ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Calcium oxalate crystals play a key role in the development and recurrence of kidney stones (also known as urolithiasis); thus, inhibiting the formation of these crystals is a central focus of urolithiasis prevention and treatment. Previously, we reported the noteworthy in vitro inhibitory effects of Aspidopterys obcordata fructo oligosaccharide (AOFOS), an active polysaccharide of the traditional Dai medicine Aspidopterys obcordata Hemsl. (commonly known as Hei Gai Guan), on the growth of calcium oxalate crystals. AIM OF THE STUDY: To investigated the effectiveness and mechanism of AOFOS in treating kidney stones. MATERIALS AND METHODS: A kidney stones rats model was developed, followed by examining AOFOS transport dynamics and effectiveness in live rats. Additionally, a correlation between the polysaccharide and calcium oxalate crystals was studied by combining crystallization experiments with density functional theory calculations. RESULTS: The results showed that the polysaccharide was transported to the urinary system. Furthermore, their accumulation was inhibited by controlling their crystallization and modulating calcium ion and oxalate properties in the urine. Consequently, this approach helped effectively prevent kidney stone formation in the rats. CONCLUSIONS: The present study emphasized the role of the polysaccharide AOFOS in modulating crystal properties and controlling crystal growth, providing valuable insights into their potential therapeutic use in managing kidney stone formation.
Subject(s)
Calcium Oxalate , Crystallization , Kidney Calculi , Animals , Calcium Oxalate/chemistry , Calcium Oxalate/metabolism , Male , Rats , Kidney Calculi/prevention & control , Kidney Calculi/drug therapy , Rats, Sprague-Dawley , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Urolithiasis/drug therapy , Urolithiasis/prevention & control , Disease Models, Animal , Inulin/chemistry , Inulin/pharmacologyABSTRACT
The 6-methoxy-cannabisin I (1), a new alkaloid, together with five known compounds oleraisoindole A (2), cannabisin F (3), apigenin (4), syringin (5) and ethyl-syringin (6) were isolated from Tinospora crispa stems. Their structures were identified by the analysis of spectroscopic data. Compound 2 was isolated from T. crispa for the first time. Anti-inflammatory activity of compound 1 was detected against NO production in LPS-activated RAW 264.7 macrophages. However, no activity was observed.
ABSTRACT
A new class of potent liver injury protective compounds, phychetins A-D (1-4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2-4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1-4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2-4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1ß. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.
ABSTRACT
Eleven densely functionalized new dihydro-ß-agarofuran sesquiterpenoid derivatives, named maytenoids A-K (1-11), as well as one known analog, were isolated and characterized from Maytenus austroyunnanensis. Their structures were assigned based on analysis of spectroscopic data and X-ray crystallography. Compounds 1-9 are macrocyclic sesquiterpene pyridine alkaloids generated by the respective acylation of the hydroxy groups at C-3 and C-13 of dihydro-ß-agarofuran sesquiterpenoids via diverse pyridine dicarboxylic acids. Compounds 1, 2, 5-10, and 12 exhibited significant inhibitory effects on NO production at 10 µM in lipopolysaccharide (LPS)-stimulated BV2 cells.
Subject(s)
Alkaloids , Maytenus , Sesquiterpenes , Maytenus/chemistry , Molecular Structure , Alkaloids/pharmacology , Alkaloids/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Pyridines/chemistryABSTRACT
Chemical investigation of medicinal plant Glycosmis lucida Wall. ex C. C. Huang leaves led to the production of ten compounds (1-10), including two previously unreported geranylated sulfur-containing amides (1 and 2) and eight known ones (3-10). Structural characterization was carried out using comprehensive spectroscopic methods including NMR, MS and CD. The inhibitory effects of all isolates on Th17 differentiation were evaluated, of which compounds 1 and 6 significantly inhibited Th17 differentiation with IC50 values of 0.36 and 1.30⠵M, respectively, while both 1 and 6 failed to bind to retinoic acid-related orphan receptor gamma t (RORγt), suggesting that their inhibition of Th17 differentiation is independent of RORγt.
Subject(s)
Amides , Nuclear Receptor Subfamily 1, Group F, Member 3 , Amides/pharmacology , Amides/chemistry , Sulfur , Cell DifferentiationABSTRACT
Seven new sesquiterpenes, named croargoid A-G (1-7), were isolated from the bark of Croton argyratus. Compounds 1-4 were the first examples of eudesmane sesquiterpene lactones containing C5-OH group. Compound 7 was a highly degraded eudesmane sesquiterpene possessing a rare eleven-carbon skeleton. Their structures with stereochemistry were mainly elucidated by NMR analyses in combination with MS and ECD data. Cytotoxicities and NO inhibitions of all isolates were evaluated and only compound 5 showed moderate NO inhibitory activity.
Subject(s)
Croton , Sesquiterpenes, Eudesmane , Sesquiterpenes , Carbon , Lactones/pharmacology , Molecular Structure , Plant Bark , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes, Eudesmane/chemistry , Sesquiterpenes, Eudesmane/pharmacologyABSTRACT
Aspidopterys obcordata vine is a Chinese Dai ethnic herb used to treat urolithiasis. However, the material basis and underlying mechanisms remain undefined. In this study, a 2.3 kD inulin-like A. obcordata fructan (AOFOS) was isolated by size exclusion column chromatography and characterized by ultrahigh-performance liquid chromatography-ion trap-time of flight mass spectrometry (UPLC-IT-TOF-MS), nuclear magnetic resonance (NMR) spectroscopy, gas chromatography mass spectrometry (GC-MS) and high-performance gel permeation chromatography (HGPC). In addition, AOFOS showed unique anti-urolithiasis activity in Drosophila kidney stone models. Mechanism study indicated that AOFOS reduced the size of calcium oxalate crystals by inhibiting the formation of large size crystals and the generation rate of calcium oxalate crystals as well as the crystal form conversion from calcium oxalate monohydrate (COM) to calcium oxalate dihydrate (COD).
Subject(s)
Kidney Calculi , Malpighiaceae , Calcium Oxalate/chemistry , Crystallization , Fructans , Inulin , Kidney Calculi/chemistryABSTRACT
Zanthoxylum avicennae fruits were traditionally used to treat many inflammatory-related diseases, such as icterohepatitis, nephritis and colitis, which inspired us to explore the active chemicals and pharmacological activity. As a result, ten quinoline alkaloids, including six new ones, avicenines A-F (1-6), were isolated and structurally characterized by solid data. Compounds 1, 7 and 8 were identified as three pairs of enantiomers by chiral HPLC separation, of which 1 was an unusual 6/6/5/5-fused quinoline alkaloid bearing a unique cis-hexahydrofuro[3,2-b]furan moiety. The putative biosynthetic pathway for enantiomeric compounds was also proposed. In addition, compound 6 significantly suppressed the gene expression and secretion of pro-inflammatory cytokines IL-1ß and IL-6 in macrophages.
Subject(s)
Alkaloids , Quinolines , Zanthoxylum , Alkaloids/chemistry , Alkaloids/pharmacology , Anti-Inflammatory Agents/pharmacology , Chromatography, High Pressure Liquid , Quinolines/pharmacology , Zanthoxylum/chemistryABSTRACT
Alpinia hainanensis is an important food spice and ethnic medicine in Southwest China. In this study, we found that the EtOAc-soluble fraction (AHE) of the A. hainanensis rhizome ethanol extract could ameliorate dextran sulfate sodium-induced ulcerative colitis (UC). To explore active constituents, five pairs of previously unreported enantiomers (1-5), together with nine known ones (6-14), were obtained. Structural characterization was achieved by comprehensive spectroscopic methods. Compounds 1 and 2 were new curcumin-butyrovanillone hybrids featuring a rare structural fragment of 2,3-dihyrofuran. The anti-inflammatory activities of isolates were evaluated, and the results indicated that compounds (-)-1, (-)-3, 6, 9, 11, and 12 significantly inhibited the nuclear factor-κB signaling pathway. These findings indicate the major active fraction of the A. hainanensis rhizome ethanol extract enriched with diarylheptanoids, flavonoids, phenolics, and their hybrid mixtures, which could be developed as a nutritional and dietary supplement for treating UC.
Subject(s)
Alpinia , Colitis, Ulcerative , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Dextran Sulfate/adverse effects , Disease Models, Animal , Humans , NF-kappa B/metabolism , Plant Extracts/chemistry , RhizomeABSTRACT
Two previously unreported monoterpenoid indole alkaloids, 19(20)E-5-carboxymethylvallesiachotamine (1) and 19(20)Z-5-carboxymethylvallesiachotamine (2), along with five known indole alkaloids (3-7) were isolated from Mappianthus iodoides stems. Their structures were characterized by extensive spectroscopic data. Among these isolates, compounds 1 and 2 were the two new Δ19(20) geometric isomers. The anti-inflammatory activities in vitro of all isolated compounds were evaluated using NO assay.[Formula: see text].
Subject(s)
Magnoliopsida , Secologanin Tryptamine Alkaloids , Anti-Inflammatory Agents , Indole Alkaloids , Magnoliopsida/chemistry , Molecular Structure , Secologanin Tryptamine Alkaloids/chemistry , Secologanin Tryptamine Alkaloids/pharmacologyABSTRACT
One novel pentacyclic triterpene, 24-dimethoxymethyl-3ß,6ß,19α- trihydroxy -12-en-28-oic acid (1), along with six known compounds 2-7, were isolated from the canes of Uncaria sessilifructus Roxb. Their structures were determined according to spectroscopic and spectrometric analysis. The anti-inflammatory activities of the isolated compounds (1-7) were scanned against NO production in LPS-activated RAW 264.7 macrophages by MTS assay, however no activities were observed.
Subject(s)
Rubiaceae , Triterpenes , Uncaria , Molecular Structure , Pentacyclic Triterpenes/pharmacology , Plant Extracts , Triterpenes/pharmacologyABSTRACT
Four new limonoids, named as trichiconlide G (1), 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), 21-oxo-23-hydroxyltrijugin F (4), along with sixteen known analogues (5-20) were isolated from the leaves and twigs of Trichilia connaroides. Their structures and absolute configurations were determined by spectroscopic analyses, X-ray diffraction analysis, and TD-DFT-ECD calculations. Trichiconlide G (1) is one rare naturally occurring 1,2-seco phragmalin-type limonoid bearing a C-7/28 δ-lactone ring. Additionally, 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), and 21-oxo-23-hydroxyltrijugin F (4) are three naturally occurring limonoids with a rare C-16/8 δ-lactone ring. All isolates were evaluated for their cytotoxic and anti-inflammatory activities. None of compounds exhibited cytotoxicity against five human cancer cell lines A-549, HepG2, 5-8F, Siha, and SCC-4 at the concentration of 40 µM. Compounds 16 and 17 showed moderate anti-inflammatory activity with IC50 values of 28.45 ± 2.51 and 22.66 ± 2.01 µM, respectively.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Limonins/pharmacology , Meliaceae/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Cell Line, Tumor , China , Humans , Limonins/isolation & purification , Mice , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Leaves/chemistry , RAW 264.7 CellsABSTRACT
Eleven previously uncharacterized steroids, along with three analogs were isolated from Aglaia lawii leaves. Their structures were definitely characterized by the methods of NMR, MS, IR, ECD and X-ray crystallography study. Among these unreported compounds, 3-epi-dyscusin C, 3-epi-lansisterone E and (Z)-2α-hydroxyaglawone were C-21 pregnane steroids incorporating a highly oxygenated ring A, while others were Δ5-3ß-hydroxy-7-ketosteroids bearing different ring D and C-17 aliphatic chains. All isolates were evaluated for nitric oxide (NO) inhibitory activities. 3-Epi-dyscusin C, 3-epi-lansisterone E, (Z)-2α-hydroxyaglawone and 17(20)E-dyscusin B showed significant anti-inflammatory activities with IC50 values of NO inhibition less than 10 µM (in the range from 4.47 ± 0.36 to 7.67 ± 0.46 µM).
Subject(s)
Aglaia , Molecular Structure , Nitric Oxide , Plant Leaves , Pregnanes/pharmacology , Steroids/pharmacologyABSTRACT
Chemical investigation of Lansium domesticum has led to the isolation of two undescribed compounds, namely 17(20)E-dyscusin B (1) and 17(20)Z-dyscusin B (2), as well as three known ones (3 - 5). Structural elucidation was accomplished by the analysis of NMR, MS and IR data. Compounds 1 and 2 were a pair of Δ17(20) geometric isomers of pregnane steroids and showed the significant nitric oxide (NO) inhibitory activities.
Subject(s)
Meliaceae/chemistry , Nitric Oxide/antagonists & inhibitors , Steroids/pharmacology , Animals , Carbon-13 Magnetic Resonance Spectroscopy , Lipopolysaccharides/pharmacology , Mice , Nitric Oxide/metabolism , Plant Extracts/chemistry , Proton Magnetic Resonance Spectroscopy , RAW 264.7 Cells , Steroids/chemistryABSTRACT
Chemical investigation of an EtOH extract of the twigs and leaves of Croton damayeshu afforded 10 new tigliane diterpenoids, crodamoids A-J (1-10), along with five known compounds. Their structures were elucidated by physical data analysis. Compounds 8, 9, and 15 displayed cytotoxic effects against two human tumor cell lines, A549 and HL-60 (IC50: 0.9-2.4 µM).
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Croton/chemistry , Diterpenes/chemistry , Phorbols/toxicity , Plant Leaves/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Croton/toxicity , Diterpenes/isolation & purification , Diterpenes/pharmacology , Diterpenes/toxicity , HL-60 Cells , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Phorbols/chemistryABSTRACT
A 17-membered macrocyclolipopeptide, named dysoxylactam A (1) comprising an unprecedented branched C19 fatty acid and an l-valine, was isolated from the plants of Dysoxylum hongkongense. The challenging relative configuration of 1 was established by means of residual dipolar coupling-based NMR analysis. The absolute configuration of 1 was determined by single-crystal X-ray diffraction on its p-bromobenzoate derivative (2). Compound 1 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 28.4 to 1039.7 at the noncytotoxic concentration of 10 µM. The mode-of-action study of 1 revealed that it inhibited the function of P-glycoprotein (P-gp), a key mediator in multidrug resistance.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Antineoplastic Agents/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Lipopeptides/pharmacology , Peptides, Cyclic/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Lipopeptides/chemical synthesis , Lipopeptides/chemistry , Lipopeptides/isolation & purification , Meliaceae/chemistry , Peptides, Cyclic/chemical synthesis , Peptides, Cyclic/isolation & purificationABSTRACT
Four highly rearranged labdane-type diterpenoids, maximumins A-D (1-4) possessing different new carbon skeletons, together with a biosynthetically related known analog 5 were isolated from Amomum maximum. The structures of new compounds with absolute configurations were characterized by spectroscopic and computational approaches. The plausible biogenetic pathways for 1-4 were proposed. These compounds showed moderate to weak activities against nuclear factor kappa B (NF-κB).
Subject(s)
Amomum/chemistry , Carbon/chemistry , Diterpenes/chemistry , Models, Molecular , Molecular ConformationABSTRACT
Dietary fiber has been shown to prevent high-fat diet induced obesity through modulating the gut microbiota; however, quality difference in fiber type is largely unknown. We performed a 6 week study on C57BL/6J mice fed a macronutrient matched high-fat diet with different fiber types including cellulose (HFC), bamboo shoot fiber (HFBS) and several other commonly consumed fibers. Our results showed that the HFBS group exhibited the lowest weight gain among all diet groups and had improved lipid profiles and glycemic control compared with the HFC group. As revealed by 16S rRNA gene sequencing, loss of diversity in the gut microbiota induced by the HFC diet was largely prevented by the HFBS diet. Moreover, compared with the HFC diet, the HFBS diet resulted in markedly increased relative abundance of Bacteroidetes and strong inhibition of Verrucomicrobia, two divisions strongly correlated with body weight. In conclusion, the present study provides evidence of a quality difference among different types of dietary fibers and shows that bamboo shoot fiber is the most effective in suppressing high-fat diet induced obesity. Our findings indicate that bamboo shoot fiber is a potential prebiotic fiber which modulates the gut microbiota and improves host metabolism.
Subject(s)
Dietary Fiber/administration & dosage , Gastrointestinal Microbiome/drug effects , Obesity/prevention & control , Sasa/metabolism , Animals , Bacteria/classification , Bacteria/drug effects , Bacteria/genetics , Dietary Fiber/pharmacology , Disease Models, Animal , Mice , Mice, Inbred C57BL , Phylogeny , Plant Shoots/metabolism , RNA, Ribosomal, 16S/genetics , Sequence Analysis, RNA , Weight Gain/drug effectsABSTRACT
BACKGROUND: Zanthoxylum myriacanthum var. pubescens is an ethnic medicine for digestive disease known as Maqian. A previous report showed that the Maqian fruits essential oil (MQEO) exhibited an NO inhibitory effect on RAW 264.7 cells, but the effect on inflammatory disease in vivo remains unknown. PURPOSE: To investigate the anti-inflammatory effect of Z. myriacanthum var. pubescens as potential candidate for the treatment of intestinal inflammation. STUDY DESIGN: Evaluation of anti-inflammatory effect of MQEO using dextran sulfate sodium (DSS)-induced intestinal inflammation in mice and exploration of the mechanisms with THP-1 cells. METHODS: C57BL/6 mice were provided drinking water containing 3% DSS for 10 days followed by normal drinking water for 3 days. MQEO (35 and 70mg/kg) were given 5 days before experiments and continued for another 13 days. At the end of experiments, mice were euthanized and colonic tissue was collected to be analyzed by H&E staining, RT-PCR and immunohistochemistry for evaluating the damage of colons, the mRNA levels of IL-1ß, IL-6, IL-12p35 and TNF-α, and the expressions of myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). The LPS-stimulated THP-1 cell line was used for exploring the role of inflammatory markers using ELISA, western blot and flow cytometry methods. RESULTS: Oral administration of MQEO (35 and 70mg/kg) markedly attenuated the symptoms of intestinal inflammation, including diarrhea, rectal bleeding, and loss of body weight. It also reduced the shortening of colon length and histopathological damage. The expressions of MPO and MMP-9 and the mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6 and IL-12p35) in colonic tissue significantly decreased after MQEQ treatment. The activation of NF-κB p65 in colonic mucosa was also markedly suppressed. In addition, MQEO significantly suppressed LPS-stimulated production of TNF-α and IL-1ß, effectively blocked phosphorylation of IKK and IκB, and dose-dependently reduced LPS-stimulated expression of TLR4 in THP-1 cells at concentrations ranging from 0.01 to 0.05 (v/v). CONCLUSION: MQEO exhibited protective effect against DSS-induced intestinal inflammation and the anti-inflammatory activity may be associated with TLR4 mediated NF-κB signaling pathway, suggesting it might be used as an anti-inflammatory agent.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Enteritis/chemically induced , Enteritis/prevention & control , Oils, Volatile/pharmacology , Protective Agents/pharmacology , Zanthoxylum/chemistry , Animals , Cell Line , Colitis/chemically induced , Colitis/metabolism , Colitis/prevention & control , Dextran Sulfate , Enteritis/pathology , Female , Male , Mice , Mice, Inbred C57BL , RAW 264.7 Cells , Transcription Factor RelA/genetics , Transcription Factor RelA/metabolismABSTRACT
Ten cedrelone limonoids were isolated from the leaves of Trichilia americana. These compounds include americanolides A-D (1-4), 1,2-dihydrodeacetylhirtin (5), 1α-hydroxy-1,2-dihydrodeacetylhirtin (6), 1α-hydroxy-1,2-dihydrohirtin (7), 1α-methoxy-1,2-dihydrodeacetylhirtin (8), 11ß-hydroxy-12α-propanoyloxycedrelone (9), and 1α,11ß-dihydroxy-1,2-dihydrocedrelone (10), as well as two previously reported compounds, deacetylhirtin (11) and hirtin (12). Their structures were characterized on the basis of spectroscopic studies, and the assignment of the absolute configuration of americanolide A (1) was supported by single-crystal X-ray diffraction studies. The cytotoxic activities of all isolated compounds were also evaluated against five human tumour cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) using an MTS assay. Compounds 11 and 12 showed significant cytotoxicity with IC50 values ranging from 0.1 to 0.5 µM, and compounds 5, 6, 7, 8, 9, and 10 exhibited potent or selective cytotoxic activity with IC50 values ranging from 1.0 to 39.6 µM.