An integrated strategy of UPLC-Q-TOF/MS and HPTLC/PAD-DESI-MSI for the analysis of chemical variations:A case study of Tibetan medicine Tiebangchui

The dried roots of Aconitum pendulum Busch are the major source of a commonly used Tibetan medicine,namely Tiebangchui(TBC)(Fig.S1).However,raw TBC contains a large amount of high toxic diester-diterpenoid alkaloids(DDAs),and the improper use would cause arrhythmia,irreversible cardiovascular damages,and even death.“Paozhi”,an appropriate processing method,is the essential prerequisite for the safe clinical application of TBC.Water-decocting and sand-frying are commonly used processing methods for toxicity attenuation and efficacy preservation for TBC.

Annual advances of Chinese minority traditional medicine in 2020

Chinese minority traditional medicine is a traditional medicine formed during the long-term medical practice of various ethnic groups and is the crystallization of the wisdom of the people in all ethnic groups in China.The unique meaning carried by Chinese minority traditional medicine makes it an inseparable and important part of traditional Chinese medicine.The rich clinical experience and theoretical studies with different Chinese minority traditional medicine provide new ideas and new methods for Chinese medicine development.The pieces of literature published in 2020 on the traditional application analyzed the phytochemical composition,pharmacological effects,and mechanisms of the different ethnic groups including Tibetan,Mongolian,Zhuang,Dai,and Uyghur medicines,among others.This study found that some projects were stalled or delayed due to the coronavirus disease 2019 outbreak in 2020 compared with 2019,resulting in a decrease in the number of articles in certain fields.However,studied on Chinese minority traditional medicine have shown an overall upward trend this year with the Tibetan,Mongolian,and Dai medicines as the top three.In addition,the Chinese minority traditional medicine application under the coronavirus disease 2019 epidemic situation background was also summarized.Consequently,this study found that among the Chinese minority traditional medicine-related publications in 2020,publications using Chinese minority traditional medicine to treat coronavirus disease 2019 account for a certain percentage.Thus,this article systematically reviews and summarizes the related research of Chinese minority traditional medicine published in 2020 and provides references for future Chinese minority traditional medicine development.

Study on Quality Standard of Tibetan Medicine Corydalis dasyptera Maxim.

[Objectives]To establish the quality standard of Tibetan medicine Corydalis dasyptera Maxim.[Methods]According to the research method of drug quality standard in the appendix of 2020 edition of Chinese Pharmacopoeia,8 batches of C.dasyptera Maxim.from different habitats were studied by character identification,microscopic identification and TLC identification.The content of water,total ash,acid-insoluble ash and alcohol-soluble extract was determined,and the content of protopine in medicinal materials was determined by high performance liquid chromatography(HPLC).[Results]The properties and microscopic characteristics of C.dasyptera Maxim.were determined.The TLC characteristic spots of the medicinal materials were clear,the degree of separation was good,and the specificity was strong.Both the test sample and the control sample showed the same yellow-green spots in the corresponding position.It was tentatively determined that the water content of C.dasyptera Maxim.should not exceed 14.0%,the total ash content should not exceed 14.0%,the acid-insoluble ash content should not exceed 3.0%,and the alcohol-soluble extract content should not be less than 18.0%.There was a good linear relationship between the concentration of protopine and the peak area in the range of 16.64-166.40μg·10-3(r=0.9996).The average recovery rate was 98.47%and the RSD was 1.21%(n=6).The content of protopine in 8 batches of C.dasyptera Maxim.was 0.023%-0.093%.[Conclusions]The established quality research method is simple,stable and reliable,and can be used for the quality control of C.dasyptera Maxim.

The impact of^(60)Co-γirradiation on the chemical constituents of Chuanxiong Rhizoma

Background:In order to clarify the inmpat ofγirradiation on the chemical composition of traditional Chinese medicine,this paper carefully choosed Chuanxiong Rhizoma to carry on a demonstration study.Methods:Through a meticulous assessment,a comprehensive comparison was made between the irradiated and unirradiated Chuanxiong Rhizoma samples.The property characteristics were investigated by colorimeter and electronic nose.The changes in chemical structures and contents was analyzed by fourier infrared spectroscopy,high performance liquid chromatography and fingerprinting.In a quest to uncover the presence of any new radiolysis products,cutting-edge techniques like ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry and gas chromatography-mass spectrometry were employed.Moreover,the difference of antioxidant activity were investigated.Results:The irradiation doses within 12 kGy had no significant effects on the content of the main chemical components,characteristics and in vitro antioxidant activity of Chuanxiong Rhizoma,while changes in some functional groups and degradation of some volatile oil components containing olefins need further study.Conclusion:This study indicates that^(60)Co-γirradiation is a stable method for sterilization of Chuanxiong Rhizoma.It’s also provide a reference for the establishment of irradiation standards for Chuanxiong Rhizoma and other aromatic medicinal plants.

The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Establishment of microneurovascular units in alginate hydrogel microspheres to reveal the anti-hypoxic effect of salidroside

Microneurovascular units(mNVUs),comprising neurons,micro-glia,and blood-brain barrier(BBB)endothelial cells,are pivotal to the central nervous system and are associated with cerebral hypoxia and brain injuries.Cerebral hypoxia triggers microglial overactivity,causing inflammation,neuronal injury,and disruption of the BBB[1].Salidroside(Sal),a key compound in Tibetan medicine Rhodiola crenulata,mitigates hypoxia-induced metabolic disorders and neuronal damage by preserving mitochondrial function[2].

Study on the intervention of Dajianzhong decoction on lipid accumulation in HepG2 cells by combining network pharmacology with in vitro experiments

Background:Nonalcoholic fatty liver disease(NAFLD)is a metabolic disorder of the liver with a complex underlying pathogenic mechanism characterized by excessive accumulation of lipids in liver cells,which can later lead to irreversible liver fibrosis.Dajianzhong decoction(DJZ)is a traditional Chinese medicine formula,and its medicinal components have the potential to treat metabolic diseases.This study aims to evaluate the effect of DJZ intervention on lipid accumulation in HepG2 cells in vitro.Methods:This study used a combination of network pharmacology and in vitro experimental validation to demonstrate the efficacy of DJZ in treating NAFLD using a commercial kit.And the key genes were characterized by PCR technology.Western blot was used to characterize the expression of core proteins in network pharmacology.Results:The results of network pharmacology indicate that DJZ shares 220 common targets with NAFLD.According to the MCOED plugin in PPI,the core targets include apoptosis regulator Bcl-2(Bcl2),apoptosis regulator BAX(BAX),Caspase-3(CASP3),mitogen-activated protein kinase 8(JNK),mitogen-activated protein kinase 1(MAPK1),peroxisome proliferator-activated receptor alpha(PPAR-α),etc.These targets also occupy important positions in the component target pathway disease network diagram,and were validated by molecular docking.In vitro experiments showed that DJZ reduced the intracellular total triglyceride(TG)and total cholesterol(TC)content of HepG2 cells,decreased the production of ROS in cells,and reduced apoptosis,playing a protective role in liver cells.The mRNA expression levels of some key fatty acid and cholesterol metabolism factors were also characterized by PCR.After administering DJZ to HepG2 cells,the mRNA levels of fatty acid synthesis proteins such as SREBP1 and FASN decreased,while the mRNA levels of fatty acid metabolism such as PPAR-αand ACOX1 increased.The core targets in network pharmacology were also validated by western blot,and the pathways involved were related to apoptosis and fatty acid oxidation.Conclusion:DJZ can effectively reduce the intracellular lipid levels and decrease cell apoptosis in HepG2 cells modeled with free fatty acids.Further research is needed in animal experiments and to improve the composition analysis of DJZ,in order to fully clarify the molecular mechanism and material basis of DJZ in treating NAFLD.

Vibralactone Biogenesis-Associated Analogues from Submerged Cultures of the Fungus Boreostereum vibrans

A scale-up fermentation of the fungus Boreostereum vibrans facilitated the isolation of six new vibralactone biogenesis-associated analogues,namely vibralactamide A(1),vibralactone T(2),13-O-lactyl vibralactone(3),10-O-acetyl vibralactone G(4),(11R,12R)-and(11S,12R)-vibradiol(5,6).Their structures were established via extensive spectroscopic analyses,specific optical rotation comparison,and Snatzke’s method.The biosynthetic pathway for vibralactamide A was postulated.The absolute configuration of vibralactone B was revised by single crystal X-ray diffraction analysis.This work puts the divergent vibralactone biosynthesis pathway one step further and expands the structural diversity of vibralactone-associated compounds.

Research hotspots and trends in Chinese minority traditional medicine during 2021:a visual bibliometrics analysis

Background:Chinese minority traditional medicine(CMTM)is an important component of Chinese traditional culture and medicine that has contributed to the health and prosperity of Chinese people of all ethnic groups.Although this type of medicine has attracted interest,its developmental trends and research status remain unclear.Therefore,we used literature metrology to evaluate the publications on CMTM during 2021 and explore hotspots and frontier areas.Methods:Reports associated with CMTM published between January 1,2021,and December 31,2021,were downloaded from the Web of Science database.The authors,institutions,countries,journals,keywords,and other standard bibliometric indicators were analyzed and visualized using CiteSpace,and research hotspots and trends were identified.Results:We retrieved 152 CMTM-related publications,among which Tibetan medicine attracted the most interest.Journals covering alternative and complementary medicine topics were the most prevalent sources of reports about CMTM,particularly the Journal of Ethnopharmacology.Most research in this field was conducted in China and frequently published by traditional Chinese medicine colleges and universities.One author,Yi Zhang,has extensively investigated Tibetan and Korean medicine.The keyword co-occurrence network revealed that investigations into ethnic groups mainly focused on the pharmacological activities and phytochemical components of ethnic medicines.The keywords of gut microbiota and autophagy in some publications reflect the direction of future CMTM investigations.Conclusion:Our findings showed the current status and trends in CMTM investigations.This information will help identify new research directions and hotspots in this field.

Peptide Cy_(RL-QN15)accelerates hair regeneration in diabetic mice by binding to the Frizzled-7 receptor

Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair,reducing the risk of infection,and enhancing overall skin health.Research has predominantly emphasized the re-epithelialization of diabetic wounds,with a paucity of in-depth studies on hair follicle regeneration.In the current study,we explored the effects of a bioactive amphibian-derived peptide,Cy_(RL-QN15),on promoting hair regeneration in a diabetic skin model.In vivo experiments demonstrated that local treatment with Cy_(RL-QN15)not only accelerated wound healing of scalded skin on the backs of diabetic Kunming(KM)mice but also improved growth of damaged hair follicles.Additionally,back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy_(RL-QN15)treatment.Further analysis indicated that the hairregenerating effects of Cy_(RL-QN15)were closely associated with the proliferation and migration of hair follicle stem cells(HFSCs).Cy_(RL-QN15)enhanced intracellularβ-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs.The up-regulation inβ-catenin modulated the levels of downstream proteins,such as cMYC,Cyclin D1,and Lef1,ultimately inducing hair regeneration.This study not only reveals the robust effects of the bioactive peptide Cy_(RL-QN15)in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.

Daphnane Diterpenoids from Trigonostemon lii and Inhibition Activities Against HIV‑1

Natural products are the important source for the discovery of more potent anti-HIV agents.In this study,six daphnane diterpenoids including three unreported structures were isolated from Trigonostemon lii,which showed signifcant activities against HIV-1 strains replication in the nanomolar/picomolar range.Meanwhile,these diterpenoids signifcantly inhibited the fusion of H9/HIV-1 IIIB cells with uninfected C8166 cells,with the EC50s from 1.06 to 8.73 ng/mL,and did not show any inhibition activities against HIV-1 reverse transcriptase.Moreover,all of the diterpenoids shows signifcant inhibitions against T20-resistan HIV-1 strains,PNL4-3gp41(36G)V38E,N42S and pNL4-3gp41(36G)V38A,N42T.The results revealed that the six diterpenoids could be a new type of potential lead candidate as an HIV entry inhibitor,particularly for those infected by T20-resistant variants.

A new peptide,VD11,promotes structural and functional recovery after spinal cord injury

The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury.Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue.While amphibians have a pronounced ability to regenerate the spinal cord,few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury.Here we report for the first time the successful identification and isolation of a new polypeptide,VD11(amino acid sequence:VDELWPPWLPC),from the spinal cord of an endemic Chinese amphibian(Odorrana schmackeri).In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide,as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia.In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury,alleviated pathological damage,and promoted axonal regeneration.Furthermore,RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways.In summary,we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.

Five new limonoids isolated from Walsura robusta

Five new toosendanin limonoids with highly oxidative furan ring walsurobustones A-D(1-4),and one new furan ring degraded limonoid walsurobustone E(5)together with one known compound toonapubesic acid B(6)were isolated from the leaves of Walsura robusta.Their structures were elucidated by NMR and MS data.Especially,the absolute configuration of toonapubesic acid B(6)was confirmed by X-ray diffraction study.Compounds 1-6 exhibited good cytotoxicity against the cancer cell lines HL-60,SMMC-7721,A-549,MCF-7,and SW480.

SDC1 acts as a novel molecular marker and prevents rheumatoid arthritis and modulates inflammatory response by targeting the miR-4531/SDC1 axis

Objective:Rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by chronic erosive arthritis.Due to the lack of effective biomarkers for diagnosis and treatment,RA patients have many complications in the later stage,seriously affecting their quality of life.Thus,this study was conducted to investigate new therapeutic targets and to discover diagnostic biomarkers in RA.Methods:In this study,the expression profiles of GSE55235 and GSE55457 were downloaded from the Gene Expression Omnibus database to obtain DEGs between RA and healthy samples.Genetic Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the common genes existing in the RA-related modules.Additionally,we used the STRING database to construct the protein‒protein interaction network.Furthermore,we established the interaction analysis of Hub Genes and microRNA(miRNA)and verified the 10 Hub genes through the GSE77298 dataset and quantitative real-time polymerase chain reaction Results:276 and 69 DEGs were screened from the GSE55235 dataset and GSE55457 dataset,respectively.Then,we obtained 42 up-regulated genes in two chip datasets intersection.Genetic Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the 42 up-regulated genes showed that they were mainly concentrated in immune response-activating cell surface receptor signaling pathway,etc.Furthermore,the protein-protein interaction network indicated that 10 hub genes are closely related to RA,including MS4A1,CD27,LCK,CD79A,SDC1,CXCL9,CXCL10,CXCL13,IGLL5,and IGJ.In addition,we found that miR-4531 is the same target miRNAs between MS4A1 and SDC1 through messenger RNA-miRNA co-expression network.Finally,the GSE77298 gene chip and quantitative real-time polymerase chain reaction verified the expression of 10 Hub genes.The six Hub genes of CD27,SDC1,CXCL9,CXCL10,CXCL13,and IGJ are significantly increased.Conclusions:We found that SDC1 may be a novel molecular marker for the prevention and treatment of RA.The miR-4531/SDC1 regulatory axis may play a key role in this process.In conclusion,our study not only provides potential biomarkers for the diagnosis and treatment of RA,but also provides a basis and new targets for further revealing the potential mechanism of RA occurrence and development and discovering targeted drugs.

Effect and mechanism of ethanol extracts of muxiang(Radix Aucklandiae) on gastric ulcers in rats

OBJECTIVE:To investigate the effect of ethanol extracts of Muxiang(Radix Aucklandiae)(RA)on gastric ulcers in rats and explore the potential mechanisms.METHODS:A model was established by ethanol(0.75 m L/kg).According to body weight,rats were pretreated with RA extracts(2.5 or 5 g/kg).The rats were administered 95%ethanol orally after 1 h.The effects of ethanol were evaluated by measuring the gastric secretion volume,p H,pepsin activity,and ulcer area.Histological analysis and immunohistochemistry were also conducted.Furthermore,the effect of the ethanol extract of RA on transiting activity of the gastrointestinal tract was observed in mice.RESULTS:Intragastric administration of RA extracts protected the gastric mucosa from ethanol-induced gastric ulcers,while reducing submucosal edema and preventing hemorrhagic damage.Moreover,the extracts increased the production of gastric mucus,upregulated Bcl-2,and downregulated Bax expression.Importantly,pretreated rats exhibited no significant change in the gastric secretion volume,gastric juice acidity,or pepsin.Furthermore,pretreatment prominently(P<0.05)enhanced propulsive movement of the gastrointestinal tract in normal mice and mice with gastrointestinal motility disorders.CONCLUSION:Ethanol extracts of RA ameliorated gastric lesions in the gastric ulcer rat model.The mechanisms of action were related to improvement of gastrointestinal dynamics,maintenance of mucus integrity,and inhibition of apoptosis by downregulating proapoptotic Bax protein and upregulating anti-apoptotic Bcl-2 protein.

Structural characterization,in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine

Objective:The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified.This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.Methods:The diterpenoid alkaloid 3-acetylaconitine was heated at 180°C for 15 min to simulate the process of sand frying.The pyrolysis products were separated using column chromatography,and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy.Further,in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared,and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.Results:Two new diterpenoid alkaloids,pyroacetylaconitine and 16-epi-pyroacetylaconitine,a pair of epimers at C-16,were isolated.After comparing the structures of these compounds,possible transformation pathways were proposed.Compared with the prototype compound,3-acetylaconitine,the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased.In the biological activity assay,the two pyrolysis products exhibited an effective increase in ventricular premature beat latency,a reduction in the occurrence of ventricular tachycardia,as well as an increase in the rate of arrhythmia inhibition,implying strong antiarrhythmic activity.Conclusion:Compared with 3-acetylaconitine,its pyrolysis products displayed lower toxicity and good antiarrhythmic effects;thus,they have potential for being developed into antiarrhythmic medicines.

Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis

Background:Wound management of diabetic foot ulcers(DFUs)is a complex and challenging task,and existing strategies fail to meet clinical needs.Therefore,it is important to develop novel drug candidates and discover new therapeutic targets.However,reports on peptides as molecular probes for resolving issues related to DFUs remain rare.This study utilized peptide RL-QN15 as an exogenous molecular probe to investigate the underlying mechanism of endogenous non-coding RNA in DFU wound healing.The aim was to generate novel insights for the clinical management of DFUs and identify potential drug targets.Methods:We investigated the wound-healing efficiency of peptide RL-QN15 under diabetic con-ditions using in vitro and in vivo experimental models.RNA sequencing,in vitro transfection,quantitative real-time polymerase chain reaction,western blotting,dual luciferase reporter gene detection,in vitro cell scratches,and cell proliferation and migration assays were performed to explore the potential mechanism underlying the promoting effects of RL-QN15 on DFU repair.Results:Peptide RL-QN15 enhanced the migration and proliferation of human immortalized keratinocytes(HaCaT cells)in a high-glucose environment and accelerated wound healing in a DFU rat model.Based on results from RNA sequencing,we defined a new microRNA(miR-4482-3p)related to the promotion of wound healing.The bioactivity of miR-4482-3p was verified by inhibiting and overexpressing miR-4482-3p.Inhibition of miR-4482-3p enhanced the migration and proliferation ability of HaCaT cells as well as the expression of vascular endothelial growth factor B(VEGFB).RLQN15 also promoted the migration and proliferation ability of HaCaT cells,and VEGFB expression was mediated via inhibition of miR-4482-3p expression by the p38 mitogen-activated protein kinase(p38MAPK)and smad3 signaling pathways.Conclusions:RL-QN15 is an effective molecule for the treatment of DFUs,with the underlying mechanism related to the inhibition of miR-4482-3p expression via the p38MAPK and smad3 signaling pathways,ultimately promoting re-epithelialization,angiogenesis and wound healing.This study provides a theoretical basis for the clinical application of RL-QN15 as a molecular probe in promoting DFU wound healing.

Seabuckthorn Berries Extract Attenuates Pulmonary Vascular Hyperpermeability in Lipopolysaccharide-Induced Acute Lung Injury in Mice

Objective:To investigate the effect of seabuckthorn berries extract(SBE)on pulmonary vascular hyperpermeability in the mice model of acute lung injury(ALI)induced by lipopolysaccharide(LPS).Methods:Sixty Kunming mice were allocated into 6 groups by a random number table,including control,LPS,dexamethasone(Dex,1 mg/kg),and 120,240 and 480 mg/kg SBE groups,10 mice in each group.Except the control group,mice were pre-treated with Dex and SBE,respectively,for 7 days before LPS was intraperitoneally injected to induce ALl.Pulmonary vascular hyperpermeabilitywas evaluated by histopathologic observation and transvascular leakagedetermination.Tumor necrosis factor alpha(TNF-α)and interleukin-6(IL-6)levels in serum were measured using enzyme-linked immunosorbent assay.The expression of nuclear factor-kappa B(NF-k B)p65 in lung cells was determined by immunofluorescence analysis.The contents of cytoplasmic inhibitorof nuclear factor-kBkinase(IKK)and nuclearp65,as wellasdownstreamproteins of E-selectin(CD62E)and intercellular adhesion molecule-1(ICAM-1),were determined using Western blot analysis.Results:Histopathological observation confirmed SBEtreatment alleviatedmorphological lesion induced by LPS.Compared with the LPS group,480 mg/kg SBE significantly decreased the water content of lung,Evans blue accumulation in lung tissue,and protein concentration and neutrophils count in bronchoalveolar lavage fluid(P<o.01);moreover,480 mg/kg SBE significantly suppressed release of TNF-αand IL-6,and down-regulated expressions of IKK,nuclear p65,ICAM-1 and CD62E(P<0.01).Conclusion:SBE maintained alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of ALl.

Natural bioactive flavonoids as promising agents in alleviating exercise-induced fatigue

Exercise-induced fatigue is a common phenomenon caused by prolonged strenuous exercise and physical labor as a feeling of exhaustion and reduction of muscle performance,which seriously affects people’s health,work efficiency and quality of life.Meanwhile,numerous studies have shown that natural flavonoids can be an excellent source for preventing and treating exercise-induced fatigue due to their extraordinary antioxidant and antiinflammatory properties.However,the review of flavonoids in alleviating exercise-induced fatigue is still limited.Therefore,this review systematically summarizes recent studies on natural bioactive flavonoids that can alleviate exercise-induced fatigue and improve physical performance,including their plant sources,structure types and features,pharmacological effects and underlying mechanisms against exercise-induced fatigue.Also,the clinical trials have also been reviewed.Flavonols,isoflavones,anthocyanins,and their corresponding glycosides are the major bioactive flavonoids in alleviating exercise-induced fatigue.The current data and the further molecular docking evidently support the potential anti-fatigue effects of these flavonoids mainly involving the inhibition of oxidative stress and inflammatory response,as well as the regulation of energy metabolism.Activation of the Keap1/Nrf2/ARE and AMPK/PGC1-αpathways are responsible for the improvement of flavonoids against exercise-induced fatigue.Hence,this review is expected to contribute to the further research and development of anti-fatigue flavonoids in the functional food and nutraceutical industry.