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1.
Nutrients ; 16(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38931222

RESUMO

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.


Assuntos
Nelumbo , Extratos Vegetais , Qualidade de Vida , Rhodiola , Distúrbios do Início e da Manutenção do Sono , Qualidade do Sono , Humanos , Rhodiola/química , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Nelumbo/química , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Adulto Jovem , Fadiga/tratamento farmacológico , Idoso , Transtornos do Sono-Vigília/tratamento farmacológico , Sono/efeitos dos fármacos
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 706-711, 2024 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-38708504

RESUMO

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.


Assuntos
Neoplasias Esofágicas , Interleucina-6 , Ventilação Monopulmonar , Rhodiola , Fator de Necrose Tumoral alfa , Humanos , Neoplasias Esofágicas/cirurgia , Fator de Necrose Tumoral alfa/sangue , Interleucina-6/sangue , Ventilação Monopulmonar/métodos , Feminino , Masculino , Pessoa de Meia-Idade
3.
Molecules ; 29(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38731603

RESUMO

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.


Assuntos
Alcaloides , Penicillium , Quinazolinonas , Rhodiola , Sementes , Penicillium/química , Quinazolinonas/química , Quinazolinonas/farmacologia , Rhodiola/química , Rhodiola/microbiologia , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Germinação/efeitos dos fármacos , Estrutura Molecular , Endófitos/química
4.
Gene ; 917: 148467, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615983

RESUMO

Rhodiola crenulata, a plant of great medicinal value found in cold high-altitude regions, has been excessively exploited due to the difficulty in cultivation. Understanding Rhodiola crenulata's adaptation mechanisms to cold environment can provide a theoretical basis for artificial breeding. Glutathione peroxidases (GPXs), critical enzymes found in plants, play essential roles in antioxidant defense through the ascorbate-glutathione cycle. However, it is unknown whether GPX5 contributes to Rhodiola crenulata's cold tolerance. In this study, we investigated the role of GPX5 in Rhodiola crenulata's cold tolerance mechanisms. By overexpressing Rhodiola crenulata GPX5 (RcGPX5) in yeast and Arabidopsis thaliana, we observed down-regulation of Arabidopsis thaliana GPX5 (AtGPX5) and increased cold tolerance in both organisms. Furthermore, the levels of antioxidants and enzyme activities in the ascorbate-glutathione cycle were elevated, and cold-responsive genes such as AtCBFs and AtCORs were induced. Additionally, RcGPX5 overexpressing lines showed insensitivity to exogenous abscisic acid (ABA), suggesting a negative regulation of the ABA pathway by RcGPX5. RcGPX5 also promoted the expression of several thioredoxin genes in Arabidopsis and interacted with two endogenous genes of Rhodiola crenulata, RcTrx2-3 and RcTrxo1, located in mitochondria and chloroplasts. These findings suggest a significantly different model in Rhodiola crenulata compared to Arabidopsis thaliana, highlighting a complex network involving the function of RcGPX5. Moreover, overexpressing RcGPX5 in Rhodiola crenulata hairy roots positively influenced the salidroside synthesis pathway, enhancing its pharmaceutical value for doxorubicin-induced cardiotoxicity. These results suggested that RcGPX5 might be a key component for Rhodiola crenulata to adapt to cold stress and overexpressing RcGPX5 could enhance the pharmaceutical value of the hairy roots.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Glutationa Peroxidase , Raízes de Plantas , Rhodiola , Rhodiola/genética , Rhodiola/metabolismo , Arabidopsis/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Plantas Geneticamente Modificadas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Temperatura Baixa , Antioxidantes/metabolismo , Ácido Abscísico/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Adaptação Fisiológica/genética
5.
Phytother Res ; 38(6): 2619-2640, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38488455

RESUMO

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.


Assuntos
Isquemia Encefálica , Fator Neurotrófico Derivado do Encéfalo , Glucosídeos , Proteínas de Choque Térmico HSC70 , Infarto da Artéria Cerebral Média , Neurogênese , Fármacos Neuroprotetores , Fenóis , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Fenóis/farmacologia , Fenóis/química , Glucosídeos/farmacologia , Neurogênese/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos , Masculino , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Isquemia Encefálica/tratamento farmacológico , Proteínas de Choque Térmico HSC70/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Duplacortina , Rhodiola/química , Receptor trkB/metabolismo , Modelos Animais de Doenças , Azepinas , Benzamidas
6.
Pharm Biol ; 62(1): 272-284, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38445620

RESUMO

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


Assuntos
Lesão Pulmonar Aguda , Rhodiola , Sepse , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Lipopolissacarídeos/toxicidade , Simulação de Acoplamento Molecular , Farmacologia em Rede , Estresse Oxidativo , Sepse/complicações , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Células Endoteliais da Veia Umbilical Humana
7.
Chem Biodivers ; 21(5): e202302075, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38527165

RESUMO

The present study investigated the role of a commercial formulation constituted by herbal extracts from Rhodiola rosea, Undaria pinnatifida, Tribulus terrestris, and Moringa oleifera. The formulation was analysed for determining the content in total phenols and flavonoids and scavenging/reducing properties. The formulation was also tested on isolated mouse hypothalamus in order to investigate effects on serotonin, dopamine, neuropeptide Y (NPY), and orexin A. The gene expression of gonadrotopin releasing hormone (GnRH) was also assayed. The formulation was able to reduce dopamine and serotonin turnover, and this could be related, albeit partially, to the capability of different phytochemicals, among which hyperoside and catechin to inhibit monoaminooxidases activity. In parallel, the formulation was effective in reducing the gene expression of NPY and orexin-A and to improve the gene expression of GnRH. In this context, the increased GnRH gene expression induced by the formulation may contribute not only to improve the resistance towards the stress related to ageing, but also to prevent the reduction of libido that could be related with a stimulation of the serotoninergic pathway. According to the in silico analysis, hyperoside could play a pivotal role in modulating the gene expression of GnRH. Regarding NPY and orexin A gene expression, no direct interactions between the formulation phytochemicals and these neuropeptides were anticipated; thus, suggesting that the pattern of gene expression observed following exposure of the hypothalamus to the formulation may be secondary to inhibitory effects of dopamine and serotonin turnover. Concluding, the present study demonstrated the efficacy of the formulation in exerting neuromodulatory effects at the hypothalamic level; thus, suggesting the potential to contrast stress and fatigue.


Assuntos
Hipotálamo , Moringa oleifera , Extratos Vegetais , Rhodiola , Tribulus , Animais , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Tribulus/química , Moringa oleifera/química , Rhodiola/química , Serotonina/metabolismo , Simulação de Acoplamento Molecular , Masculino , Dopamina/metabolismo , Neurotransmissores/metabolismo
8.
Phytomedicine ; 128: 155376, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503152

RESUMO

BACKGROUND: The apoptosis of pulmonary artery endothelial cells (PAECs) is an important factor contributing to the development of pulmonary hypertension (PH), a serious cardio-pulmonary vascular disorder. Salidroside (SAL) is a bioactive compound derived from an herb Rhodiola, but the potential protective effects of SAL on PAECs and the underlying mechanisms remain elusive. PURPOSE: The objective of this study was to determine the role of SAL in the hypoxia-induced apoptosis of PAECs and to dissect the underlying mechanisms. STUDY DESIGN: Male Sprague-Dawley (SD) rats were subjected to hypoxia (10% O2) for 4 weeks to establish a model of PH. Rats were intraperitoneally injected daily with SAL (2, 8, and 32 mg/kg/d) or vehicle. To define the molecular mechanisms of SAL in PAECs, an in vitro model of hypoxic cell injury was also generated by exposed PAECs to 1% O2 for 48 h. METHODS: Various techniques including hematoxylin and eosin (HE) staining, immunofluorescence, flow cytometry, CCK-8, Western blot, qPCR, molecular docking, and surface plasmon resonance (SPR) were used to determine the role of SAL in rats and in PAECs in vitro. RESULTS: Hypoxia stimulation increases AhR nuclear translocation and activates the NF-κB signaling pathway, as evidenced by upregulated expression of CYP1A1, CYP1B1, IL-1ß, and IL-6, resulting in oxidative stress and inflammatory response and ultimately apoptosis of PAECs. SAL inhibited the activation of AhR and NF-κB, while promoted the nuclear translocation of Nrf2 and increased the expression of its downstream antioxidant proteins HO-1 and NQO1 in PAECs, ameliorating the hypoxia-induced oxidative stress in PAECs. Furthermore, SAL lowered right ventricular systolic pressure, and decreased pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-exposed rats. CONCLUSIONS: SAL may attenuate the apoptosis of PAECs by suppressing NF-κB and activating Nrf2/HO-1 pathways, thereby delaying the progressive pathology of PH.


Assuntos
Apoptose , Células Endoteliais , Heme Oxigenase (Desciclizante) , Artéria Pulmonar , Transdução de Sinais , Animais , Masculino , Ratos , Apoptose/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Glucosídeos/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/metabolismo , Rhodiola/química , Transdução de Sinais/efeitos dos fármacos
9.
Int J Biol Macromol ; 267(Pt 1): 131150, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556236

RESUMO

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.


Assuntos
Inibidores Enzimáticos , Microbioma Gastrointestinal , Simulação de Acoplamento Molecular , Rhodiola , Rhodiola/química , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Medicina Tradicional Tibetana , Cinética , Masculino
10.
Phytomedicine ; 128: 155365, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38552436

RESUMO

BACKGROUND: Ferroptosis, a form of regulated cell death (RCD) that relies on excessive reactive oxygen species (ROS) generation, Fe2+accumulation, abnormal lipid metabolism and is involved in various organ ischemia/reperfusion (I/R) injury, expecially in myocardium. Mitochondria are the powerhouses of eukaryotic cells and essential in regulating multiple RCD. However, the links between mitochondria and ferroptosis are still poorly understood. Salidroside (Sal), a natural phenylpropanoid glycoside isolated from Rhodiola rosea, has mult-bioactivities. However, the effects and mechanism in alleviating ferroptosis caused by myocardial I/R injury remains unclear. PURPOSE: This study aimed to investigate whether pretreated with Sal could protect the myocardium against I/R damage and the underlying mechanisms. In particular, the relationship between Sal pretreatment, AMPKα2 activity, mitochondria and ROS generation was explored. STUDY DESIGN AND METHODS: Firstly, A/R or I/R injury models were employed in H9c2 cells and Sprague-Dawley rats. And then the anti-ferroptotic effects and mechanism of Sal pretreatment was detected using multi-relevant indexes in H9c2 cells. Further, how does Sal pretreatment in AMPKα2 phosphorylation was explored. Finally, these results were validated by I/R injury in rats. RESULTS: Similar to Ferrostatin-1 (a ferroptosis inhibitor) and MitoTEMPO, a mitochondrial free radical scavenger, Sal pretreatment effectively alleviated Fe2+ accumulation, redox disequilibrium and maintained mitochondrial energy production and function in I/R-induced myocardial injury, as demonstrated using multifunctional, enzymatic, and morphological indices. However, these effects were abolished by downregulation of AMPKα2 using an adenovirus, both in vivo and in vitro. Moreover, the results also provided a non-canonical mechanism that, under mild mitochondrial ROS generation, Sal pretreatment upregulated and phosphorylated AMPKα2, which enhanced mitochondrial complex I activity to activate innate adaptive responses and increase cellular tolerance to A/R injury. CONCLUSION: Overall, our work highlighted mitochondria are of great impotance in myocardial I/R-induced ferroptosis and demonstrated that Sal pretreatment activated AMPKα2 against I/R injury, indicating that Sal could become a candidate phytochemical for the treatment of myocardial I/R injury.


Assuntos
Proteínas Quinases Ativadas por AMP , Ferroptose , Glucosídeos , Traumatismo por Reperfusão Miocárdica , Fenóis , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Rhodiola , Ferroptose/efeitos dos fármacos , Fenóis/farmacologia , Animais , Glucosídeos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ratos , Masculino , Rhodiola/química , Proteínas Quinases Ativadas por AMP/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/efeitos dos fármacos
11.
Metab Eng ; 82: 274-285, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428730

RESUMO

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.


Assuntos
Dissacarídeos , Glucose , Rhodiola , Glucose/genética , Glucose/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Arabinose/metabolismo , Rhodiola/genética , Rhodiola/metabolismo , Xilose/metabolismo
12.
Phytomedicine ; 128: 155529, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503156

RESUMO

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.


Assuntos
Barreira Hematoencefálica , Metabolismo Energético , Extratos Vegetais , Rhodiola , Animais , Rhodiola/química , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Camundongos , Extratos Vegetais/farmacologia , Metabolismo Energético/efeitos dos fármacos , Masculino , Apoptose/efeitos dos fármacos , Glucosídeos/farmacologia , Modelos Animais de Doenças , Fenóis/farmacologia , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Linhagem Celular , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Doença da Altitude/tratamento farmacológico , Doença da Altitude/metabolismo , Hipóxia/tratamento farmacológico
13.
J Neural Transm (Vienna) ; 131(3): 203-212, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38347175

RESUMO

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.


Assuntos
COVID-19 , Disfunção Cognitiva , Rhodiola , Humanos , Ginkgo biloba , COVID-19/complicações , SARS-CoV-2 , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia
14.
Molecules ; 29(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38398618

RESUMO

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.


Assuntos
Extratos Vegetais , Rhodiola , Humanos , Extratos Vegetais/farmacologia , Doenças Neuroinflamatórias , Adaptação Fisiológica , Transdução de Sinais , NF-kappa B/farmacologia
15.
Fish Shellfish Immunol ; 146: 109362, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218423

RESUMO

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


Assuntos
Microbiota , Rhodiola , Animais , NF-kappa B , Fator de Necrose Tumoral alfa , Quimotripsina , Disbiose , Interleucina-8 , Ocludina , Intestinos/fisiologia , Dieta/veterinária , Peixes , Lipase , RNA Mensageiro , Amido , Fator de Crescimento Transformador beta , Ração Animal/análise
16.
Br J Nutr ; 131(3): 461-473, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-37641937

RESUMO

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.


Assuntos
Substâncias para Melhoria do Desempenho , Rhodiola , Masculino , Adulto , Feminino , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/farmacologia , Rhodiola/química , Substâncias para Melhoria do Desempenho/farmacologia , Exercício Físico/fisiologia
17.
Plant J ; 117(2): 464-482, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872890

RESUMO

Rhodiola L. is a genus that has undergone rapid radiation in the mid-Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an important adaptogen in traditional medicines for centuries. However, a lack of high-quality chromosome-level genomes hinders in-depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome-level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat-retrotransposons (LTR-RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high-altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF-VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.


Assuntos
Glucosídeos , Fenóis , Rhodiola , Rhodiola/genética , Rhodiola/metabolismo , Vias Biossintéticas , Tamanho do Genoma , Cromossomos , Evolução Molecular
18.
Colloids Surf B Biointerfaces ; 234: 113692, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104466

RESUMO

Different types and ratios of surfactant, co-surfactant, and oil phase, have a greater impact on nanoemulsion preparation. The presence of surfactants in the nanoemulsion can reduce surface tension and characteristic stability. In this study, four groups of oil-in-water (O/W) nanoemulsions (NEs) with different ratios of surfactant and co-surfactant, and two oils were formulated as carriers of Rhodiola rosea. The variable optimization was investigated and then indicated as optimization group A (Opt A) with the formula of 10% of transcutol, 16.63% of tween 80, Opt B with 10% of tween 80, 29.87% of span 80, Opt C with 28.42% of transcutol, 30% of labrasol, and Opt D with 30% of transcutol, 30% of tween 80. Labrafac and soybean oil were used as the oil phase. The optimized formula using the response surface method (RSM) by design expert software showed the ideal conditions with a higher desirability score. Desirability score are 0.72% (Opt A), 0.81% (Opt B), 0.76% (Opt C) and 0.98% (Opt D), the desirability rating close to 1 indicates a high possibility that the projected values would closely match the experimental results for the optimum formula. All of the optimized formulation were also checked for the characteristics of nanoemulsion including particle size, polydispersity index (PDI), zeta potential, viscosity, encapsulation efficiency, transmission electron microscope (TEM), antioxidant activity, skin irritation test and stability studies. Our study provides a promising combination of surfactant-co-surfactant and oil phases to produce a stable nanoemulsion that can be used in pharmaceuticals and cosmetics in the future.


Assuntos
Etilenoglicóis , Rhodiola , Tensoativos , Polissorbatos , Tamanho da Partícula , Óleos , Água , Emulsões
19.
Immun Inflamm Dis ; 11(12): e1127, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38156377

RESUMO

PURPOSE: The present study aimed to explore the potential components and mechanisms of Rhodiola rosea-Euonymus alatus drug pair (TY) that ameliorate rheumatoid arthritis (RA). METHODS: The main active components, core targets, and important pathways of TY against RA were predicted by network pharmacology analysis. The binding activity between the main active components and the core targets was verified by the molecular docking technique. Collagen-induced arthritis (CIA) rat model and tumor necrosis factor (TNF)-α-induced fibroblast-like synovial cells in human RA (HFLS-RA) model were established, respectively. The core targets were verified by cell counting kit-8 assay, hematoxylin eosin, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis, and the therapeutic effect of TY was evaluated. RESULTS: A total of 18 possible components and 34 core targets were obtained by network pharmacology, among which inflammatory response, phosphatidylinositide 3-kinases (PI3K)-AKT and MAPK pathways were involved in the therapeutic effect of TY on RA. The results of molecular docking showed that kaempferol and quercetin had high binding affinity to interleukin (IL)-1ß, IL-6, matrix metalloproteinase (MMP)9, and TNF-α. In vivo and in vitro experiments showed that TY dose-dependently inhibited the proliferation of HFLS-RA cells induced by TNF-α, and significantly reduced the paw swelling and arthritis scores in CIA rats. At the same time, TY inhibited the production of inflammatory factors in CIA rat serum and TNF-α-induced HFLS-RA cells. It also decreased the expression of PI3K, phospho-protein kinase B, MMP1, MMP3, MMP9, and increased the protein and mRNA levels of tissue inhibitors of MMPs (TIMP)1 in synovial tissue. CONCLUSION: TY can inhibit the PI3K/AKT signaling pathway and regulate the balance between MMPs and TIMP, thus playing a therapeutic role in RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Euonymus , Rhodiola , Humanos , Ratos , Animais , Euonymus/metabolismo , Rhodiola/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Proto-Oncogênicas c-akt , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Metaloproteinases da Matriz/uso terapêutico
20.
Molecules ; 28(21)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37959831

RESUMO

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.


Assuntos
Extratos Vegetais , Rhodiola , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Dissacarídeos/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico
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