Elucidating the role of Rhodiola rosea L. in sepsis-induced acute lung injury via network pharmacology: emphasis on inflammatory response, oxidative stress, and the PI3K-AKT pathway.

CONTEXT: Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects. OBJECTIVE: This study elucidates the molecular mechanisms of RR against sepsis-induced ALI. MATERIALS AND METHODS: The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 µg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 µg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation. RESULTS: We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED50) = 18.98 µg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results. DISCUSSION AND CONCLUSION: This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.

Effects of the PREMEN-CALM® in the Management of the Premenstrual Syndrome: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Premenstrual syndrome is a common disorder in women of reproductive age characterized by a variety of cyclical symptoms with a great impact on their lifestyle. Available pharmacological options include both antidepressants and oral contraceptives, both of which have side effects, are expensive and not always effective. Vitamins, minerals and plant extracts have been proven to alleviate the symptomatology of the premenstrual syndrome. For this reason, the purpose of this study was to test the effectiveness of a commercial phytotherapeutic dietary supplement (PREMEN-CALM®: γ-aminobutyric acid, Rhodiola rosea L., Vitex agnus-castus, vitamin B6 and melatonin) as an alternative treatment for this condition. A randomized, double-blind, and placebo-controlled pilot study was performed. Participants (n = 42) were assessed before and after 3 months of taking the supplement (n = 21) or the placebo (n = 21). Outcome measures include antioxidant and inflammatory biomarkers, body composition, subjective sleep quality, mood state profile, quality of life, and certain characteristics of the menstrual cycle. The within-group analysis revealed a significant improvement in the total antioxidant status (1.49 ± 0.34 vs reference value 1, p = 0.002), mood state profile (p = 0.02), and affective symptoms (p = 0.01) in the women receiving the commercial phytotherapeutic dietary supplement PREMEN-CALM®. On the contrary, the between-group analysis showed no statistical differences, suggesting a plausible placebo effect. The phytotherapeutic supplement PREMEN-CALM® might be effective in treating or alleviating the symptoms of the premenstrual syndrome without adverse events. Integrative medicine approaches in the clinical practice may help improve the health of women suffering from this and other gynecological conditions.

Rhodiola rosea L. improved intestinal digestive enzyme activities, inflammatory response, barrier and microbiota dysbiosis in Lateolabrax maculatus juveniles fed with high-carbohydrate diets.

A 56-d feeding trial was conducted to evaluate the influences of Rhodiola rosea L. on digestive enzyme activities, intestinal barrier, inflammatory response, and microbiota dysbiosis in Lateolabrax maculatus juveniles (9.37 ± 0.03 g) fed with high-carbohydrate diets. Six diets were designed: a control diet (20% corn starch, Control), high-carbohydrate diet (30% corn starch, HC1), and four high-carbohydrate diets supplemented with Rhodiola rosea L. at 30, 60, 90 and 120 mg/kg (HC2, HC3, HC4 and HC5, respectively). Compared with the control group, the HC1 diet remarkably increased α-amylase, lipase, and chymotrypsin activities in the intestine (p < 0.05), as well as the mRNA levels of Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 (p < 0.05) and the relative abundance of Proteobacteria and Photobacterium in the intestine, which belong to the phylum and genus level, respectively. But the opposite trend was found in muscular thickness and villus lengths (p < 0.05), the mRNA levels of Occludin, ZO-1, and TGF-ß (p < 0.05), at the level of phylum and genus level in the HC1 group, and the relative abundance of Firmicutes, Bacteroidetes, and Bacillus in the intestine compared with the control group. Intestinal chymotrypsin activity was significantly higher in the HC3 group and intestinal muscular thickness and villus lengths were also significantly higher in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). In addition, Occludin mRNA expression in the intestine was significantly increased in the HC2, HC4, and HC5 groups compared to the HC1 group. ZO-1 and TGF-ß mRNA expression in the intestine were significantly increased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). At the phylum level, the relative abundance of Firmicutes and Bacteroidetes was higher in the intestine in the HC2, HC3, HC4, and HC5 groups than that in the HC1 group. On the contrary, intestinal lipase and chymotrypsin activities were significantly decreased in the HC2 group compared to the HC1 group, respectively (p < 0.05). The Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 mRNA expression in the intestine were significantly decreased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). Besides, at the genus level, compared to the HC1 group, the relative abundance of Photobacterium in the intestine and the diversity of the intestinal microbiota in the HC2, HC3, HC4, and HC5 groups were all decreased. In conclusion, these results demonstrated that the addition of Rhodiola rosea L. in high-carbohydrate diets can improve intestinal digestive enzyme activities, inflammatory response and intestinal barrier-related gene expression, and microbiota dysbiosis in L. maculatus. The suitable supplemental level of Rhodiola rosea L. in high-carbohydrate diets of L. maculatus is 60 mg/kg.

Rosavin: Research Advances in Extraction and Synthesis, Pharmacological Activities and Therapeutic Effects on Diseases of the Characteristic Active Ingredients of Rhodiola rosea L.

Rhodiola rosea L. (RRL) is a popular plant in traditional medicine, and Rosavin, a characteristic ingredient of RRL, is considered one of the most important active ingredients in it. In recent years, with deepening research on its pharmacological actions, the clinical application value and demand for Rosavin have been steadily increasing. Various routes for the extraction and all-chemical or biological synthesis of Rosavin have been gradually developed for the large-scale production and broad application of Rosavin. Pharmacological studies have demonstrated that Rosavin has a variety of biological activities, including antioxidant, lipid-lowering, analgesic, antiradiation, antitumor and immunomodulation effects. Rosavin showed significant therapeutic effects on a range of chronic diseases, including neurological, digestive, respiratory and bone-related disorders during in vitro and vivo experiments, demonstrating the great potential of Rosavin as a therapeutic drug for diseases. This paper gives a comprehensive and insightful overview of Rosavin, focusing on its extraction and synthesis, pharmacological activities, progress in disease-treatment research and formulation studies, providing a reference for the production and preparation, further clinical research and applications of Rosavin in the future.

Phenolic Compounds of Rhodiola rosea L. as the Potential Alternative Therapy in the Treatment of Chronic Diseases.

The roots and rhizomes of Rhodiola rosea L. (Crassulaceae), which is widely growing in Northern Europe, North America, and Siberia, have been used since ancient times to alleviate stress, fatigue, and mental and physical disorders. Phenolic compounds: phenylpropanoids rosavin, rosarin, and rosin, tyrosol glucoside salidroside, and tyrosol, are responsible for the biological action of R. rosea, exerting antioxidant, immunomodulatory, anti-aging, anti-fatigue activities. R. rosea extract formulations are used as alternative remedies to enhance mental and cognitive functions and protect the central nervous system and heart during stress. Recent studies indicate that R. rosea may be used to treat diabetes, cancer, and a variety of cardiovascular and neurological disorders such as Alzheimer's and Parkinson's diseases. This paper reviews the beneficial effects of the extract of R. rosea, its key active components, and their possible use in the treatment of chronic diseases. R. rosea represents an excellent natural remedy to address situations involving decreased performance, such as fatigue and a sense of weakness, particularly in the context of chronic diseases. Given the significance of mitochondria in cellular energy metabolism and their vulnerability to reactive oxygen species, future research should prioritize investigating the potential effects of R. rosea main bioactive phenolic compounds on mitochondria, thus targeting cellular energy supply and countering oxidative stress-related effects.

Application of Natural Deep Eutectic Solvents for Extraction of Bioactive Components from Rhodiola rosea (L.).

Rhodiola rosea (L.) is a valuable source of nutrients. Nutrients have adaptogenic, immunostimulating, nootropic, anti-inflammatory and anti-cancer properties. Natural deep eutectic solvents (NADES) consisting of choline chloride and malonic, malic, tartaric or citric acids have been first used to extract biologically active substances from R. rosea. The total content of polyphenols has been determined by the Folin-Ciocalteu method for all extracts. Antioxidant activity has been determined by the phosphomolybdate method, and antiradical activity has been determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Rosavin concentration has been determined by high-performance liquid chromatography (HPLC). Extraction kinetics has been evaluated regarding the effectiveness of NADES with each other and with reference solvents (water and 50% ethanol) has been made. Extraction conditions have been optimized according to the Box-Behnken design of the experiment. The optimal parameters of the extraction process have been established. The antibacterial activity of NADES-based extracts against bacterial cultures of Micrococcus luteus, Pseudomonas fluorescens, and Bacillus subtilis has been studied.

Total glycosides of Rhodiola rosea L. attenuate LPS-induced acute lung injury by inhibiting TLR4/NF-κB pathway.

Acute lung injury (ALI) is a common respiratory disease in clinics, which is characterized by alveolar-capillary membrane loss, plasma protein leakage, pulmonary edema, massive neutrophil infiltration, and the release of proinflammatory cytokines and mediators. Rhodiola rosea L. an adaptogenic plant rich in phenylethanoloids, phenylpropanoids, monoterpenes, has anti-inflammatory and antioxidant effects. We hope to verify the relieving effect of total glycosides of Rhodiola rosea L. (RTG) on ALI in mice and clarify its mechanism through this study. In this study, we identified the effect and mechanism of RTG on ALI through LPS-induced ALI mice. After RTG treatment, the pathological structure of lung tissue in ALI mice induced by LPS was significantly improved, and the infiltration of inflammatory cells was reduced. In addition, RTG reduced the production of IL-6, IL-1ß, and TNF-α in the serum of ALI mice and reduced the content or activity of MPO, T-SOD, GSH, and MDA in lung tissue. RNAseq analysis showed that RTG ameliorated LPS-induced ALI through anti-inflammatory, reduced immune response, and anti-apoptotic activities. The western blotting analysis confirmed that RTG could down-regulate the expression levels of TLR4, MyD88, NF-κB p65, and p-IκBα/IκBα. These results suggest that RTG can attenuate LPS-induced ALI through antioxidants and inhibition of the TLR4/NF-κB pathway.

Rhodiola rosea polysaccharides promote the proliferation of bone marrow haematopoietic progenitor cells and stromal cells in mice with aplastic anaemia.

CONTEXT: The effects of Rhodiola rosea L. (Crassulaceae) polysaccharides (RRPs) on haematopoiesis are poorly understood. OBJECTIVE: To determine the effects of RRPs on haematopoiesis in mice with aplastic anaemia. MATERIALS AND METHODS: Aplastic anaemia was induced in Kunming mice by 60Coγ (2.0 Gy) irradiation and cyclophosphamide administration (50 mg/kg/day for 3 consecutive days; intraperitoneal injection). The in vivo effects of RRPs (10, 20, and 40 mg/kg; intraperitoneal injection) on haematopoiesis were analyzed using peripheral blood tests, histopathological examination of haematopoietic tissues, culture of haematopoietic progenitors and bone marrow stromal cells (BMSCs), and Western blotting of Fas and Fas ligand (FasL). The in vitro effects of RRPs on bone-marrow haematopoietic progenitors and BMSCs were also evaluated. RESULTS: Compared to anaemic controls, high-dose RRPs (40 mg/kg) significantly increased red blood cells (8.21 ± 0.57835 versus 6.13 ± 1.34623 × 1012/L), white blood cells (5.11 ± 1.6141 versus l.54 ± 1.1539 × 109/L), and BMSCs (10.33 ± 1.5542 versus 5.87 ± 3.1567 × 1012/L) in mice with aplastic anaemia (all p < 0.01). High-dose RRPs significantly increased the formation of colony-forming unit-granulocyte macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E; p < 0.01). Fas and FasL protein expression in BMSCs decreased after RRPs administration. Especially at the high dose, RRPs (150 µg/mL) significantly promoted in vitro CFUs-E, BFUs-E, and CFUs-GM formation. RRPs (150-300 µg/mL) also promoted BMSC proliferation. DISCUSSION AND CONCLUSIONS: RRPs helped to promote haematopoietic recovery in mice with aplastic anaemia, facilitating haematopoietic tissue recovery. This study indicated some mechanisms of the haematopoietic regulatory effects of RRPs. Our findings provide a laboratory basis for clinical research on RRPs.

Preclinical Evidence and Possible Mechanisms of Rhodiola rosea L. and Its Components for Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background: Rhodiola rosea L. has long been used as traditional medicines in Europe and Asia to treat a variety of common conditions and diseases including Alzheimer's disease, cardiovascular disease, cognitive dysfunctions, cancer, and stroke. Previous studies reported that Rhodiola rosea L. and its components (RRC) improve ischemia stroke in animal models. Here, we conducted a systematic review and meta-analysis for preclinical studies to evaluate the effects of RRC and the probable neuroprotective mechanisms in ischemic stroke. Methods: Studies of RRC on ischemic stroke animal models were searched in seven databases from inception to Oct 2021. The primary measured outcomes included the neural functional deficit score (NFS), infarct volume (IV), brain water content, cell viability, apoptotic cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, B-cell lymphoma-2 (Bcl-2) level and tumor necrosis factor-α (TNF-α) level. The secondary outcome measures were possible mechanisms of RRC for ischemic stroke. All the data were analyzed via RevMan version 5.3. Results: 15 studies involving 345 animals were identified. Methodological quality for each included studies was accessed according to the CAMARADES 10-item checklist. The quality score of studies range from 1 to 7, and the median was 5.53. Pooled preclinical data showed that compared with the controls, RRC could improve NFS (Zea Longa (p < 0.01), modified neurological severity score (mNSS) (p < 0.01), rotarod tests (p < 0.01), IV (p < 0.01), as well as brain edema (p < 0.01). It also can increase cell viability (p < 0.01), Bcl-2 level (p < 0.01) and reduce TNF-α level (p < 0.01), TUNEL-positive cells (p < 0.01), apoptotic cells (p < 0.01). Conclusion: The findings suggested that RRC can improve ischemia stroke. The possible mechanisms of RRC are largely through antioxidant, anti-apoptosis activities, anti-inflammatory, repressing lipid peroxidation, antigliosis, and alleviating the pathological blood brain barrier damage.

Effect-directed analysis as a method for quality and authenticity estimation of Rhodiola rosea L. preparations.

Adulterations of food and pharmaceutical preparations are the important global problem. On the one hand, fraud practices are becoming more and more sophisticated while on the other, monitoring and uncovering falsifications are insufficient. One of the most common consumer concern is the quality and authenticity of the purchased products, related to the confidence that they have composition and properties in accordance with the manufacturer's declaration on the label. This refers also to pharmaceuticals potentially delivering great health benefits such as Rhodiola rosea L. supplements. The aim of this study was defining authenticity and possible adulterations of two R. rosea preparations basing on their TLC-bioprofiles and the presence of biomarker compounds characteristic for this plant. The effect-directed analysis (EDA), i.e. TLC hyphenated with micro-chemical and biological assays performed directly on TLC plates followed by HPLC-ESI-MS was used for the bioprofiling of antioxidants, antibacterials, and inhibitors of lipase, acetylcholine, α-glucosidase and tyrosinase as well as for the identification of the biomarkers. The results pointed to the possible adulteration of one of the tested products related to the absence of two rosavins, the most important quality markers of R. rosea.

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.

Systems pharmacology unravels the synergic target space and therapeutic potential of Rhodiola rosea L. for non-small cell lung cancer.

BACKGROUND: Lung cancer is the most common and mortal cancer worldwide. Rhodiola rosea L. (RR), a well-known traditional Chinese medicine (TCM), has been turned out to be effective in anti-lung cancer therapy, but its molecular mechanism of action has not been clearly understood. PURPOSE: In this study, we aimed to elucidate the possible molecular mechanism underlying the effect of RR against non-small cell lung cancer (NSCLC) by systems pharmacology. METHODS: The effects of RR on NSCLC were examined in Lewis lung carcinoma (LLC) tumor-bearing mice models. The possible molecular mechanism was unraveled by systems pharmacology, which includes pharmacokinetics evaluation, active compounds screening, target prediction and network analysis. Cell proliferation was examined by cell counting kit-8 (CCK-8) assay; cell apoptosis was detected by flow cytometry; protein and proinflammatory cytokines expression were evaluated by Western blot and qRT-PCR. RESULTS: In vivo, RR significantly inhibited the tumor growth and prolonged the survival of the tumor bearing mice. In silico, we identified 19 potential active molecules (e.g., salidroside and rhodiosin), 112 targets (e.g., COX-2 and AKT) and 27 pathways (e.g., PI3K/AKT signaling pathway and NF-κB signaling pathway) for RR. Additionally, targets analysis and networks construction further revealed that RR exerted anti-cancer effects by regulating apoptosis, angiogenesis and inflammation. In vitro, salidroside could significantly decrease expression of pro-angiogenic factors (e.g., VEGF and eNOS) and proinflammatory cytokines (e.g., COX-2, iNOS and TNF-α). Also, Bcl-2, an anti-apoptotic protein was decreased whereas Bax, a pro-apoptotic protein, was increased. Further flow cytometry analysis showed that salidroside could induce apoptosis in H1975 cells. CONCLUSIONS: Mechanistically, the antitumor effect of RR on NSCLC was responsible for the synergy among anti-inflammatory, anti-angiogenic and pro-apoptotic.

Rhodiola rosea L. modulates inflammatory processes in a CRH-activated BV2 cell model.

BACKGROUND: Rhodiola rosea L. (Crassulaceae) has been used for years in the traditional medicine of several countries as an adaptogen drug, able to preserve homeostasis in response to stress stimuli. Currently R. rosea roots and rhizome are classified as a traditional herbal medicinal product for temporary relief of symptoms of stress, such as fatigue and sensation of weakness by the European Medicines Agency. HYPOTHESIS/PURPOSE: Increasing evidences suggest the involvement of neuroinflammation in response to stress. However, whether the modulation of neuroinflammatory parameters could be involved in the anti-stress effect of R. rosea has been barely studied. Thus, the aim of this work is to investigate the possible modulation of molecular inflammatory processes elicited by a R. rosea roots and rhizome ethanolic extract in an in vitro model of corticotropin releasing hormone (CRH)-stimulated BV2 microglial cells. METHODS: BV2 cells were stimulated with CRH 100 nM and changes in cell viability, cytokines production and heat shock protein 70 (HSP70) levels were evaluated. Intracellular pathways related to inflammation, such as nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) nuclear translocation and mitogen-activated protein kinases (MAPK) activation were also analyzed. RESULTS: We found that R. rosea extract (2.7% m/m rosavin and 1% m/m salidroside) 20 µg/ml was able to counteract the neuroinflammatory effect of CRH by inhibiting NF-κB nuclear translocation with a mechanism of action involving the modulation of mitogen-activated protein kinase-activated protein kinase 2 (MKK2), extracellular signal-regulated kinase 1/2 (ERK 1/2) and c-Jun n-terminal kinase (JNK), resulting in a reduction of HSP70 expression. CONCLUSION: This work expands the knowledge of the intracellular mechanisms involved in R. rosea anti-stress activity and may be useful for the study of other adaptogen drugs.

Anti-inflammatory effects of Rhodiola rosea L.: A review.

Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.

Rhodiola rosea root extract has antipsychotic-like effects in rodent models of sensorimotor gating.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant arctic root (Rhodiola rosea, L.) is growing in northern regions of Europe, Asia and North America. Extracts of R. rosea are used in traditional medicine for various conditions related to nervous system function. According to scientific studies from the last decades, the plant might have potential for use in the treatment of memory impairments, stress and depression, but reports concerning other neuropsychiatric disorders are scarce. AIM OF THE STUDY: In this context, our study aimed to examine potential antipsychotic-like effects of R. rosea root extract. MATERIALS AND METHODS: We tested the effects of R. rosea root extract on prepulse inhibition in rats and mice. Prepulse inhibition is an established operational measure of sensorimotor gating, which is impaired in schizophrenia and other psychotic disorders. RESULTS: R. rosea root extract increased prepulse inhibition in rats and mice. Interestingly, the R. rosea extract had stronger effects in those individual animals that had low baseline levels of prepulse inhibition. Therefore, we performed further experiments in which we pharmacologically induced a prepulse inhibition deficit by two different psychostimulants, either the dopamine D2 receptor agonist apomorphine or the NMDA receptor antagonist dizocilpine (MK-801). Pre-treatment with the R. rosea extract significantly restored both, apomorphine- and dizocilpine-induced prepulse inhibition deficits. CONCLUSIONS: The present study demonstrates that R. rosea extract robustly reverses prepulse inhibition deficits in rodents. This suggests antipsychotic-like effects of R. rosea extract. Future studies should focus on the pharmacological mechanisms underlying these effects.

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.

Rhodiola rosea L. Improves Learning and Memory Function: Preclinical Evidence and Possible Mechanisms.

Rhodiola rosea L. (R. rosea L.) is widely used to stimulate the nervous system, extenuate anxiety, enhance work performance, relieve fatigue, and prevent high altitude sickness. Previous studies reported that R. rosea L. improves learning and memory function in animal models. Here, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for R. rosea L. effect on learning and memory function. Ultimately, 36 studies involving 836 animals were identified by searching 6 databases from inception to May 2018. The primary outcome measures included the escape latency in Morris water maze (MWM) test on behalf of learning ability, the frequency and the length of time spent on the target quadrant in MWM test representing memory function, and the number of errors in step down test, dark avoidance test and Y maze test on behalf of memory function. The secondary outcome measures were mechanisms of R. rosea L. for learning and/or memory function. Compared with control, the pooled results of 28 studies showed significant effects of R. rosea L. for reducing the escape latency (P < 0.05); 23 studies for increasing the frequency and the length of time spent on the target quadrant (P < 0.05); and 6 studies for decreasing the number of errors (P < 0.01). The possible mechanisms of R. rosea L. are largely through antioxidant, cholinergic regulation, anti-apoptosis activities, anti-inflammatory, improving coronary blood flow, and cerebral metabolism. In conclusion, the findings suggested that R. rosea L. can improve learning and memory function.

Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats.

Rhodiola rosea L. (RRL) possesses a wide range of pharmacological properties, including lung-protective activity, and has been utilized in folk medicine for several 100 years. However, the lung-protective mechanism remains unclear. This study investigated the possible lung-protective activity mechanism of RRL in a pulmonary fibrosis (PF) rat model. Lung fibrotic injury was induced in Sprague-Dawley rats by single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg). The rats were administered 125, 250, or 500 mg/kg of a 95% ethanol extract of RRL for 28 days. The animals were killed to detect changes in body weight, serum levels of glutathione (GSH) and total superoxide dismutase (T-SOD), as well as lung tissue hydroxyproline (HYP) content. Tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme-linked immunosorbent assay. Hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining were performed to observe the histopathological changes in lung tissues. Additionally, target-related proteins were measured by Western blotting. RRL alleviated the loss of body weight induced by instilling BLM in PF rats, particularly at the 500 mg/kg per day dose. RRL reduced HYP (p < 0.01) and increased GSH and T-SOD contents. BALF levels of TNF-α, TGF-ß1, and IL-6 decreased significantly in the RRL-treated groups. Expression levels of matrix metalloproteinase-9 (MMP-9) and α-smooth muscle actin decreased significantly in a dose-dependent manner in response to RRL. Moreover, the levels of TGF-ß1 and tissue inhibitor of metalloproteinase-1 in lung tissues also decreased in the RRL-treated groups. RRL alleviated BLM-induced PF in rats. Our results reveal that the protective effects of RRL against fibrotic lung injury in rats are correlated with its anti-inflammatory, antioxidative, and anti-fibrotic properties. MMP-9 may play important roles in BLM-induced PF.

Rhodiola rosea L. as a putative botanical antidepressant.

BACKGROUND: Rhodiola rosea (R. rosea) is a botanical adaptogen with putative anti-stress and antidepressant properties. Evidence-based data supporting the effectiveness of R. rosea for depression in adults is limited, and therefore a comprehensive review of available animal and human studies suggesting a putative antidepressant action is warranted. PURPOSE: A review of the literature was undertaken to ascertain studies of possible antidepressant mechanisms of action and studies of the safety and effectiveness of R. rosea extracts in animals and adult humans. METHODS: A search of MEDLINE and the Russian state library database was conducted (up to October 2015) on R. rosea. MECHANISM OF ACTION: R. rosea extracts and its purified constituent, salidroside, has been shown to produce a variety of mediator interactions with several molecular networks of neuroendocrine-immune and neurotransmitter receptor systems likely to be involved in the pathophysiology of depression. A wide variety of preclinical in vivo and ex vivo studies with laboratory animals suggests the presence of several biochemical and pharmacological antidepressant-like actions. EFFECTIVENESS: Clinical assessment of R. rosea L. rhizome extracts in humans with various depressive syndromes is based upon results from two randomized, double-blind, placebo-controlled trials of 146 subjects with major depressive disorder and seven open-label studies totaling 714 individuals with stress-induced mild depression (diagnosed as asthenic syndrome or psychoneurosis). Overall, results of these studies suggests a possible antidepressant action for R. rosea extract in adult humans. SAFETY: In contrast to most conventional antidepressants, R. rosea extract appears to be well-tolerated in short-term studies with a favorable safety profile. CONCLUSIONS: R. rosea demonstrates multi-target effects on various levels of the regulation of cell response to stress, affecting various components of the neuroendocrine, neurotransmitter receptor and molecular networks associated with possible beneficial effects on mood.

The Effects of Rhodiola rosea L. Extract on Anxiety, Stress, Cognition and Other Mood Symptoms.

This trial evaluated the impact of a Rhodiola rosea L. extract on self-reported anxiety, stress, cognition, and other mood symptoms. Eighty mildly anxious participants were randomized into two different groups of either Rhodiola rosea L (2 × 200 mg dose Vitano®, 1 tablet taken before breakfast and 1tablet before lunch) or a control condition (no treatment). Self-report measures and cognitive tests were completed at four testing sessions over a period of 14 days. Relative to the controls, the experimental group demonstrated a significant reduction in self-reported, anxiety, stress, anger, confusion and depression at 14 days and a significant improvements in total mood. No relevant differences in cognitive performance between the groups were observed. Rhodiola rosea L (Vitano®) presented a favourable safety tolerability profile. Although this was a non-placebo controlled trial, it is unlikely that the findings were the result of placebo effects as changes appeared gradual and were specific to certain psychological measures. However, we cannot determine a causal relationship; further investigations are recommended to support the effects of Rhodiola rosea L. extract on stress related symptoms.