Therapeutic Promises of Bioactive Rosavin: A Comprehensive Review with Mechanistic Insight.

Rosavin is an alkylbenzene diglycoside primarily found in Rhodiola rosea (L.), demonstrating various pharmacological properties in a number of preclinical test systems. This study focuses on evaluating the pharmacological effects of rosavin and the underlying molecular mechanisms based on different preclinical and non-clinical investigations. The findings revealed that rosavin has anti-microbial, antioxidant, and different protective effects, including neuroprotective effects against various neurodegenerative ailments such as mild cognitive disorders, neuropathic pain, depression, and stress, as well as gastroprotective, osteoprotective, pulmoprotective, and hepatoprotective activities. This protective effect of rosavin is due to its capability to diminish inflammation and oxidative stress. The compound also manifested anticancer properties against various cancer via exerting cytotoxicity, apoptotic cell death, arresting the different phases (G0/G1) of the cancerous cell cycle, inhibiting migration, and invading other organs. Rosavin also regulated MAPK/ERK signaling pathways to exert suppressing effect of cancer cell. However, because of its high-water solubility, which lowers its permeability, the phytochemical has low oral bioavailability. The compound's relevant drug likeness was evaluated by the in silico ADME, revealing appropriate drug likeness. We suggest more extensive investigation and clinical studies to determine safety, efficacy, and human dose to establish the compound as a reliable therapeutic agent.

High-level production of Rhodiola rosea characteristic component rosavin from D-glucose and L-arabinose in engineered Escherichia coli.

Rosavin is the characteristic component of Rhodiola rosea L., an important medicinal plant used widely in the world that has been reported to possess multiple biological activities. However, the endangered status of wild Rhodiola has limited the supply of rosavin. In this work, we successfully engineered an Escherichia coli strain to efficiently produce rosavin as an alternative production method. Firstly, cinnamate: CoA ligase from Hypericum calycinum, cinnamoyl-CoA reductase from Lolium perenne, and uridine diphosphate (UDP)-glycosyltransferase (UGT) from Bacillus subtilis (Bs-YjiC) were selected to improve the titer of rosin in E. coli. Subsequently, four UGTs from the UGT91R subfamily were identified to catalyze the formation of rosavin from rosin, with SlUGT91R1 from Solanum lycopersicum showing the highest activity level. Secondly, production of rosavin was achieved for the first time in E. coli by incorporating the SlUGT91R1 and UDP-arabinose pathway, including UDP-glucose dehydrogenase, UDP-xylose synthase, and UDP-xylose 4-epimerase, into the rosin-producing stain, and the titer reached 430.5 ± 91.4 mg/L. Thirdly, a two-step pathway derived from L-arabinose, composed of L-arabinokinase and UDP-sugar pyrophosphorylase, was developed in E. coli to further optimize the supply of the precursor UDP-arabinose. Furthermore, 1203.7 ± 32.1 mg/L of rosavin was produced from D-glucose and L-arabinose using shake-flask fermentation. Finally, the production of rosavin reached 7539.1 ± 228.7 mg/L by fed-batch fermentation in a 5-L bioreactor. Thus, the microbe-based production of rosavin shows great potential for commercialization. This work provides an effective strategy for the biosynthesis of other valuable natural products with arabinose-containing units from D-glucose and L-arabinose.

Rosavin Alleviates LPS-Induced Acute Lung Injure by Modulating the TLR-4/NF-κB/MAPK Singnaling Pathways.

Acute lung injury (ALI) is a serious inflammatory disease with high morbidity and mortality. Rosavin is an anti-inflammatory and antioxidant phenylpropanoid and glucoside, which is isolated from Rhodiola rosea L. However, its potential molecular mechanisms and whether it has protective effects against lipopolysaccharide (LPS)-induced ALI remain to be elucidated. To assess the in vitro anti-inflammatory effects and anti-lung injury activity of rosavin, RAW264.7 and A549 cells were stimulated using 1 µg/mL LPS. Rosavin attenuated LPS-induced activation of the TLR-4/NF-κB signaling pathway in RAW264.7 cells and inhibited LPS-induced release of inflammatory factors in A549 cells. A mouse model of acute lung injury was constructed by intraperitoneal injection of 5 mg/kg LPS to observe the therapeutic effect of rosavin. Transcriptomics analysis and Western blot assays were utilized to verify the molecular mechanism, rosavin (20, 40, and 80 mg/kg) dose-dependently ameliorated histopathological alterations, reduced the levels of inflammatory factors, and inhibited the TLR-4/NF-κB/MAPK signaling pathway and apoptosis activation. Rosavin is a promising therapeutic candidate for acute lung injury by inhibiting the TLR-4/NF-κB/MAPK pathway.

The Role of Rosavin in the Pathophysiology of Bone Metabolism.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

Rosavin extends lifespan via the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.

Rosavin, a phenylpropanoid glycoside, is the specific index component and one of the main active components of Rhodiola rosea. Currently, there are few studies describing the antiaging effect of rosavin, and most of them are mainly based on in vitro antioxidant research. Our study aimed to investigate the antiaging activities and mechanisms of rosavin in Caenorhabditis elegans. Using Caenorhabditis elegans as the model, the lifespan of Caenorhabditis elegans under various stressors (heat and juglone) and normal conditions was studied, and the antioxidant activities of rosavin were discussed. To discover the underlying mechanisms, we analyzed daf-16 nuclear localization, the expression of the sod-3p::GFP fusion protein, mRNA levels, and loss-of-function mutants of IIS-associated genes. The results showed that rosavin significantly improved the lifespan of Caenorhabditis elegans under stress and normal conditions. Rosavin can increase the expression and activity of antioxidant enzymes and suppress the generation of malondialdehyde and ROS in nematodes. Additionally, it promotes the nuclear localization of daf-16 and improves the expression of the sod-3 gene in Caenorhabditis elegans. The data revealed that rosavin activated the insulin/IGF-1 signaling pathway by downregulating the upstream components daf-2 and age-1. In summary, these results verify that rosavin could increase the lifespan of Caenorhabditis elegans through the insulin/IGF-1 signaling pathway.

Rhodiola rosea as an adaptogen to enhance exercise performance: a review of the literature.

Rhodiola rosea (RR) is a plant whose bioactive components may function as adaptogens, thereby increasing resistance to stress and improving overall resilience. Some of these effects may influence exercise performance and adaptations. Based on studies of rodents, potential mechanisms for the ergogenic effects of RR include modulation of energy substrate stores and use, reductions in fatigue and muscle damage and altered antioxidant activity. At least sixteen investigations in humans have explored the potential ergogenicity of RR. These studies indicate acute RR supplementation (∼200 mg RR containing ∼1 % salidroside and ∼3 % rosavin, provided 60 min before exercise) may prolong time-to-exhaustion and improve time trial performance in recreationally active males and females, with limited documented benefits of chronic supplementation. Recent trials providing higher doses (∼1500 to 2400 mg RR/d for 4­30 d) have demonstrated ergogenic effects during sprints on bicycle ergometers and resistance training in trained and untrained adults. The effects of RR on muscle damage, inflammation, energy system modulation, antioxidant activity and perceived exertion are presently equivocal. Collectively, it appears that adequately dosed RR enhances dimensions of exercise performance and related outcomes for select tasks. However, the current literature does not unanimously show that RR is ergogenic. Variability in supplementation dose and duration, concentration of bioactive compounds, participant characteristics, exercise tests and statistical considerations may help explain these disparate findings. Future research should build on the longstanding use of RR and contemporary clinical trials to establish the conditions in which supplementation facilitates exercise performance and adaptations.

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.

Rosavin regulates bone homeostasis through HDAC1-induced epigenetic regulation of EEF2.

Bioactive constituents from Rhodiola rosea L. show a myriad of pharmacological effects on diverse diseases. Rosavin has been linked to reduced osteoclastogenesis, while its role in regulating osteogenesis remains unclear. The present study investigated whether and how Rosavin alleviates ovariectomy (OVX)-induced osteoporosis (OP) in mice. Rosavin had a therapeutic effect on OP in ovariectomized mice and inhibited osteoclast viability and promoted osteoblast viability. Integrated transcriptome sequencing, GO enrichment analysis, and PPI network construction revealed that the HDAC1/EEF2 axis was an important axis of gene action for Rosavin treatment. Mechanistically, HDAC1 suppressed EEF2 expression through histone deacetylation. Rescue experiments exhibited that HDAC1 promoted osteoclast viability, while EEF2 reversed the action of HDAC1 to restore bone homeostasis. In mice with OP, HDAC1 mitigated the effects of Rosavin, resulting in enhanced bone resorption and diminished bone formation, while EEF2 contributed to reduced bone resorption and elevated bone formation in mice. NF-κB and MAPK pathways were inhibited by Rosavin, enhanced by HDAC1, and blocked again by EEF2. To summarize, our results proved that Rosavin maintained bone homeostasis in OP via regulation of histone acetylation of EEF2, thus playing a key role as a therapeutic candidate for OP treatment.

Rosavin inhibits neutrophil extracellular traps formation to ameliorate sepsis-induced lung injury by regulating the MAPK pathway.

BACKGROUND: Sepsis is a systemic organ dysfunction caused by infection, and the most affected organ is the lungs. Rosavin, a traditional Tibetan medicine, exerts an impressive anti--inflammatory effect. However, its effects on sepsis-related lung damage have not been investigated. PURPOSE: This study aimed to investigate the effects of Rosavin on cecal ligation and puncture (CLP)-induced lung injury. METHODS: The sepsis mouse model was established by CLP, and the mice were pretreated with Rosavin to explore whether it contributed to the alleviation of lung injury. Hematoxylin-eosin (H&E) stain and lung injury score were used to assess the severity of lung injury. The bronchoalveolar lavage fluid (BALF) inflammatory mediators (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], IL-1ß, and IL-17A) were detected by ELISA. The number of neutrophils in BALF was detected using flow cytometry. The immunofluorescence assay was used to detect histone and myeloperoxidase (MPO) in lung tissues. Then, the western blot was performed to detect the expression of mitogen-activated protein kinase (MAPK) pathways (extracellular regulated kinase [ERK], p-ERK, p38, p-p38, Jun N-terminal kinase 1/2 [JNK1/2], and p-JNK1/2) in lung tissues. RESULTS: We found that Rosavin significantly attenuated sepsis-induced lung injury. Specifically, Rosavin significantly inhibited inflammation response by decreasing the secretion of inflammatory mediators. The level of neutrophil extracellular traps (NETs) and MPO activity in CLP were decreased after administration with Rosavin. Moreover, the western blot showed that Rosavin could suppress NETs formation by inhibiting the MAPK/ERK/p38/JNK signaling pathway. CONCLUSION: These findings demonstrated that Rosavin inhibited NETs formation to attenuate sepsis-induced lung injury, and the inhibitory effect may be exerted via deregulation of the MAPK pathways.

Rosavin exerts an antitumor role and inactivates the MAPK/ERK pathway in small-cell lung carcinoma in vitro.

This study attempts to explore the function and mechanism of action of rosavin in small-cell lung cancer (SCLC) in vitro. The viability and clone formation of SCLC cells were assessed using cell counting kit-8 and colony formation assays, respectively. Apoptosis and cell cycle were detected using flow cytometry and cell cycle analysis, respectively. Wound healing and transwell assays were performed to evaluate the migration and invasion of SCLC cells. Besides, protein levels of p-ERK, ERK, p-MEK and MEK were determined using Western blot analysis. Rosavin repressed the viability and clone formation of SCLC cells, and promoted apoptosis and G0/G1 arrest of SCLC cells. At the same time, rosavin suppressed migration and invasion of SCLC cells. Moreover, protein levels of p-ERK/ERK and p-MEK/MEK were decreased after rosavin addition in SCLC cells. Rosavin impaired malignant behaviors of SCLC cells, which may be associated with inhibition of the MAPK/ERK pathway in vitro.

Rosavin protects the blood-brain barrier against ischemia/reperfusion-induced cerebral injury by regulating MAPK-mediated MMPs pathway.

Ischemia-reperfusion (I/R) injury is a common pathophysiological condition in ischemic stroke, involving various pathophysiological events, such as inflammation, cytotoxicity, neuronal loss and disruption of the blood-brain barrier (BBB). Rosavin is the major bioactive ingredient of Rhodiola Rosea L. with multiple therapeutic effects. The purpose of this was to investigate the role of rosavin in I/R-induced cerebral injury. A cell oxygen-glucose deprivation and reoxygenation (OGD/R) model and a mouse middle cerebral artery occlusion (MCAO) model were established to induce I/R injury in vitro and in vivo, respectively. MCAO-treated mice and OGD/R-challenged human brain microvascular endothelial cells (HBMVECs) were administrated with or without rosavin at various concentrations. Rosavin-treated mice showed reduced infarct volume, neuronal loss and neuronal cytotoxicity in I/R-injured brains. Rosavin treatment downregulated the expression of pro-inflammatory cytokines, reduced apoptosis and inhibited the activation of nuclear factor κ B in I/R-injured mice and HBMVECs. Administration with rosavin also alleviated mouse brain oedema and upregulated tight junction proteins in mouse brains after I/R injury, suggesting that rosavin protected mice against I/R-induced BBB disruption. Further analysis revealed that rosavin reduced the BBB permeability in I/R-injured mice and HBMVECs by inhibiting autophagy. Moreover, rosavin intervention inhibited I/R injury-induced activation of the mitogen-activated protein kinase (MAPK) pathway and upregulation of matrix metalloproteinases in both mouse and cell models. In conclusion, rosavin protects the BBB against I/R injury possibly by regulating the MAPK pathway. The above results provide a rationale for further exploration of rosavin as a therapeutic candidate for cerebral I/R injury.

Phytochemical profile, in vitro bioaccessibility, and anticancer potential of golden root (Rhodiola rosea L.) extracts.

The effects of water and ethanolic (40 %, 70 %, and 96 %) extraction on the Rhodiola rosea L. phytochemical profile (HPLC analysis), stability during extract drying, potential bioaccessibility in simulated gastric and intestinal conditions, and cytotoxic activity against human colorectal adenocarcinoma cells (Caco-2 and HT-29 cell lines) were investigated. The phytochemical profile, extractability, and stability during extract processing depend on the solvent type. In general, compounds derived from dry extracts were characterized by higher bioaccessibility than those extracted from powdered plant material. In the case of salidroside, tyrosol, and rosavins, one of the highest bioaccessibilities (often about 100 %) were found for the 70 % ethanolic extract after gastric digestion. Furthermore, the 70 % ethanolic extract most effectively reduced the viability of Caco-2 cells (IC50 85.8 µg∙mL-1). The results suggest that golden root extracts, in particular 70 % ethanolic extract, seem to be promising supplements for the food industry.

Rosavin inhibits neutrophil extracellular traps formation to ameliorate sepsis-induced lung injury by regulating the MAPK pathway

Background: Sepsis is a systemic organ dysfunction caused by infection, and the most affected organ is the lungs. Rosavin, a traditional Tibetan medicine, exerts an impressive anti--inflammatory effect. However, its effects on sepsis-related lung damage have not been investigated. Purpose: This study aimed to investigate the effects of Rosavin on cecal ligation and puncture (CLP)-induced lung injury. Methods: The sepsis mouse model was established by CLP, and the mice were pretreated with Rosavin to explore whether it contributed to the alleviation of lung injury. Hematoxylin-eosin (H&E) stain and lung injury score were used to assess the severity of lung injury. The bronchoalveolar lavage fluid (BALF) inflammatory mediators (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], IL-1β, and IL-17A) were detected by ELISA. The number of neutrophils in BALF was detected using flow cytometry. The immunofluorescence assay was used to detect histone and myeloperoxidase (MPO) in lung tissues. Then, the western blot was performed to detect the expression of mitogen-activated protein kinase (MAPK) pathways (extracellular regulated kinase [ERK], p-ERK, p38, p-p38, Jun N-terminal kinase 1/2 [JNK1/2], and p-JNK1/2) in lung tissues. Results: We found that Rosavin significantly attenuated sepsis-induced lung injury. Specifically, Rosavin significantly inhibited inflammation response by decreasing the secretion of inflammatory mediators. The level of neutrophil extracellular traps (NETs) and MPO activity in CLP were decreased after administration with Rosavin. Moreover, the western blot showed that Rosavin could suppress NETs formation by inhibiting the MAPK/ERK/p38/JNK signaling pathway. Conclusion: These findings demonstrated that Rosavin inhibited NETs formation to attenuate sepsis-induced lung injury, and the inhibitory effect may be exerted via deregulation of the MAPK pathways (AU)

Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. AIM: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (HSPD1/TNF/MMP14/ITGB1) mRNAs and their upstream noncoding RNA regulators (miRNA-6881-5P and lnc-SPARCL1-1:2) in NASH rats. RESULTS: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (HSPD1/TNF/MMP14/ITGB1) mRNAs and their epigenetic regulators (miRNA-6881-5P and lnc-SPARCL1-1:2). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. CONCLUSION: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (HSPD1, TNF, MMP14, and ITGB1) mRNAs-(miRNA-6881-5P-(lnc-SPARCL1-1:2) RNA panel.

Biosynthesis of a rosavin natural product in Escherichia coli by glycosyltransferase rational design and artificial pathway construction.

Phytochemicals are rich resources for pharmaceutical and nutraceutical agents. A key challenge of accessing these precious compounds can present significant bottlenecks for development. The cinnamyl alcohol disaccharides also known as rosavins are the major bioactive ingredients of the notable medicinal plant Rhodiola rosea L. Cinnamyl-(6'-O-ß-xylopyranosyl)-O-ß-glucopyranoside (rosavin E) is a natural rosavin analogue with the arabinopyranose unit being replaced by its diastereomer xylose, which was only isolated in minute quantity from R. rosea. Herein, we described the de novo production of rosavin E in Escherichia coli. The 1,6-glucosyltransferase CaUGT3 was engineered into a xylosyltransferase converting cinnamyl alcohol monoglucoside (rosin) into rosavin E by replacing the residue T145 with valine. The enzyme activity was further elevated 2.9 times by adding the mutation N375Q. The synthesis of rosavin E from glucose was achieved with a titer of 92.9 mg/L by combining the variant CaUGT3T145V/N375Q, the UDP-xylose synthase from Sinorhizobium meliloti 1021 (SmUXS) and enzymes for rosin biosynthesis into a phenylalanine overproducing E. coli strain. The production of rosavin E was further elevated by co-overexpressing UDP-xylose synthase from Arabidopsis thaliana (AtUXS3) and SmUXS, and the titer in a 5 L bioreactor with fed-batch fermentation reached 782.0 mg/L. This work represents an excellent example of producing a natural product with a disaccharide chain by glycosyltransferase engineering and artificial pathway construction.

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.

Morphological, Histochemical and Biochemical Features of Cultivated Rhodiola rosea (Altai Mountains Ecotype).

The study analyzed the content and localization of phenolic compounds, in particular phenylpropanoids, of Rodiola rosea plants of Altai Mountains ecotype during the introduction period of 2-4 years in the conditions of the forest-steppe zone of Western Siberia. The plant material for the introduction experiment was obtained by in vitro method. HPLC was used to identify 11 phenolic compounds, including gallic acid, rosarin, rosavin, rosin, cinnamyl alcohol, rhodiosin, rhodionin, and kaempferol. The highest content of phenylpropenoids was found in rhizomes of the 4-year-old R. rosea plants: 1.02% rosarin, 2.64% rosavin, 1.05% rosin, 3.39% cinnamyl alcohol. Analysis of the phenylpropanoid profile showed that the predominant component in all the studied samples was cinnamyl alcohol (up to 58%). Histochemical studies identified phenolic substances in the rhizomes and roots of R. rosea, which are localized in parenchymal and vascular tissues. It was revealed that the total rhizome biomass exceeded that of the root, and by the 4th year of introduction, it was approximately 2-fold greater in dry weight. The study showed high biosynthetic potential and biological productivity of the studied R. rosea ecotype upon introduction.

5-HT1A receptors mediate the analgesic effect of rosavin in a mouse model of oxaliplatin-induced peripheral neuropathic pain.

Oxaliplatin, a third-generation platinum derivative, is the mainstay of current antineoplastic medications for advanced colorectal cancer therapy. However, peripheral neuropathic complications, especially cold allodynia, undermine the lifeprolonging outcome of this anti-cancer agent. Rosavin, a phenylpropanoid derived originally from Rhodiola rosea, exhibits a wide range of therapeutic properties. The present study explored whether and how rosavin alleviates oxaliplatin-induced cold hypersensitivity in mice. In the acetone drop test, cold allodynia behavior was observed from days 3 to 5 after a single injection of oxaliplatin (6 mg/kg, i.p.). Cold allodynia was significantly attenuated following rosavin treatment (10 mg/kg, i.p.). Specific endogenous 5-HT depletion by three consecutive pretreatments with parachlorophenylalanine (150 mg/kg/day, i.p.) abolished the analgesic action of rosavin; this effect was not observed following pretreatment with naloxone (opioid receptor antagonist, 10 mg/kg, i.p.). Furthermore, 5-HT1A receptor antagonist WAY-100635 (0.16 mg/kg, i.p.), but not 5-HT3 receptor antagonist MDL-72222 (1 mg/kg, i.p.), blocked rosavin-induced analgesia. These results suggest that rosavin may provide a novel approach to alleviate oxaliplatin-induced cold allodynia by recruiting the activity of 5-HT1A receptors.

Rosavin suppresses osteoclastogenesis in vivo and in vitro by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways.

BACKGROUND: Bone homeostasis is mediated by osteoblast-related bone formation and osteoclast-related resorption. The imbalance of bone homeostasis due to excessive osteoclastogenesis or reduced osteogenesis can result in various disorders, such as postmenopausal osteoporosis (PMOP). The receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways are essential in osteoclastogenesis. In this study, we aimed to investigate the effects of rosavin, an alkylbenzene diglycoside compound from the traditional Chinese medicine Rhodiola Rosea L, on RANKL-induced osteoclastogenesis in vitro and in vivo. METHODS: The effects of rosavin on osteoclastogenesis were assessed by TRAP staining of bone marrow monocyte cells (BMMCs) and RAW 264.7 cells. The effects of rosavin on osteogenesis were determined using alkaline phosphatase (ALP) and alizarin red staining, as well as real-time quantitative reverse transcription polymerase chain reaction. Actin ring formation and bone formation experiments were performed to evaluate osteoclast function. Western blotting was carried out to determine the expression of osteoclastogenesis-related genes, and the activation of the NF-κB and MAPK pathways was evaluated by performing western blotting and immunofluorescence staining. Ovariectomized mice were used to explore the effect of rosavin on bone loss. RESULTS: Rosavin could inhibit osteoclastogenesis, suppress the function of osteoclasts, and decrease the expression of osteoclast differentiation-related genes, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, matrix metalloproteinase-9 (MMP-9), calcitonin receptor (CTR), TNF receptor-associated factor 6 (TRAF-6), receptor activator of nuclear factor-κB (RANK), and colony-stimulating factor-1 receptor (c-fms). Rosavin inhibited RANKL-induced phosphorylation of p65 and inhibitory subunit of NF-κB alpha (IκBα), and suppressed p65 nuclear translocation. Rosavin was also found to inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Furthermore, rosavin promoted osteogenesis in bone marrow mesenchymal stem cells (BMSCs). In vivo experiments showed that treatment with rosavin could alleviate ovariectomy-induced osteoporosis in mice. CONCLUSIONS: Our results indicated that rosavin suppressed RANKL-induced osteoclastogenesis in vivo and in vitro by blocking the NF-κB and MAPK pathways. Rosavin treatment is a potential therapy for the clinical treatment of osteoclastogenesis-related disorders.

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.