The mechanism of L-perilla alcohol(L-POH) in intervening hypoxic pulmonary hypertension(HPAH) was discussed based on network pharmacology, and experimental verification. The active components and potential targets of the volatile oil of Rhodiola tangutica(VORA) in the intervention of HPAH were screened by network pharmacology. The biological process of Gene Ontology(GO) and the signaling pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed for the core targets, and a "component-common target-disease" network was constructed. Four active components were screened from VORA: L-POH, linalool, geraniol, and(-)-myrtenol. The core targets for treating HPAH were HSP90AA1, AKT1, ESR1, PIK3CA, EP300, EGFR, and JAK2. GO enrichment analysis mainly involved biological processes such as reaction to hypoxia, heme binding, and steroid binding. KEGG enrichment analysis mainly involved hypoxia-inducing factor 1(HIF-1) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and Janus kinase/activator of signal transduction and transcription(JAK/STAT) signaling pathway. The vasodilation effects of the four active components were screened by perfusion experiment of extracorporeal vascular rings, and the mechanism of the main active component L-POH was studied by channel blockers. The inhibitory effects of the four active components on the proliferation of pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia were screened by cell proliferation experiment, and the mechanism of the main active component L-POH was studied by flow cytometry, cell cycle experiment, and Western blot. The results showed that L-POH could directly act on vascular smooth muscle to relax pulmonary arterioles, induce ATP-sensitive potassium channels to open, and inhibit extracellular Ca~(2+) influx through voltage-gated calcium channels to relax blood vessels. In addition, L-POH could inhibit the abnormal proliferation of PASMCs induced by hypoxia and promote its apoptosis, and its mechanism may be related to the increase in Bax protein expression and the decrease in p-JAK2, p-STAT3, Bcl-2, and cyclinA2 protein expression. In summary, L-POH can interfere with HPAH by relaxing pulmonary arterioles and inhibiting the proliferation of smooth muscle cells.
Network Pharmacology ; Animals ; Hypertension, Pulmonary/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Hypoxia/metabolism* ; Rhodiola/chemistry* ; Signal Transduction/drug effects* ; Humans ; Monoterpenes/chemistry* ; Male ; Cell Proliferation/drug effects* ; Rats, Sprague-Dawley

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P＜0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P＜0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P＜0.05, P＜0.01) and the content of MDA was decreased significantly (P＜0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P＜0.01, P＜0.05) and the content of MDA was decreased significantly (P＜0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.
Animals ; Astragalus Plant ; Ethanol ; Hypoxia ; Male ; Mice ; Plant Extracts/pharmacology* ; Rhodiola ; Sodium Nitrite ; Superoxide Dismutase/metabolism* ; Water

OBJECTIVE: To study the effects of notoginseng, gingko leaf and rhodiola on cardiac functions and the serum inflammatory factors interleukin-6,interleukin-10, and TNF-α of rats with hypoxia deacclimatization, to explore the mechanism of hypoxia detoxification. METHODS: Forty SD rats were randomly divided into notoginseng group(n=10), gingko leaf group(n=10), rhodiola group(n=10) and high altitude control group(n=10) after fed in a hypobaric hypoxia chamber(simulated altitude of 5 000 m) for 3 month, while 10 rats fed at normal pressure and oxygen environment for 3 month were used as the plain control group. Rats in notoginseng group, gingko leaf group and rhodiola group were treated with notoginseng, gingko leaf tablets or rhodiola suspension through intragastric administration (200 mg/kg,twice a day, for 10 days). After the rats got intraperitoneal anesthesia with 10% urethane, 5 min pulmonary artery pressure curve were traced continuously while pulmonary artery pressure (PAP). Left and right ventricular systolic pressure (VSP) and ventricular diastolic pressure (VEDP), the hemodynamic parameters were detected through a multi-channel physiological recorder. Serum tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. RESULTS: Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), mean pulmonary artery pressure (mPAP), left vent-ricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),IL-6,and IL-10 were higher in notoginseng group, gingko leafgroup, rhodiola group and high altitude control group than those in plain control group(P＜0.05 or P＜0.01). The contents of MDA and TNF-α were higher while the level of SOD was lower in rhodiola group and high altitude control group than those in plain control group(P＜0.01). The contents of MDA and TNF-α were lower while the level of SOD was higher in notoginseng group, gingko leaf group and rhodiola group than those in high altitude control group(P＜0.01). The levels of RV,RVHI,RVSP,RVEDP,LVSP,LVEDP,IL-10 and TNF-α were statistically changed in notoginseng group than those in gingko leaf group and rhodiola group(P＜0.05orP＜0.01). CONCLUSION Notoginseng, gingkoleaf and rhodiola can enhance antioxidant capacity of body and improve ventricular functions and Notoginseng, gingko leaf and rhodiola can effectively enhance the functions of ventricular and hypoxia tolerance and inhibit the expressions of inflammatory factors in rats during the hypoxia deacclimatization.
Animals ; Ginkgo biloba ; chemistry ; Heart ; drug effects ; physiology ; Hypoxia ; Plant Extracts ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rhodiola ; chemistry ; Tablets

BACKGROUND AND OBJECTIVES: Neuroinflammation is involved in the pathogenesis of neurodegenerative disorders. Conditioned medium (CM) derived from bone marrow mesenchymal stem cells (MSCs) revealed substantial benefits due to its rich content of trophic factors. Salidroside (Sal), extracted from Rhodiola rosea, is known for its anti-inflammatory and neuroprotective effects. This study was designed to investigate the effect of Sal pretreated CM (CM-Sal) derived from bone marrow MSCs in lipopolysaccharide (LPS) induced neuroinflammation. MATERIAL AND METHODS: Fifty adult male mice were equally divided into 5 groups: Group I (Normal Control), Group II (LPS): single 0.8 mg/kg LPS intraperitoneally; Group III (LPS-DMEM), Group IV (LPS-CM) and Group V (LPS-CM-Sal): LPS was injected as group II followed, 24 hours later, by intranasal injection of 50 μl of filtered serum-free Dulbecco's Modified Eagle's medium (DMEM), CM or CM-Sal, respectively, twice daily for 4 days. Animals were sacrificed at day 6 and paraffin cerebral sections were subjected to Hematoxylin and Eosin staining and immunohistochemistry with caspase 3 (apoptosis), glial fibrillary acidic protein GFAP (astrocytes) and CD68 (active microglia) followed by quantitative morphometric study. RESULTS: Examination of LPS and LPS-DMEM groups revealed neuronal apoptosis with reactive astrogliosis and increased active microglia. LPS-CM and LPS-CM-Sal groups showed less apoptosis, less astrocytes and less active microglia. The regression in neuroinflammation was more evident in LPS-CM-Sal group and the difference was statistically significant compared to other groups. CONCLUSION: CM-Sal derived from MSCs culture elicited significant histopathological improvement in LPS induced neuroinflammation which could be used as new therapeutic modality.
Adult ; Animals ; Apoptosis ; Astrocytes ; Bone Marrow ; Caspase 3 ; Culture Media, Conditioned* ; Eosine Yellowish-(YS) ; Glial Fibrillary Acidic Protein ; Hematoxylin ; Humans ; Immunohistochemistry ; Male ; Mesenchymal Stromal Cells* ; Mice* ; Microglia ; Neurodegenerative Diseases ; Neurons ; Neuroprotective Agents ; Paraffin ; Rhodiola

To study the anti-tumor metastatic constituents in Rhodiola wallichiana (HK) S H Fu var Cholaensis (Praeg) S H Fu, chemical constituents were isolated and purified by repeated column chromatography (silica gel, Toyopearl HW-40C and preparative HPLC). Their structures were elucidated on the basis of spectral data analysis. The anti-tumor metastasis assay was applied to evaluate the activities of the isolated compounds. Ten compounds (1-10) were isolated and their structures were identified by comparison of their spectral data with literature as follows: syringic acid (1), salidroside (2), tyrosol (3), scaphopetalone (4), berchemol (5), 2,6-dimethoxyacetophenone (6), rhobupcyanoside A (7), miyaginin (8), chavicol-4-O-β-D-apiofuranosyl-(1 --> 6)-O-β-D-glucopyranoside (9), eugenyol-O-β-D-apiofuranosyl-(1 --> 6)-O-β-D-glucopyranoside (10). Compounds 4-6 and 8-10, were isolated from this genus for the first time, while compound 7 was isolated from this plant for the first time. Compounds 2, 6-8 showed positive anti-tumor metastatic activities, and compounds 2 and 8 showed significant anti-tumor metastatic activities.
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Humans ; Neoplasm Metastasis ; prevention & control ; Rhodiola ; chemistry

Tyrosol, crenulatin and salidroside are the main active constituents of Rhodiola crenulata, with extensive pharmacological activities. In the study, grams of high purity tyrosol, crenulatin and salidroside were simultaneously separated from R. crenulata by the first time. Firstly, R. crenulata was extracted by 70% alcohol. Then, with the yields of three compounds as the index, the macroporous resin was optimized. At last, grams of high purity tyrosol, crenulatin and salidroside were isolated by D-101 macroporousresin, purified by column chromatography. Detected by HPLC, the purity of three compounds were higher than 98%. This method has the advantages of simple process and operation, less dosage of organic solvent, highly yield and reproducibility, suitable for the simultaneously preparation of tyrosol, crenulatin and salidroside.
Chemical Fractionation ; methods ; Chemistry, Pharmaceutical ; Chromatography, High Pressure Liquid ; Coumarins ; analysis ; isolation & purification ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; Glucosides ; analysis ; isolation & purification ; Phenols ; analysis ; isolation & purification ; Phenylethyl Alcohol ; analogs & derivatives ; analysis ; isolation & purification ; Rhodiola ; chemistry

The extracting technology of salidroside, tyrosol, crenulatin and gallic acid from Rhodiolae Crenulatae Radix et Rhizoma was optimized. With extraction rate of salidroside, tyrosol, crenulatin and gallic acid as indexes, orthogonal test was used to evaluate effect of 4 factors on extracting technology, including concentration of solvent, the dosage of solvent, duration of extraction, and frequency of extraction. The results showed that, the best extracting technology was to extract in 70% alcohol with 8 times the weight of herbal medicine for 2 times, with 3 hours once. High extraction rate of salidroside, tyrosol, crenulatin and gallic acid were obtained with the present technology. The extracting technology was stable and feasible with high extraction rate of four compounds from Rhodiolae Crenulatae Radix et Rhizoma, it was suitable for industrial production.
Chemical Fractionation ; methods ; Chemistry, Pharmaceutical ; methods ; Coumarins ; isolation & purification ; Drugs, Chinese Herbal ; isolation & purification ; Gallic Acid ; isolation & purification ; Glucosides ; isolation & purification ; Phenols ; isolation & purification ; Phenylethyl Alcohol ; analogs & derivatives ; isolation & purification ; Rhizome ; chemistry ; Rhodiola ; chemistry

OBJECTIVETo explore the effect of Rhodiola on the expression of iNOS mRNA in severe acute pancreatitis (SAP) associated renal injury rats.

METHODSA total of 72 healthy rats were randomly divided into the sham-operated group (S), the SAP associated renal injury group (M), and the Rhodiola-treated group (RHO), 24 in each group. Rats in S and M groups were peritoneally injected with 10 mL/kg saline 3h before modeling, while rats in the RHO group were peritoneally injected with 10 mL/kg Rhodiola Injection 3 h before modeling. The peripheral ligament of pancreas was bluntly dissociated in rats of M and RHO groups. The head of pancreas was occlused by nontraumatic blood vessel forceps 3 h later to establish the model. Eight rats were randomly selected from each group at 12, 24, and 36 h after modeling to detect levels of serum amylase, creatinine, and blood urea nitrogen. Serum levels of interleukin 1β (IL-1β) and interleukin 10 (IL-10) were detected by enzyme-linked immunosorbent assay (ELISA). Pathological changes of the left kidney were observed under light microscope. The expression of inducible nitric oxide synthase (iNOS) mRNA in the right kidney was detected with real time polymerase chain reaction (RT-PCR).

RESULTSCompared with the S group, serum levels of amylase, creatinine (Cr), blood urea nitrogen (BUN), IL-1β, IL-10, and iNOS mRNA expression significantly increased in the M group (P < 0.01). The function of kidney and pancreas were obviously improved in the RHO group than in the M group. Levels of IL-1β and iNOS significantly decreased, but IL-10 levels significantly increased in the RHO group with statistical difference (P < 0.05).

CONCLUSIONRhodiola had better protective effect on SAP associated renal injury, which might be achieved through inhibiting the expression of IL-1β, stimulating the expression of IL-10, down-regulating iNOS mRNA expression, reducing the generation of oxygen free radicals and NO damage to cells, and improving hypoxia tolerance capabilities of the kidney.

Amylases ; Animals ; Blood Urea Nitrogen ; Creatinine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Interleukin-1beta ; Kidney ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Pancreas ; Pancreatitis ; drug therapy ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Rhodiola

Nuclear magnetic resonance (1H-NMR) fingerprint of Rhodiola rosea medicinal materials was established, and used to distinguish the quality of raw materials from different sources. Pulse sequence for water peak inhibition was employed to acquire 1H-NMR spectra with the temperature at 298 K and spectrometer frequency of 400.13 MHz. Through subsection integral method, the obtained NMR data was subjected to similarity analysis and principal component analysis (PCA). 10 batches raw materials of Rhodiola rosea from different origins were successfully distinguished by PCA. The statistical results indicated that rhodiola glucoside, butyl alcohol, maleic acid and alanine were the main differential ingredients. This method provides an auxiliary method of Chinese quality approach to evaluate the quality of Rhodiola crenulata without using natural reference substances.
Magnetic Resonance Spectroscopy ; methods ; Principal Component Analysis ; Rhizome ; chemistry ; Rhodiola ; chemistry