A total of eight nitrogen-containing dihydro-β-agarofuran derivatives (1-8), seven of which (2-8) are new compounds, together with four known 13-membered macrocyclic spermidine alkaloids (9-12), were isolated from aqueous ethanol extracts of the dried stems of Tripterygium wilfordii. These compounds were evaluated for their in vitro inhibitory activities against several cancer cell lines. Nitrogen-containing dihydro-β-agarofuran derivatives exhibited very weak inhibitory activities, while 13-membered macrocyclic spermidine alkaloids displayed differential effects. Notably, the IC50 values of celacarfurine in 72 h on MCF-7, AFC, AGS, RL95-2 and AN3 CA cell lines were 14.33, 8.36, 9.40, 11.97 and 21.92 μM, respectively. In addition, celacarfurine and celafurine exhibited synergistic effects on 5-fluorouracil-resistant HCT116 cell model. The calculate combination indexes of 40 μM celacarfurine and 200 μM celafurine against this model were 0.50 and 0.66, respectively. The potent anti-tumor activity of celacarfurine is likely to be attributed to hydrogen-bonding interactions formed by the three amide moieties within its 13-membered macrocyclic scaffold.

Six previously undescribed biphenyl derivatives, named as 10-hydroxyl-multiflorabiphenyl B (1), 11-hydroxyl-multiflorabiphenyl B (2), yunnabiphenyl A (3), 8-O-phenylacetoxyl- yunnabiphenyl A (4), 8-O-β-d-glucopyranosyl-yunnabiphenyl A (5), 8-O-acetyl-yunnabiphenyl A (6), together with one known analogue multiflorabiphenyl B (7), were isolated from the twigs of Garcinia yunnanensis. Their structures were elucidated by comprehensive analysis of HRESI-MS, NMR spectroscopy, and comparison with literature data. Compounds 3-6 represent the first reported natural biphenyl derivatives featuring a 2‑oxygenated ethyl substituent, which serve as chemotaxonomic markers for this species. Additionally, all six new compounds were evaluated for their ability to inhibit LPS-induced nitric oxide (NO) release in BV2 microglial cells, demonstrating moderate anti-inflammatory activity.

Background/Objectives: Tripterygium glycosides (TG) are used to treat inflammatory and autoimmune diseases, but their clinical application is limited by toxicity and the lack of process-responsive quality markers. This study examined whether roasting and dealkalization remodel the TG metabolite profile and alter the post-dose serum profile of circulating prototype constituents. Methods: Self-prepared TG, roasted TG (RTG), roasted-dealkalized TG (RDTG), and five marketed products were profiled by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Seven representative compounds were quantified by validated high-performance liquid chromatography (HPLC). Rat serum after oral administration was analyzed to compare circulating prototype constituents. Results: We characterized 243 constituents in material samples and 63 circulating prototype constituents in serum. Roasting primarily reshapes the profiles of diterpenoids and triterpenoids. Celastrol was not detected in the RTG and RDTG material samples, nor in the corresponding single-time-point serum profiles under the current analytical conditions. In contrast, wilforlide A exhibited an increase in material samples. Dealkalization preferentially reduced alkaloid-related constituents, including wilforine in material samples and tripterygiumine T in serum. Conclusions: Integrated material profiling, targeted quantification, and serum prototype analysis identified candidate process-responsive markers for processed TG preparations. Because the serum study was based on relative signal intensities rather than full pharmacokinetics, these markers require further pharmacokinetic and toxicological validation.

OBJECTIVES:Drynaria fortunei, a species within the Drynaria genus, is a widely distributed medicinal plant with abundant resources. Its rhizome, Drynariae rhizoma, has been extensively utilized in traditional Chinese medicine for its therapeutic efficacy in promoting wound healing, alleviating pain, tonifying the kidneys, and strengthening bones. With a well-documented historical presence in classical texts, Drynariae rhizoma has played a significant role in traditional medical systems across various cultures. Recent phytochemical investigations have identified a diverse array of compounds in Drynariae rhizoma, including flavonoids, phenolic acids, lignans, steroids, and glycosides. Among these, flavonoids represent the principal active constituents, attracting considerable research attention due to their extensive pharmacological activities. This review systematically integrates and critically analyzes the recent research progress in this field,providing a comprehensive overview of the current research landscape,with the aim of identifying promising future directions for Drynariae rhizome. METHODS:This review leveraged a wide range of online databases, including SciFinder, PubMed, SpringerLink, Baidu Scholar, Google Scholar, ScienceDirect, American Chemical Society (ACS) Publications, Web of Science, and China National Knowledge Infrastructure (CNKI), to collect relevant literature. Comprehensive searches were conducted using keywords such as "Drynariae Rhizoma", "flavonoids", "extraction", "chemical constituents", "analytical characterization". To ensure the scientific accuracy of this study, the botanical name of the plant was meticulously cross-verified using authoritative platforms such as "World Flora Online" and "The Plant List." KEY FINDINGS:This article provides a comprehensive overview of the botany (including characteristics, distribution, and origin) and traditional applications (such as its historical evolution, botanical sources, and multi-ethnic as well as cross-national therapeutic practices) of Drynariae rhizoma. Additionally, it highlights the latest research advancements on its flavonoid compounds, encompassing extraction methods (e.g. solvent extraction, ultrasound-assisted extraction, and microwave-assisted extraction), analytical characterization (e.g. ultraviolet spectroscopy, high-performance liquid chromatography, and nuclear magnetic resonance), chemical constituents (with 60 flavonoid compounds identified to date), biological activities (e.g. anti-osteoporosis, anti-osteoarthritis, renal protection, dental health promotion, neuroprotection, lipid-lowering, and immunomodulation), and clinical applications. Furthermore, the review discusses current quality control strategies, highlighting the impact of geographical origin and processing methods on flavonoid content. Further in-depth studies are essential to comprehensively explore these areas, paving the way for enhanced understanding and application of Drynariae rhizoma in both traditional and modern medicines. CONCLUSIONS:A comprehensive analysis of existing literature reveals that the flavonoid constituents of Drynariae rhizoma exhibit remarkable therapeutic potential owing to their structural diversity and extensive pharmacological properties. Nevertheless, current understanding of its pharmacodynamic material basis and quality control parameters remains inadequate, highlighting the urgent need for more rigorous investigations to facilitate its broader applications in both traditional and contemporary medical practices. This review is anticipated to provide a rigorous scientific basis for subsequent investigations and clinical translation of therapies based on Drynariae rhizoma.

Using bioactivity-guided isolation, we identified 11 monoterpenoids from V. officinalis, including 7 previously undescribed compounds (1-3, 5, and 8-10), two of which feature a rare C4-4'/C5-2' skeleton. At 12.5 μM, all isolated compounds significantly suppressed NO and pro-inflammatory cytokine production in LPS-stimulated BV2 microglial cells. Notably, compound 5 demonstrated the most potent anti-neuroinflammatory effects by modulating the NF-κB/MAPK signaling pathway, positioning it as a potential lead compound for AD treatment. These findings not only underscore the therapeutic value of V. officinalis but also broaden the pharmacological understanding of its monoterpenoid constituents.

Pterosins, 1H-inden-1-one-type sesquiterpenes, are characteristic components of ferns with unique structures and notable pharmacological activity. Despite the diversity and wide distribution of ferns, relatively few natural pterosins have been identified, likely due to inefficient identification methods. This study developed a high-throughput strategy for rapid pterosin identification by combining ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). By analyzing characteristic fragmentation patterns and diagnostic ions, the method enables efficient structural elucidation and targeted screening of pterosins in complex plant matrices. Results showed that the positive ion mode was more effective than the negative ion mode for detecting pterosins due to the abundance of characteristic fragment ions. Five diagnostic ions (m/z 156, 141, 143, 128, and 115) were identified, with the ion m/z 128 serving as key evidence for distinguishing the parent nucleus of pterosins. Differences in fragment ion abundance and specific ions formed by alpha cleavage were used to identify isomers based on glycosyl-binding and hydroxyl substitution sites. This method was applied to the extract of Pteris grevilleana pretreated with D101 macroporous resin column chromatography, resulting 46 pterosins, including 34 known and 12 novel compounds. The proposed LC-MS strategy not only enhances analytical throughput and compound coverage but also provides an effective tool for pterosin separation, rapid analysis, and structural identification. Its broad applicability across Pteris species supports its use in metabolite analysis and quality evaluation.

Trimethylamine (TMA) metabolism comprises choline-containing compounds’ metabolization, TMA production and trimethylamine N-oxide (TMAO) generation. However, the presence of numerous compounds in the carnitine and phosphatidylcholine (PC) pool compositions complicates profiling work significantly. This study is aimed at developing an efficient method for profiling TMA metabolic pathways, including quantifying known compounds and semi-quantifying the differential metabolites in the carnitine and PC pool compositions. Pseudo-targeted metabolomics is applicable for characterization. Firstly, multivariate statistics were performed to identify valuable metabolites (variable importance in the projection ＞1) from quality control biological samples. Given that TMA metabolism involved in host-gut microbiota interaction, co-metabolites were defined as the intersections of valuable metabolites from different biological samples (serum, liver, and intestinal contents) and further screened. Finally, alterations in TMA metabolism were observed in dextran sulfate sodium-induced colitis, with semi-quantitative analysis for excavated co-metabolites including 11 PCs, 6 lyso-phosphatidylcholines, and 2 acyl-carnitines and quantitative analysis for 10 known metabolites. The findings revealed increased TMA production and accumulation of choline-containing compounds in the gut during ulcerative colitis exacerbation. Correspondingly, the circulating level of TMAO was elevated in the colitis group. A comprehensive understanding of TMA metabolism can contribute to disease differential diagnoses and potential mechanism studies.

Eight chlorinated illudalane sesquiterpenoids were isolated from the aerial parts of Saxiglossum angustissimum, including a pair of new pterosin enantiomers, (2R)-angupterosin (1) and (2S)-angupterosin (2), as well as a new pteroside, angupteroside (3). The structures of these compounds were determined through comprehensive analysis of HRESI-MS, NMR spectral data, ECD, and comparisons with previously reported literature. Remarkably, these chlorine-containing compounds (1-8) are rare and represent the first discovery of such metabolites within the family Pyrrosioideae. The chlorinated illudalane sesquiterpenoids from S. angustissimum may serve as valuable chemotaxonomic markers for this species. Furthermore, compounds 1-8 demonstrated inhibitory effects on LPS-induced NO release in BV2 cells, highlighting their potential anti-inflammatory properties.

In recent years, transition-metal-catalyzed C-N bond formation from nitroarenes and aryl Grignard reagents has emerged as a promising and highly efficient method. Despite this, dinitro aromatic compounds have received limited attention in this context. Herein, we disclose a novel approach for synthesizing diarylamines via Nicatalyzed cross-coupling of Grignard reagents with both mono- and di-nitro aromatic compounds. This method demonstrates remarkable tolerance towards a wide range of functional groups, including COOEt, F, Cl, CN, CF3, OCF3, SCH3, and pyridyl groups, allowing for the synthesis of various aminated arenes in moderate to good yields. This C-N bond formation method offers a general and step-economical pathway to diaryl and polyaryl amines, paving the way for new synthetic possibilities.

Three macrocyclic polyamine alkaloids with a 13-membered ring, named celafurine, celacarfurine, and celabenzine, isolated from Tripterygium wilfordii Hook.f., Celastraceae, were evaluated for their neuroprotective effects in an Alzheimer’s disease cell model, which was established by inducing human neuroblastoma SH-SY5Y cells with amyloid β-peptide (1-42). Celabenzine exhibited remarkable protective effects on SH-SY5Y cells induced by amyloid β-peptide (1-42) by increasing cell viability from 60 to 80

Three new pterosins, named as semipterosin A (1), B (2) and C (3), together with 11 known pterosins (4-14), were isolated from the aerial parts of Pteris semipinnata. Their structures were elucidated by HRESI-MS, NMR spectral data, CD and literature comparisons. Three new pterosins were assessed for their anti-inflammatory activity. Compounds 1-3 inhibited the NF-kB induction by 40.7%, 61.9% and 34.0%, respectively. This is the first report of the isolation of compounds 6-14 from this plant.

Two novel illudalane sesquiterpenoids, named as semipterosin D (1) and semipterosode A (2), together with eight known illudalane sesquiterpenoids (3–10), were isolated from the aerial parts of Pteris semipinnata. Their structures were elucidated by HR-ESI-MS, NMR spectral data, CD and literature comparisons. Compound 1 is the first C12 illudalane sesquiterpenoid, and compound 2 is the second report of the C13 illudalane sesquiterpenoid in natural products. Compounds 4–6 and 10 were isolated from this plant for the first time. New compounds were assessed for their anti-inflammatory activity. Compounds 1 and 2 inhibited the NF-κB induction by 26.6

目的 观察雷公藤Tripterygium wilfordii煨制前后对胶原诱导型关节炎(collagen-induced arthritis,CIA)模型大鼠的影响,并基于代谢组学与琥珀酸/血管内皮生长因子(vascular endothelial growth factor,VEGF)炎症信号通路共同探索雷公藤煨制的增效机制.方法 采用大鼠尾根部皮内注射牛Ⅱ型胶原乳剂复制CIA大鼠模型,分别给予醋酸地塞米松、雷公藤生品总提取物、雷公藤煨制品总提取物治疗20d.通过大鼠足肿胀度、关节炎评分、血清中白细胞介素-1β(interleukin-1β,IL-1β)水平、滑膜病理组织切片评估药效;采用代谢组学技术对各组间的代谢差异进行表征;检测滑膜中琥珀酸脱氢酶(succinate dehydrogenase,SDH)活力以及琥珀酸和富马酸的含量;采用免疫组化法检测滑膜组织VEGFA、血小板-内皮细胞黏附分子(platelet endothelial cell adhesion molecule-1,CD31)表达.结果 与模型组比较,雷公藤生品总提取物组和煨制品总提取物组大鼠足肿胀度和关节炎评分显著降低(P＜0.05),血清中IL-1β水平显著降低(P＜0.05),滑膜组织病理改变明显减轻,滑膜中琥珀酸含量显著降低(P＜0.05),SDH活力无明显改变,滑膜组织VEGFA和CD31表达均显著下调(P＜0.05).与生品总提取物组比较,煨制品总提取物组SDH活力无明显改变,其余各项指标明显更向对照组接近(P＜0.05).代谢组学结果表明,从模型组中共筛选出15个差异代谢物,经煨制总提取物治疗后,6个差异代谢物较模型组明显回调(P＜0.05),且与生品总提取物组相比明显更接近对照组(P＜0.05).这些代谢物的变化涉及了缬氨酸、亮氨酸和异亮氨酸生物合成、色氨酸代谢、能量代谢、花生四烯酸代谢.结论 煨制可显著提高雷公藤对CIA模型大鼠的治疗效果,其增效作用机制可能与调控缬氨酸、亮氨酸和异亮氨酸生物合成,色氨酸代谢,能量代谢,花生四烯酸代谢途径有关.雷公藤可通过调节琥珀酸/VEGF信号通路改善类风湿关节炎,煨制可增强雷公藤对该信号通路的调控从而发挥增效作用.

目的 探究厚朴温中汤治疗脾胃虚寒型胃病的潜在靶点和机制.方法 运用TCMSP数据库、疾病数据库和化合物靶点预测平台,收集活性成分、疾病靶点,预测潜在作用靶点;应用Cytoscape 3.7.2和String平台进行关键化学成分和核心靶点筛选,构建PPI网络图;将degree值大于30的活性成分与关键靶点进行分子对接,并进行细胞实验.结果 厚朴温中汤治疗脾胃虚寒型胃病的关键活性成分包括橙皮苷、厚朴酚、6-姜辣素等;关键靶点包括JUN、AKT1、IL-8等;相关通路主要涉及免疫应答、信号转导、细胞增殖与凋亡等;分子对接显示关键活性成分与关键靶点结合活性较好.细胞实验结果显示,厚朴酚、橙皮苷、6-姜辣素均对IL-8有很好的抑制作用,且呈剂量依赖关系.结论 推测厚朴温中汤可能通过关键活性成分作用于关键靶点,参与PI3K-AKT、NF-κB等信号通路调控,实现治疗脾胃虚寒型胃病相关疾病作用;首次发现6-姜辣素能够与多个治疗脾胃虚寒型胃病的疾病靶点(如AKT1、IL-8等)稳定结合,提示6-姜辣素值得进一步研究;根据IL-8细胞实验结果,推测厚朴酚、橙皮苷、6-姜辣素可能通过降低胃黏膜中IL-8含量,对幽门螺杆菌感染引起的胃病产生作用.

Without changing the host-guest materials of the optimized single-emitting layer (S-EML), a series of double-emitting layer (D-EML) was constructed by the same host material and the same guest material to improve the exciton distribution of the EML; thereby, a better performance of the D-EML blue device was obtained. The best D-EML device showed that the luminance and the current efficiency were enhanced, respectively, to 1437 cd/m2 and 6.92 cd/A at the current density 20 mA/cm2, which was 22.9% higher than that of the optimized S-EML device. A simple physics model was constructed to analyze the mechanism of the D-EML devices. It was found that the balance of the carriers and the distribution of the exciton could be improved via this D-EML structure in two situations, which could improve the performance of the device. So, this new doping method was certified by the experiments and by the theory in our work, which would be helpfully for improving the performances of some S-EML structure devices.

Three new flavonoid glycosides, (S)-4′,6,8-trihydroxyflavanone-7-C-glucoside (1), (R)-4′,6,8- trihydroxyflavanone-7-C-glucoside (2) and distenin-7-O-β-D-glucoside (3), along with nine known flavonoids (4-12) were isolated from the aerial of Pteridium acquilinum. Their structures were elucidated by the analysis of spectroscopy data and their comparison with the reported values. The two C-glycosyl flavanones (1 and 2), were isolated from this specie, which might be chemotaxonomic markers of this specie. In addition, three new flavonoids were preliminarily examined for their anti-inflammatory activity. Compounds 1-3 inhibited the NF-κB induction by 46.3%, 59.6% and 29.2%, respectively.

Tripterygium wilfordii (TW), a well-known traditional Chinese medicine, was widely used in the treatment of autoimmune disorders and inflammatory diseases. However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity. Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW.

There has been a lively interest on macrocyclic polyamine alkaloids due to their remarkable pharmacological activities such as anti-tumor, anti-inflammatory, anti-Alzheimer's disease and anti-parasitic. Tripterygium wilfordii is a widely used traditional Chinese medicine, which is abundant in alkaloids including macrocyclic polyamine alkaloids. However, there are rarely studies on macrocyclic spermidine alkaloids of T. wilfordii so far. In this article, we use three known macrocyclic spermidine alkaloids celafurine, celabenzine and celacinnine, and successfully develop a simple and sensitive HPLC method for simultaneous quantification of macrocyclic spermidine alkaloids in root, stem and leaf of T. wilfordii.

Spermidine and spermine are special polyamines in organisms, and produced in vivo by putrescine and S-adenosylmethionine catalyzed by a variety of enzymes. Spermidine and spermine possess multiple amino groups, and are closely related to cell division, growth and survival. Spermidine and spermine alkaloids are widely distributed in plants, bacteria and marine organisms, and can be divided into macrocyclic and open chain according to the skeletons. Spermidine and spermine alkaloids exhibited numerous pharmacological effects such as anti-inflammatory, antibiotics, anti-tumor, anti-Alzheimer and anti-virus. However, up to now, there are few systematic reviews on spermidine and spermine alkaloids. In this review, based on the number of atoms in the ring, we summarized the distributions and pharmacological effects of spermidine and spermine alkaloids. Spermidine and spermine alkaloids have special chemophenetic significances in the plant kingdom, especially the macrocyclic spermidine and spermine alkaloids. Spermidine alkaloids are much more abundant in nature than spermine alkaloids. The pharmacological activities of the open chain spermidine and spermine alkaloids are studied in depth. Polycyclic guanidine spermidine alkaloids, isolated from marine sponge, exhibit great potential in various cancer cells. However, pharmacological studies of macrocyclic spermidine and spermine alkaloids are scarce. Synthesis is an effective way to get more spermidine and spermine alkaloids and their analogues for further study.

雷公藤作为一种传统中药,具有抗炎、免疫抑制、抗肿瘤等多种药理活性,在肾脏疾病、自身免疫性疾病、皮肤病及肿瘤的治疗上取得了良好的效果.近年来,雷公藤在临床的使用越来越广泛,但其严重的毒副作用大大限制了它的临床应用.代谢组学技术对于研究有毒中药的药理与毒理机制优势明显.为了雷公藤的临床合理使用,本文首次总结了代谢组学技术在雷公藤及其活性成分的药理、毒理和减毒机制等方面的应用,梳理了相关生物标志物和代谢通路,以期为雷公藤的深入研究开发提供思路.