Rhodiola crenulata alleviates hypobaric hypoxia-induced brain injury by maintaining BBB integrity and balancing energy metabolism dysfunction.

BACKGROUND/PURPOSE: Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba (R. crenulate), a famous and characteristic Tibetan medicine, has been demonstrated to exert an outstanding brain protection role in the treatment of high-altitude hypoxia disease. However, the metabolic effects of R. crenulate on high-altitude hypoxic brain injury (HHBI) are still incompletely understood. Herein, the anti-hypoxic effect and associated mechanisms of R. crenulate were explored through both in vivo and in vitro experiments. STUDY DESIGN/METHODS: The mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE, 0.5, 1.0 and 2.0 g/kg) and salidroside (Sal, 25, 50 and 100 mg/kg) was given by gavage for 7 days. Pathological changes and neuronal apoptosis of mice hippocampus and cortex were evaluated using H&E and TUNEL staining, respectively. The effects of RCE and Sal on the permeability of blood brain barrier (BBB) were detected by Evans blue staining and NIR-II fluorescence imaging. Meanwhile, the ultrastructural BBB and cerebrovascular damages were observed using a transmission electron microscope (TEM). The levels of tight junction proteins Claudin-1, ZO-1 and occludin were detected by immunofluorescence. Additionally, the metabolites in mice serum and brain were determined using UHPLC-MS and MALDI-MSI analysis. The cell viability of Sal on hypoxic HT22 cells induced by CoCl2 was investigated by cell counting kit-8. The contents of LDH, MDA, SOD, GSH-PX and SDH were detected by using commercial biochemical kits. Meanwhile, intracellular ROS, Ca2+ and mitochondrial membrane potential were determined by corresponding specific labeled probes. The intracellular metabolites of HT22 cells were performed by the targeted metabolomics analysis of the Q300 kit. The cell apoptosis and necrosis were examined by YO-PRO-1/PI, Annexin V/PI and TUNEL staining. In addition, mitochondrial morphology was tested by Mito-tracker red with confocal microscopy and TEM. Real-time ATP production, oxygen consumption rate, and proton efflux rate were measured using a Seahorse analyzer. Subsequently, MCU, OPA1, p-Drp1ser616, p-AMPKα, p-AMPKß and Sirt1 were determined by immunofluorescent and western blot analyses. RESULTS: The results demonstrated that R. crenulate and Sal exert anti-hypoxic brain protection from inhibiting neuronal apoptosis, maintaining BBB integrity, increasing tight junction protein Claudin-1, ZO-1 and occludin and improving mitochondrial morphology and function. Mechanistically, R. crenulate and Sal alleviated HHBI by enhancing the tricarboxylic acid cycle to meet the demand of energy of brain. Additionally, experiments in vitro confirmed that Sal could ameliorate the apoptosis of HT22 cells, improve mitochondrial morphology and energy metabolism by enhancing mitochondrial respiration and glycolysis. Meanwhile, Sal-mediated MCU inhibited the activation of Drp1 and enhanced the expression of OPA1 to maintain mitochondrial homeostasis, as well as activation of AMPK and Sirt1 to enhance ATP production. CONCLUSION: Collectively, the findings suggested that RCE and Sal may afford a protective intervention in HHBI through maintaining BBB integrity and improving energy metabolism via balancing MCU-mediated mitochondrial homeostasis by activating the AMPK/Sirt1 signaling pathway.

Salidroside directly activates HSC70, revealing a new role for HSC70 in BDNF signalling and neurogenesis after cerebral ischemia.

Salidroside, a principal bioactive component of Rhodiola crenulata, is neuroprotective across a wide time window in stroke models. We investigated whether salidroside induced neurogenesis after cerebral ischemia and aimed to identify its primary molecular targets. Rats, subjected to transient 2 h of middle cerebral artery occlusion (MCAO), received intraperitoneal vehicle or salidroside ± intracerebroventricular HSC70 inhibitor VER155008 or TrkB inhibitor ANA-12 for up to 7 days. MRI, behavioural tests, immunofluorescent staining and western blotting measured effects of salidroside. Reverse virtual docking and enzymatic assays assessed interaction of salidroside with purified recombinant HSC70. Salidroside dose-dependently decreased cerebral infarct volumes and neurological deficits, with maximal effects by 50 mg/kg/day. This dose also improved performance in beam balance and Morris water maze tests. Salidroside significantly increased BrdU+/nestin+, BrdU+/DCX+, BrdU+/NeuN+, BrdU-/NeuN+ and BDNF+ cells in the peri-infarct cortex, with less effect in striatum and no significant effect in the subventricular zone. Salidroside was predicted to bind with HSC70. Salidroside dose-dependently increased HSC70 ATPase and HSC70-dependent luciferase activities, but it did not activate HSP70. HSC70 immunoreactivity concentrated in the peri-infarct cortex and was unchanged by salidroside. However, VER155008 prevented salidroside-dependent increases of neurogenesis, BrdU-/NeuN+ cells and BDNF+ cells in peri-infarct cortex. Salidroside also increased BDNF protein and p-TrkB/TrkB ratio in ischemic brain, changes prevented by VER155008 and ANA-12, respectively. Additionally, ANA-12 blocked salidroside-dependent neurogenesis and increased BrdU-/NeuN+ cells in the peri-infarct cortex. Salidroside directly activates HSC70, thereby stimulating neurogenesis and neuroprotection via BDNF/TrkB signalling after MCAO. Salidroside and similar activators of HSC70 might provide clinical therapies for ischemic stroke.

Anti-Neuroinflammatory Effects of Adaptogens: A Mini-Review.

Introduction: Adaptogens are a group of plants that exhibit complex, nonspecific effects on the human body, increasing its ability to adapt, develop resilience, and survive in stress conditions. They are found in many traditional medicinal systems and play a key role in restoring the body's strength and stamina. Research in recent years has attempted to elucidate the mechanisms behind their pharmacological effects, but it appears that these effects are difficult to define precisely and involve multiple molecular pathways. Neuroinflammation: In recent years, chronic inflammation has been recognized as one of the common features of many central nervous system disorders (dementia and other neurodegenerative diseases, depression, anxiety, ischemic stroke, and infections). Because of the specific nature of the brain, this process is called neuroinflammation, and its suppression can result in an improvement of patients' condition and may promote their recovery. Adaptogens as anti-inflammatory agents: As has been discovered, adaptogens display anti-inflammatory effects, which suggests that their application may be broader than previously thought. They regulate gene expression of anti- and proinflammatory cytokines (prostaglandins, leukotriens) and can modulate signaling pathways (e.g., NF-κB). Aim: This mini-review aims to present the anti-neuroinflammatory potential of the most important plants classified as adaptogens: Schisandra chinensis, Eleutherococcus senticosus, Rhodiola rosea and Withania somnifera.

Multi-target drugs for the treatment of cognitive impairment and fatigue in post-COVID syndrome: focus on Ginkgo biloba and Rhodiola rosea.

Cognitive impairment, depression and (mental) fatigue represent the most frequent neuropsychiatric symptoms of the post-COVID syndrome. Neuroinflammation, oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological mechanisms underlying these symptoms. Attempts to treat post-COVID-associated cognitive impairment and fatigue with different drugs available for other diseases have not yet been successful. One probable explanation could be that these drugs work by one specific mechanism of action only and not in a broad multi-target way. Therefore, they will not address the broad pathophysiological spectrum possibly responsible for cognitive impairment, depression and fatigue in post-COVID syndrome. Notably, nearly all drugs currently under investigation for fatigue in post-COVID syndrome are rather addressing one single target instead of the several pathomechanisms underlying this condition. Contrary to this approach, herbal drugs often consist of many different ingredients with different pharmacological properties and pharmacological targets. Therefore, these drugs might be a promising approach for the treatment of the broad symptomatic presentation and the pathophysiological mechanisms of cognitive impairment and fatigue following a SARS-CoV-2 infection. Of these herbal drugs, extracts of Ginkgo biloba and Rhodiola rosea probably are the best investigated candidates. Their broad pharmacological spectrum in vitro and in vivo includes anti-oxidative, anti-inflammatory, antidepressant as well as properties reducing cognitive impairment and fatigue. In several studies, both drugs showed positive effects on physical and mental fatigue and impaired cognition. Moreover, depressive symptoms were also reduced in some studies. However, even if these results are promising, the data are still preliminary and require additional proof by further studies.

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.

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.

Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study.

Introduction: This randomized, controlled, single-blinded trial assessed the effect of magnesium (Mg)-Teadiola (Mg, vitamins B6, B9, B12, Rhodiola, and green tea/L-theanine) versus placebo on the brain response to stressful thermal stimulus in chronically stressed, but otherwise healthy subjects. Impacts on stress-related quality-of-life parameters (depression, anxiety, sleep, and perception of pain) were also explored. Methods: The study recruited a total of 40 adults (20 per group), suffering from stress for more than 1 month and scaling ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire at the time of inclusion. Individuals received oral Mg-Teadiola or placebo for 28 days (D). fMRI analysis was used to visualize the interplay between stress and pain cerebral matrices, using thermal stress model, at baseline (D0) and after D28. Results: Based on blood-oxygen-level-dependent (BOLD) signal variations during the stress stimulation (before pain perception), a significantly increased activation between D0 and D28 was observed for left and right frontal area (p = 0.001 and p = 0.002, respectively), left and right anterior cingulate cortex (ACC) (p = 0.035 and p = 0.04, respectively), and left and right insula (p = 0.034 and p = 0.0402, respectively) in Mg-Teadiola versus placebo group. During thermal pain stimulation, a significantly diminished activation of the pain matrix was observed between D0 and D28, for left and right prefrontal area (both p = 0.001), left and right insula (p = 0.008 and p = 0.019, respectively), and left and right ventral striatum (both p = 0.001) was observed in Mg-Teadiola versus placebo group. These results reinforce the clinical observations, showing a perceived benefit of Mg-Teadiola on several parameters. After 1 month of treatment, DASS-42 stress score significantly decreased in Mg-Teadiola group [effect size (ES) -0.46 (-0.91; -0.01), p = 0.048]. Similar reductions were observed on D14 (p = 0.011) and D56 (p = 0.008). Sensitivity to cold also improved from D0 to D28 for Mg-Teadiola versus placebo [ES 0.47 (0.02; 0.92) p = 0.042]. Conclusion: Supplementation with Mg-Teadiola reduced stress on D28 in chronically stressed but otherwise healthy individuals and modulated the stress and pain cerebral matrices during stressful thermal stimulus.

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.

Effect of different plant growth regulators on callus and adventitious shoots induction, polysaccharides accumulation and antioxidant activity of Rhodiola dumulosa.

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.

Rhodiola rosea and salidroside commonly induce hormesis, with particular focus on longevity and neuroprotection.

The biological effects of Rhodiola rosea extracts and one of its major constituents, salidroside, were evaluated for their capacity to induce hormesis/hormetic effects. The findings indicate that the Rhodiola rosea extracts and salidroside commonly induce hormetic dose responses within a broad range of biological models, cell types and across a broad range of endpoints, with particular emphasis on longevity and neuroprotective endpoints. This paper represents the first integrative documentation and assessment of Rhodiola rosea extracts and salidroside induction of hormetic effects. These findings have important biomedical applications and should have an important impact with respect to critical study design, dose selection and other experimental features.

Integrating UPLC-Q-Exactive Orbitrap/MS, network pharmacology and experimental validation to reveal the potential mechanism of Tibetan medicine Rhodiola granules in improving myocardial ischemia-reperfusion injury.

ETHNOPHARMACOLOGY RELEVANCE: Rhodiola granules (RG) is a traditional Tibetan medicine prescription that can be used to improve the symptoms of ischemia and hypoxia in cardiovascular and cerebrovascular diseases. However, there is no report on its use to improve myocardial ischemia/reperfusion (I/R) injury, and its potential active ingredients and mechanism against myocardial ischemia/reperfusion (I/R) injury remain unclear. AIM OF THE STUDY: This study aimed to reveal the potential bioactive components and underlying pharmacological mechanisms of RG in improving myocardial I/R injury through a comprehensive strategy. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap/MS technology was used to analyze the chemical components of RG, the potential bioactive components and targets were tracked and predicted by the SwissADME and SwissTargetPrediction databases, and the core targets were predicted through the PPI network, as well the functions and pathways were determined by GO and KEGG analysis. In addition, the molecular docking and ligation of the anterior descending coronary artery-induced rat I/R models were experimentally validated. RESULTS: A total of 37 ingredients were detected from RG, including nine flavones, ten flavonoid glycosides, one glycoside, eight organic acids, four amides, two nucleosides, one amino acid, and two other components. Among them, 15 chemical components, such as salidroside, morin, diosmetin, and gallic acid were identified as key active compounds. Ten core targets, including AKT1, VEGF, PTGS2, and STAT3, were discovered through the analysis of the PPI network constructed from 124 common potential targets. These possible targets were involved in the regulation of oxidative stress and HIF-1/VEGF/PI3K-Akt signaling pathways. Furthermore, molecular docking confirmed that the potential bioactive compounds in RG have good potential binding abilities to AKT1, VEGFA, PTGS2, STAT3, and HIF-1α proteins. Then, the animal experiments showed that RG could significantly improve the cardiac function of I/R rats, reduce the size of myocardial infarction, improve the myocardial structure, and reduce the degree of myocardial fibrosis, inflammatory cell infiltration, and myocardial cell apoptosis rate in I/R rats. In addition, we also found that RG could decrease the concentration of AGE, Ox-LDL, MDA, MPO, XOD, SDH, Ca2+, and ROS, and increase the concentration of Trx, TrxR1, SOD, T-AOC, NO, ATP, Na+k+-ATPase, Ca2+-ATPase, and CCO. Moreover, RG could significantly down-regulate the expressions of Bax, Cleaved-caspase3, HIF-1α, and PTGS2, as well up-regulate the expressions of Bcl-2, VEGFA, p-AKT1, and p-STAT3. CONCLUSION: In summary, we revealed for the first time the potential active ingredients and mechanisms of RG for myocardial I/R injury therapy through a comprehensive research strategy. RG may synergistically improve myocardial I/R injury through anti-inflammatory, regulating energy metabolism, and oxidative stress, improving I/R-induced myocardial apoptosis, which may be related to the HIF-1/VEGF/PI3K-Akt signaling pathway. Our study provides new insights into the clinical application of RG and also provides a reference for the development and mechanism research of other Tibetan medicine compound preparations.

Reshaped Gut Microbial Composition and Functions Associated with the Antifatigue Effect of Salidroside in Exercise Mice.

SCOPE: Salidroside (SA) is an active compound derived from Rhodiola rosea and is widely used in healthcare foods. However, the underlying mechanism and its specific role in regulating the gut microbial community during exercise (Ex) remains unknown. METHODS AND RESULTS: Mice are subjected to a weight-loaded swimming test (WST) Ex to determine how gut microbiota affects the antifatigue activity of SA. The SA-treated group mice (100 mg kg-1 .bw.) display a significant increase in swimming time compared to the control group (26.2 versus 10.5 min, p < 0.01), as well as an increase in respiratory enzymatic activities after swimming. The respiratory enzymatic activities are significantly higher in the SA-treated group than in the RS (regular rest) group after swimming. The bacteria profiles in the Ex + SA group change significantly with higher species diversity and abundance. Receiver operating characteristic (ROC) curves of Alistipes, Rikenellaceae, Parabacteroides, Candidatus Arthromitus, and Lactobacillus indicate a high diagnostic utility to distinguish SA treatment. Microbial function analysis shows that SA may improve Ex-induced fatigue by modulating energy metabolism-related processes. CONCLUSIONS: SA demonstrates antifatigue effects on various levels of regulating energy metabolism and microbial composition, providing insights into the underlying mechanisms of SA as a natural prebiotic.

Proanthocyanidin Structure-Activity Relationship Analysis by Path Analysis Model.

To fully explore the influence mechanism of interactions between different monomer units of proanthocyanidins (PAs) on biological activity, a path analysis model of the PA structure-activity relationship was proposed. This model subdivides the total correlation between each monomer unit and activity into direct and indirect effects by taking into account not only each monomer unit but also the correlation with its related monomer units. In addition, this method can determine the action mode of each monomer unit affecting the activity by comparing the direct and total indirect effects. Finally, the advantage of this model is demonstrated through an influence mechanism analysis of Rhodiola crenulata PA monomer units on antioxidant and anti-diabetes activities.

Efficacy and safety of three species of Rhodiola L. in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic hypoxia, inflammation, oxidative stress, and irreversible airflow limitations. Rhodiola L. is a genus of botanical drugs used in traditional medicine that may influence COPD. Objective: A systematic review of the safety and efficacy of Rhodiola L. in patients with COPD. Material and methods: We searched the PubMed, Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), Chongqing VIP, Wanfang, and SinoMed databases. The search strategy used terms including "COPD" and "Rhodiola." Two independent reviewers conducted the literature screening, data extraction, and risk of bias assessment, with a third reviewer involved to resolve disagreements. Statistical analysis was conducted in Review Manager (version 5.4.1), following the Cochrane Handbook. Results: This review included nine studies, of which two focused on Rhodiola crenulata (Hook.f. and Thomson) H. Ohba (R. crenulata) and two on Rhodiola kirilowii (Regel) Maxim (R. kirilowii); the remaining five focused on Rhodiola wallichiana (Hook.) S.H.Fu (R. wallichiana). Compared with the placebo, patients who received Rhodiola L. presented no more adverse events (p = 0.65) but showed significant improvement in the percentage of forced expiratory volume in 1 s at prediction (FEV1%pred), forced expiratory volume in 1 s (FEV1), the ratio of forced expiratory volume in 1 s on forced vital capacity (FEV1/FVC), saturation of oxygen in arterial blood, partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), systolic pulmonary arterial pressure, diastolic pulmonary arterial pressure, COPD assessment test, efficient rate, C-reactive protein, and N-terminal pro-B-type natriuretic peptide (all p < 0.01). Compared with ambroxol, R. kirilowii provided additional benefits to patients with COPD in FEV1%pred, FEV1, FEV1/FVC, PaO2, PaCO2, 8-iso-prostaglandin F2α, superoxide dismutase, glutathione, malondialdehyde, and total antioxidant capacity (all p < 0.01). Conclusion: Among the Rhodiola L. genus, this review included R. wallichiana, R. crenulata, and R. kirilowii, which might be safe and effective in COPD. Although this study has several limitations, further RCTs are needed. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/ display_record.php?RecordID=302881], identifier [CRD42022361890].

Anti-Inflammatory Salidroside Delivery from Chitin Hydrogels for NIR-II Image-Guided Therapy of Atopic Dermatitis.

Atopic dermatitis (AD) is the most common heterogeneous skin disease. Currently, effective primary prevention approaches that hamper the occurrence of mild to moderate AD have not been reported. In this work, the quaternized ß-chitin dextran (QCOD) hydrogel was adopted as a topical carrier system for topical and transdermal delivery of salidroside for the first time. The cumulative release value of salidroside reached ~82% after 72 h at pH 7.4, while in vitro drug release experiments proved that QCOD@Sal (QCOD@Salidroside) has a good, sustained release effect, and the effect of QCOD@Sal on atopic dermatitis mice was further investigated. QCOD@Sal could promote skin repair or AD by modulating inflammatory factors TNF-α and IL-6 without skin irritation. The present study also evaluated NIR-II image-guided therapy (NIR-II, 1000-1700 nm) of AD using QCOD@Sal. The treatment process of AD was monitored in real-time, and the extent of skin lesions and immune factors were correlated with the NIR-II fluorescence signals. These attractive results provide a new perspective for designing NIR-II probes for NIR-II imaging and image-guided therapy with QCOD@Sal.

Synergistic Effect of Rhodiola rosea and Caffeine Supplementation on the Improvement of Muscle Strength and Muscular Endurance: A Pilot Study for Rats, Resistance Exercise-Untrained and -Trained Volunteers.

Multi-level studies have shown that Rhodiola rosea (RHO) and Caffeine (CAF) have the potential to be nutritional supplements to enhance physical performance in resistance exercise-untrained and -trained subjects. This study examined the synergistic effects of RHO (262.7 mg/kg for rats and 2.4 g for volunteers) and CAF (19.7 mg/kg for rats and 3 mg/kg for volunteers) supplementation on improving physical performance in rats, resistance exercise-untrained volunteers and resistance exercise-trained volunteers. Rats and volunteers were randomly grouped into placebo, CAF, RHO and CAF+RHO and administered accordingly with the nutrients during the training procedure, and pre- and post-measures were collected. We found that RHO+CAF was effective in improving forelimb grip strength (13.75%), erythropoietin (23.85%), dopamine (12.65%) and oxygen consumption rate (9.29%) in the rat model. Furthermore, the current results also indicated that the combination of RHO+CAF significantly increased the bench press one-repetition maximum (1RM) (16.59%), deep squat 1RM (15.75%), maximum voluntary isometric contraction (MVIC) (14.72%) and maximum repetitions of 60% 1RM bench press (22.15%) in resistance exercise-untrained volunteers. Additionally, despite the excellent base level of the resistance exercise-trained volunteers, their deep squat 1RM and MVIC increased substantially through the synergistic effect of RHO and CAF. In conclusion, combined supplementation of RHO+CAF is more beneficial in improving the resistance exercise performance for both resistance exercise-untrained and -trained volunteers. The present results provide practical evidence that the synergies of RHO and CAF could serve as potential supplementary for individuals, especially resistance exercise-trained subjects, to ameliorate their physical performances effectively and safely.

Investigating the Effects and Mechanism of Rhodiola Rosea Injection on Cardiac Function in Rats with Chronic Heart Failure.

AIM: To study the effect of Rhodiola Rosea injection on cardiac function and the reninangiotensin- aldosterone system (RASS) in rats with chronic heart failure. BACKGROUND: Rhodiola Rosea injection, a traditional Chinese medication for relieving blood stasis and improving blood circulation, is an excellent therapeutic for treating coronary heart disease-angina pectoris. Rhodiola Rosea injection's major component, salidroside, protects the cardiovascular system. But there isn't much first-hand evidence about how injectable Rhodiola Rosea affects heart failure. OBJECTIVES: In this study, a rat model of heart failure was established, and the effect of Rhodiola rosea injection on myocardial cell morphology, cardiac function, and ventricular remodelling in rats with heart failure was investigated. METHODS: 66 SD male rats were selected; 10 were randomly selected as a blank control group, and 56 were treated intraperitoneally with doxorubicin (4 g/g). After 6 weeks, all animals had LVEF 60%. Established a heart failure model. Each group had 14 rats: model control, low-dose, mediumdose, and high-dose Rhodiola Rosea injection. The 2 mL/kg of Rhodiola Rosea injection was injected into the tail vein once a day for 2 weeks. Both the blank and control groups received normal daily saline. After 2 weeks, the echocardiographic index, RASS-related index, and serum BNP level were assessed in all rats, and myocardial tissue morphology was observed. MiRNA423-5p, miRNA499-5p, and miRNA210-3p were extracted from peripheral blood. Rhodiola rosea injection on its expression was compared to healthy control rats. RESULTS: 6 mL/kg Rhodiola Rosea injection lowered LVEDV and LVESV while increasing LVEF and LVFS. Injections of 6 mL/kg Rhodiola Rosea reduce plasma levels of miR-210-3p, miR-423- 5p, miRNA-499, and BNP in heart failure model rats. The 6 mL/kg Rhodiola Rosea injection can restore the RASS indexes of heart failure rats to the level of the normal group. CONCLUSION: The present study offers preliminary evidence supporting the use of Rhodiola Rosea injection in the treatment of heart failure and offers a solid foundation for clinical off-label medication use.

Bioactivity Profiles on 15 Different Effect Mechanisms for 15 Golden Root Products via High-Performance Thin-Layer Chromatography, Planar Assays, and High-Resolution Mass Spectrometry.

Planar chromatography has recently been combined with six different effect-directed assays for three golden root (Rhodiola rosea L.) samples. However, the profiles obtained showed an intense tailing, making zone differentiation impossible. The profiling was therefore improved to allow for the detection of individual bioactive compounds, and the range of samples was extended to 15 commercial golden root products. Further effect-directed assays were studied providing information on 15 different effect mechanisms, i.e., (1) tyrosinase, (2) acetylcholinesterase, (3) butyrylcholinesterase, (4) ß-glucuronidase, and (5) α-amylase inhibition, as well as endocrine activity via the triplex planar yeast antagonist-verified (6-8) estrogen or (9-11) androgen screen, (12) genotoxicity via the planar SOS-Umu-C bioassay, antimicrobial activity against (13) Gram-negative Aliivibrio fischeri and (14) Gram-positive Bacillus subtilis bacteria, and (15) antioxidative activity (DPPH• radical scavengers). Most of the golden root profiles obtained were characteristic, but some samples differed substantially. The United States Pharmacopeia reference product showed medium activity in most of the assays. The six most active compound zones were further characterized using high-resolution mass spectrometry, and the mass signals obtained were tentatively assigned to molecular formulae. In addition to confirming the known activities, this study is the first to report that golden root constituents inhibit butyrylcholinesterase (rosin was tentatively assigned), ß-glucuronidase (rosavin, rosarin, rosiridin, viridoside, and salidroside were tentatively assigned), and α-amylase (stearic acid and palmitic acid were tentatively assigned) and that they are genotoxic (hydroquinone was tentatively assigned) and are both agonistic and antagonistic endocrine active.

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.

Anti-senescence effects of Rhodiola crenulate extracts on LO2 cells and bioactive compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata (Rc) is a traditional herb, used in Tibetan medicine, has shown promise efficacy in physical performance improvement, work capacity enhancement, fatigue elimination, and altitude sickness prevention. Also, Rc exhibited therapeutic effects on aging-related diseases. However, relevant researches on Rc and their bioactive components are quite few and needs further investigation. AIM OF THE STUDY: The objective of this study was to understand the relationship between phytochemical profiles and their activities of Rc extracts. MATERIALS AND METHODS: Rc extracts prepared by solvents with various hydrophilicity (i.e. aqueous ethanol (70%, v/v), water, and ethyl acetate), and their chemical compositions and specific compounds were analyzed by chemical analysis method and ultra-performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS). The regulate effects of Rc extracts on senescence and antioxidant activity were evaluated using the models of LO2 cells and Caenorhabditis elegans. RESULTS: The 70% ethanol extracts exhibited better regulating effects on senescence via the assays of senescence -associated ß-galactosidase (SAßG) staining and lifespan, which was consistent with the higher antioxidant activities observed based on the results of antioxidant assays. A total of 14 phytochemicals have been identified in 70% ethanol extracts, whereas the other two extracts contained much fewer compounds in varieties. Phytochemical profile of water extract was similar to the first half (polar compounds, running time: 0-6 min) of 70% ethanol extract profile, while those of ethyl acetate extract was consistent with its second half (more nonpolar compounds, running time: 6-12 min). CONCLUSIONS: The 14 phytochemicals in Rc might exhibit additive or synergistic effects on senescence regulating and antioxidant activities, providing theoretical basis for daily administration of Rc.