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1.
J Proteome Res ; 22(8): 2669-2682, 2023 08 04.
Article in English | MEDLINE | ID: mdl-37475705

ABSTRACT

Ulcerative colitis (UC), belonging to inflammatory bowel disease (IBD), is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, which has not been completely cured in patients so far. Valeriana jatamansi is a Chinese medicine used clinically to treat "diarrhea," which is closely related to UC. This study was to elucidate the therapeutic effects of V. jatamansi extract (VJE) on dextran sodium sulfate (DSS)-induced UC in mice and its underlying mechanism. In this work, VJE effectively ameliorates the symptoms and histopathological scores and reduces the production of inflammatory factors in UC mice. The colon untargeted metabolomics analysis and 16S rDNA sequencing showed remarkable differences in colon metabolite profiles and intestinal microbiome composition between the control and DSS groups, and VJE intervention can reduce these differences. Thirty-two biomarkers were found and modulated the primary pathways including pyrimidine metabolism, arginine biosynthesis, and glutathione metabolism. Meanwhile, twelve significant taxa of gut microbiota were found. Moreover, there is a close relationship between endogenous metabolites and intestinal flora. These findings suggested that VJE ameliorates UC by inhibiting inflammatory factors, recovering intestinal maladjustment, and regulating the interaction between intestinal microbiota and host metabolites. Therefore, the intervention of V. jatamansi is a potential therapeutic treatment for UC.


Subject(s)
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Microbiota , Valerian , Animals , Mice , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Metabolomics , Colon , Dextran Sulfate , Disease Models, Animal , Colitis/chemically induced , Colitis/drug therapy , Mice, Inbred C57BL
2.
J Asian Nat Prod Res ; 25(8): 810-817, 2023.
Article in English | MEDLINE | ID: mdl-36394297

ABSTRACT

Investigation on the chemical components of Valeriana jatamansi Jones (Caprifoliaceae), a new lignan with pyran-ring, dipsalignan G (1), along with eight known compounds (2-9) were isolated. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HR-ESI-MS spectroscopic data. Additionally, possible biosynthetic pathway of 1 was proposed. Finally, biological evaluation results showed that 8 had significant scavenging ability to ABTS and DPPH free radicals, with IC50 values of 1.35 ± 0.01 and 2.94 ± 0.01 µg/ml, respectively.

3.
J Sep Sci ; 45(13): 2273-2300, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35389521

ABSTRACT

Mycotoxin contamination is a globally concerned problem for food and agricultural products since it may directly or indirectly induce severe threats to human health. Sensitive and selective screening is an efficient strategy to prevent or reduce human and animal exposure to mycotoxins. However, enormous challenges exist in the determination of mycotoxins, arising from complex sample matrices, trace-level analytes, and the co-occurrence of diverse mycotoxins. Appropriate sample preparation is essential to isolate, purify, and enrich mycotoxins from complicated matrices, thus decreasing sample matrix effects and lowering detection limits. With the cross-disciplinary development, new solid-phase extraction strategies have been exploited and integrated with nanotechnology to meet the challenges of mycotoxin analysis. This review summarizes the advance and progress of solid-phase extraction techniques as the methodological solutions for mycotoxin analysis. Emphases are paid on nanomaterials fabricated as trapping media of solid-phase extraction techniques, including carbonaceous nanoparticles, metal/metal oxide-based nanoparticles, and nanoporous materials. Advantages and limitations are discussed, along with the potential prospects.


Subject(s)
Mycotoxins , Nanostructures , Animals , Drug Contamination , Food , Food Analysis/methods , Food Contamination/analysis , Humans , Mycotoxins/analysis , Nanostructures/analysis , Solid Phase Extraction
4.
Phytother Res ; 36(8): 3102-3119, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35701855

ABSTRACT

Natural compounds (NPs) have historically made a major contribution to pharmacotherapy in various diseases and drug discovery. In the past decades, studies on gut microbiota have shown that the efficacy of NPs can be affected by the interactions between gut microbiota and NPs. On one hand, gut microbiota can metabolize NPs. On the other hand, NPs can influence the metabolism and composition of gut microbiota. Among gut microbiota metabolites, bile acids (BAs) have attracted widespread attention due to their effects on the body homeostasis and the development of diseases. Studies have also confirmed that NPs can regulate the metabolism of BAs and ultimately regulate the physiological function of the body and disease progresses. In this review, we comprehensively summarize the interactions among NPs, gut microbiota, and BAs. In addition, we also discuss the role of microbial BAs metabolism in understanding the toxicity and efficacy of NPs. Furthermore, we present personal insights into the future research directions of NPs and BAs.


Subject(s)
Bile Acids and Salts , Gastrointestinal Microbiome , Homeostasis , Lipid Metabolism
5.
Phytother Res ; 36(4): 1545-1575, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35253930

ABSTRACT

Quercitrin is a naturally available type of flavonoid that commonly functions as the dietary ingredient and supplement. So far, a wide spectrum of bioactivities of quercitrin have been revealed, including antioxidative stress, antiinflammation, anti-microorganisms, immunomodulation, analgesia, wound healing, and vasodilation. Based on these various pharmacological activities, increasing studies have focused on the potency of quercitrin in diverse diseases in recent years, such as bone metabolic diseases, gastrointestinal diseases, cardiovascular and cerebrovascular diseases, and others. In this paper, by collecting and summarizing publications from the recent years, the natural sources, pharmacological activities and roles in various diseases, pharmacokinetics, structure-activity relationship, as well as the toxicity of quercitrin were systematically reviewed. In addition, the underlying molecular mechanisms of quercitrin in treating related diseases, the dose-effect relationships, and the novel preparations were discussed on the purpose of broadening the application prospect of quercitrin as functional food and providing reference for its clinical application. Notably, clinical studies of quercitrin are insufficient at present, further high-quality studies are needed to firmly establish the clinical efficacy of quercitrin.


Subject(s)
Flavonoids , Quercetin , Antioxidants/metabolism , Antioxidants/pharmacology , Flavonoids/pharmacology , Oxidative Stress , Quercetin/analogs & derivatives , Quercetin/chemistry , Quercetin/pharmacology
6.
Molecules ; 27(17)2022 Aug 25.
Article in English | MEDLINE | ID: mdl-36080236

ABSTRACT

The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds 1-3, were isolated from Ajuga ovalifolia var. calantha. Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound 2 selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound 2 targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound 2 passed the majority of the parameters of common drug discovery rules. Compound 2 restrained A549 proliferation (IC50 = 8.68 ± 0.96 µM), invasion and caused A549 cell apoptosis by inhibiting the SHP2-ERK/AKT signaling pathway. Finally, compound 2 (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment.


Subject(s)
Abietanes , Ajuga , A549 Cells , Abietanes/chemistry , Abietanes/pharmacology , Apoptosis , Humans , Molecular Docking Simulation
7.
Bioorg Chem ; 107: 104523, 2021 02.
Article in English | MEDLINE | ID: mdl-33339668

ABSTRACT

Chuanxiongdiolides R4-R6 (1-3), three novel phthalide dimers featuring two classes of unreported monomeric units (ligustilide/senkyunolide A and ligustilide/neocnidilide) with an unprecedented linkage style (3a,7'/7a,7'a), were isolated from the aerial parts of Ligusticum chuanxiong, together with three pairs of enantiomeric phthalide dimers [(-)/(+)-4a/4b, 5a/5b, and 6a/6b]. The bioassays revealed that compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects, and the mechanism may be attributed to Cav1.2 activation blockade. Based on the established compounds library, the structure activity relationship of the phthalides was proposed. Our findings afford possible leads for developing new vasodilator against cardiovascular and cerebrovascular diseases such as hypertension and ischemic stroke.


Subject(s)
Benzofurans/pharmacology , Heterocyclic Compounds, Bridged-Ring/pharmacology , Ligusticum/chemistry , Vasodilator Agents/pharmacology , Animals , Benzofurans/chemistry , Benzofurans/isolation & purification , Benzofurans/metabolism , Calcium Channel Blockers/chemistry , Calcium Channel Blockers/isolation & purification , Calcium Channel Blockers/metabolism , Calcium Channel Blockers/pharmacology , Calcium Channels, L-Type/metabolism , HEK293 Cells , Heterocyclic Compounds, Bridged-Ring/chemical synthesis , Heterocyclic Compounds, Bridged-Ring/isolation & purification , Heterocyclic Compounds, Bridged-Ring/metabolism , Humans , Molecular Docking Simulation , Molecular Structure , Plant Components, Aerial/chemistry , Protein Binding , Rabbits , Rats, Sprague-Dawley , Stereoisomerism , Structure-Activity Relationship , Vasodilator Agents/chemistry , Vasodilator Agents/isolation & purification , Vasodilator Agents/metabolism
8.
Bioorg Chem ; 87: 136-141, 2019 06.
Article in English | MEDLINE | ID: mdl-30884307

ABSTRACT

Chlorovaltrates U-W (1-3), three previously undescribed iridoids, together with four known analogues were isolated from the roots of Valeriana jatamansi. Their structures were elucidated by means of spectroscopic analyses (HRESIMS, NMR). The cytotoxicity of all isolates was evaluated. Compounds 5-7 exhibited selective cytotoxicity against HCT116 cells, with IC50 values of 9.3, 1.7 and 2.2 µM, respectively. The preliminary mechanistic study revealed that, the cytotoxicity effect of 6 was attributed to Akt/mTOR activation blockade via inhibition of PDK1 phosphorylation. Meanwhile, compound 6 could induce autophagosome formation in HCT116 cells via suppressing its downstream Akt/mTOR. These findings show that compound 6 could be of great importance to the development of anti-colon cancer agents.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Autophagy/drug effects , Iridoids/pharmacology , Protein Kinase Inhibitors/pharmacology , Valerian/chemistry , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Cell Death/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HCT116 Cells , Humans , Iridoids/chemistry , Iridoids/isolation & purification , Models, Molecular , Molecular Structure , Plant Roots/chemistry , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/antagonists & inhibitors , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism , Structure-Activity Relationship , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism
9.
Phytother Res ; 32(8): 1521-1529, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29672953

ABSTRACT

Astragalus polysaccharides (APS), one of the major active components in Astragalus membranaceus, is an effective immunomodulator used in the treatment of immunological diseases in China. However, the anti-infective action and mechanism of APS is not fully known. In the present study, we found that APS induced the expression of human cathelicidin antimicrobial peptide LL-37, a key host anti-infective molecule, in both mRNA and protein levels in respiratory epithelial cells HBE16 and A549. Furthermore, the lysate and supernatant from APS-treated HBE16 cells both exhibited an obvious antibacterial action, which was partially neutralizated by LL-37 monoclonal antibody. In addition, APS also significantly elevated the phosphorylation of p38 MAPK and JNK and caused the degradation of IκBα. Specific inhibitors of p38 MAPK, JNK, or NF-κB obviously abolished APS-induced LL-37 synthesis and antibacterial activity, respectively. Taken together, our results confirmed the enhancement of APS on LL-37 induction and antibacterial action in respiratory epithelial cells, which may be attributed to activation of p38 MAPK/JNK and NF-κB pathways. Furthermore, these results also supported the clinical application of APS in the treatment of infectious diseases.


Subject(s)
Astragalus propinquus/chemistry , Cathelicidins/biosynthesis , Epithelial Cells/drug effects , Anti-Infective Agents , Antimicrobial Cationic Peptides , Cell Line , Epithelial Cells/metabolism , Humans , I-kappa B Proteins/metabolism , NF-KappaB Inhibitor alpha , NF-kappa B/metabolism , Phosphorylation/drug effects , Polysaccharides/pharmacology , Transcription Factor RelA , p38 Mitogen-Activated Protein Kinases/metabolism
10.
Molecules ; 23(9)2018 Aug 31.
Article in English | MEDLINE | ID: mdl-30200284

ABSTRACT

Poria cocos (Schw.) Wolf (PC) is a well-known saprophytic fungus, and its sclerotium without the epidermis (PCS) is widely used in traditional Chinese medicine and as a functional food in many countries. PCS is normally collected from multiple geographical regions, but whether and how the quality of PCS correlates with where it grows have not been determined. This correlation could be significant both for quality control and optimum utilization of PCS as a natural resource. In this study, a qualitative fingerprint profiling method performed by ultra-performance liquid chromatography (UHPLC) with diode array detection (DAD) combining quadrupole time-of-flight-mass spectrometry (QTOF-MS/MS) and a quantitative UHPLC coupled with triple quadrupole mass spectrometry (QqQ-MS/MS) approach were established to investigate whether and how the quality of PCS correlates with its collection location. A standard fingerprint of PCS was generated by median simulation of 25 tested samples collected from four main producing areas of China, and similarity analysis was applied to evaluate the similarities between the fingerprints of samples and the standard fingerprint. Twenty three common peaks occurring in the fingerprint were unequivocally or tentatively identified by UHPLC-QTOF-MS/MS. Meanwhile, principal component analysis (PCA), supervised orthogonal partial least squares-discriminate analysis (OPLS-DA) and hierarchical cluster analysis (HCA) were employed to classify 25 batches of PCS samples into four groups, which were highly consistent with the four geographical regions. Ten compounds were screened out as potential markers to distinguish the quality of PCS. Nine triterpene acids, including five compounds that played important roles in the clusters between different samples collected from the four collection locations, were simultaneously quantified by using the multiple reaction monitoring (MRM) mode of UHPLC-QqQ-MS/MS. The current strategy not only clearly expounded the correlation between quality and geographical origins of PCS, but also provided a fast, accurate and comprehensive qualitative and quantitative method for assessing the quality of PCS.


Subject(s)
Geography , Triterpenes/analysis , Triterpenes/chemistry , Wolfiporia/chemistry , Chromatography, High Pressure Liquid , Cluster Analysis , Discriminant Analysis , Least-Squares Analysis , Multivariate Analysis , Principal Component Analysis , Reproducibility of Results , Software , Tandem Mass Spectrometry , Triterpenes/isolation & purification
11.
Pharm Biol ; 56(1): 649-657, 2018 Dec.
Article in English | MEDLINE | ID: mdl-31070535

ABSTRACT

CONTEXT: Ajuga ovalifolia Bur. et Franch. var. calantha (Diels) C. Y. Wu et C. Chen (Labiatae), a traditional Chinese medicine, has been used to treat several inflammatory diseases. OBJECTIVE: To assess the anti-inflammatory activity of ajudecumin A isolated from Ajuga ovalifolia var. calantha, and its possible mechanisms. MATERIALS AND METHODS: Lipopolysaccharide (LPS, 0.5 µg/mL)-stimulated RAW264.7 macrophages were used to assess the anti-inflammatory activity of ajudecumin A (1-40 µM) in vitro. Nitric oxide levels were evaluated by Griess reagent. The mRNA levels of iNOS, COX-2, TNF-α, IL-1ß and IL-6 were determined using qRT-PCR. Phosphorylation of ERK, JNK, p38 MAPK and IκBα were detected by western Blot. To further assess the anti-inflammatory of ajudecumin A in vivo, mice were oral treated with ajudecumin A (10 mg/kg) or dexamethasone (0.25 mg/kg, positive control) for 5 days before administration of carrageenan or xylene. Paw and ear edema were then measured, respectively. RESULTS: Ajudecumin A (10-40 µM) decreased LPS-induced nitric oxide production with an IC50 value of 16.19 µM. Ajudecumin A (20 and 40 µM) also attenuated cell spreading and formation of pseudopodia-like structures, and decreased the mRNA levels of iNOS (55.23-67.04%, p < 0.001), COX-2 (57.58-70.25%, p < 0.001), TNF-α (53.75-58.94%, p < 0.01-0.001), IL-1ß (79.41-87.85%, p < 0.001) and IL-6 (54.26-80.52%, p < 0.01-0.001) in LPS-activated RAW264.7 cells. Furthermore, ajudecumin A suppressed LPS-induced phosphorylation of ERK, p38 MAPK, and IκBα, as well as IκBα degradation (p < 0.05-0.001). Finally, ajudecumin A (10 mg/kg) attenuated carrageenan- and xylene-induced inflammation in mice by about 28 and 24%, respectively. DISCUSSION AND CONCLUSIONS: Ajudecumin A exhibited a potent anti-inflammatory activity in vitro and in vivo through inhibition on NF-κB and ERK/p38 MAPK pathways, suggesting that ajudecumin A may be potentially developed as a lead compound in anti-inflammatory drug discovery.


Subject(s)
Ajuga , Anti-Inflammatory Agents/therapeutic use , Disease Models, Animal , Lipopolysaccharides/toxicity , Macrophages/drug effects , Plant Extracts/therapeutic use , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Dose-Response Relationship, Drug , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Macrophages/metabolism , Macrophages/pathology , Male , Mice , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , RAW 264.7 Cells
12.
Zhongguo Zhong Yao Za Zhi ; 41(8): 1405-1414, 2016 Apr.
Article in Zh | MEDLINE | ID: mdl-28884531

ABSTRACT

The recent progresses on chemical components and pharmacological activities of the genus Valerianawere summarized.Besides-essential oil, the chemical composition of Valerianais mainly focused on monoterpenoids,sesquiterpenoids,lignans, flavonoids, alkaloids, etc. Iridoids are the main chemical components ofmonoterpenoids. There are two types ofiridoidson the basis of the cyclopentane open or not. The Valerianahas been drawmuch attention for their significant sedation,spasmolysis,antidepression,antitumor, against adenosine A1 receptors and cytotoxicityactivity,and had certain function for cardiovascular disease treatment. Given to the fact of the lack of systematic review and summary of studies on the Valeriana, we summarized and analyze the study literatures on the pharmacological activity of Valerianain recent years, and providedsome basisfor further study.


Subject(s)
Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Valerian/chemistry , Humans , Iridoids/analysis
13.
J Ethnopharmacol ; 323: 117693, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38176669

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves. AIM OF THE STUDY: Using plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications. MATERIALS AND METHODS: UHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites. RESULTS: A total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers. CONCLUSION: Given the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development.


Subject(s)
Aconitum , Drugs, Chinese Herbal , Animals , Aconitum/toxicity , Alkaloids/metabolism , Aporphines/metabolism , Cardiotoxicity , Chemical and Drug Induced Liver Injury , Diterpenes/metabolism , Drugs, Chinese Herbal/toxicity , Drugs, Chinese Herbal/metabolism , Plant Leaves , Plant Roots , Tandem Mass Spectrometry , Zebrafish
14.
Bioresour Technol ; 402: 130830, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38734264

ABSTRACT

In this study, the sorption properties of Cr(VI), As(III), and Pb(II) on chitosan-modified magnetic biochar (CMBC) derived from residues of Ligusticum chuanxiong Hort. were investigated. CMBC was found to be a valuable material for removing three heavy metals from water simultaneously. Kinetic analysis suggested Cr(VI), As(III), and Pb(II) were chemisorbed onto CMBC, while isotherm data conformed well to Langmuir model, the maximum adsorption capacity of CMBC was found to be 65.74 mg/g for Cr(VI), 49.32 mg/g for As(III), and 69.45 mg/g for Pb(II). Experiments, characterization, and density functional theory (DFT) calculations were employed to explore the mechanisms. Furthermore, CMBC demonstrated excellent removal rates of over 95% for Cr(VI), 99% for As(III) and Pb(II) from contaminated water bodies. This work shows that CMBC holds significant potential for wastewater treatment of heavy metals and provides an effective solution for the utilization of Chinese herb residues in environmental remediation.


Subject(s)
Charcoal , Chitosan , Metals, Heavy , Water Pollutants, Chemical , Chitosan/chemistry , Charcoal/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Kinetics , Water Purification/methods , Chromium/chemistry , Drugs, Chinese Herbal/chemistry
15.
Fitoterapia ; 175: 105882, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38452906

ABSTRACT

Falonolide A (1) and B (2), two novel polyyne hybrid phthalides resulting from unprecedented carbon skeleton polymerized by Z-ligustilide and falcarindiol, along with six new related phthalides (3-8), were isolated from Ligusticum chuanxiong Hort. Their structures were elucidated by spectroscopic analysis, computer-assisted structure elucidation (CASE) analysis, DP4+ probability analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1-8 was proposed, and the production mechanism of 2 was revealed by density functional theory (DFT) method. Compounds 4 and 6 exhibited significant vasodilatory activity with EC50 of 8.00 ± 0.86 and 6.92 ± 1.02 µM, respectively. Compound 4 also displayed significant inhibitory effect of NO production with EC50 value of 8.82 ± 0.30 µM. Based on the established compounds library, structure-activity relationship analysis of phthalides was explored to provide insights into the drug development of vasodilators and anti-flammatory.


Subject(s)
Benzofurans , Ligusticum , Phytochemicals , Plant Roots , Ligusticum/chemistry , Plant Roots/chemistry , Molecular Structure , Benzofurans/pharmacology , Benzofurans/isolation & purification , Benzofurans/chemistry , Animals , Structure-Activity Relationship , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Vasodilator Agents/pharmacology , Vasodilator Agents/isolation & purification , Vasodilator Agents/chemistry , Mice , Nitric Oxide/metabolism , Rats , China , Male , RAW 264.7 Cells , Rats, Sprague-Dawley
16.
Phytomedicine ; 135: 156019, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39305747

ABSTRACT

BACKGROUND: Neurological diseases are the primary cause of disability and death and impose substantial financial burdens. However, existing treatments only relieve symptoms and may cause many adverse effects. Natural products are a promising source of neurological therapeutic agents due to their excellent neuroprotective effect and safety. The gut microbiota has an essential impact on maintaining brain homeostasis via the gut-brain axis. Multiple investigations show that natural products offer neuroprotective effects by regulating gut microbiota-driven signaling networks. OBJECTIVES: This review aims to provide a systematic review of how natural products promote neurological health by harnessing the power of gut microbiota. METHODS: The pre-January 1, 2024 literature was gathered from several databases, including Scopus, PubMed, Google Scholar, and Web of Science, utilizing appropriate keywords. The gathered publications underwent a review process and were classified based on their study content, specifically focusing on the impact of natural products on gut microbiota and neurological health. RESULTS: Here, we review how natural products promote neurological health by regulating the gut microbiota-brain axis. Specifically, we focus on the following areas. (1) Altering microorganism community structure, including increasing α-diversity and altering ß-diversity. (2) Regulating the population of certain bacteria, including enriching beneficial microorganisms Akkermansia and Bifidobacterium, and inhibiting potentially hazardous microorganisms Bilophila, Klebsiella, and Helicobacter. (3) Regulating microbial neuroactive metabolites levels, including short-chain fatty acids, tryptophan and its derivatives, trimethylamine N-oxide, dopa/dopamine, γ-aminobutyric acid, and lipopolysaccharide. Furthermore, we review how natural products promote neurological health by regulating intestinal barrier homeostasis. CONCLUSION: Natural products promote neurological health by harnessing the power of gut microbiota. This review will contribute to understanding how natural products promote neurological health by orchestrating the gut microbiota-brain axis.

17.
J Ethnopharmacol ; 335: 118645, 2024 Dec 05.
Article in English | MEDLINE | ID: mdl-39089661

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. AIM OF THE STUDY: The goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. MATERIALS AND METHODS: To investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. RESULTS: FLZP contains 109 components, including liquiritin (584.8176 µg/g), benzoylaconine (16.3087 µg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 µg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. CONCLUSIONS: FLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.


Subject(s)
Colitis, Ulcerative , Drugs, Chinese Herbal , Gastrointestinal Microbiome , Rats, Sprague-Dawley , Yang Deficiency , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/microbiology , Colitis, Ulcerative/chemically induced , Yang Deficiency/drug therapy , Drugs, Chinese Herbal/pharmacology , Gastrointestinal Microbiome/drug effects , Male , Rats , Metabolomics , RNA, Ribosomal, 16S/genetics , Spleen/drug effects , Spleen/metabolism , Kidney/drug effects , Kidney/metabolism , Metabolome/drug effects , Disease Models, Animal
18.
Sci Adv ; 10(6): eadj6547, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38324681

ABSTRACT

Butylphthalide is one of the first-line drugs for ischemic stroke therapy, while no biosynthetic enzyme for butylphthalide has been reported. Here, we present a haplotype-resolved genome of Ligusticum chuanxiong, a long-cultivated and phthalide-rich medicinal plant in Apiaceae. On the basis of comprehensive screening, four Fe(II)- and 2-oxoglutarate-dependent dioxygenases and two CYPs were mined and further biochemically verified as phthalide C-4/C-5 desaturases (P4,5Ds) that effectively promoted the forming of (S)-3-n-butylphthalide and butylidenephthalide. The substrate promiscuity and functional redundancy featured for P4,5Ds may contribute to the high phthalide diversity in L. chuanxiong. Notably, comparative genomic evidence supported L. chuanxiong as a homoploid hybrid with Ligusticum sinense as a potential parent. The two haplotypes demonstrated exceptional structure variance and diverged around 3.42 million years ago. Our study is an icebreaker for the dissection of phthalide biosynthetic pathway and reveals the hybrid origin of L. chuanxiong, which will facilitate the metabolic engineering for (S)-3-n-butylphthalide production and breeding for L. chuanxiong.


Subject(s)
Benzofurans , Drugs, Chinese Herbal , Ligusticum , Ligusticum/genetics , Ligusticum/chemistry , Haplotypes , Plant Breeding
19.
Phytomedicine ; 119: 154979, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37552899

ABSTRACT

BACKGROUND: Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time. In recent years, interaction with gut microbiota is hypothesized to be a reasonable explanation of the potential mechanisms for natural compounds especially polyphenols. OBJECTIVES: This review aims to present a persuasive explanation for the contradiction between the limited bioavailability and the remarkable bioactivities of polyphenols by examining their interactions with gut microbiota. METHODS: We assessed literatures published before April 10, 2023, from several databases, including Scopus, PubMed, Google Scholar, and Web of Science. The keywords used include "polyphenols", "gut microbiota", "short-chain fatty acids", "bile acids", "trimethylamine N-oxide", "lipopolysaccharides" "tryptophan", "dopamine", "intestinal barrier", "central nervous system", "lung", "anthocyanin", "proanthocyanidin", "baicalein", "caffeic acid", "curcumin", "epigallocatechin-3-gallate", "ferulic acid", "genistein", "kaempferol", "luteolin", "myricetin", "naringenin", "procyanidins", "protocatechuic acid", "pterostilbene", "quercetin", "resveratrol", etc. RESULTS: The review first demonstrates that polyphenols significantly alter gut microbiota diversity (α- and ß-diversity) and the abundance of specific microorganisms. Polyphenols either promote or inhibit microorganisms, with various factors influencing their effects, such as dosage, treatment duration, and chemical structure of polyphenols. Furthermore, the review reveals that polyphenols regulate several gut microbiota metabolites, including short-chain fatty acids, dopamine, trimethylamine N-oxide, bile acids, and lipopolysaccharides. Polyphenols affect these metabolites by altering gut microbiota composition, modifying microbial enzyme activity, and other potential mechanisms. The changed microbial metabolites induced by polyphenols subsequently trigger host responses in various ways, such as acting as intestinal acid-base homeostasis regulators and activating on specific target receptors. Additionally, polyphenols are transformed into microbial derivatives by gut microbiota and these polyphenols' microbial derivatives have many potential advantages (e.g., increased bioactivity, improved absorption). Lastly, the review shows polyphenols maintain intestinal barrier, central nervous system, and lung function homeostasis by regulating gut microbiota. CONCLUSION: The interaction between polyphenols and gut microbiota provides a credible explanation for the exceptional bioactivities of polyphenols. This review aids our understanding of the underlying mechanisms behind the bioactivity of polyphenols.


Subject(s)
Gastrointestinal Microbiome , Polyphenols , Polyphenols/pharmacology , Polyphenols/metabolism , Fatty Acids , Oxides/pharmacology
20.
Front Immunol ; 14: 1127785, 2023.
Article in English | MEDLINE | ID: mdl-37205093

ABSTRACT

Background: Atractylodes macrocephala Koidz. (AM) is a functional food with strong ant-colitis activity. AM volatile oil (AVO) is the main active ingredient of AM. However, no study has investigated the improvement effect of AVO on ulcerative colitis (UC) and the bioactivity mechanism also remains unknown. Here, we investigated whether AVO has ameliorative activity on acute colitis mice and its mechanism from the perspective of gut microbiota. Methods: Acute UC was induced in C57BL/6 mice by dextran sulfate sodium and treated with the AVO. Body weight, colon length, colon tissue pathology, and so on were assessed. The gut microbiota composition was profiled using 16s rRNA sequencing and global metabolomic profiling of the feces was performed. The results showed that AVO can alleviate bloody diarrhea, colon damage, and colon inflammation in colitis mice. In addition, AVO decreased potentially harmful bacteria (Turicibacter, Parasutterella, and Erysipelatoclostridium) and enriched potentially beneficial bacteria (Enterorhabdus, Parvibacter, and Akkermansia). Metabolomics disclosed that AVO altered gut microbiota metabolism by regulating 56 gut microbiota metabolites involved in 102 KEGG pathways. Among these KEGG pathways, many metabolism pathways play an important role in maintaining intestine homeostasis, such as amino acid metabolism (especially tryptophan metabolism), bile acids metabolism, and retinol metabolism. Conclusion: In conclusion, our study indicated that AVO can be expected as novel prebiotics to treat ulcerative colitis, and modulating the composition and metabolism of gut microbiota may be its pharmacological mechanism.


Subject(s)
Actinobacteria , Atractylodes , Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Animals , Mice , Mice, Inbred C57BL , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , RNA, Ribosomal, 16S
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