Insights into Euphorbia diversity: Probing the contrasts between Euphorbia fischeriana Steud and Euphorbia ebracteolata Hayata.

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A multidimensional strategy for characterization, distinction, and quality control of two Clinopodium medicinal plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense Kuntze (CC) and Clinopodium polycephalum (Vaniot) C. Y. Wu & S. J. Hsuan (CP) are both included in the Pharmacopoeia of the People's Republic of China (edition 2020) as the legitimate source of "Duan Xue Liu" (DXL), which is a crucial traditional Chinese medicine used as a clinical remedy for bleeding diseases. However, the differences in plant endogenous metabolites and bioactivities between CC and CP are still unclear. AIM OF THE STUDY: This study aims to provide a scientific basis to investigate the differences between CC and CP ensuring the efficient and safe use of DXL. MATERIALS AND METHODS: A multidimensional strategy including plant metabolomics, digital reference standard (DRS) analyzer, and biological activities assay was creatively constructed for the characterization, distinction, and quality control of CC and CP. RESULTS: There were apparent differences in the metabolites between CC and CP. 7 compounds contributing to the differences were successfully identified. On that basis, linear calibration using two reference substances (LCTRS) methods was proved as a more accurate and specific quality analysis method for CC and CP. In addition, bioactivity assays showed that both CC and CP exhibited obvious hemostatic activity, while CC showed greater potential to resist inflammation and free radicals. CONCLUSION: In summary, it was the first time to investigate the chemical constituents and bioactivities differences between CC and CP with the help of plant metabolomics, DRS study, and biological activity assays. These two plants were significantly separated in the integrated analysis, suggesting that we should pay attention to the distinction to prevent unexpected risks caused by medicinal materials.

Anti-necroptosis and anti-ferroptosis compounds from the Deep-Sea-Derived fungus Aspergillus sp. MCCC 3A00392.

Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.

Monoterpenoid indole alkaloids from Melodinus axillaris W.T.Wang exhibit anti-inflammatory activities by inhibiting the NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Melodinus axillaris W.T.Wang has been widely used as an important medicine in China. In the folk of China, its whole plant has been used for fractures, rheumatic heart disease, testitis, hernia, abdominal pain, and dyspepsia, etc. Despite its extensive use, there is a shortage of literature investigating the specific bioactive compounds and underlying mechanisms responsible for their anti-inflammatory effects. This knowledge gap serves as the primary impetus for conducting this study, which aims to shed light on the previously unexplored therapeutic potential of M. axillaris. AIM OF THE STUDY: This study aims to investigate the material basis and potential mechanism of anti-inflammatory activity of M. axillaris. MATERIALS AND METHODS: Compounds were isolated from the 95% ethanol extract of M. axillaris using a systematic phytochemical method. The structures were established by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD calculation, and DP4+ analysis. The anti-inflammatory activities of ethanol extract and compounds from M. axillaris were tested by an inflammation model of LPS-stimulated RAW264.7 cells in vitro. Western blot analysis was employed to evaluate the expressions of COX-2, iNOS, and NF-κB signaling pathways, aiming to elucidate the underlying mechanisms. RESULTS: Eleven undescribed monoterpenoid indole alkaloids (MIAs), axillines A-K (1-11), along with thirteen known analogs were isolated from M. axillaris. Compound 1 was the first representative of vincadine alkaloid with unprecedented 6/5/9/6/6 skeletons. Compounds 1-11 and ethanol extract showed significant anti-inflammatory effects in vitro. Among them, compound 2 had the best activity of inhibiting NO release (IC50 = 3.7 ± 0.9 µM). Additionally, subsequent Western blot analysis revealed that 2 could significantly inhibit the up-regulation of NF-κB signaling pathways, iNOS, and COX-2 in LPS-stimulated RAW264.7 cells, thereby demonstrating its anti-inflammatory activity. CONCLUSION: This study provides support for the traditional use of M. axillaris in terms of its anti-inflammatory properties and highlights the potential of MIAs as promising candidates for further development as anti-inflammatory drugs.

Undescribed compounds from Clinopodium chinense (Benth.) O. Kuntze and their coagulation activity studies.

Four rare compounds (1-4), including one 1,4-epoxy-benzoxepane derivative and one ringed prenylated naphthoquinoid skeleton, as well as one isopimarane-type diterpenoid and one megastigmane-type glycoside, along with three known megastigmane-type glycosides (5-7) were isolated from the ethanol extracts of C. chinense. Their structures were determined on the basis of 1D, 2D NMR, HR-ESI-MS and DP4+ analysis. Meanwhile, the in vitro evaluation indicated that compound 2 and 6 exhibited excellent procoagulant activities, which can significantly shorten prothrombin time (PT) and activated partial thromboplastin time (APTT), respectively.

From Tea to Health: Exploring Abrus mollis for Liver Protection and Unraveling Its Potential Mechanisms.

Abrus mollis Hance is a characteristic medicinal herb which is used in Guangdong and Guangxi provinces of China for making soup, medicinal meals, and herbal tea to treat dampheat jaundice and rib discomfort. Current phytochemical study on A. mollis led to the isolation of four new flavones, mollisone A-D (1-4), and thirty two known compounds (5-36). Their structures were characterized by an extensive analysis of spectroscopic data including IR, UV, HR-ESI-MS, and 1D and 2D NMR, as well as electronic circular dichroism calculation. In addition, in order to initially understand their biological activities for traditional applications, in vitro antioxidant and hepatoprotective tests were carried out, whose results illustrated that 25 compounds had significant free radical scavenging ability, and compounds 13 and 16 exhibited protective activities on D-GalN-induced LO2 cell damage than the positive control. Moreover, network pharmacological analysis revealed that the hepatoprotective activity of A. mollis involved multitargets and multipathways such as PI3K/Akt, MAPK, and JAK-STAT pathways and various biological processes such as positive regulation of phosphorylation and regulation of kinase activity. These results suggested that this species could serve as a potential hepatoprotective agent for functional food or medicinal use.

Chemical Constituents of the Deep-sea Gammarid Shrimp-Derived Fungus Penicillium citrinum XIA-16.

One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC50 =2.0 µM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 µM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.

Monoterpenoid indole alkaloid dimers from the Melodinus axillaris induce G2/M phase arrest and apoptosis via p38 MAPK activation in HCT116 cells.

Four monoterpenoid indole alkaloid dimers (MIADs), axidimins A-D (1-4), which possesses unprecedented apidosperma-aspidosperma-type skeletons, along with twelve known MIAs were isolated from Melodinus axillaris. Their structures were established by comprehensive analysis of the HRESIMS, NMR, ECD calculation and DP4 + analysis. A possible biosynthetic pathway for axidimins A-D was proposed. In vitro, axidimins C and D exhibited significant cytotoxicities against HCT116 cells with IC50 values of 5.3 µM and 3.9 µM, respectively. The results obtained from flow cytometry and Western blot analysis clearly demonstrated that axidimins C and D significantly induced a reverse G2/M phase arrest and apoptosis of HCT116 cells. The potential mechanism of axidimins C and D on HCT116 cells were thoroughly discussed through the utilization of network pharmacology and molecular docking research. Subsequently, the selected targets were validated using Western blot and CETSA analysis, confirming that axidimins C and D exert its cytotoxic effects through the activation of the p38 MAPK pathway, ultimately leading to HCT116 cells death. This study provides evidence indicating that axidimins C and D have the potential to induce cell cycle arrest and apoptosis in HCT116 cells by modulating the p38 MAPK signaling pathway. These findings offer a novel perspective for the development of anti-colorectal cancer drugs.

Triterpenoids from Meehania fargesii with Cytotoxic Activity1.

In the investigation of Meehania fargesii, eighteen triterpenoids were isolated and identified, including a previously unknown compound with an 13,27-cycloursane skeleton, using techniques like 1D and 2D NMR, and HR-MS. Furthermore, the cytotoxicity of these compounds were evaluated against HCT116, MCF-7, and AGS cell lines using the CCK-8 method to examine their structure-activity relationship. Remarkably, compounds 13 and 16 exhibited higher cytotoxicity across all three cell lines compared to the positive drug. Western blot analysis revealed that these compounds activated apoptosis in HCT116 cells by promoting the Bax protein and inhibiting the Bcl-2 protein. This suggests that compounds 13 and 16 have potential as apoptosis-inducing agents in HCT116 cells.

Kamaonensine A-G: Lycaconitine-type C19-diterpenoid alkaloids with anti-inflammatory activities from Delphinium kamaonense Huth.

Delphinium kamaonense Huth is a sort of folkloric plant resource which is cultivated and planted with great ornamental and medicinal values. In this work, seven undescribed lycaconitine-type C19-diterpenoid alkaloids, especially a rare skeleton with -CH=N and N-oxide moieties, along with ten known compounds, were isolated from D. kamaonense, of which the structures were determined by various spectroscopic data, combined with calculated electronic circular dichroism (ECD) and single-crystal X-ray diffraction analysis. In vitro nitric oxide inhibitory activities assay of these compounds indicated that lycaconitine-type C19-diterpenoid alkaloids had significant anti-inflammatory inhibitory activities, with kamaonensine E being the most potent (0.9 ± 0.2 µM) stronger than positive (9.0 ± 1.3 µM). In the network pharmacology studies, binding three key targets mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14), and heat shock protein HSP 90-alpha (HSP90α), the anti-inflammatory mechanism might be related to MAPK signaling pathways. Furthermore, the molecular docking results revealed that the uncommon amides and methylenedioxy groups might be the most two promising pharmacophores for lycaconitine-type C19-diterpenoid alkaloids.

Three Undescribed Flavonoids and Amide from Abrus mollis Hance with Hepatoprotective Effects.

Through a phytochemical investigation of Abrus mollis Hance, a folk medicinal plant in China, we isolated and identified three undescribed compounds, including two flavonoids and one amides alkaloid, along with nine known from this plant. Their structures were elucidated by analyses of 1D, 2D NMR, HR-ESI-MS, ECD, and DP4+ analysis. Furthermore, we evaluated the hepatoprotective effects of all twelve compounds on D-GalN-induced Brl-3 A cells. According to the results, at a concentration of 25 µM, the cell survival rates were observed to be 71.92±0.34 %, 70.03±1.29 %, and 69.11±1.90 % for compound 2, 4, and 11, respectively. Further experimental studies showed that compound 2 (EC50 5.76±0.37 µM) showed more significant protective activity than the bicyclol.

Polycephalums A and B, New Anticoagulant Constituents Isolated from Clinopodium polycephalum.

Two previously undescribed compounds (1 and 2) were isolated from Clinopodium polycephalum, a medicinal plant distributed in southwestern and eastern China. Their structures were elucidated using MS analyses and extensive 2D-homo and heteronuclear NMR data interpretations. Both compounds 1 and 2 could significantly shorten APTT and PT, and their procoagulant effect was comparable to that of positive drugs. At the same time, compound 2 had certain antioxidant activity (IC50 value of 2.25±0.05 µM in ABTS assay).

Clinopodium chinense Kuntze ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by reducing systematic inflammation and regulating metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Clinopodium chinense Kuntze (CC), traditional Chinese medicine with anti-inflammatory, anti-diarrheal, and hemostatic activities, has been used to treat dysentery and bleeding diseases for thousands of years, which are similar to the symptoms of ulcerative colitis (UC). AIM OF THE STUDY: To obtain a novel treatment for UC, an integrated strategy was developed in this study to investigate the effect and mechanism of CC against UC. MATERIALS AND METHODS: The chemical characterization of CC was scanned by UPLC-MS/MS. Network pharmacology analysis was performed to predict the active ingredients and pharmacological mechanisms of CC against UC. Further, the results of network pharmacology were validated using LPS-induced RAW 264.7 cells and DSS-induced UC mice. The production of pro-inflammatory mediators and biochemical parameters was tested using the ELISA kits. The expression of NF-κB, COX-2, and iNOS proteins was evaluated using Western blot analysis. Body weight, disease activity index, colon length, histopathological examination, and metabolomics analysis in colon tissues were carried out to confirm the effect and mechanism of CC. RESULTS: Based on the chemical characterization and literature collection, a rich database of ingredients in CC was constructed. Network pharmacology analysis provided five core components as well as revealed that the mechanism of CC against UC was highly related to inflammation, especially the NF-κB signaling pathway. In vitro experiments showed CC could inhibit inflammation by LPS-TLR4-NF-κB-iNOS/COX-2 signaling pathway in RAW264.7 cells. Meanwhile, in vivo experimental results proved that CC significantly alleviated pathological features with increased body weight and colonic length, decreased DAI and oxidative damage, as well as mediated inflammatory factors like NO, PGE2, IL-6, IL-10, and TNF-ɑ. In addition, colon metabolomics analysis revealed CC could restore the abnormal endogenous metabolite levels in UC. 18 screened biomarkers were further enriched in four pathways including Arachidonic acid metabolism, Histidine metabolism, Alanine, aspartate and glutamate metabolism as well as the Pentose phosphate pathway. CONCLUSION: This study demonstrates that CC could alleviate UC by reducing systematic inflammation and regulating metabolism, which is beneficial for providing scientific data for the development of UC treatment.

Two New Compounds Isolated from the Leaves of Ohwia caudata and Their Neuroprotective Effect against LPS-Induced BV2 Cells.

From the dried leaves of Ohwia caudata, two new compounds, namely (4E)-(4-hydroxyphenyl)-3-butenoic acid butyl ester (1), and 4-benzyl-1,3-phenylenedicarbamic acid methyl ester (2), together with five known compounds, were isolated and identified. The structures of compounds 1 and 2 were established using 1D-NMR, 2D-NMR and HR-ESI-MS spectral analysis. Previous studies on O. caudata had been reported to protect against Alzheimer's disease, two new compounds were evaluated for their neuroprotective effect against lipopolysaccharide-induced BV2 microglia cells. The result indicated two compounds showed well anti-neuroinflammatory activity at 12.5 µM.

Chemical constituents and biological activities of Artemisia argyi H.Lév. & vaniot.

Artemisia argyi is a widely distributed and inexpensive plant resource, and study on its chemical compositions and biological activities will provide an important basis for its food applications and pharmaceutical developments. In this study, fourteen known guaiane-type sesquiterpenes (1-14), four known eudesmane-type sesquiterpenes (15-18), two known germacranolide-type sesquiterpenes (19, 20), and eight other types of terpenoids (20-28) were isolated from the leaves of A. argyi by polyamide and ODS CC and HPLC. The structures of all compounds are determined by 1 D NMR (1H-NMR、13C-NMR) and literature comparison. Among them, compounds 1 and 8 were isolated from Chinese folk medicine A. argyi for the first time. Besides, the LPS-induced RAW264.7 cell model has been evaluated the anti-inflammatory activities in vitro by the Griess reagent. The results indicated that the guaianolide sesquiterpenoids obtained from A. argyi have an excellent ability to inhibit NO production, especially Argyin A, a guaianolide sesquiterpenoid with isovaleryloxy substitution.

Chemical constituents from the leaves of psidium guajava linn. and their chemotaxonomic significance.

The phytochemical investigation on the leaves of Psidium guajava Linn. led to the isolation and identification of 18 compounds, including six guavinoside (1-6), four flavonoids (7-10), eight triterpenoids (11-17) and one lignans (18). All chemical structures were elucidated via NMR spectroscopic methods, and further supported by comparison with literature data. Compounds 12, 14, 16 and 18 was isolated from the Myrtaceae family for the first time. The chemotaxonomic significance of these compounds was also discussed based on their structure types, as well as compounds-genus/family network analysis. The results showed that there were close chemotaxonomic relationships among the Myrtaceae, Asteraceae, and Lamiaceae families. Guavinosides A-F could be considered as valuable chemotaxonomic markers of Myrtaceae family, while guavinosides C-F might serve as chemotaxonomic markers for distinguishing the P. guajava.

Barrigenol-like triterpenoid saponins from the husks of Xanthoceras sorbifolia bunge and their anti-inflammatory activity by inhibiting COX-2 and iNOS expression.

The husks of Xanthoceras sorbifolia Bunge were explored resulting in the isolation of nine undescribed compounds and seven known compounds. Their structures were defined by NMR spectroscopic techniques, HRESIMS analyses and DP4+ possibility analysis. Three of them showed evident inhibition on NO productions in LPS-induced BV-2 cells by controlling the expression of the nuclear factor-kappa-B (NF-κB) signaling pathway. Furthermore, they also markedly decreased the expression of the proteins COX-2 and iNOS. In addition, most compounds showed no cytotoxicity against Hep 3B, A549, HCT 116, AGS, MCF-7 cell lines. These findings showed that the husks of X. sorbifolia might have considerable potential for the prevention of inflammation-related neurodegenerative disorders.

Hepatoprotective Effect Associated with Alkaloids from Corydalis tomentella Franch. based on Network Pharmacology, Molecular Docking and in Vitro Experiment.

Liver is an important metabolic organ with numerous functions in human body. Hepatitis is defined as the inflammation of the liver tissue, which could lead to acute liver failure, liver fibrosis, liver cirrhosis and hepatocellular carcinoma. Corydalis tomentella Franch., a precious herb in China, is often used in the treatment of hepatitis, liver cirrhosis and liver cancer. In this study, 41 isoquinoline alkaloids and derivatives isolated by our lab from C. tomentella and 61 related targets were analyzed by network pharmacology. Their activities were further verified by cell assay evaluated for antitumor activity against HepG2 cells and molecular docking. The results confirmed that the alkaloids from C.tomentella had extensive hepatoprotective effects, and TNF-α was the key target of hendersinate B methyl ester against acute liver damage by viral hepatitis and HCC, which provided a foundation for further in vivo studies.

Diterpene glycosides, acetophenone glycosides and tannins from polar extracts of the root of Euphorbia fischeriana with cytotoxicity and antibacterial activities.

The phytochemical study on Euphorbia fischeriana, a folk medicinal plant in China, led to the isolation of eight undescribed glycosides, including two diterpene glycosides, three acetophenone glycosides and three tannins together with eight known ones. Their planar structures were elucidated by extensive analyses of 1D, 2D NMR experiments and HRESIMS. The absolute configurations were determined by NOESY experiments, ECD calculations. All undescribed compounds were evaluated for their cytotoxicity and antibacterial activities in vitro. Two diterpene glycosides (1-2) showed cytotoxic activity with IC50 values ranging from 5.4 to 16.2 µM toward Hep-G2, Hep-3B, A549, NCI-H460 and AGS cells. Tannins (6-8) showed the significant antibacterial activity with MIC values in the range of 1.56-6.25 µg/mL.

Three New Compounds from Delphinium kamaonense Hunth and Their in†Vitro Cytotoxic and Potential Antioxidant Activities.

A new amide (1), two new phenylpropanoid derivatives (2, 3), along with three new natural products, including three nitrogen chirality compounds, N-(3-methoxy-1,3-dioxopropyl)-D-phenylalanine methyl ester (4), N-(3-methoxy-1,3-dioxopropyl)-L-phenylalanine methyl ester (5), and N-acetyl-L-phenylalanine methyl ester (6), as well as dimethyl (2R,3R)-2-hydroxy-3-(((E)-3-(4-hydroxyphenyl)acryloyl)oxy)succinate (7) and dimethyl (S,E)-2-((3-(4-hydroxy-3-methoxyphenyl)acryloyl)oxy)succinate (8) were isolated from Delphinium kamaonense Hunth. Their structures were elucidated by extensive analysis of 1D and 2D NMR, and HR-ESI-MS experiments, and the absolute configurations were determined by comparative analysis of specific optical rotation. Compound 1 exhibited a moderate cytotoxicity effect against Hep-3B cancer cell lines (IC50 41.39±0.13 µM) and an excellent antioxidant activity (IC50 0.527±0.06 µM in ABTS assay, and 1.235±0.09 µM in DPPH assay, respectively), which was superior to vitamin C in ABTS (IC50 1.670±0.07 µM) and DPPH (IC50 19.10±0.40 µM) methods.