Pulmonary arterial hypertension(PAH)is a devastating pulmonary circulation disease lacking high-efficiency therapeutics.The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata,a well-known t...Pulmonary arterial hypertension(PAH)is a devastating pulmonary circulation disease lacking high-efficiency therapeutics.The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata,a well-known traditional chinese medicine with cardiopulmonary protection capacity,on PAH by exploiting functional lipidomics.The rat model with PAH was successfully established for first,following Rhodiola crenulata water extract(RCE)treatment,then analysis of chemical constituents of RCE was performed,additional morphologic,hemodynamic,echocardiographic measurements were examined,further targeted lipidomics assay was performed to identify differential lipidomes,at last accordingly mechanism assay was done by combining qRT-PCR,Western blot and ELISA.Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls,mostly assigned to acylcarnitines,phosphatidylcholines,sphingomyelin associated with the PAH development.Excitingly,RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH.Furthermore,RCE was observed to reduce autophagy,confirmed by significantly inhibited PPARγ,LC3B,ATG7 and upregulated p62,and inactivated LKB1-AMPK signal pathway.Notably,we accurately identified the constituents in RCE,and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy.Altogether,RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH.This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.展开更多
Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly...Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5e35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 mM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.展开更多
[Objectives] To measure and analyze chemical composition of R. crenulata. [Methods] Taking R. crenulata in Lang County of Tibet as the research object,the routine nutritional components,trace elements and amino acid w...[Objectives] To measure and analyze chemical composition of R. crenulata. [Methods] Taking R. crenulata in Lang County of Tibet as the research object,the routine nutritional components,trace elements and amino acid were determined,and the nutrition was evaluated by the international general evaluation method. [Results]The protein content of R. crenulata in Lang County of Tibet was 2. 08%,and fat was 5. 67%. Amino acid was incomplete amino acid,and Ile,Met + Cys were the first limiting amino acids of rhodiola root protein,while Leu was the second limiting amino acid of rhodiola root protein. The final amino acid score was 0. Magnesium,iron,zinc and other mineral elements were abundant,and there was no mercury,cadmium,lead and other heavy metals residues. [Conclusions]The research could provide a powerful basis for industrialization development of rhodiola.展开更多
[Objectives]To study the optimal extraction process of total flavonoids in Rhodiola rosea L.,and further facilitate the development and utilization of Rhodiola rosea L. [Methods]With Rhodiola crenulata as raw material...[Objectives]To study the optimal extraction process of total flavonoids in Rhodiola rosea L.,and further facilitate the development and utilization of Rhodiola rosea L. [Methods]With Rhodiola crenulata as raw material,ethanol as extractant,ultrasonic extraction as the extraction method,the single factor method was first used for preliminary investigation of effect of ethanol volume fraction,solid-liquid ratio,extraction temperature and extraction time on the flavonoids extraction rate,and then the Box-Behnken response surface method was used to optimize the extraction process of total flavonoids in R. crenulata. [Results] The optimal extraction conditions: ethanol concentration of 72%;solid-liquid ratio of 1∶ 43; extraction temperature of 66℃; extraction time of 50 min. Under these conditions,the extraction rate of total flavonoids from R. crenulata was 2. 591%. [Conclusions] The results showed that the method of response surface was reasonable and feasible for the optimization of ultrasonic extraction of total flavonoids from R. crenulata.展开更多
In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor explo...In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis.The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30%(V/V)in DESs.AB-8 macroporous resin and ethyl acetate were used for separation and refining,and the oligomer-rich proanthocyanidin components were eventually obtained.The ultraviolet(UV)and infrared(IR)spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin.To further clarify the chemical composition of proanthocyanidin,an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering(MDF)algorithm,combined with the full mass spectrometry(MS)/dd-MS2 scan mode that turns on the“if idle pick others”function.By using ultra-high performance liquid chromatography and high-resolution MS(UHPLC/HRMS),the analysis used both targeted and nontargeted methods to detect proanthocyanidins.Finally,50 oligomeric proanthocyanidin(OPC)compounds were identified,including 7 monomers,22 dimers,20 trimers,and 1 tetramer,most of which were procyanidins of proanthocyanidins(84%),and a small amount of prodelphinidin(14%)and other types of proanthocyanidins(2%),which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes.Meanwhile,the comparison with the grape seeds OPCs standard(United States Pharmacopeia)revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant,suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.展开更多
A novel gallotannin, crenulatin (1), was isolated from the stem of Rhodiola crenulata, and its structure was determined by means of spectral analyses(including ~1H—~1H COSY, ~1H—^(13)C COSY and ~1H—^(13)C COLOC spe...A novel gallotannin, crenulatin (1), was isolated from the stem of Rhodiola crenulata, and its structure was determined by means of spectral analyses(including ~1H—~1H COSY, ~1H—^(13)C COSY and ~1H—^(13)C COLOC spectral measurements)and chemical evidence.展开更多
Rhodiola crenulata(Hook.F.et Thoms.)H.Ohba(Hongjingtian,RC)thrives mainly in high-altitude regions including but not limited to the Himalayan region,Xizang areas in China,northwest Yunnan,and Western Sichuan.(1.2)The ...Rhodiola crenulata(Hook.F.et Thoms.)H.Ohba(Hongjingtian,RC)thrives mainly in high-altitude regions including but not limited to the Himalayan region,Xizang areas in China,northwest Yunnan,and Western Sichuan.(1.2)The dried root and rhizome of RC have a long history of medicinal use,primarily valued for its adaptogenic effects and significant potential for further development.展开更多
[目的]探讨红景天[Rhodiola crenulata(Hook.f.et.Thoms.)H.Ohba]提取物对小鼠免疫功能的影响。[方法]将192只BALB/c小鼠随机分为4批,每批分为4组,分别为低、中、高3个剂量组和1个溶剂对照组,连续灌药(20 m l/kg.体重)30 d,测定各免疫...[目的]探讨红景天[Rhodiola crenulata(Hook.f.et.Thoms.)H.Ohba]提取物对小鼠免疫功能的影响。[方法]将192只BALB/c小鼠随机分为4批,每批分为4组,分别为低、中、高3个剂量组和1个溶剂对照组,连续灌药(20 m l/kg.体重)30 d,测定各免疫指标。[结果]高剂量组红景天提取物可提高小鼠碳廓清能力(P<0.05);中剂量和高剂量组能增强绵羊红细胞诱导小鼠DTH能力(P<0.05),促进NK细胞活性(P<0.05)和血清凝血素的生成(P<0.05),增加抗体生成细胞数的生成(P<0.05),并且能提高小鼠腹腔巨噬细胞吞噬鸡红细胞的能力(P<0.05),但对免疫器官/体重质量值和ConA诱导的小鼠脾淋巴细胞转化能力无显著影响。[结论]红景天提取物具有增强正常小鼠免疫力的功能,该研究为开发有食用价值的保健食品提供了试验依据。展开更多
基金the National Natural Science Foundation of China(No.81302764)the Science and Technology Grant for Excellent Talents of Harbin(No.2017RAXXJ-060).
文摘Pulmonary arterial hypertension(PAH)is a devastating pulmonary circulation disease lacking high-efficiency therapeutics.The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata,a well-known traditional chinese medicine with cardiopulmonary protection capacity,on PAH by exploiting functional lipidomics.The rat model with PAH was successfully established for first,following Rhodiola crenulata water extract(RCE)treatment,then analysis of chemical constituents of RCE was performed,additional morphologic,hemodynamic,echocardiographic measurements were examined,further targeted lipidomics assay was performed to identify differential lipidomes,at last accordingly mechanism assay was done by combining qRT-PCR,Western blot and ELISA.Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls,mostly assigned to acylcarnitines,phosphatidylcholines,sphingomyelin associated with the PAH development.Excitingly,RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH.Furthermore,RCE was observed to reduce autophagy,confirmed by significantly inhibited PPARγ,LC3B,ATG7 and upregulated p62,and inactivated LKB1-AMPK signal pathway.Notably,we accurately identified the constituents in RCE,and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy.Altogether,RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH.This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82160739,81922070,81973286,and 81973393)Sailing Special Project of Shanghai Rising-Star Program(Grant No.:22YF1441500)+6 种基金Program for Innovative Leading Talents of Qinghai Province(2018&2019)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202004)Shanghai Science and Technology Innovation Action Plans(Grant Nos.:20S21901500 and 20S21900900)supported by the Shanghai Science and Technology CommitteeProject of the National Multidisciplinary Innovation Team of Traditional Chinese Medicine supported by the National Administration of Traditional Chinese MedicineKey R&D and Transformation Science and Technology Cooperation Project of Qinghai Province(Grant No.:2019-HZ-819)Basic Public Welfare Research Program of Zhejiang Province(Grant No.:LGF22H280012).
文摘Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5e35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 mM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.
文摘[Objectives] To measure and analyze chemical composition of R. crenulata. [Methods] Taking R. crenulata in Lang County of Tibet as the research object,the routine nutritional components,trace elements and amino acid were determined,and the nutrition was evaluated by the international general evaluation method. [Results]The protein content of R. crenulata in Lang County of Tibet was 2. 08%,and fat was 5. 67%. Amino acid was incomplete amino acid,and Ile,Met + Cys were the first limiting amino acids of rhodiola root protein,while Leu was the second limiting amino acid of rhodiola root protein. The final amino acid score was 0. Magnesium,iron,zinc and other mineral elements were abundant,and there was no mercury,cadmium,lead and other heavy metals residues. [Conclusions]The research could provide a powerful basis for industrialization development of rhodiola.
基金Supported by Tibetan 13th Five-Year Agricultural Product Processing and Product Development Project
文摘[Objectives]To study the optimal extraction process of total flavonoids in Rhodiola rosea L.,and further facilitate the development and utilization of Rhodiola rosea L. [Methods]With Rhodiola crenulata as raw material,ethanol as extractant,ultrasonic extraction as the extraction method,the single factor method was first used for preliminary investigation of effect of ethanol volume fraction,solid-liquid ratio,extraction temperature and extraction time on the flavonoids extraction rate,and then the Box-Behnken response surface method was used to optimize the extraction process of total flavonoids in R. crenulata. [Results] The optimal extraction conditions: ethanol concentration of 72%;solid-liquid ratio of 1∶ 43; extraction temperature of 66℃; extraction time of 50 min. Under these conditions,the extraction rate of total flavonoids from R. crenulata was 2. 591%. [Conclusions] The results showed that the method of response surface was reasonable and feasible for the optimization of ultrasonic extraction of total flavonoids from R. crenulata.
基金supported by the Science and Technology Program of Tianjin in China(Grant No.:23ZYJDSS00030)the Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,China(Grant Nos.:22HHZYSS00007 and 22HHZYJC00003).
文摘In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis.The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30%(V/V)in DESs.AB-8 macroporous resin and ethyl acetate were used for separation and refining,and the oligomer-rich proanthocyanidin components were eventually obtained.The ultraviolet(UV)and infrared(IR)spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin.To further clarify the chemical composition of proanthocyanidin,an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering(MDF)algorithm,combined with the full mass spectrometry(MS)/dd-MS2 scan mode that turns on the“if idle pick others”function.By using ultra-high performance liquid chromatography and high-resolution MS(UHPLC/HRMS),the analysis used both targeted and nontargeted methods to detect proanthocyanidins.Finally,50 oligomeric proanthocyanidin(OPC)compounds were identified,including 7 monomers,22 dimers,20 trimers,and 1 tetramer,most of which were procyanidins of proanthocyanidins(84%),and a small amount of prodelphinidin(14%)and other types of proanthocyanidins(2%),which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes.Meanwhile,the comparison with the grape seeds OPCs standard(United States Pharmacopeia)revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant,suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.
文摘A novel gallotannin, crenulatin (1), was isolated from the stem of Rhodiola crenulata, and its structure was determined by means of spectral analyses(including ~1H—~1H COSY, ~1H—^(13)C COSY and ~1H—^(13)C COLOC spectral measurements)and chemical evidence.
基金Supported by the National Natural Science Foundation of China(No.82204614 and No.82304755)Pioneer′and“Leading Goose”R&D Program of Zhejiang(No.2023C03004 and No.2025C01110)。
文摘Rhodiola crenulata(Hook.F.et Thoms.)H.Ohba(Hongjingtian,RC)thrives mainly in high-altitude regions including but not limited to the Himalayan region,Xizang areas in China,northwest Yunnan,and Western Sichuan.(1.2)The dried root and rhizome of RC have a long history of medicinal use,primarily valued for its adaptogenic effects and significant potential for further development.
文摘[目的]探讨红景天[Rhodiola crenulata(Hook.f.et.Thoms.)H.Ohba]提取物对小鼠免疫功能的影响。[方法]将192只BALB/c小鼠随机分为4批,每批分为4组,分别为低、中、高3个剂量组和1个溶剂对照组,连续灌药(20 m l/kg.体重)30 d,测定各免疫指标。[结果]高剂量组红景天提取物可提高小鼠碳廓清能力(P<0.05);中剂量和高剂量组能增强绵羊红细胞诱导小鼠DTH能力(P<0.05),促进NK细胞活性(P<0.05)和血清凝血素的生成(P<0.05),增加抗体生成细胞数的生成(P<0.05),并且能提高小鼠腹腔巨噬细胞吞噬鸡红细胞的能力(P<0.05),但对免疫器官/体重质量值和ConA诱导的小鼠脾淋巴细胞转化能力无显著影响。[结论]红景天提取物具有增强正常小鼠免疫力的功能,该研究为开发有食用价值的保健食品提供了试验依据。
