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Objective: To explore the potential strategies and mechanisms for enhancing the bioavailability of Rhodiola rosea. Methods: 36 Sprague-Dawley rats (8-weeks-old) were randomly assigned to six groups (n = 6 per group). Groups I and II received nano-dose forms of R. rosea, groups III and IV received normal dose form of R. rosea, and groups V and VI served as distilled water control groups. Groups II, IV, and VI were combined with moderate -intensity treadmill exercise. Each group received a daily gavage with 0.5 mL of nano -R. rosea solution (0.01 mg/mL), normal R. rosea solution, and distilled water. All rats were subjected to exhaustive swimming after 4 weeks. Outcome measures include GSH-px activity, T-AOC activity, MDA content, hepatic glycogen content, and T-SOD activity. Results: For plasma MDA content, group I was lower than group III (p < 0.01) and group V (p < 0.01), group II was lower than group III (p < 0.01), group VI was higher than group II (p < 0.05) and group IV (p < 0.05). For plasma T-AOC activity, group II was higher than group VI (p < 0.01). For plasma GSH-px activity, group I was lower than group IV (p < 0.05), groups II, III, and IV were higher than group V (p < 0.05), and group V was lower than that of group VI (p < 0.05). For T-SOD activity of quadriceps muscle, groups I and III were higher than that in group V (p < 0.05). Conclusion: R. rosea has a positive effect on anti-exercise fatigue in rats, with the nano-dosage form of R. rosea showing more significant efficacy than the normal form especially combined with aerobic exercise.

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Leg disorders frequently occur in fast-growing broiler chickens, constituting severe health and welfare problems. Although salidroside (SAL) promotes osteogenesis and inhibits apoptosis of chondrocytes in rats, it remains to be determined whether SAL can effectively improve bone growth in broilers. The present study was designed to investigate the effects of dietary SAL supplementation on bone and cartilage characteristics in broiler chickens. Ninety-six Arbor Acres broiler chickens were randomly divided into 4 groups: control, low-dose SAL, medium-dose SAL, and high-dose SAL groups. The broiler chickens were raised until 42 d of age, with samples of bone and cartilage collected for biomechanical testing and bone metabolism index detection. The results showed that SAL significantly increased the vertical external diameter, cross-sectional moment of inertia, and cross-sectional area of the femur and tibia. Additionally, SAL enhanced bone mineral density and strength, as evidenced by significant increases in stiffness, Young's modulus, ultimate load, and fracture work of the femur and tibia. Furthermore, SAL influenced the relative content of phosphate, carbonate, and amide I in cortical bone. Moreover, SAL upregulated the expression of osteogenic genes (Collagen-1, RUNX2, BMP2, and ALP) in a dose-dependent manner and maintained the homeostasis of the extracellular matrix (ECM) of chondrocytes. These results indicated that SAL promoted leg health in broilers by improving bone and cartilage quality and enhancing chondrocyte activity.

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Zika virus (ZIKV) and Japanese encephalitis virus (JEV) can cause permanent neurological damage and death, yet no approved drugs exist for these infections. Rhodiola crenulate, an herb used in traditional Chinese medicine for its antioxidation and antifatigue properties, was studied for its antiviral activity against ZIKV and JEV in vitro. The cytotoxicity of Rhodiola crenulata extract (RCE) was evaluated using the CCK-8 reagent. Antiviral effects of RCE were assessed in ZIKV-infected or JEV-infected Vero cells via quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, fluorescent focus assay (FFA), and immunofluorescence assay (IFA). The cell-free antiviral effects of RCE were evaluated using an inactivation assay. To determine the stage of the viral life cycle affected by RCE, time-of-addition, binding, and entry assays were conducted. Three bioactive constituents of RCE (salidroside, tyrosol, and gallic acid) were tested for antiviral activity. RCE exhibited dose-dependent anti-ZIKV and anti-JEV activities at non-cytotoxic concentrations, which were likely achieved by disrupting viral binding and stability. Gallic acid exhibited antiviral activity against ZIKV and JEV. Our findings indicate that RCE disrupts viral binding and stability, presenting a potential strategy to treat ZIKV and JEV infections.

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OBJECTIVE: The objective of this study was to examine the impact of "Tianyu" Pairing on oxidative stress in the development of Rheumatoid arthritis (RA) and approach its potential mechanism using cell experiments. METHODS: A cell model of RA was developed by stimulating rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) with tumor necrosis factor-α (TNF-α). This model aimed to assess the impact of serum containing Rhodiola rosea-Euonymus alatus drug pair (TYP) on inflammation and oxidative stress in the development of RA, specifically through the Keap1/Nrf2/HO-1 pathway. RESULTS: The findings from the in vitro experiment demonstrated that the presence of TYP in the serum effectively suppressed the proliferation of RA-FLS induced by TNF-α. Additionally, TYP facilitated the apoptosis of afflicted cells, attenuated the migratory and invasive capabilities of diseased cells, and decreased the levels of Kelch ECH associating protein 1 (Keap1), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) (p < 0.01). The influence of inflammation and oxidative stress in RA-FLS cells was reduced by increasing the nuclear-cytoplasmic ratio of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and levels of phosphorylated Nrf2, Heme Oxygenase 1 (HO-1), and Superoxide Dismutase (SOD) (p < 0.01). CONCLUSION: TYP can regulate inflammation and oxidative stress in RA-FLS cells by activating the Keap1/Nrf2/HO-1 pathway.

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Rhodiola rosea, a long-lived herbaceous plant from the Crassulaceae group, contains the active compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key regulatory proteins including runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone development with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2-related factor 2 pathway. Salidroside has the capability to counteract the negative effects of glucocorticoids on bone cells and prevents steroid-induced osteonecrosis. Additionally, it exhibits multifaceted anti-inflammatory actions, notably through the inhibition of tumor necrosis factor-alpha and interleukin-6 expression, while enhancing the expression of interleukin-10. This publication presents a comprehensive review of the literature on the impact of salidroside on various aspects of bone tissue metabolism, emphasizing its potential role in the prevention and treatment of osteoporosis and other diseases affecting bone physiology.

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Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 µM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 µg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.

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Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin-Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases.

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Rhodiola rosea L. is recognized for its adaptogenic properties and ability to promote muscle health, function and recovery from exercise. The plethora of biological effects of this plant is ascribed to the synergism existing among the molecules composing its phytocomplex. In this manuscript, we analyze the activity of a bioactive fraction extracted from Rhodiola rosea L. controlled cultivation. Biological assays were performed on human skeletal myoblasts and revealed that the extract is able to modulate in vitro expression of transcription factors, namely Pax7 and myoD, involved in muscle differentiation and recovery. The extract also promotes ROS scavenging, ATP production and mitochondrial respiration. Untargeted metabolomics further reveals that the mechanism underpinning the plant involves the synergistic interconnection between antioxidant enzymes and the folic/acid polyamine pathway. Finally, by examining the phytochemical profiles of the extract, we identify the specific combination of secondary plant metabolites contributing to muscle repair, recovery from stress and regeneration.

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The genus Rhodiola L., an integral part of traditional Chinese medicine and Tibetan medicine in China, exhibits a broad spectrum of applications. This genus contains key compounds such as ginsenosides, polysaccharides, and flavonoids, which possess anti-inflammatory, antioxidant, hypoglycaemic, immune-enhancing, and anti-hypoxic properties. As a vital raw material, Rhodiola L. contributes to twenty-four kinds of Chinese patent medicines and 481 health food products in China, finding extensive application in the health food sector. Recently, polysaccharides have emerged as a focal point in natural product research, with applications spanning the medicine, food, and materials sectors. Despite this, a comprehensive and systematic review of polysaccharides from the genus Rhodiola L. polysaccharides (TGRPs) is warranted. This study undertakes a systematic review of both domestic and international literature, assessing the research advancements and chemical functional values of polysaccharides derived from Rhodiola rosea. It involves the isolation, purification, and identification of a variety of homogeneous polysaccharides, followed by a detailed analysis of their chemical structures, pharmacological activities, and molecular mechanisms, structure-activity relationship (SAR) of TGRPs. The discussion includes the influence of molecular weight, monosaccharide composition, and glycosidic bonds on their biological activities, such as sulfation and carboxymethylation et al. Such analyses are crucial for deepening the understanding of Rhodiola rosea and for fostering the development and exploitation of TGRPs, offering a reference point for further investigations into TGRPs and their resource utilization.

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3,5-Dimethyl-8-methoxy-3,4-dihydro-1H-isochromen-6-ol (DMD) is a polyketide compound obtained from the endophytic fungus Penicillium sp. HJT-A-10 of Rhodiola tibetica. R. tibetica is a nourishing food and also used in traditional Chinese medicine and Xizang medicine. In dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice, DMD significantly alleviated the pathological symptom of UC. Network pharmacology studies have shown that nucleotide-binding domain-like receptor family pyrin domain containing (NLRP) 3 is the primary target protein of DMD associated with anti-UC. In molecular biology studies, DMD suppressed the activation of NLRP3 and decreased the expression of downstream inflammatory proteins and pro-inflammatory cytokines in UC. The finding was further verified in knockout mice. DMD lost the effect of attenuating DSS-induced UC in NLRP3-/- mice. In conclusion, this study demonstrates that DMD reduces inflammatory response and balances the barrier integrity to attenuate UC via targeting NLRP3, and DMD is a potential natural agent or dietary supplement for attenuating UC.

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Rhodiola, belonging to the Crassulaceae family, is a perennial herbaceous plant genus. There are about 90 Rhodiola species worldwide, some of which have been reported to have medicinal properties. Rhodiola sachalinensis is a perennial medicinal herb within this genus and, in the present study, its chloroplast genome was sequenced, assembled, annotated and compared with 24 other Rhodiola species. The results obtained show that the chloroplast genome of R. sachalinensis is 151 595 bp long and has a CG content of 37.7%. The inverted repeats (IR) region of the Rhodiola chloroplast genome is the most conserved region, with the main differences being observed in the ycf1 and ndhF genes at the IRb-small single copy boundary, and rps19 and trnH genes at the IRa-large single copy boundary. Phylogenetic analysis showed that Rhodiola species form two major clades, and species with recorded medicinal properties, clustered together in one branch except for R. dumulosa. Within the genus, R. sachalinensis is most closely related to Rhodiola rosea, although comparative analyses showed that only R. sachalinensis and Rhodiola subopposita contained the psbZ gene, which encodes a highly conserved protein subunit of the Photosystem II core complex. Overall, the present study contributes to the understanding of the chloroplast genome of Rhodiola species, and provides a theoretical basis for the study of their genetic diversity and possible use as medicinal plants.

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Objectives: Chewing gum has been shown to improve aspects of cognition and mood with sustained attention being particularly receptive to the effects of chewing. Chewing gum may also be a useful vehicle for administering functional ingredients. The herbal extract Rhodiola rosea and certain B-vitamins have previously been shown to improve aspects of cognition and subjective state, but their combined effects have not been studied to date.Methods: The current randomised, placebo-controlled, double-blind, balanced crossover study compared the effects of a functional gum containing Rhodiola rosea and B-vitamins to flavour-matched regular chewing gum and a flavour-matched placebo. Thirty-six healthy young participants completed measures of attention and mood at baseline, during chewing, and 1-h after chewing.Results: Chewing both functional and regular gum was shown to reduce errors on a digit vigilance task compared to placebo irrespective of whether measured during or after chewing. There were no benefits to adding functional ingredients to the gum.Discussion: Future chewing research should consider different formats of placebo. Sex differences in response to chewing and the impact of rate and intensity of chewing should also be explored.Trial registration: ClinicalTrials.gov identifier: NCT05544500.

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BACKGROUND: Effective control of postprandial blood glucose (PBG) level is essential for the prevention and treatment of diabetes and its complications. Several flavonoids have attracted much attention due to their significant PBG-lowering effects. However, there is still a certain gap in the in vivo hypoglycemic activity of most flavonoids compared to first-line drugs available on the market, and are still lack of the PBG-lowering effects of 8-hydroxyflavones and their structure-activity relationship. PURPOSE: Evaluate hypoglycemic effects of 8-hydroxyflavones from Rhodiola crenulata in vitro and in vivo, especially comparatively analyze the relationship between hypoglycemic effects and flavonoid configuration and reveal the possible mechanism of 8-hydroxyflavones in lowering hyperglycemia. METHODS: Starch, maltose, sucrose, and glucose tolerance tests in both diabetic and normal mice were used to evaluate and compare the hypoglycemic effects of 8-hydroxyflavones rhodiosin (RHS), rhodionin (RHN), and herbacetin (HBT). Molecular docking, enzyme kinetics, and immunofluorescence analysis were used to research the possible hypoglycemic mechanisms of 8-hydroxyflavones. RESULTS: RHS (5 and 10 mg/kg) could efficiently decrease PBG levels in both normal and diabetes mice. Moreover, RHS, RHN, and HBT all had significant PBG-lowering effects in transgenic diabetes mice, and the effects were equivalent to or stronger than acarbose. Further mechanism research indicated that 8-hydroxyflavones achieved PBG-lowering effects by inhibiting both the activity and production of glycosidase. Notably, we have innovatively discovered that inhibiting the expression of glycosidases rather than just their activities may be a new target for hypoglycemic drugs. CONCLUSION: We have firstly comprehensively and systematically clarified PBG-lowering effects of 8-hydroxyflavones from Rhodiola crenulata, and revealed their structure-activity relationships and hypoglycemic mechanisms. The study demonstrated that the substitution of 8-hydroxy groups in flavonoids could significantly enhance their hypoglycemic effects, which were equivalent to or stronger than commercially available drug acarbose. 8-Hydroxyflavones could be used as therapeutic or health drugs with significant potential to reduce postprandial hyperglycemia.

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A natural "medicine and food" plant, Rhodiola rosea (RR) is primarily made up of organic acids, phenolic compounds, sterols, glycosides, vitamins, lipids, proteins, amino acids, trace elements, and other physiologically active substances. In vitro, non-clinical and clinical studies confirmed that it exerts anti-inflammatory, antioxidant, and immune regulatory effects, balances the gut microbiota, and alleviates vascular circulatory disorders. RR can prolong life and has great application potential in preventing and treating suboptimal health, non-communicable diseases, and COVID-19. This narrative review discusses the effects of RR in preventing organ damage (such as the liver, lung, heart, brain, kidneys, intestines, and blood vessels) in non-communicable diseases from the perspective of predictive, preventive, and personalised medicine (PPPM/3PM). In conclusion, as an adaptogen, RR can provide personalised health strategies to improve the quality of life and overall health status.

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Chronic sleep disturbance affects daily functioning, leading to decreased concentration, fatigue, and higher healthcare costs. Traditional insomnia medications are often associated with adverse side effects. This study investigated the efficacy of a novel compound derived from Rhodiola rosea and Nelumbo nucifera extracts (named RNE) in improving sleep quality with fewer side effects. The study included individuals between the ages of 20 and 65 with subthreshold insomnia and evaluated the effects of RNE on sleep, fatigue, and quality of life. Participants took 750 mg of RNE daily at bed-time for two weeks. The study used the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), a sleep diary, the Fatigue Severity Scale (FSS), and the Short Form 36 Health Survey (SF-36) for assessments. Of the 20 participants, 13 completed the study and showed significant improvements in sleep quality. The results showed improvements in ISI and PSQI scores, a 57% reduction in wake-time after sleep onset, and improved sleep efficiency. Although FSS scores remained unchanged, significant improvements were seen in SF-36 physical and mental health scores. The results suggest that RNE is an effective, low-risk option for sleep disturbance, significantly improving sleep quality and overall wellbeing without significant side effects.

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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.

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OBJECTIVE: To explore the effects of Rhodiola rosea injection on pulmonary shunt and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels during single lung ventilation in patients undergoing radical resection of esophageal cancer. METHODS: Forty-six patients undergoing radical operation for esophageal cancer were randomized equally into control group and Rhodiola rosea injection group. In the Rhodiola group, 10 mL of Rhodiola rosea injection was added into 250 mL of normal saline or 5% glucose solution for slow intravenous infusion, and normal saline of the same volume was used in the control group after the patients entered the operation room. At T0, T1 and T3, PaO2 of the patient was recorded and 2 mL of deep venous blood was collected for determination of serum TNF-α and IL-6 levels. The incidence of postoperative atelectasis of the patients was recorded. RESULTS: Compared with those in the control group, the patients receiving Rhodiola rosea injection had significantly higher PaO2 and Qs/Qt at T1 and T2 (P<0.05) and lower serum IL-6 and TNF-α levels at T3 (P<0.05). No significant difference in the incidence of postoperative atelectasis was observed between the two groups (P>0.05). CONCLUSION: Rhodiola rosea injection before anesthesia induction can reduce intrapulmonary shunt during single lung ventilation, improve oxygenation, reduce serum IL-6 and TNF-α levels, and alleviate intraoperative lung injury in patients undergoing radical resection of esophageal cancer.

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Rhodiola L. is a genus exhibiting rapid radiation and represents a typical case for studying plastid gene adaptation in species that spread from high altitudes to low altitudes. In this study, 23 samples of 18 Rhodiola species were collected from the Qinghai-Tibetan Plateau and five scattered alpine areas, and the plastid genomes (plastomes) of these species were sequenced, annotated, and compared between high-altitude and widely distributed groups. The plastomes of Rhodiola were found to be highly conserved in terms of gene size, content, and order but highly variable in several lineage-specific features, such as codon usage bias, IR boundary shifting, and distinct repeat sequence structures binding to SSRs. Codon usage in the genes of photosystem II exhibited an obvious preference, reflecting significant environmental adaptation pressures. In this study, three repeat regions compounded with trinucleotide and mononucleotide repeats were found for the first time in R. forrestii, R. himalensis, and R. yunnanensis. High-variability regions such as ndhF, ycf1, trnH-psbA, and rpoC1-rpoB were screened, laying the foundation for the precise identification of these species. The phylogenetic analysis revealed the occurrence of cyto-nuclear discordance, likely originating from the frequent interspecific hybridization events observed within Rhodiola species during rapid radiation. Dioecious and hermaphrodite species can be broadly categorized into two subclades, probably they have different environmental adaptation strategies in response to climate change. In addition, the phylogenetic tree supported the monophyly of R. forrestii and R. yunnanensis, which compose R. Sect. Pseudorhodiola. In conclusion, plastome data enrich the genetic information available for the Rhodiola genus and may provide insight into species migration events during climate change.

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The pharmacokinetics (PK) of Rhodiola crenulata in rats were studied, and pharmacokinetic-pharmacodynamic (PK-PD) correlation analysis was performed to elucidate their time-concentration-effect relationship. The myocardial ischemia model was made with pituitrin. Rats were divided into sham operation, sham operation administration, model, and model administration groups (SG, SDG, MG, and MDG, respectively; n = 6). Blood was collected from the fundus venous plexus at different time points after oral administration. The HPLC-QQQ-MS/MS method was established for the quantification of five components of Rhodiola crenulata. CK, HBDH, SOD, LDH, and AST at different time points were detected via an automatic biochemical analyzer. DAS software was used to analyze PK parameters and PK-PD correlation. The myocardial ischemia model was established successfully. There were significant differences in the PK parameters (AUC0-t, AUC0-∞, Cmax) in MDG when compared with SDG. Two PD indicators, CK and HBDH, conforming to the sigmoid-Emax model, had high correlation with the five components, which indicated a delay in the pharmacological effect relative to the drug concentration in plasma. The difference in the PK parameters between modeled and normal rats was studied, and the time-concentration-effect of composition and effect indicators were investigated. This study can provide reference for the rational clinical application of Rhodiola crenulata and for related studies of other anti-myocardial ischemia drugs.

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A new quinazolinone alkaloid named peniquinazolinone A (1), as well as eleven known compounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), and conidiogenone B (12), were isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all the compounds were elucidated by comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher's method. Compounds 2, 3, and 7 exhibited an optimal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed germination period of Rhodiola tibetica up to the 11th day.

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