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1.
Chemosphere ; 353: 141562, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38417493

ABSTRACT

The UV/sulfite-based advanced reduction process (ARP) emerges as an effective strategy to combat per- and polyfluoroalkyl substances (PFAS) pollution in water. Yet, the UV/sulfite-ARP typically operates at highly alkaline conditions (e.g., pH > 9 or even higher) since the generated reductive radicals for PFAS degradation can be quickly sequestered by protons (H+). To overcome the associated challenges, we prototyped a biochar-surfactant-system (BSS) to synergistically enhance PFAS sorption and degradation by UV/sulfite-ARP. The degradation and defluorination efficiencies of perfluorooctanoic acid (PFOA) depended on solution pH, and concentrations of surfactant (cetyltrimethylammonium bromide; CTAB), sulfite, and biochar. At high pH (8-10), adding biochar and BSS showed no or even small inhibitory effect on PFOA degradation, since the degradation efficiencies were already high enough that cannot be differentiated. However, at acidic and neutral pH (6-7), an evident enhancement of PFOA degradation and defluorination efficiencies occurred. This is due to the synergies between biochar and CTAB that create favorable microenvironments for enhanced PFOA sorption and deeper destruction by prolonging the longevity of reductive radicals (e.g., SO3•-), which is less affected by ambient pH conditions. The performance of UV/sulfite/BSS was further optimized and used for the degradation of four PFAS. At the optimal experimental condition, the UV/sulfite/BSS system can completely degrade PFOA with >30% defluorination efficiency for up to five continuous cycles (n = 5). Overall, our BSS provides a cost-effective and sustainable technique to effectively degrade PFAS in water under environmentally relevant pH conditions. The BSS-enabled ARP technique can be easily tied into PFAS treatment train technology (e.g., advanced oxidation process) for more efficient and deeper defluorination of various PFAS in water.


Subject(s)
Caprylates , Charcoal , Fluorocarbons , Pulmonary Surfactants , Water Pollutants, Chemical , Surface-Active Agents , Cetrimonium , Water , Hydrogen-Ion Concentration , Fluorocarbons/analysis , Sulfites , Water Pollutants, Chemical/analysis
2.
Phytochemistry ; 212: 113720, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37187247

ABSTRACT

A phytochemical investigation led to the isolation of five undescribed compounds (1-5) from the methanol extract of the rhizomes and roots of Patrinia heterophylla. The structures and configurations of these compounds were characterized by HRESIMS, ECD, and NMR data analyses. These compounds were assayed for their anti-inflammatory potential using LPS-stimulated BV-2 cells, of which compound 4 showed strong nitric oxide (NO) inhibitory effects with an IC50 of 6.48 µM. The potential anti-inflammatory mechanism was examined utilizing Western blotting and molecular docking. Further in vivo anti-inflammatory experiments revealed that compound 4 inhibited the NO production and reactive oxygen species in the zebrafish model.


Subject(s)
Patrinia , Animals , Patrinia/chemistry , Iridoids/chemistry , Molecular Docking Simulation , Zebrafish , Anti-Inflammatory Agents/pharmacology , Nitric Oxide , Molecular Structure
3.
Phytochemistry ; 205: 113502, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36356672

ABSTRACT

Four undescribed highly oxidized and rearranged limonoids, secotrijugins A-D, were purified from the leaves and twigs of Trichilia sinensis. Within them, secotrijugin A was characterized as a rare 30-nortrijugin-type limonoid with an unusual cleavage of 1,14-ether bond, secotrijugins B and C represented new examples with the cleavage of δ-lactone ring D, and secotrijugin D was a rare trijugin-type limonoid with an unusual 2,6-oxygen bridge. The structures of limonoids were characterized by means of spectroscopic analysis and ECD calculations. The cellular screening revealed that secotrijugin B was the most active against LPS-stimulated NO production in BV-2 cells, which played an anti-inflammatory role by downregulating COX-2 and iNOS protein expression. The further in vivo experiments confirmed that secotrijugin B had strong in vivo anti-inflammatory effect via suppressing NO and ROS generation.


Subject(s)
Limonins , Meliaceae , Limonins/pharmacology , Anti-Inflammatory Agents/pharmacology
4.
Phytomedicine ; 102: 154118, 2022 Jul 20.
Article in English | MEDLINE | ID: mdl-35576741

ABSTRACT

BACKGROUND: Nonsmall-cell lung cancer (NSCLC) is one of the most common malignant tumors, and the current drugs have not achieved ideal therapeutic effects. The abnormal activation of STAT3 and FAK signal transduction in tumor cells is highly correlated with their proliferation and migration ability. Therefore, bioactive compounds that can inhibit STAT3 and FAK activation have the potential to become agents to treat NSCLC. PURPOSE: This study aims to discover new antitumor compounds from Garcinia xipshuanbannaensis and investigate the molecular mechanism by which they inhibit lung cancer proliferation and metastasis in vivo and in vitro, all of which may lead to obtainment of a potential antitumor agent. METHODS: Xipsxanthone H was obtained by various chromatography methods (including silica gel, medium pressure liquid chromatography (MPLC), and preparative high-performance liquid chromatography (HPLC)). 1D and 2D nuclear magnetic resonance (NMR) spectra were used to analyze the structure. Cell viability and wound healing assays were employed to detect changes in the proliferation and migration of cancer cells. Cell cycle and apoptosis were analyzed by flow cytometry. The protein expression of STAT3 and FAK signaling pathways affected by xipsxanthone H was determined by Western blotting. The zebrafish model was used to evaluate the in vivo effects of xipshantone H on tumor proliferation and metastasis. Molecular docking was utilized to explore the interaction between xipsxanthone H and STAT3. Cellular thermal shift assays (CETSAs) were employed to explore the possible target of xipsxanthone H. RESULTS: The novel compound xipsxanthone H was purified and characterized from G. xipshuanbannaensis. Xipsxanthone H exhibited strong anti-proliferation activity in a variety of tumor cell lines. In addition to inducing reactive oxygen species (ROS) production and arresting the cell cycle, mechanistic studies demonstrated that xipsxanthone H suppressed STAT3 and FAK phosphorylation and regulated the downstream protein expression of the STAT3 and FAK signaling pathways. The in vivo studies using the zebrafish model revealed that xipsxanthone H inhibited tumor proliferation, metastasis, and angiogenesis. CONCLUSIONS: A new xanthone was obtained from G. xipshuanbannaensis, and this compound had the property of inhibiting tumor proliferation and metastasis by targeting STAT3 and FAK signaling pathways in NSCLC. These findings suggested that xipsxanthone H might be a potential candidate agent for NSCLC treatment.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Xanthones , Animals , Apoptosis , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Lung Neoplasms/pathology , Molecular Docking Simulation , STAT3 Transcription Factor/metabolism , Signal Transduction , Xanthones/pharmacology , Xanthones/therapeutic use , Zebrafish/metabolism
5.
Environ Technol ; 43(16): 2516-2529, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33512309

ABSTRACT

Heavy metal immobilization using biochar (BC) is different from the usual soil incubation due to the low molecular weight organic acids (LMWOAs) in the rhizosphere and is an issue worth evaluating. Therefore, the impacts of rice husk BC (5%), tartaric acid, and oxalic acid, coupled with combinations of BC and tartaric acid/oxalic acid on the transformation of cadmium (Cd), lead (Pb), and zinc (Zn) among their geochemical forms, including their bioavailability in a metal-contaminated soil, were investigated in an incubation experiment. The application of BC, low concentration of tartaric acid (2 mmol kg-1 soil) (TA2), and the combined BC plus a low level of tartaric acid (BC-TA2) markedly reduced the acid-soluble and available (CaCl2-extractable) Cd, Pb, and Zn compared to control (CK) in which BC-TA2 was found to be the most effective treatment. The trends were reversed in the case of the high concentrations of tartaric acid (>5-20 mmol kg-1 soil), all levels of oxalic acid (2-20 mmol kg-1 soil), and the combined BC plus high levels of tartaric acid/oxalic acid treatments. The BC-TA2 transformed the highest amounts of acid-soluble and reducible Cd, Pb, and Zn to the oxidizable and residual fractions with incubation time. The results suggested that the low concentration of tartaric acid enhanced Cd, Pb, and Zn immobilization, while the higher level of tartaric acid and all concentrations of oxalic acid increased their mobilization. In conclusion, BC-TA2 could immobilize the most heavy metals and serve as an amendment for metals' immobilization/redistribution in contaminated soils.


Subject(s)
Metals, Heavy , Oryza , Soil Pollutants , Acids/metabolism , Cadmium/chemistry , Charcoal/chemistry , Lead/metabolism , Metals, Heavy/analysis , Molecular Weight , Organic Chemicals/metabolism , Oryza/chemistry , Oxalates/metabolism , Soil/chemistry , Soil Pollutants/chemistry , Zinc/chemistry
6.
Front Pharmacol ; 12: 756491, 2021.
Article in English | MEDLINE | ID: mdl-34899310

ABSTRACT

Accumulating evidences suggested an association between gut microbiome dysbiosis and impaired glycemic control. Ginsenoside Rb1 (Rb1) is a biologically active substance of ginseng, which serves anti-diabetic effects. However, its working mechanism especially interaction with gut microbes remains elusive in detail. In this study, we investigated the impact of Rb1 oral supplementation on high fat diet (HFD) induced obesity mice, and explored its mechanism in regulating blood glucose. The results showed that higher liver weight and lower cecum weight were observed in HFD fed mice, which was maintained by Rb1 administration. In addition, Rb1 ameliorated HFD induced blood lipid abnormality and improved insulin sensitivity. Several mRNA expressions in the liver were measured by quantitative real-time PCR, of which UCP2, Nr1H4, and Fiaf were reversed by Rb1 treatment. 16S rRNA sequencing analysis indicated that Rb1 significantly altered gut microbiota composition and increased the abundance of mucin-degrading bacterium Akkermansia spp. compared to HFD mice. As suggested via functional prediction, amino acid metabolism was modulated by Rb1 supplementation. Subsequent serum amino acids investigation indicated that several diabetes associated amino acids, like branched-chain amino acids, tryptophan and alanine, were altered in company with Rb1 supplementation. Moreover, correlation analysis firstly implied that the circulation level of alanine was related to Akkermansia spp.. In summary, Rb1 supplementation improved HFD induced insulin resistance in mice, and was associated with profound changes in microbial composition and amino acid metabolism.

7.
Carbohydr Polym ; 270: 118365, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34364610

ABSTRACT

In this study, an inulin fructan (TMP50-2) with moderate anti-tumor activity was obtained from dandelion. To further improve the anti-tumor activity of TMP50-2, a monodisperse and stable spherical nanoparticle (Tw-TMP-SeNP, 50 nm) was fabricated. Physico-chemical analysis revealed that TMP50-2 and Tween 80 were tightly wrapped on the surface of SeNPs by forming CO⋯Se bonds or through hydrogen bonding interaction (OH⋯Se). In vitro anti-tumor assay showed that Tw-TMP-SeNP treatment could significantly inhibit the proliferation of cancer cells (HepG2, A549, and HeLa) in a dose-dependent manner, while HepG2 cells were more susceptible to Tw-TMP-SeNP with an IC50 value of 46.8 µg/mL. The apoptosis induction of HepG2 cells by Tw-TMP-SeNP was evidenced by increasing the proportion of apoptotic cells ranging from 12.5% to 27.4%. Furthermore, in vivo zebrafish model confirmed the anti-tumor activity of Tw-TMP-SeNP by inhibiting the proliferation and migration of tumor cells as well as the angiogenesis of zebrafish embryos.


Subject(s)
Nanoparticles/chemistry , Neoplasms/drug therapy , Polysaccharides/pharmacology , Selenium/pharmacology , Taraxacum/chemistry , A549 Cells , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Fructans/chemistry , Fructans/pharmacology , HeLa Cells , Hep G2 Cells , Humans , Hydrogen Bonding , Neoplasms/metabolism , Neoplasms/pathology , Polysaccharides/chemistry , Selenium/chemistry , Zebrafish
8.
Front Oncol ; 11: 688195, 2021.
Article in English | MEDLINE | ID: mdl-34249737

ABSTRACT

Casearlucin A, a diterpenoid obtained from Casearia graveolens, has been reported to possess strong cytotoxic activity. However, the in vivo anti-tumor effects and the action mechanism of casearlucin A remain poorly understood. Our study revealed that casearlucin A arrested cell cycle at G0/G1 stage and induced cell apoptosis in cell level. Additionally, casearlucin A inhibited HepG2 cell migration via regulating a few of metastasis-related proteins. Furthermore, it inhibited tumor angiogenesis in zebrafish in vivo. More importantly, casearlucin A significantly inhibited cell proliferation and migration in an in vivo zebrafish xenograft model. Collectively, these results are valuable for the further development and application of casearlucin A as an anticancer agent.

9.
Int J Biol Macromol ; 188: 904-913, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34331980

ABSTRACT

Selenium nanoparticles (SeNPs), a potential cancer therapeutic agent, have attracted widespread attention owing to their high bioavailability and remarkable anticancer activity. Nevertheless, the poor water solubility and dispersibility of SeNPs seriously limit their applications. In the present study, we synthesized stable and individual spherical selenium nanoparticles (CL90-Tw-SeNP2) with an average diameter of approximately 79 nm using a polysaccharide extracted from Citrus limon (CL90) and Tween-80 as the decorator and stabilizers. The proportion of selenium in CL90-Tw-SeNP2 was 10.6%. CL90-Tw-SeNP2 possessed high stability and good dispersion in water for more than three months. The subsequent biological assay revealed that CL90-Tw-SeNP2 showed remarkable antitumor effects against HepG2 cells, with an IC50 value of 49.13 µg/mL, by inducing cell apoptosis. Furthermore, an in vivo zebrafish assay to explore possible applications indicated that CL90-Tw-SeNP2 could inhibit the proliferation and migration of tumors and the zebrafish angiogenesis. These results indicated that CL90-Tw-SeNP2 could be a potential agent for cancer treatment, especially against human liver hepatoma cancer.


Subject(s)
Antineoplastic Agents/pharmacology , Citrus/chemistry , Metal Nanoparticles/chemistry , Polysaccharides/isolation & purification , Selenium/pharmacology , Animals , Animals, Genetically Modified , Apoptosis/drug effects , HeLa Cells , Hep G2 Cells , Humans , Metal Nanoparticles/ultrastructure , Monosaccharides/analysis , Neovascularization, Pathologic/pathology , Polysaccharides/chemistry , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Xenograft Model Antitumor Assays , Zebrafish
10.
Carbohydr Polym ; 265: 118080, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-33966844

ABSTRACT

A neutral water-soluble polysaccharide (RLP50-2) was extracted and purified from the fruits of Rosa laevigata. The absolute molecular weight was determined as 1.26 × 104 g/mol. Monosaccharide composition analysis showed that RLP50-2 mainly consisted of glucose, arabinose, and galactose. Structural analysis revealed that RLP50-2 consisted of →5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→, →3,6)-ß-D-Glcp-(1→, →4)-α-D-Galp-(1→, →6)-ß-D-Galp-(1→, →2)-ß-D-Xylp-(1→, terminal α-L-arabinose, and terminal ß-D-mannose. Biological assays showed that RLP50-2 had immunomodulatory activities using cell and zebrafish models. Moreover, RLP50-2 showed significantly antitumor activities by inhibiting tumor cell proliferation and migration and blocking angiogenesis. These results suggested that RLP50-2 could be developed as a potential immunomodulatory agent or antitumor candidate drug in biomedicine field.


Subject(s)
Fruit/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Rosa/chemistry , Animals , Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Immunologic Factors/pharmacology , Immunomodulation/drug effects , K562 Cells , Mice , Molecular Weight , Monosaccharides/analysis , Nitric Oxide/analysis , RAW 264.7 Cells , Reactive Oxygen Species , Zebrafish
11.
J Nat Prod ; 84(5): 1515-1523, 2021 05 28.
Article in English | MEDLINE | ID: mdl-33905250

ABSTRACT

Eight prenylated xanthones including four new analogues were extracted and purified from the leaves of Garcinia xipshuanbannaensis. Multiple techniques including UV, 1D and 2D NMR, and HRESIMS were used to determine the structures of the isolated xanthones. These xanthones were evaluated for their cytotoxicity toward human cancer cells, and compound 4 exhibited activity against HeLa cells. A cytotoxic mechanism examination revealed the active compound induced cell apoptosis by arresting the cell cycle, increasing the levels of ROS, and inhibiting the expression of p-STAT3 in HeLa cells. In in vivo zebrafish experiments, compound 4 was found to block tumor proliferation and migration and have antiangiogenetic activity, and thus seems worthy of further laboratory evaluation.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Garcinia/chemistry , Xanthones/pharmacology , Angiogenesis Inhibitors/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , China , HeLa Cells , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Leaves/chemistry , Prenylation , Xanthones/isolation & purification , Xenograft Model Antitumor Assays , Zebrafish
12.
Huan Jing Ke Xue ; 42(3): 1152-1157, 2021 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-33742911

ABSTRACT

In brown-red soil, the effect of phosphorus and citric acid co-existence on the adsorption of cadmium was studied using indoor experiments and isothermal equilibrium adsorption analysis. After treatment with different doses of phosphorus and citric acid, the fractions of cadmium were altered by varying dry and wet conditions. The results showed that:① Soil treated with 10 mg·L-1 of CdCl2 solution showed no notable effect on cadmium adsorption when a low concentration of phosphorus was added (40 mg·L-1); however, higher a concentration of added phosphorus (80 mg·L-1) significantly increased cadmium adsorption (an increase of 78 g·kg-1 and 7.89% compared to the control treatment); ② Using a 40 mg·L-1 phosphorus solution, the addition of citric acid proportionally reduced cadmium adsorption. This inhibition effect was more notable for the soil treated with low-dose phosphorus (40 mg·L-1) than the high-dose treatment with 1 mmol·L-1 and 5 mmol·L-1 citric acid (cadmium adsorption decreased by 30.89% and 40.97%, respectively). The effect of citric acid was not significant, however, at higher concentrations of phosphorus. When the concentration of citric acid reached 5 mmol·L-1, cadmium adsorption was only 1% lower than without citric acid treatment; ③ Periodic dry-wet alternation significantly promoted the transformation of cadmium from a weak acid extractable and reducible state to an oxidizable and residual state in the soil. That is, the availability of cadmium in soil subjected to the combined action of phosphorus and citric acid decreased with an increase in wet and dry alternations.

13.
Bioorg Chem ; 104: 104331, 2020 11.
Article in English | MEDLINE | ID: mdl-33142407

ABSTRACT

Inflammation, especially chronic inflammation, has been found to be closely related to the pathology of many diseases and the discovery of bioactive natural products to inhibit NO production is one of strategies to treat inflammation. In our continuous search for bioactive natural substances as potential anti-inflammatory agents, five new compounds (1-5) were extracted and purified from Patrinia heterophylla. The NMR and MS data analysis, along with electronic circular dichroism (ECD) calculations, led to the identification of these isolates, which were new iridoids. Using cell and zebrafish models, the in vitro and in vivo anti-inflammatory effects were conducted to evaluate the potency of anti-inflammation of these compounds. The preliminary mechanism was explored using molecular docking and Western blotting experiments.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biological Products/pharmacology , Inflammation/drug therapy , Iridoids/pharmacology , Patrinia/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Biological Products/chemistry , Biological Products/isolation & purification , Cell Survival/drug effects , Dose-Response Relationship, Drug , Inflammation/metabolism , Inflammation/pathology , Iridoids/chemistry , Iridoids/isolation & purification , Mice , Molecular Docking Simulation , Molecular Structure , Nitric Oxide/analysis , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Reactive Oxygen Species/analysis , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Zebrafish
14.
J Nat Prod ; 83(10): 2844-2853, 2020 10 23.
Article in English | MEDLINE | ID: mdl-32993289

ABSTRACT

Ten new ent-kaurane diterpenoids, including two pairs of epimers 1/2 and 4/5 and a 6,7-seco-ent-kauranoid 10, were obtained from the aerial parts of Isodon serra. The structures of the new compounds were confirmed by extensive spectroscopic methods and electronic circular dichroism (ECD) data analysis. An anti-inflammatory assay was applied to evaluate their nitric oxide (NO) inhibitory activities by using LPS-stimulated BV-2 cells. Compounds 1 and 9 exhibited notable NO production inhibition with IC50 values of 15.6 and 7.3 µM, respectively. Moreover, the interactions of some bioactive diterpenoids with inducible nitric oxide synthase (iNOS) were explored by employing molecular docking studies.


Subject(s)
Anti-Inflammatory Agents/analysis , Diterpenes, Kaurane/analysis , Isodon/chemistry , Diterpenes, Kaurane/chemistry , Molecular Docking Simulation , Molecular Structure
15.
Bioorg Chem ; 101: 104004, 2020 08.
Article in English | MEDLINE | ID: mdl-32629274

ABSTRACT

Bioactive natural products play an important role in the research and development of new drugs. In our search for bioactive natural substances as potential lead compounds for inflammation, four new (1-4) and six known (6-10) triterpenoids were acquired from Lantana camara. Using NMR and MS techniques and electronic circular dichroism (ECD) calculations, these isolates were characterized and the new compounds (1-4) were found to be euphane-type triterpenoids. The in vitro anti-inflammatory effects of all the isolates were evaluated and the more bioactive compounds were selected for the investigation of preliminary mechanism using molecular docking and Western blotting experiments, as well as the in vivo anti-inflammatory evaluation using a zebrafish model.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Lantana/chemistry , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Blotting, Western , Cell Line , In Vitro Techniques , Mice , Microglia/drug effects , Microglia/metabolism , Molecular Docking Simulation , Nitric Oxide/metabolism , Triterpenes/chemistry , Zebrafish
16.
Bioorg Chem ; 101: 103974, 2020 08.
Article in English | MEDLINE | ID: mdl-32512268

ABSTRACT

Five new iridoids, jatadomins A-E (1-5), together with six known analogues (6-11) and one known sesquiterpenoid (12), were isolated from the roots of Valeriana jatamansi Jones. Their structures were determined by analysis of their NMR, HRESIMS, and electronic circular dichroism calculations (ECD) data. The biological evaluation revealed that compounds 1-6 had anti-inflammatory activities by inhibiting nitric oxide (NO) release in LPS-induced murine microglial BV-2 cells, with IC50 values of 24.4, 9.2, 21.2, 25.9, 30.6, and 0.4 µM, respectively. Further molecular docking studies revealed a potential mechanism for NO inhibition by the bioactive compounds.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Iridoids/chemistry , Iridoids/therapeutic use , Molecular Docking Simulation/methods , Nitric Oxide/antagonists & inhibitors , Valerian/chemistry , Animals , Anti-Inflammatory Agents/pharmacology , Humans , Mice , Molecular Structure , Structure-Activity Relationship
17.
Bioorg Chem ; 101: 103966, 2020 08.
Article in English | MEDLINE | ID: mdl-32506016

ABSTRACT

A phytochemical survey to obtain bioactive natural products from Ajuga pantantha afforded five new neo-clerodane diterpenoids (1-5). The structures were established by analysis of their NMR spectroscopic data, and electronic circular dichroism calculations were applied to define their absolute configurations. Compounds 2 and 5 were found to have the property of inhibiting NO production (IC50 values < 40 µM). Molecular docking and Western blotting were used to study the mechanism of anti-inflammatory action. Furthermore, compound 5 with the highest activity was tested for its in vivo anti-inflammatory effects using a zebrafish model.


Subject(s)
Ajuga/chemistry , Anti-Inflammatory Agents/chemistry , Diterpenes, Clerodane/therapeutic use , Molecular Docking Simulation/methods , Animals , Disease Models, Animal , Diterpenes, Clerodane/pharmacology , Molecular Structure , Phytochemicals , Zebrafish
18.
Biomolecules ; 9(12)2019 11 29.
Article in English | MEDLINE | ID: mdl-31795455

ABSTRACT

Two new aryltetralin lactone lignans, petasitesins A and B were isolated from the hot water extract of the leaves of butterbur (Petasites japonicus) along with six known compounds. The chemical structures of lignans 1 and 2 were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Petasitesin A and cimicifugic acid D showed significant inhibitory effects on the production of both prostaglandin E2 (PGE2) and NO in RAW264.7 macrophages. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by compound 1 in RAW264.7 cells. Furthermore, compounds 1 and 3 exhibited strong affinities with both iNOS and COX-2 enzymes in molecular docking studies.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Lignans/pharmacology , Petasites , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/analysis , Anti-Inflammatory Agents/chemistry , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Lignans/analysis , Lignans/chemistry , Lipopolysaccharides/pharmacology , Mice , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , Plant Leaves/chemistry , RAW 264.7 Cells
19.
Bioorg Chem ; 87: 447-456, 2019 06.
Article in English | MEDLINE | ID: mdl-30925429

ABSTRACT

In our continuous search for new nitric oxide (NO) inhibitory compounds as potential anti-inflammatory agents or lead compounds for inflammatory diseases, the chemical constituents of Euonymus verrucosus var. pauciflorus were investigated, leading to the isolation of eleven terpenoids including six new diterpenoids, designated as euonymupenes A-F. The structures were elucidated on the basis of NMR and ECD data analysis. Euonymupenes A, C, and F feature rare labdane-type norditerpenoid skeletons. The NO inhibitory effects were evaluated and all of the isolates were found to inhibit lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. Western blotting analysis indicated that the most active compound (5) can regulate iNOS (inducible nitric oxide synthase) expression. The further molecular docking studies exhibited the affinities of bioactive compounds with iNOS.


Subject(s)
Euonymus/chemistry , Nitric Oxide/antagonists & inhibitors , Terpenes/pharmacology , Animals , Cell Line , Density Functional Theory , Dose-Response Relationship, Drug , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Docking Simulation , Molecular Structure , Nitric Oxide/biosynthesis , Structure-Activity Relationship , Terpenes/chemistry , Terpenes/isolation & purification
20.
Bioorg Chem ; 87: 417-424, 2019 06.
Article in English | MEDLINE | ID: mdl-30921743

ABSTRACT

Studies on the relationship of nitric oxide (NO) and inflammation have revealed that compounds with NO inhibitory effects are potentially useful for inflammation and related inflammatory disorders. A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of two new cleistanthane diterpenoids (1 and 2) and 11 known terpenoids (3-13) from Trigonostemon heterophyllus. The structures of these terpenoids were established by analysis of their NMR, MS, and electronic circular dichroism (ECD) data. Compounds 1 and 2 possess rare 3,4-seco-cleistanthane diterpenoid skeletons. All of the isolates were evaluated biologically for their NO inhibitory effects in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells and compounds 1, 6, and 8-10 showed strong NO inhibitory effects with IC50 values less than 40 µM. Using Western blotting experiments and molecular docking, the possible mechanism of NO inhibition was investigated.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Euphorbiaceae/chemistry , Nitric Oxide/antagonists & inhibitors , Phytochemicals/pharmacology , Plant Stems/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cell Line , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Docking Simulation , Molecular Structure , Nitric Oxide/biosynthesis , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Structure-Activity Relationship
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