Hemsleya chinensis tubers, abundantly produced in southwestern China, are commonly used as a folk medicine that excel in anti-inflammation to treat enteritis, bronchitis, and tonsillitis. In this study, three previously undescribed cucurbitane glycosides, hemchinins G–H (1–3), that were characterized by the presence of four glucose substitutions, as well as eleven ones with one to three β-glucoses, were isolated from the tubers of H. chinensis. The structures were confirmed using comprehensive UV, IR, HR-ESI-MS, and NMR analyses, and absolute configurations were determined through a comparison of calculated and experimental ECD after acid hydrolysis. Compounds 1–3 showed NO inhibition effects on LPS-induced RAW 264.7 cells. Finally, molecular docking analyses were conducted to obtain the affinities of the isolated cucurbitane glycosides and our previously reported 19 cucurbitane triterpenes, focusing on targets involved in anti-inflammatory effects. The results indicated that they showed high docking scores of affinities with the proteins in the NF-κB, AMPK, and Nrf2 signaling pathways. Among them, cucurbitane triterpenes with sugar moiety substitution at C-3 and C-26/27 showed better affinity ability. The findings can provide insights into the anti-inflammatory mechanisms of this species and facilitate the development of novel therapeutic agents.
Seven previously undescribed sesquiterpenes, including three norlasseranes (1, 3 - 4) and one 1,10-secolasserane (2) and three straight-chain sesquiterpenes (5- 7), together with ten known sesquiterpenes, were isolated from the aerial parts of Chloranthus japonicus. Compounds 1 and 3 - 4 possessed a C12 and C13 norsesquiterpene skeleton respectively, which might be formed by a possible 7,13-oxidative cleavage and retroDiels-Alder reaction respectively. Their structures were confirmed by comprehensive UV, IR, HR-ESI-MS and NMR analyses, along with quantum chemical calculations of ECD curves and 13C NMR data. Bioassay results showed that lindenane sesquiterpenoid dimer 9 and norlasseranes 1 and 3 - 4 could significantly increase the sensitivity of U2 OS cells to DOX.
Six previously undescribed cucurbitane glycosides, hemchinosides A-F (1-6), along with eleven ones were isolated from Hemsleya chinensis tubers. Compounds 1-6 were characterized by the presence of one to three glucoses substitutions at C-26, and sometimes one glucose at C-3. The structures were confirmed by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and absolute configurations were determined by a comparison of calculated and experimental ECD after acid-hydrolysis. The anti-inflammatory effects of the isolated compounds were further evaluated on lipopolysaccharides-induced RAW 264.7 cells.
Phytochemical investigation of 70% ethanol extract of Euphorbia helioscopia L. led to eight diterpenoids, including four jatrophane-type (1-4), three abietane-type (5-7) and one lathyrane-type (8). Among them, (5E,11E)-3 beta-benzoyloxy-7 beta,14 alpha,15 beta-trihydroxyjatropha-9-one (1) was a new jatrophane diterpenoid. An extensive array of spectral analyses, including HR-ESI-MS, IR, UV, 1D and 2D NMR, as well as quantum chemical calculations of ECD curve, were utilized for their structural elucidation. Bioassay results showed that compounds 2-3 and 6-8 could significantly inhibit NO release on LPS-induced RAW 264.7 cells, especially for jatrophane diterpenoid 3 and abietane diterpenoid 8 that showed stronger activities with the IC50 values of 9.16 +/- 0.70 and 5.74 +/- 0.27 mu M. (c) 2025 ACG Publications. All rights reserved.
Purpose: Rheumatoid arthritis (RA) is an immune system disorder disease accompanied with severe joint damage. However, the molecular mechanism of RA with insensitive to medicine remains insufficient. Thus, this study aims to identify the biomarkers of RA patients with inadequate responses (IR) toward disease-modifying antirheumatic drug (DMARD) and antitumor necrosis factor (TNF) therapies, using multidimensional analyses. Methods: Gene expression data GSE45291 originating from clinics were downloaded from the Gene Expression Omnibus public database (GEO). Differentially expressed genes (DEGs) closely associated with DMARD&TNF-IR RA were identified using the Limma R package. Weighted gene co-expression network analysis (WGCNA) was carried out to identify critical genes. The CIBERSORT algorithm and single sample Gene Set Enrichment Analysis (ssGSEA) were employed for immune infiltration analysis and functional enrichment analysis, respectively. Lastly, mRNA expression levels of the identified hub genes in inflammatory conditions of collagen-induced arthritis (CIA) rats and lipopolysaccharide (LPS)-induced RAW264.7 cells were further observed using RT-qPCR. Results: In this work, a total of 17 genes were identified as hub genes. Of these, the expression levels of UHMK1, ELK4, APOC2, and SFT2D1 were significantly lowered in inflammatory conditions. GSEA indicated B cells with the immune-related genes play an essential role in the course of DMARD&TNF-IR RA. Notable differences in immune cell proportions (activated. Dendritic. cell, CD56 bright. Natural. killer. Cell, gamma. Delta. T. cell, MDSC, macrophage) were observed between normal and disease groups, suggesting immune involvement. Conclusion: The findings of this study provide additional understanding of the detection of DMARD&TNF-IR RA.
Seven compounds(1-7)were isolated from Isodon henryi through silica gel,Sephadex LH-20,ODS,MCI column chromatography and semi-preparative HPLC.Their structures were identified as isogallicacid(1),caffeic acid(2),syringic acid(3),protocatechuic acid(4),oresbiusin A(5),lophanthoside A(6),and 8-hydroxypinoresinol(7),by spectroscopic techniques including HR-MS,IR,UV,NMR,and ECD.Compound 1 was a new galloyl derivative.Moreover,it demonstrated a significant inhibitory effect on the lipopolysaccharide-induced release of nitric oxide from RAW264.7 cells.
Corni fructus (CF) is always subjected to wine processing before prescription in clinic, for an enhancing effect of nourishing liver and kidney. While, the underlying mechanism for this processing on CF remains obscure. In this study, a sensitive ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method combined multi-dimensional analyses was established to monitor chemical characterizations of raw and wine-processed CF (WCF) and hence reveal the effects and underlying mechanism of wine processing on CF. As indicated, a total of 216 compounds were tentatively identified, including 98 structurally complex and variable home/hetero-polymers, that were composed of iridoid glucosides, gallic acids, caffeic acid and/or 5-HMF. Interestingly, 53 of these compounds probably characterized potential novel, including 35 iridoid glucosides or their dimers, 9 iridoid glucoside-gallic acid dimers, 7 gallic acids derivatives and 2 gallic acid-caffeic acid dimers, which provides ideas for natural product researchers. Meanwhile, the multi-dimensional analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regression analysis were used to explore the differences between CF and WCF. The results showed that 23 compounds as chemical markers greatly contributing to the distinction were screened out, and 3 of which (7α/β-O-ethyl-morroniside, gallic acid and 5-HMF) in WCF indicated an increasing trend in intensities in relative to those in CF. Additionally, linear regression analysis showed that in WCF 53 compounds exhibited an increasing in intensities, while 132 ones did a decreasing trend, compared with those in CF. As our investigation demonstrated, acetal reaction of morroniside, ester hydrolysis in different organic acid derivatives as well as glycoside bond cleavage during wine processing probably resulted in the distinctions. The findings of this study provide a further understanding of the effect and mechanism of wine processing on CF.
Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudo afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). 1 - 9 ). Compounds 1 - 6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2 - 6 all contained a free alpha-methylene-gamma-carboxylic acid. Compound 6 was also a rare 6,8cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu K alpha) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 50 values of 15.99 +/- 0.75 and 18.19 +/- 0.42 mu M, respectively.
A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A-F (1-6), together with six known diarylheptanoids (7-12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC50 values of 14.91 ± 0.62 and 12.78 ± 1.12 μM.
A new salvianolic acid derivative, (7'E)-(7S, 8S)-salvianolic acid V (1), together with four previously described compounds (2-5) were obtained from the n-butanol fraction of Salvia miltiorrhiza flowers. Their structures were established by a series of spectroscopic methods, and the absolute configuration of 1 was determined by electronic circular dichroism (ECD) calculation. Salvianolic acids (1) and phenolic acids (2-4) showed stronger DPPH free radical scavenging abilities and certain protective effects against H2O2-induced human skin fibroblast (HSF) cells oxidative damage, in which compound 1 (IC50 7.12 μM) possessed more noticeable free radical scavenging activity than the positive control vitamin C (IC50 14.98 μM).
Ethnopharmacological relevance: Atherosclerosis (AS), a lipid-induced inflammatory condition of the arteries, is a primary contributor to atherosclerotic cardiovascular diseases including stroke. Arctium lappa L. leaf (ALL), an edible and medicinal herb in China, has been documented and commonly used for treating stroke since the ancient times. However, the elucidations on its anti-AS effects and molecular mechanism remain insufficient. Aim of the study: To investigate the AS-ameliorating effects and the underlying mechanism of action of an ethanolic extract of leaves of Arctium lappa L. (ALLE). Materials and methods: ALLE was reflux extracted using with 70% ethanol. An HPLC method was established to monitor the quality of ALLE. High fat diet (HFD) and vitamin D3-induced experimental AS in rats were used to determine the in vivo effects; and oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro assays. Simvatatin was used as positive control. Biochemical assays were implemented to ascertain the secretions of lipids and pro-inflammatory mediators. Haematoxylin-eosin (H&E) and Oil red O stains were employed to assess histopathological alterations and lipid accumulation conditions, respectively. CCK-8 assays were used to measure cytotoxicity. Immunoblotting assay was conducted to measure protein levels. Results: ALLE treatment significantly ameliorated lipid deposition and histological abnormalities of aortas and livers in AS rats; improved the imbalances of serum lipids including total cholesterol (TC), triglyceride (TG), lowdensity lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); notably attenuated serum concentrations of inflammation-associated cytokines/molecules including TNF-alpha, IL-6, IL-1 beta, VCAM-1, ICAM-1and MMP-9. Mechanistic studies demonstrated that ALLE suppressed the phosphorylation/activation of PI3K, Akt and NF-kappa B in AS rat aortas and in cultured foam cells. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of ALLE on lipid deposition, productions of TC, TNF-alpha and IL-6, and protein levels of molecules of PI3K/Akt and NF-kappa B singnaling pathways. Conclusions: ALLE ameliorates HFD- and vitamin D3-induced experimental AS by modulating lipid metabolism and inflammatory responses, and underlying mechanisms involves inhibition of the PI3K/Akt and NF-kappa B singnaling pathways. The findings of this study provide scientific justifications for the traditional application of ALL in managing atherosclerotic diseases.
Ethnopharmacological relevance: Sea buckthorn ( Hippophae rhamnoides L.) has been designated a "medicine food homology" fruit by the National Health Commission of China due to its nutritional value. In traditional Chinese ethnomedicine, Hippophae rhamnoides L. is commonly used to treat nonhealing wounds such as burns, sores, and gastric ulcers. The aim of this study was to explore the healing effects of the ethyl acetate extract of sea buckthorn seeds (SBS-EF) on burn wounds. Aim of the study: The primary objectives of this research were to determine the most effective medicinal site of action for treating burns with sea buckthorn seeds (SBS) and to investigate the underlying material basis and mechanisms of their therapeutic effects. Materials and methods: The effects of different components of SBS-EF on the proliferation and migration of human skin fibroblasts (HSFs) were evaluated via MTT assays, scratch assays, transwell assays, and hydroxyproline secretion analysis. SBS-EF displayed the greatest activity amongst the extracts. Subsequent analyses included network pharmacology methodology, molecular docking studies, ultraperformance liquid chromatography UPLC-Orbitrap-Exploris-120-MS and a severe second-degree burn rat model to investigate the chemical constituents and potential therapeutic mechanisms of the SBS-EF. Results: In vitro studies demonstrated the efficacy of SBS-EF in promoting HSF growth and migration. UPLCOrbitrap-Exploris-120-MS analysis revealed that SBS-EF had ten major constituents, with flavonoids being the predominant compounds, especially catechin, quercetin, and kaempferol derivatives. Network pharmacology and molecular docking analyses indicated that SBS-EF may exert its healing effects by modulating the Wnt/ (3-catenin signalling pathway. Subsequent in vivo experiments demonstrated that SBS-EF accelerated burn wound healing in rats, increased hydroxyproline expression in skin tissue, facilitated skin structure repair, and enhanced collagen production and organisation over a 21 d period. Additionally, exposure to SBS-EF upregulated WNT3a and (3-catenin while downregulating GSK-3(3 levels in rat skin tissue. Conclusions: The wound healing properties of SBS-EF were attributed to its ability to enhance HSF growth and migration, increase hydroxyproline levels in the skin, promote collagen accumulation, reduce scarring, and decrease the skin water content. SBS-EF may also provide therapeutic benefits for burns by modulating the Wnt/ (3-catenin signalling pathway, as evidenced by its effective site and likely mechanism of action in the treatment of burned rats.
A new caffeoylquinic acid, 1, 5-di-O-caffeoyl-3-O-(1-O-methoxy-2-O-caffeoyl-4-maloyl)-quinic acid (1), and a new 5-hydroxymethylfurfural dimer, 5-(((2-methoxymethyl) furan-5-methanol) methyl) furan-2carbaldehyde (2), were discovered from Arctium lappa roots. A comprehensive HRMS, UV, IR, 1D and 2D NMR techniques were used for structural identification. These two compounds had Nitric Oxide (NO) inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 inflammatory cell in a dose-dependent manner.
利用超高效液相色谱-四极杆静电场轨道阱高分辨质谱(UPLC-Orbitrap-Exploris-120)联合核磁共振(NMR)技术鉴定泽漆乳汁的化学成分.对新鲜泽漆乳汁的石油醚萃取部位采用Thermo Hypersil GOLD Vanquish C18 色谱柱(2.1 mm×100 mm,1.9 μm),以乙腈/0.1%甲酸水溶液为流动相进行梯度洗脱,在正负离子模式下检测供试液;根据一级高分辨率质谱精确质荷比、二级高分辨率质谱碎片信息,联合Compound Discoverer 3.2 软件分析、标准品比对并参考相关文献报道,鉴定泽漆乳汁的化学成分.首次从泽漆乳汁中分析鉴定了43 个化学成分,包括二萜类、三萜类、甾体类、脂肪酸类等.采用NMR技术对从泽漆乳汁中分离得到化合物11、16、22 进行结构鉴定,证实为3 个二萜类成分,分别是大戟宁G、大戟宁A和大戟宁.
Four new 5-hydroxymethylfurfural derivatives, named cornusfurans A-D (1-4), together with three known ones (5-7) were isolated from wine -processed Corni fructus. They were a group of special components in Cornus officinalis processed with wine, in which compounds 1-4 were unusually constructed by a 5-hydroxymethylfurfural or 5-hydroxymethylfuroic acid and a small organic acid. Their structures were elucidated by comprehensive analyses of spectroscopic data and the absolute configurations of compounds 1-2 and 4 were solved by comparison of experimental and calculated electronic circular dichroism (ECD) curve. Bioassay results showed compounds 1-2 exhibited the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, with IC50 values of 29.44 & PLUSMN; 3.79 and 42.30 & PLUSMN; 1.49 & mu;M, respectively, and each isolated compounds had the protective effects against hydrogen peroxide (H2O2)-induced oxidative stress damage in normal rat kidney tubule epithelioid (NRK-52E) cells at 25-100 & mu;M.
Cinnamomi ramulus (CR) and Cinnamomi cortex (CC), both sourced from Cinnamomum cassia Presl, are commonly used Chinese medicines in the Chinese Pharmacopeia. However, while CR functions to dissipate cold and to resolve external problems of the body, CC functions to warm the internal organs. To clarify the material basis of these different functions and clinical effects, a simple and reliable UPLC-Orbitrap-Exploris-120-MS/MS method combined with multivariate statistical analyses was established in this study with the aim of exploring the difference in chemical compositions of aqueous extracts of CR and CC. As the results indicated, a total of 58 compounds was identified, including nine flavonoids, 23 phenylpropanoids and phenolic acids, two coumarins, four lignans, four terpenoids, 11 organic acids and five other components. Of these compounds, 26 significant differential compounds were identified statistically including six unique components in CR and four unique components in CC. Additionally, a robust HPLC method combined with hierarchical clustering analysis (HCA) was developed to simultaneously determine the concentrations and differentiating capacities of five major active ingredients in CR and CC: coumarin, cinnamyl alcohol, cinnamic acid, 2-methoxycinnamic acid and cinnamaldehyde. The HCA results showed that these five components could be used as markers for successfully distinguishing CR and CC. Finally, molecular docking analyses were conducted to obtain the affinities between each of the abovementioned 26 differential components, focusing on targets involved in diabetes peripheral neuropathy (DPN). The results indicated that the special and high-concentration components in CR showed high docking scores of affinities with targets such as HbA1c and proteins in the AMPK–PGC1–SIRT3 signaling pathway, suggesting that CR has greater potential than CC for treating DPN.
Six new cucurbitane-type triterpenes, hemchinins A-F (1-6), together with thirteen known ones (7-19) were isolated from ethyl acetate extraction of Hemsleya chinensis tubers. Compounds 1-2 were a group of cucurbitane triterpenes possessing an infrequent pentacyclic framework. Their structures were established by comprehensive UV, IR, HRMS, 1D/2D NMR, and ECD analyses. Bioassay results showed that most isolated compounds exhibited anti-inflammatory actions, in which compounds 13 and 15 exhibited stronger activities at 6.25 μM, with NO inhibition rates of 49.00 ± 0.05 % and 48.40 ± 0.10 %, respectively.Six new cucurbitane-type triterpenes, hemchinins A-F (1-6), together with thirteen known ones (7-19) were isolated from ethyl acetate extraction of Hemsleya chinensis tubers. Compounds 1-2 were a group of cucurbitane triterpenes possessing an infrequent pentacyclic framework. Their structures were established by comprehensive UV, IR, HRMS, 1D/2D NMR, and ECD analyses. Bioassay results showed that most isolated compounds exhibited anti-inflammatory actions, in which compounds 13 and 15 exhibited stronger activities at 6.25 μM, with NO inhibition rates of 49.00 ± 0.05 % and 48.40 ± 0.10 %, respectively.
Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-β-glucopyranoside(3),(-)-isolariciresinol 3α-O-β-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-β-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC_(50) values of(4.18±1.96) and(21.45±1.19) μmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H_2O_2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 μmol·L~(-1) was 96.09%±1.77%.
A new isoflavonoid glycoside, achyranthoside C (1), along with two known compounds (2 and 3) were isolated from the rhizomes of Achyranthes bidentata. Compounds 1-2 were two rare natural isoflavonoid glycosides with C8 hydroxymethylene derivatization. Their structures were elucidated through comprehensive 1D and 2D NMR, UV, IR, and HRMS analyses. Bioassay results showed all the three compounds had obviously cell-protective effects against H2O2-induced H9c2 cardiomyocytes injury in a concentration-dependent manner.