng-Rhodiola rosea were screened through the TCMSP database and literature supplementation, and the GEN-EC ARDS ,DISGENET and DRUGBANK databases were searched to obtain the targets of MIRI. Functional pro¬tein interaction networks (PPIs) and the STRING database were used to screen out core targets. The DAVID database was also selected for gene ontology functional analysis ( GO) and KEGG signaling pathway enrich¬ment analysis. Lastly, the preliminary validation was performed with the help of molecular docking techniques and experimental studies. Results Forty-three active ingredients and 348 potential targets of Ginseng-Rhodiola were obtained, and targets such as IL-6 , TNF-α and VEGFA were found to be closely related to MIRI, mainly involving TNF, PDK-Akt, HIF-1 and other signaling pathways.The molecular docking results showed that soysterol, ginsenoside rh2 and rhodioloside had good binding effects and high matching with IL-6, TNF-α,Caspase-3,VEGFA,MAPK1 and other targets, among which the best binding was between Caspase-3 and ginsenoside rh2. The results of the experimental study further showed that Ginseng-Rhodiola rosea could improve myocardial tissue necrosis after myocardial ischemia-reperfusion , reduce myocardial cell edema and vascular congestion, and decrease the expression levels of TNF-α and IL-6 in MIRI rats. Conclusions Ginseng-Rhodiola may modulate multiple targets such as IL-6,TNF-α, Caspase-3, VEGFA and MAPK1 through dousterol, ginsenoside rh2 and rhodiol glycosides to inhibit inflammatory response and oxidative stress, reduce cardiomyocyte damage and exert therapeutic effects on MIRI.

Effect of different plant growth regulators on callus and adventitious shoots induction, polysaccharides accumulation and antioxidant activity of Rhodiola dumulosa / 中草药·英文版

OBJECTIVE@#As a medicinal plant, the resource of Rhodiola dumulosa is deficient along with the large collection. For the protection and utilization of R. dumulosa, the influence of plant growth regulators (PGRs) on callus induction and adventitious shoots differentiation, polysaccharide production and the antioxidant activity were tested.@*METHODS@#Internodes of R. dumulosa were used as explants and cultured on MS medium plus different plant growth regulators (PGRs). The anti-oxidative activities of polysaccharides were evaluated using radical scavenging assays.@*RESULTS@#By response surface plot, 0.85 mg/L N6-benzyladenine (BA), 0.34 mg/L naphthaleneacetic acid (NAA) and 0.33 mg/L 2,4-dicholorophenoxyacetic acid (2,4-D) were the optimal factors for callus induction (90.03%) from internodes explants on MS medium. The fresh weight of green callus increased 47.26 fold, when callus was inoculated on MS + thidiazuron (TDZ) 0.5 mg/L + NAA 2.0 mg/L. Adventitious buds regenerated from callus on the media of MS were fortified with BA 1.0 mg/L plus NAA 0.5 mg/L, and the induction rate was 40.00%. MS plus indole-3-butyric acid (IBA) 1.0 mg/L produced the highest rooting rate with 10 to 15 roots in a length of 2-3 cm per shoot. The content of total polysaccharides in callus developed on MS + TDZ 0.5 mg/L + NAA 2.0 mg/L and MS + BA 1.0 mg/L + NAA 0.5 mg/L was as high as 1.72%-2.15%. At the dose of 0.5 mg/mL polysaccharides extracted from different callus induced on MS + NAA 2.0 mg/L + TDZ 0.5 mg/L or MS + BA 1.0 mg/L + NAA 0.5 mg/L or MS + BA 0.5 mg/L + 2,4-D 0.5 mg/L, the ABTS radical eliminating percentages were 82.78%, 80.18% and 68.59%, respectively, much higher than that of wild plant.@*CONCLUSION@#A rapid micropropagation system for R. dumulosa has been developed. The combination of TDZ and NAA or BA and NAA can increase the yield of the total polysaccharides. The polysaccharides isolated from callus and whole wild plants had stronger free radicals scavenging activities, indicating that polysaccharides from R. dumulosa are the potential pharmaceutical supplements.

Discovery of human pancreatic lipase inhibitors from root of Rhodiola crenulata via integrating bioactivity-guided fractionation,chemical profiling and biochemical assay / 药物分析学报

Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

Quantitative analysis of active ingredient content of Rhodiola rosea at different harvest months / 国际中医中药杂志

Objective:To establish a method for quantitative analysis of the active ingredients including salidroside, rosarin and rosavin and content determination in Rhodiola rosea at different harvest months. Methods:HPLC was used on an X selectHSS T3 (250 mm×4.6 mm, 5 μm) column with mobile phase consisting of methol-acetonitrile-phosphoric acid (0.05%) aqueous solution for gradient elution at a flow rate of 1 ml/min. The wavelength was detected at 275 nm (salidroside) and 254 nm (rosarin, rosavin). The column temperature was set at 30 ℃ and the injection volume was 5 μl.Results:The peak areas of Salidroside, rosarin and rosavin showed good linear relationships ( r > 0.999) with the content in the ranges of 44-1 420, 10-307 and 18-573 μg, respectively. The method was precise, stable, repeatable and the sample recovery test all well satisfied the requirements of quantitative analysis. The highest accumulation of the active ingredients was observed in Rhodiola rosea in September and the content of salidroside, rosarin and rosavin were 0.66, 0.07 and 0.53 mg/g, respectively. Conclusion:This method is simple and rapid to evaluate the content of active ingredients in Rhodiola rosea.

Rhodiola crenulata extract decreases fatty acid oxidation and autophagy to ameliorate pulmonary arterial hypertension by targeting inhibiton of acylcarnitine in rats / 中国天然药物

Pulmonary arterial hypertension (PAH) is a devastating pulmonary circulation disease lacking high-efficiency therapeutics. The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata, a well-known traditional chinese medicine with cardiopulmonary protection capacity, on PAH by exploiting functional lipidomics. The rat model with PAH was successfully established for first, following Rhodiola crenulata water extract (RCE) treatment, then analysis of chemical constituents of RCE was performed, additional morphologic, hemodynamic, echocardiographic measurements were examined, further targeted lipidomics assay was performed to identify differential lipidomes, at last accordingly mechanism assay was done by combining qRT-PCR, Western blot and ELISA. Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls, mostly assigned to acylcarnitines, phosphatidylcholines, sphingomyelin associated with the PAH development. Excitingly, RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH. Furthermore, RCE was observed to reduce autophagy, confirmed by significantly inhibited PPARγ, LC3B, ATG7 and upregulated p62, and inactivated LKB1-AMPK signal pathway. Notably, we accurately identified the constituents in RCE, and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy. Altogether, RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH. This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.

Synthesis of the active ingredient rosavin of Rhodiola rosea / 药学实践杂志

Objective To establish the chemical synthesis of the active ingredient rosavin of Rhodiola rosea. Methods β-D-pentaacetylglucose, 1-hydroxy-2,3,4-triacetylarabinose and cinnamyl alcohol were used as starting materials. The target compound was prepared by 1-position selective of β-D-pentaacetylglucose deacetylation, glycosylation reaction, glucose 6-OH selective protection and deprotection and other 8-step reactions. Results The target product, rosavage, was successfully obtained with high yield. The structure was confirmed by ESI-MS, 1H-NMR and 13C-NMR. The protection of 6-OH with high selectivity and high yield of tert-butyldiphenyl chlorosilane played a vital role in the synthesis process,. Conclusion The synthetic route has the advantages of simple operation, high yield, and good safety.

Cloning and expression analysis of RcUDPGTs genes in Tibetan Rhodiola crenulata / 药学学报

UDP glucosyltransferase (UDPGT) catalyzes the synthesis of secondary metabolites and plant hormones to regulate plant growth and development, pathogen defense and environmental adaptability. In this study 18 members of the RcUDPGT gene family were cloned from Tibetan Rhodiola crenulata and analyzed using bioinformatics. The tissue-specific expression, abiotic stresses and plant hormones (abscisic acid, auxin, methyl jasmonate) induced expression patterns were identified by real-time quantitative PCR. The bait vector of RcUDPGT (JX228125.1) was constructed to select interacting proteins from an Arabidopsis yeast library. The results of the bioinformatics analysis revealed that RcUDPGT nucleotide sequences were about 1 400 bp and encoded 452-498 amino acids. In the primary protein sequences, C-terminal sequences were more conserved compared with N-terminal regions, which held a PSPG (plant secondary product glycosyltransferase) domain. In the tertiary structures, RcUDPGTs contained a UDP sugar donor recognition binding site. In addition, all genes had multiple phosphorylation sites. The results of qRT-PCR showed that RcUDPGTs genes were expressed in root, stem and leaf. The expression levels were regulated by low temperature/ultraviolet light and various plant hormones (ABA, IAA, MeJA), but the expression patterns were quite different among them. For example, RcUDPGT6, RcUDPGT11, and RcUDPGT17 had the highest expression in leaves and were induced by all three hormones, suggesting that the functions of these genes might be to respond to environmental changes. RcUDPGT9, RcUDPGT10, RcUDPGT14 were most abundantly expressed in roots and were significantly induced by ABA and MeJA hormones, indicating that these genes may be involved in the synthesis and accumulation of salidroside. Yeast two-hybrid results showed that RcUDPGT did not exhibit autoactivation and cell toxicity, and two significant interactional genes were identified, AtKCR1 (AT1G67730.1) and AtSNL4 (AT1G70060). The AtKCR1 gene encodes a β-ketoacyl reductase (KCR) involved in synthesis of very long chain fatty acids. The AtSNL4 gene encodes a homolog of the transcriptional repressor SIN3, which could participate in the ABA hormone signaling pathway and enhance the transcriptional repression of AP2/EREBP class factors in Arabidopsis. These results suggest that the accumulation of the secondary metabolite salidroside in Rhodiola crenulata might be affected by several regulatory mechanisms. The above results may lay the foundation for understanding the adaptive mechanism of Rhodiola crenulata in a high altitude environment and stimulate an in-depth study of the synthesis and accumulation of secondary metabolites in this species.

To evalate the effect of “Vitos” shilajit shot preparation on rat femur fracture using X-ray / Монголын эм зүй, эм судлал

Introduction@#Shilajit and Rhodiola Rosa L are widely used in Mongolian Traditional medicine for the management of diseases and for fracture healing. The aim of this study was to evaluate the pharmacology effects of the “Vitos” Shilajit Shot preparation on fracture healing and callus stages in rats by X-ray.@*Material and methods@#We used non-liner Wistar rats for <i>in vivo</i> experiments, there are sixteen rats were randomly grouped as a positive control, negative control, “Vitos” Shilajit shot experimental and standard groups. The positive group was as healthy animals and other groups were created femoral fracture by Bonnaren’s device. Then negative control group was oral administered distilled water, whereas 4.1ml/kg of “Vitos’ Shilajit shot administrated via oral gavage to experimental group through 56 days. X-rays were performed to assess fracture healing effects within 14, 28, 42, 56 days and callus stages.@*Results@#Significantly higher callus volume and callus staging were observed in the “Vitos” Shilajit shot group compared with the negative control and standard groups. Also “Vitos” Shilajit shot group was becoming as bridging between both end of fractures and get hard callus formulation ready observation of X-Ray radiograph on 4 weeks post fracture. The fracture healing process was slightly reached to callus remodulation such as final stage of bone formulation on 56^th day.@*Conclusion@#The results of this study reveal that, “Vitos’ shot preparation, which contains an extract of <i>Rhodiola Rosa L</i> and thick extract of Shijilat has a treatment effect and enhancing and supporting callus of bone fracture healing.

Results of determination of salidroside content in roots and rhizomes of cultivated and natural Rhodiola rosea L / Монголын Анагаах Ухаан

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.

Rhodiola intervention improves mitochondrial autophagy and fusion-division in skeletal muscle cells of mice with high intensity exercise / 中国组织工程研究

BACKGROUND: Excessive exercises cause a large accumulation of oxidative active substances in the body to damage skeletal muscle cells. Mitochondria play a key role in energy metabolism during exercise. Studies have shown that Rhodiola can reduce the level of lipid peroxidation in muscle tissue and protect damaged endothelial cells. OBJECTIVE: To explore the mechanism underlying Rhodiola improving skeletal muscle function of mice with high intensity exercise by regulating mitochondrial function. METHODS: The study protocol was approved by the Ethics Committee of Xi’an Shiyou University in China. Forty BALB/c mice were divided into blank control group, exercise group, Rhodiola control group and Rhodiola intervention group. Mice in the blank control had no exercise and intervention. Mice in exercise group were given intragastric administration of normal saline followed by high intensity exercise. Mice in Rhodiola intervention group and Rhodiola control group were given intragastric administration of the mixture of Rhodiola and normal saline, followed by exercise or not. The interventions were performed once a day for 28 consecutive days. Body mass, forearm grip strength and exhaustion time were observed. Western blot assay was used to detect expression of manganese superoxide dismutase protein, p53 protein, mitochondrial origin and autophagy-associated protein in the skeletal muscle. RT-qPCR was used to detect skeletal muscle Mfn-1, Mfn-2, Opa-1, Drp-1, and fis-1 mRNA expression. RESULTS AND CONCLUSION: (1) From the 2nd week, the grip strength of forelimbs in the exercise group was significantly lower than that in the other three groups (P 0.05). (2) At the 3rd and 4th weeks, the exhaustion time of weight-bearing swimming training was significantly shorter in the exercise group than the Rhodiola intervention group (P 0.05). Compared with the blank control group, the Rhodiola exercise intervention group also showed a downward trend in the expression of fusion gene and an upward trend in the expression of Drp-1 mRNA, but there was no significant difference between the two groups (P > 0.05). To conclude, Rhodiola can significantly improve the exercise endurance of mice with high intensity exercise, which may be related to the improvement of skeletal muscle mitochondrial autophagy, origin and fusion-division.

Protective effect of rhodiola rosea extract on alveolar bone loss in diabetic rats / 中国药理学通报

Aim: To investigate the protective effect of Rhodiola rosea extract on alveolar bone injury in diabetic osteoporosis rats. Methods: A diabetic rat model was established by intraperitoneal injection of streptozo-tocin 60 mg · kg-1. After successful establishment of the model, the animals were divided into control group, model group and Rhodiola rosea group. Rhodiola rosea extract was administered orally for eight weeks at a dose of 150 mg · kg-1. The levels of blood glucose, serum ALP, Ca, OPG and RANKL were measured, and the ratio of OPG to RANKL was calculated. At the same time, the alveolar bone histopathology was analyzed, and the number of osteoclasts were counted. Results: After treated with Rhodiola rosea extract for eight weeks, the blood glucose, the levels of serum ALP and RANKL in Rhodiola rosea group were significantly lower than those in model group (P < 0. 01). The serum levels of Ca, OPG and the ratio of OPG/RANKL significantly increased in Rhodiola rosea group compared with those of model group (P < 0. 05). Histological examination showed that alveolar bone trabecule in model group were sparse and fractured, bone resorption was serious, and alveolar bone structure was restored after Rhodiola rosea extract administration. The number of osteoclasts in model group increased significantly, and the number of alveolar osteoclasts decreased after Rhodiola rosea extract administration. Conclusions: Rhodiola rosea extract has protective effect on early alveolar bone injury in diabetic rats, and its mechanism is mainly by regulating ALP and OPG/RANKL/RANK system, and accordingly promoting bone formation and inhibiting bone resorption, and balancing bone turnover.

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 .

Effects of salidroside on the growth of xenograft tumor of human pancreatic cancer BxPC-3 cells in nude mice / 中华胰腺病杂志

Objective To investigate the effect of salidroside on xenograft tumor of human pancreatic cancer cells BxPC-3 in nude mice.Methods BxPC-3 subcutaneous xenograft tumor nude mice model was established,and the mice were randomly divided into control group,salidroside 25 mg group and salidroside 50 mg group using random number method (6 mice in each group).25 mg/kg and 50 mg/kg salidroside by intragastric administration was performed per day for 3 weeks and the tumor was resected.The tumor was weighed and the diameter was measured.Cell apoptosis was detected by Tunel staining.Results As result,tumor weight was (1.561 ± 0.416)g in the control group,(0.742 ± 0.272)g in the 25 mg group and (0.276 ± 0.064) g in the 50 mg group respectively;tumor volume was (2354.35 ± 523.11) mm3,(991.43 ± 348.91) mm3 and (403.60 ± 130.98) mm3,respectively;and the apoptosis rate of the transplanted tumor cells was (23.74 ± 5.88) ％,(49.30 ± 6.75) ％ and (64.97 ± 6.99) ％,respectively,with significant difference among three groups (all P ＜ 0.01).The effect of salidroside on inhibiting proliferation and promoting apoptosis was dose dependent.Conclusions Salidroside can significantly inhibit the proliferation and growth of pancreatic cancer BxPC-3 cells via promoting cell apoptosis and inhibiting cell proliferation.

Protective effect of Rhodiola rosea on vascular endothelium in rats with intermittent hypoxia / 中国中西医结合急救杂志

Objective To observe the protective effect of Rhodiola rosea on vascular endothelium in rats with intermittent hypoxia (IH) and to explore its possible mechanism. Methods According to random number table method, 45 male Sprague-Dawley (SD) rats were divided into normal control group, IH group and Rhodiola rosea low, medium and high dose groups, with 9 rats in each group. The IH model was reproduced by putting the rats into IH model chamber, and then feeding them with nitrogen, oxygen and compressed air for 45 days. The feeding bin and feeding time of rats in the normal control group were consistent with those in other groups, and the oxygen concentration in the tank was maintained at 20%-21%. The rats in Rhodiola rosea high, medium and low dose groups were intraperitoneally injected with Rhodiola rosea (0.2, 0.1 and 0.05 mL/100 g), starting from the 15 th day in IH chamber, and the injection continued for 30 days. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) in the coronary arteries of rats in each group were detected by automatic biochemical analyzer. The contents of coronary hypoxia-inducible factor-1α(HIF-1α) and tumor necrosis factor-α(TNF-α) in rats were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) in coronary artery tissues of rats in each group were measured by reverse transcription-polymerase chain reaction (RT-PCR). The pathological changes of aorta in each group were observed under light microscope. Results Compared with the normal control group, SOD and NO in the IH group decreased [SOD (U/mg): 4.43±0.22 vs. 8.60±0.34, NO (μmol/g): 3.09±0.07 vs. 4.81±0.41, both P < 0.01], MDA, TNF-α, HIF-1α and mRNA expression of ET-1 and VEGF increased [MDA (nmol/mg): 0.78±0.03 vs. 0.50±0.03, TNF-α(pg/mg): 6.35±0.29 vs. 3.27±0.14, HIF-1α (ng/mg): 14.55±0.70 vs. 7.16±0.17, ET-1 mRNA (2-ΔΔCt): 1.75±0.03 vs. 1.10±0.07, VEGF mRNA (2-ΔΔCt):4.38±0.10 vs. 1.20±0.07, all P < 0.01]. Compared with the IH group, SOD and NO were increased in three Rhodiola rosea groups, MDA, TNF-α, HIF-1α and mRNA expression of ET-1 and VEGF were decreased in three Rhodiola rosea groups, and the changes in the Rhodiola rosea high dose group were more significant than those in the low and medium dose Rhodiola rosea groups [SOD(U/mg): 7.47±0.19 vs. 5.41±0.37, 6.71±0.28, MDA (nmol/mg): 0.57±0.20 vs. 0.74±0.04, 0.70±0.03, NO (μmol/g): 4.00±0.28 vs. 3.27±0.18, 3.47±0.28, TNF-α(pg/mg): 3.90±0.17 vs. 5.08±0.27, 4.39±0.26, HIF-1α(ng/mg): 8.40±0.23 vs. 11.07±0.41, 9.81±0.44, ET-1 mRNA (2-ΔΔCt): 1.12±0.04 vs. 1.71±0.03, 1.63±0.07, VEGF mRNA (2-ΔΔCt): 2.45±0.09 vs. 3.99±0.12, 3.27±0.08, all P < 0.05]. Under light microscope, the inner membrane of the normal control group was intact, and the endothelial cells were loose and slightly stained on the surface of the inner membrane; in the IH group, part of the arterial areas showed endointima edema or even abscission, and interstitial edema in the vascular wall. The pathological changes in three Rhodiola rosea groups were less than that in the IH group, and the changes of Rhodiola rosea high dose group were more significant. Conclusion Rhodiola rosea can protect the vascular endothelium caused by IH exposure through improving the level of anti-hypoxia in tissues and inhibiting oxidative stress and inflammatory response.

Effects of Rhodiola sachalinensis on ocular blood flow in diabetic retinopathy rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of Rhodiola sachalinensis on ocular blood flow in diabetic retinopathy rats. METHODS:A total of 90 SD rats were randomly divided into control group (n=30), model group (n= 30) and intervention group (n=30). Rats in the model group and intervention group were fed with high glucose and high fat diet and injected with streptozotocin (40mg/kg) in order to construct DR model rats,while rats in the control group were fed with basic diet and injected with the same amount of normal saline. After 4wk, the rats in the intervention group were injected with Rhodiola sachalinensis injection(10mL,one per day),while rats in the control group and the model group were injected with normal saline. The course of intervention treatment was 4wk. The ocular blood flow in rats was detected by laser doppler flowmetry, the apoptosis of retinal cells in rats was detected by TUNEL method, the expression of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein ( GFAP ) and glutamate/aspartate transporter (GLAST) in retina of rats was detected by RT-PCR method and Western blot method. RESULTS:The whole blood viscosity,whole blood high shear viscosity,low shear blood viscosity and erythrocyte sedimentation of rats in the model group and intervention group were higher than those in the control group (P<0 01),while the indexes of intervention group were lower than that of model group (P<0.01). The PSV and EDC of rats in the model group and intervention group were lower than those in the control group (P<0.01), and the Rl was higher than that in control group (P<0.01). The PSV and EDC in the intervention group were higher than those in the model group (P<0.01), and Rl was lower than that in the model group (P<0.01). The apoptosis rate of retinal cells of model group and intervention group was higher than that of the control group (P<0.01), that in the intervention group was lower than that in the model group (P<0.01). The expression of VEGF and GFAP in retina tissue of model group and intervention group was higher than that of the control group (P<0.01), and the expression of GLAST was lower than that in the control group(P<0 01). The expression of VEGF and GFAP in the intervention group was lower than that in the model group(P<0.01),and the expression of GLAST was higher than that in the model group (P<0.01). CONCLUSION: Rhodiola sachalinensis injection can significantly improve the ocular blood flow in diabetic retinopathy rats, reduce the apoptosis of retinal cells in rats, down regulate the expression of VEGF and GFAP, and up regulate the expression of GLAST.

Identification of Rhodiola quadrifida and Rhodiola crenulata based on NMR fingerprint and chemical pattern recognition method / 中草药

Objective A method for classification and identification of Rhodiola quadrifida and Rhodiola crenulata was established based on nuclear magnetic resonance 1H-NMR fingerprints-chemical pattern recognition technique. Methods Using high resolution (600 MHz) NMR fingerprints pattern technique, the total component information 1H-NMR fingerprint of R. quadrifida and R. crenulata was determinated, combined with the similarity analysis, hierarchical cluster analysis, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) methods for chemical pattern recognition analysis. Results 1H-NMR fingerprints techniques combined with chemical pattern recognition analysis was an effective method to discriminate and identify R. quadrifida and R. crenulata. The difference of the 1H-NMR fingerprint of R. quadrifida and R. crenulata was obvious, which truly and comprehensively reflected the characteristic components and internal qualities of Rhodiola. The main different components of R. quadrifida and R. crenulata were terpenoids and flavonoids, in particular, crenulatin of the terpenoid was a characteristic ingredient in the identification of R. quadrifida and R. crenulata, which can be used as the identification and classification index of R. quadrifida and R. crenulata. Conclusion 1H-NMR fingerprints techniques combined with chemical pattern recognition analysis method is an effective method for classification and identification of Rhodiola, which lays the foundation for variety identification and quality evaluation of medicinal plants of Rhodiola.

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.

Molecular mechanism of Tibetan medicine Rhodiola crenulata prevents oxidative stress through network pharmacology / 中国中药杂志

In this study, a computer-based network pharmacology approach was applied to investigate the potential mechanism and important components of Rhodiola crenulata in the protection of H9c2 cells against hydrogen peroxide (H₂O₂)-induced oxidative stress. The intestinal absorption liquid of R. crenulata enhanced the cell viability, maintained cell morphology and inhibited cell apoptosis in the H₂O₂-induced oxidative stress in H9c2. Then, computer-based network pharmacology was used to analyze the relevant mechanism. A total of 133 oxidative stress-related compounds were screened out; and 26 of them occupied the top 20%, and all of the compounds enriched in 43 oxidative stress-related key targets. Finally, a "compound-target-pathway-function" network was constructed. Based on the analysis of the network pharmacology, R. crenulata protected H9c2 cells against H₂O₂-induced oxidative stress probably by affecting apoptosis-related processes, such as cell death, nitric oxide metabolism, oxidative stress, mitochondrial mechanism, redox process, redox-related enzyme activty and other oxidative stress-related process. And salidroside, ethyl gallate and catechins, which were the main components of R. crenulata, played an important role in this process. Therefore, the potential mechanism and important components of R. crenulata revealed the protective effect on oxidative stress. This study shows a multi-component, multi-target and overall regulation effect of R. crenulata on the oxidative stress, and provides a reliable reference for subsequent systematic experimental studies for the pharmacodynamic material foundation and mechanism of action R. crenulata.

Effect of fertilization combinations of nitrogen, phosphorus, and potassium on four phenolic compounds of cultivated Rhodiola crenulata / 中国中药杂志

This study is aimed to explore the effect of nitrogen, phosphorus and potassium combined application on the active components of Rhodiola crenulata. R. crenulata was used as the research object, "3414" fertilization experiment were conducted with regular fertilization of NPK(N 60 kg·hm⁻², P₂O₅ 100 kg·hm⁻²,KCl 160 kg·hm⁻²) to study the effect of different rates of NPK fertilization on the total amount of 4 phenolic constituents of gallic acid, salidroside, tyrol and ethyl gallate through field test. The results show that the content of salidroside was higher in the treatment of N₁P₂K₁ and N₁P₂K₂, andthe total amount of four phenols was higher in the treatment of N₁P₂K₂ and N₂P₂K₂. The suitable level of nitrogen, phosphorus and potassium promoted the accumulation of the 4 kinds of phenols.The amount of fertilizer recommended by the three factor fertilizer effect equation,(N 0 kg·hm⁻²,P₂O₅ 150 kg·hm⁻²,KCl 31.71 kg·hm⁻²) obtained the highest content of salidroside, and it was 1.54%.（N 35.54 kg·hm⁻²,P₂O₅ 150 kg·hm⁻²,KCl 237.73 kg·hm⁻²）obtained the highest content of 4 kinds of phenolic compounds, and it was 1.93%. This study provides a reference for the standardization of artificial planting of endangered Tibetan medicine.

Clinical analysis of the effect of Rhodiola kirilowii Regel combined with calcium dobesilate in the treatment of early diabetic nephropathy / 中国基层医药

Objective To explore the effect of Rhodiola kirilowii Regel combined with calcium dobesilate in the treatment of early diabetic nephropathy.Methods 80 patients with early diabetic nephropathy were selected,and they were divided into treatment group and control group according to the digital table,40 cases in each group.The two groups were given diet control and appropriate exercise and positive controlled blood sugar,blood fat,blood pressure.The control group was given calcium dobesilate,based on this,the treatment group was given Rhodiola kirilowii Regel 10mL into 5％ glucose injection 250mL and 3 unit insulin to intravenous drip.The period of treatment was fifteen days.The UAER,Scr and BUN were compared between two groups before treatment and fifteen days after treatment.Results Before treatment,the Scr,BUN and UAER in the control group were (88.00 ± 18.19) μmol/L,(5.98 ± 1.92) mmol/L,(123.31 ± 60.01) μg/min respectively,which in the treatment group were (85.80 ± 18.31) μmol/L,(5.96 ± 1.94) mmol/L,(140.21 ± 62.92) μg/min respectively,there were no statistically significant differences between the two groups(t =-1.191,-0.016,0.432,all P ＞0.05).After treatment,the Scr,BUN and UAER in the control group were (84.61 ± 11.71) μmol/L,(6.30 ± 1.37) mmol/L,(97.81 ± 49.16) μg/min respectively,which in the treatment group were (75.60 ± 11.44) μmol/L,(5.25 ± 1.24) mmol/L,(39.81 ± 23.43) μg/min.There were no statistically significant differences in Scr and BUN of the two groups compared with before treatment (the control group:t =0.767,-0.657;the treatment group:t =1.947,1.219,all P ＞ 0.05).There was statistically significant difference in UAER of the two groups compared with before treatnent (t =2.850,5.402;P =0.046,0.006),but UAER of the treatment group after treatment decreased significantly.After treatment,there were no statistically significant differences in Scr and BUN between the two groups (t =-1.229,-1.236,all P ＞ 0.05),while there was statistically significant difference in UAER between the two groups (t =-2.394,P =0.044).The effective rate in the treatment group was 87.5 ％,which was higher than 57.5 ％ of the control group (x2 =9.028,P ＜ 0.05).Conclusion Rhodiola kirilowii Regel combined with calcium dobesilate can ameliorate protenuria and improve renal function of the patients with early diabetic nephropathy.