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1.
J Ethnopharmacol ; 327: 118062, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38492790

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort (LCH), with the accepted name of Ligusticum striatum DC in "The Plant List" database, is a widely used ethnomedicine in treating ischemic stroke, and borneol (BO) is usually prescribed with LCH for better therapy. Our previous study confirmed their synergistic effect on neurogenesis against cerebral ischemia. However, the underlying mechanism is still unclear. AIM OF THE STUDY: More and more evidence indicated that astrocytes (ACs) might be involved in the modulation of neurogenesis via polarization reaction. The study was designed to explore the synergic mechanism between LCH and BO in promoting astrocyte-mediated neurogenesis. MATERIALS AND METHODS: After primary cultures and identifications of ACs and neural stem cells (NSCs), the oxygen-glucose deprivation (OGD) model and the concentrations of LCH and BO were optimized. After the OGD-injured ACs were treated by LCH, BO, and their combination, the conditioned mediums were used to culture the OGD-injured NSCs. The proliferation, migration, and differentiation of NSCs were assessed, and the secretions of BDNF, CNTF, and VEGF from ACs were measured. Then the expressions of C3 and PTX3 were detected. Moreover, the mice were performed a global cerebral ischemia/reperfusion model and treated with LCH and (or) BO. After the assessments of Nissl staining, the expressions of Nestin, DCX, GFAP, C3, PTX3, p65 and p-p65 were probed. RESULTS: The most appropriate duration of OGD for the injury of both NSCs and ACs was 6 h, and the optimized concentrations of LCH and BO were 1.30 µg/mL and 0.03 µg/mL, respectively. The moderate OGD environment induced NSCs proliferation, migration, astrogenesis, and neurogenesis, increased the secretions of CNTF and VEGF from ACs, and upregulated the expressions of C3 and PTX3. For the ACs, LCH further increased the secretions of BDNF and CNTF, enhanced PTX3 expression, and reduced C3 expression. Additionally, the conditioned medium from LCH-treated ACs further enhanced NSC proliferation, migration, and neurogenesis. The in vivo study showed that LCH markedly enhanced the Nissl score and neurogenesis, and decreased astrogenesis which was accompanied by downregulations of C3, p-p65, and p-p65/p65 and upregulation of PTX3. BO not only decreased the expression of C3 in ACs both in vitro and in vivo but also downregulated p-p65 and p-p65/p65 in vivo. Additionally, BO promoted the therapeutic effect of LCH for most indices. CONCLUSION: A certain degree of OGD might induce ACs to stimulate the proliferation, astrogenesis, and neurogenesis of NSCs. LCH and BO exhibited a marked synergy in promoting ACs-mediated neurogenesis and reducing astrogenesis, in which LCH played a dominant role and BO boosted the effect of LCH. The mechanism of LCH might be involved in switching the polarization of ACs from A1 to A2, while BO preferred to inhibit the formation of A1 phenotype via downregulating NF-κB pathway.


Assuntos
Isquemia Encefálica , Canfanos , Ligusticum , Camundongos , Animais , Astrócitos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Ciliar/metabolismo , Fator Neurotrófico Ciliar/farmacologia , Fator Neurotrófico Ciliar/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neurogênese , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral
2.
J Hazard Mater ; 468: 133851, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394901

RESUMO

As the most famous and widely used traditional Chinese medicine (TCM), Ligusticum sinense cv. Chuanxiong (L. Chuaniong) has been affected by cadmium (Cd) exceeding with high ability of Cd accumulation. There is relatively little research on Cd absorption and storage process in L. Chuanxiong, which is an important reason for the poor remediation efficiency. Hence, this study takes L. Chuanxiong as the point of penetration to explore how L. Chuanxiong affects rhizobacteria through root exudates to alter soil Cd intake, as well as to explore the migration and storage of Cd in its body with 0.10 (T0), 5.00 (T5), 10.00 (T10) mg/kg Cd contaminations. The results showed that the relative abundance of amino acids and phospholipids secreted from L. Chuanxiong root noticeably increased with increasing Cd levels, which directly activated soil Cd or extremely significantly (P < 0.01) recruited bacteria such as Bacillus, Arthrobacter to indirectly increase Cd availability. Under the interaction of root exudates and rhizobacteria, Cd bioavailability increased by 80.00% in rhizosphere soil and Cd accumulation in L. Chuanxiong increased 5.44-6.65 mg/kg. Cd subcellular distribution analysis demonstrated that Cd was mainly stored in the root (10-fold more than in the leaf), whose Cd content was cytoderm>cytoplasm>organelle in tissues. The sequential extraction results found that non-soluble phosphate and protein-chelated Cd dominated (85.00-90.00%) in the cell, while Cd cheated with alcohol soluble protein, amino acid salts, water-soluble organic acid in cell was minimal (5.50%). The phenomenon indicated that L. Chuanxiong fixed Cd in root (the medical part) with low translocation ability. This study can provide theoretical support for the high-quality production of L. Chuanxiong and other root medical plant in heavy metal influenced sites.


Assuntos
Ligusticum , Metais Pesados , Poluentes do Solo , Cádmio/metabolismo , Ligusticum/química , Ligusticum/metabolismo , Rizosfera , Metais Pesados/análise , Aminoácidos , Solo/química , Poluentes do Solo/metabolismo , Raízes de Plantas/metabolismo
3.
Sci Adv ; 10(6): eadj6547, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38324681

RESUMO

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.


Assuntos
Benzofuranos , Medicamentos de Ervas Chinesas , Ligusticum , Ligusticum/genética , Ligusticum/química , Haplótipos , Melhoramento Vegetal
4.
J Ethnopharmacol ; 319(Pt 3): 117337, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37866462

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong, the rhizome of Ligusticum chuanxiong Hort., is an ancient herbal medicine that has gained extensive popularity in alleviating migraines with satisfying therapeutic effects in China. As the major bioactive component of Chuanxiong, the essential oil also exerts a marked impact on the treatment of migraine. It is widely recognized that neuroinflammation contributes to migraine. However, it remains unknown whether Chuanxiong essential oil has anti-neuroinflammatory activity. AIM OF THE STUDY: To explore the anti-neuroinflammatory properties of Chuanxiong essential oil and its molecular mechanisms by network pharmacology analysis and in vitro experiments. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to identify the chemical components of Chuanxiong essential oil. Public databases were used to predict possible targets, build the protein-protein interaction network (PPI), and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Moreover, cytological experiments, nitric oxide assay, enzyme-link immunosorbent assay, western blotting, and immunofluorescence assay were adopted to prove the critical signaling pathway in lipopolysaccharide (LPS)-induced BV2 cells. RESULTS: Thirty-six compounds were identified from Chuanxiong essential oil by GC-MS, and their corresponding putative targets were predicted. The network pharmacology study identified 232 candidate targets of Chuanxiong essential oil in anti-neuroinflammation. Furthermore, Chuanxiong essential oil was found to potentially affect the C-type lectin receptor, FoxO, and NF-κB signaling pathways according to the KEGG analysis. Experimentally, we verified that Chuanxiong essential oil could significantly reduce the overproduction of inflammatory mediators and pro-inflammatory factors via the NF-κB signaling pathway. CONCLUSION: Chuanxiong essential oil alleviates neuroinflammation through the NF-κB signaling pathway, which provides a theoretical foundation for a better understanding of the clinical application of Chuanxiong essential oil in migraine treatment.


Assuntos
Ligusticum , Transtornos de Enxaqueca , NF-kappa B , Lipopolissacarídeos/toxicidade , Farmacologia em Rede , Doenças Neuroinflamatórias
5.
Int J Mol Sci ; 24(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38139246

RESUMO

Butylphthalide, a prescription medicine recognized for its efficacy in treating ischemic strokes approved by the State Food and Drug Administration of China in 2005, is sourced from the traditional botanical remedy Ligusticum chuanxiong. While chemical synthesis offers a viable route, limitations in the production of isomeric variants with compromised bioactivity necessitate alternative strategies. Addressing this issue, biosynthesis offers a promising solution. However, the intricate in vivo pathway for butylphthalide biosynthesis remains elusive. In this study, we examined the distribution of butylphthalide across various tissues of L. chuanxiong and found a significant accumulation in the rhizome. By searching transcriptome data from different tissues of L. chuanxiong, we identified four rhizome-specific genes annotated as 2-oxoglutarate-dependent dioxygenase (2-OGDs) that emerged as promising candidates involved in butylphthalide biosynthesis. Among them, LcSAO1 demonstrates the ability to catalyze the desaturation of senkyunolide A at the C-4 and C-5 positions, yielding the production of butylphthalide. Experimental validation through transient expression assays in Nicotiana benthamiana corroborates this transformative enzymatic activity. Notably, phylogenetic analysis of LcSAO1 revealed that it belongs to the DOXB clade, which typically encompasses genes with hydroxylation activity, rather than desaturation. Further structure modelling and site-directed mutagenesis highlighted the critical roles of three amino acid residues, T98, S176, and T178, in substrate binding and enzyme activity. By unraveling the intricacies of the senkyunolide A desaturase, the penultimate step in the butylphthalide biosynthesis cascade, our findings illuminate novel avenues for advancing synthetic biology research in the realm of medicinal natural products.


Assuntos
Medicamentos de Ervas Chinesas , Ligusticum , Ligusticum/química , Filogenia , Medicamentos de Ervas Chinesas/química , Rizoma/química
6.
Pest Manag Sci ; 79(12): 5374-5386, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37656744

RESUMO

BACKGROUND: Peanut stem rot caused by Sclerotium rolfsii is an epidemic disastrous soil-borne disease. Recently, natural products tend to be safe alternative antifungal agents to combat pathogens. RESULTS: This work determined the preliminary antifungal activity of 29 essential oils against S. rolfsii and found that Ligusticum chuanxiong essential oil (LCEO) showed the best antifungal activity, with an EC50 value of 81.79 mg L-1 . Sixteen components (98.78%) were identified in LCEO by gas chromatography-mass spectrometry analysis, the majority by volume comprising five phthalides (93.14%). Among these five phthalides, butylidenephthalide was the most effective compound against S. rolfsii. Butylidenephthalide not only exhibited favorable in vitro antifungal activity against the mycelial growth, sclerotia production and germination of S. rolfsi, but also presented efficient in vivo efficacy in the control of peanut stem rot. Seven days after application in the glasshouse, the protective and curative efficacy of butylidenephthalide at 300 mg L-1 (52.02%, 44.88%) and LCEO at 1000 mg L-1 (49.60%, 44.29%) against S. rolfsii were similar to that of the reference fungicide polyoxin at 300 mg L-1 (54.61%, 48.28%). Butylidenephthalide also significantly decreased the oxalic acid and polygalacturonase content of S. rolfsii, suggesting a decreased infection ability on plants. Results of biochemical actions indicated that butylidenephthalide did not have any effect on the cell membrane integrity and permeability but significantly decreased nutrient contents, disrupted the mitochondrial membrane, inhibited energy metabolism and induced reactive oxygen species (ROS) accumulation of S. rolfsii. CONCLUSION: Our results could provide an important reference for understanding the application potential and mechanisms of butylidenephthalide in the control of S. rolfsii. © 2023 Society of Chemical Industry.


Assuntos
Fabaceae , Ligusticum , Óleos Voláteis , Antifúngicos/química , Ligusticum/metabolismo , Arachis
7.
J Pharm Biomed Anal ; 234: 115540, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37418871

RESUMO

Ligusticum chuanxiong Hort (LCH) is a well-known traditional Chinese medicinal herb for treating coronary heart disease (CHD). This study investigated the differential preventive mechanisms of Rhizome Cortex (RC) and Rhizome Pith (RP) of LCH. Solid-phase microextraction combined with comprehensive two-dimensional gas chromatography-tandem mass spectrometry analysis identified 32 differential components, and network pharmacology revealed 11 active ingredients and 191 gene targets in RC, along with 12 active ingredients and 318 gene targets in RP. Primary active ingredients in RC were carotol, epicubenol, fenipentol, and methylisoeugenol acetate, while 3-undecanone, (E)- 5-decen-1-ol acetate, linalyl acetate, and (E)- 2-Methoxy-4-(prop-1-enyl) phenol were dominant in RP. KEGG mapping analysis associated 27 pathways with RC targets and 116 pathways with RP targets. Molecular docking confirmed the efficient activation of corresponding targets by these active ingredients. This study provides valuable insights into the preventive and therapeutic effects of RC and RP in CHD.


Assuntos
Doença das Coronárias , Medicamentos de Ervas Chinesas , Ligusticum , Humanos , Cromatografia Gasosa-Espectrometria de Massas , Microextração em Fase Sólida , Farmacologia em Rede , Simulação de Acoplamento Molecular , Ligusticum/química , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/análise
8.
Chem Biodivers ; 20(8): e202201249, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37358062

RESUMO

In the current study, both the essential oil composition and biological activity of Saussurea lappa and Ligusticum sinensis were investigated by means of microwave-assisted hydrodistillation (MAHD) and characterized by Gas chromatography/mass spectrometry (GC/MS), whereas the antimicrobial efficiency of MAHD essential oils was examined against four pathogens: Staphylococcus aureus, Escherichia coli, Aspergillus niger, and Candida albicans responsible for microbial infections. The goal was to spot synergy and a favorable method that gives essential oils to possibly use as alternatives to common antimicrobial agents for the treatment of bacterial infections using a microdilution assay. S. lappa's 21 compounds were characterized by MAHD extraction. Sesquiterpene lactones (39.7 % MAHD) represented the major components, followed by sesquiterpene dialdehyde (25.50 % MAHD), while L. sinensis's 14 compounds were identified by MAHD extraction. Tetrahydroisobenzofurans (72.94 % MAHD) was the predominant compound class. S. lappa essential oil collection showed the strongest antimicrobial activity with MIC values of 16 µg/ml against all pathogens tested, while L. sinensis showed strong antibacterial activity and moderate antifungal activity with MIC values of 32 µg/ml and 500 µg/ml, respectively. The principal components of both oils, (velleral, eremanthin and neocnidilide), were docked into the bacterial histidine kinase (HK) and the fungal heat shock protein 90 (Hsp90).


Assuntos
Anti-Infecciosos , Ligusticum , Óleos Voláteis , Saussurea , Sesquiterpenos , Óleos Voláteis/química , Simulação de Acoplamento Molecular , Micro-Ondas , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana
9.
Clin Exp Pharmacol Physiol ; 50(8): 647-663, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37308175

RESUMO

Ligustilide, a natural phthalide mainly derived from chuanxiong rhizomes and Angelica Sinensis roots, possesses anti-inflammatory activity, particularly in the context of the nervous system. However, its application is limited because of its unstable chemical properties. To overcome this limitation, ligusticum cycloprolactam (LIGc) was synthesized through structural modification of ligustilide. In this study, we combined network pharmacological methods with experimental verification to investigate the anti-neuroinflammatory effects and mechanisms of ligustilide and LIGc. Based on our network pharmacology analysis, we identified four key targets of ligustilide involved in exerting an anti-inflammatory effect, with the nuclear factor (NF)-κB signal pathway suggested as the main signalling pathway. To verify these results, we examined the expression of inflammatory cytokines and inflammation-related proteins, analysed the phosphorylation level of NF-κB, inhibitor of κBα (IκBα) and inhibitor of κB kinase α and ß (IKKα+ß), and evaluated the effect of BV2 cell-conditioned medium on HT22 cells in vitro. Our results, demonstrate for the first time that LIGc can downregulate the activation of the NF-κB signal pathway in BV2 cells induced by lipopolysaccharide, suppress the production of inflammatory cytokines and reduce nerve injury in HT22 cells mediated by BV2 cells. These findings suggest that LIGc inhibits the neuroinflammatory response mediated by BV2 cells, providing strong scientific support for the development of anti-inflammatory drugs based on natural ligustilide or its derivatives. However, there are some limitations to our current study. In the future, further experiments using in vivo models may provide additional evidence to support our findings.


Assuntos
Ligusticum , NF-kappa B , NF-kappa B/metabolismo , Ligusticum/metabolismo , Doenças Neuroinflamatórias , Farmacologia em Rede , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Microglia , Lipopolissacarídeos/farmacologia
10.
J Ethnopharmacol ; 314: 116643, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37220808

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As an effective medicinal plant, Ligusticum chuanxiong (L. chuanxiong) is traditionally used in China to treat various kinds of dysesthesia caused by liver qi stagnation, chest paralysis and heart pain caused by liver blood stagnation, and bruises and injuries caused by blood stasis. Recent research has confirmed the efficacy of L. chuanxiong in treating liver injury. AIM OF THE STUDY: L. chuanxiong has significant hepatoprotective effects, but its material basis and mechanism of action are still ambiguous. This work was to reveal the potential active ingredients (parts) of L. chuanxiong for liver protection and to investigate the pharmacological mechanism of its liver protection. MATERIALS AND METHODS: The hepatoprotective substance basis and mechanism of L. chuanxiong were investigated using network pharmacology, and the active components of L. chuanxiong extract were studied using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analytical techniques. Molecular docking was adopted to verify the interaction between the active ingredients in L. chuanxiong and the key targets involved in liver injury. To confirm the hepatoprotective effects of the effective part in L. chuanxiong, a carbon tetrachloride (CCl4)-induced acute liver injury model in mice was used. RESULTS: As a result, network pharmacological analysis techniques were used to screen out potential active ingredients such as ferulic acid, caffeic acid, and p-coumaric acid, which were concentrated in the organic acid site and acted on 19 key targets related to liver protection. The biological process involved the positive regulation of nitric oxide biosynthesis, and various signaling pathways were implicated, including the Toll-like receptor signaling pathway, the NOD-like receptor signaling pathway, the TNF signaling pathway, and others. LC-MS and GC-MS qualitatively analyzed the effective components from L. chuanxiong extract, and 50 active components were identified. The molecular docking of key components with the core targets showed good activity, which validated the predicted results. In the final analysis, a mouse model of acute liver injury induced by CCl4 further verified the greater protective effect of the organic acid fraction of L. chuanxiong on liver injury in mice compared with other parts. CONCLUSION: The results reveal that L. chuanxiong may relieve liver damage, and the organic acids were the main active part in it. Its mechanism of alleviating liver injury is related to positive regulation of nitric oxide biosynthesis, the Toll-like receptor signaling pathway, the NOD-like receptor signaling pathway, the TNF signaling pathway, and so on.


Assuntos
Medicamentos de Ervas Chinesas , Ligusticum , Camundongos , Animais , Ligusticum/química , Simulação de Acoplamento Molecular , Óxido Nítrico , Fígado , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptores Toll-Like , Proteínas NLR , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
11.
Phytochem Anal ; 34(4): 443-452, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37038738

RESUMO

INTRODUCTION: Ligusticum chuanxiong ('chuanxiong') is a traditional Chinese medicine for promoting blood circulation and removing blood stasis, which is often used to treat thrombotic diseases. However, its potential anticoagulant active ingredients have been unexplored. OBJECTIVES: The study aims to establish an affinity ultrafiltration mass spectrometry (AUF-MS) method for rapid screening of anti-thrombin active components of chuanxiong and to verify it in vitro. METHOD: In this study, the chemical constituents of different parts of chuanxiong were determined. A method for rapid screening of anticoagulant active ingredients by AUF-MS was established using thrombin as an affinity receptor target. Subsequently, the anticoagulant effect of such ligands was verified by in vitro anticoagulation experiments such as chromogenic substrate method and in vitro coagulation assay. Then the possible interaction mechanism between these ligands and thrombin was further studied by molecular docking. RESULTS: Twenty-one components were detected from different parts of chuanxiong. And three potential anti-thrombin active components were screened: ferulic acid, chlorogenic acid, isochlorogenic acid A by AUF coupled with high-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (HPLC-Q-Orbitrap-MSn ). The in vitro activity experiments and molecular docking revealed that these potential ligands exhibited strong binding ability and inhibitory activities on thrombin. CONCLUSION: The present study revealed that chuanxiong is a traditional Chinese medicine with excellent anticoagulation effects. Meanwhile, the integrated strategy based on AUF-MS, in vitro experiments and molecular docking also provided a powerful tool for further exploration of active ingredients responsible for the anticoagulant activity in chuanxiong.


Assuntos
Medicamentos de Ervas Chinesas , Ligusticum , Cromatografia Líquida de Alta Pressão/métodos , Ligusticum/química , Simulação de Acoplamento Molecular , Ultrafiltração , Trombina , Anticoagulantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química
12.
Food Chem Toxicol ; 175: 113723, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36935074

RESUMO

The essential oils of Ligusticum chuanxiong Hort. (CXEO) are considered to be important parts of the pharmacological action of Ligusticum chuanxiong Hort. CXEO have a wide range of applications in various fields. Despite the interesting properties of CXEO, the volatility and low solubility have limited the application. Liposomes are vesicles composed of concentric bilayer lipids arranged around the water environment. Therefore, this study aimed to prepare stable CXEO liposomes (CXEO-LP) to improve the properties. Then, CXEO-LP were prepared by thin film dispersion method and optimized. The results showed that CXEO-LP were well dispersed. Subsequently, in vitro release and antioxidant properties of CXEO-LP were researched. CXEO-LP had slow release effect and oxidation resistance, indicating CXEO-LP may be a potential drug for treating cerebral ischemia-reperfusion injury (CIRI). The nasal mucosa toxicity test and acute toxicity test showed that CXEO-LP had no obvious toxicity to nasal cavity, heart, liver, spleen, lung and kidney tissues. Pharmacodynamic studies found that CXEO-LP significantly improved neurological deficits and brain pathology in a mouse model of CIRI compared to CXEO after intranasal administration. In general, this study showed that CXEO-LP were easy to prepare and continuously released, and had an important development prospect in the treatment of CIRI.


Assuntos
Medicamentos de Ervas Chinesas , Ligusticum , Óleos Voláteis , Traumatismo por Reperfusão , Camundongos , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Lipossomos , Medicamentos de Ervas Chinesas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico
13.
Drug Des Devel Ther ; 17: 743-759, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923106

RESUMO

Background: Traditional medicine is a common treatment option for endometrioid-related symptoms. In the past few decades, Guixiong Xiaoyi formula has been widely used as a traditional medicine for the treatment of endometriosis. Purpose: This study aimed to prepare compound Angelica Ligusticum wallichii granule (CALG) by modern technological methods and to study its pharmacodynamics and mechanisms of treating endometriosis. Methods: The ingredients of CALG were determined by UPLC-Q-TOF/MS. Target prediction of compounds and diseases was performed using databases, and the mechanisms of CALG were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes and verified by molecular docking. Furthermore, a rat model of endometriosis was established to study the effects of CALG on endometriosis in vivo. Results: CALG with good specificity, durability, and stability was obtained following a detailed preparation process and quality control standard. Using network systems pharmacology, 109 chemical compositions and 104 core targets were identified for the treatment of endometriosis. The composition-target-channel-disease network topology analysis of the top 15 chemical compositions of CALG showed that the beneficial effect of CALG on endometriosis was attributed to phenolic compounds. In addition, CALG treatment reduced the volume of ectopic uterine lesions, promoted apoptosis, inhibited the secretion of inflammatory cytokines, and increased HIF-1 expression in rats with endometriosis. Conclusion: CALG induces apoptosis and inhibits inflammation and is a promising drug for the treatment of endometriosis.


Assuntos
Angelica , Medicamentos de Ervas Chinesas , Endometriose , Ligusticum , Feminino , Humanos , Animais , Ratos , Simulação de Acoplamento Molecular , Endometriose/tratamento farmacológico , Farmacologia em Rede , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa
14.
J Photochem Photobiol B ; 242: 112692, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36958087

RESUMO

Ligusticum chuanxiong Hort. (Chuanxiong) is an important Chinese medicinal herb, whose rhizomes are widely used as raw materials for treating various diseases caused by blood stasis. The fresh tender stems and leaves of Chuanxiong are also consumed and have the potential as microgreens. Here, we investigated the effect of light spectra on yield and total flavonoid content of Chuanxiong microgreens by treatment with LED-based white light (WL), red light (RL), blue light (BL), and continuous darkness (DD). The results showed that WL and BL reduced biomass accumulation but significantly increased total flavonoid content compared to RL or DD treatments. Widely targeted metabolomics analysis confirmed that BL promoted the accumulation of flavones and flavonols in Chuanxiong microgreens. Further integration of transcriptomics and metabolomics analysis revealed the mechanism by which BL induces the up-regulation of transcription factors such as HY5 and MYBs, promotes the expression of key genes targeted for flavonoid biosynthesis, and ultimately leads to the accumulation of flavones and flavonols. This study suggests that blue light is a proper light spectra to improve the quality of Chuanxiong microgreens, and the research results lay a foundation for guiding the de-etiolation of Chuanxiong microgreens to obtain both yield and quality in production practice.


Assuntos
Flavonas , Ligusticum , Flavonóis , Transcriptoma , Flavonoides , Metabolômica
15.
Phytochemistry ; 209: 113613, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36804478

RESUMO

Three unprecedented thioether-linked dimeric pyrimidines, namely ligusticumines A-C, together with twelve known compounds were isolated and identified from the traditional Chinese medicinal-edible herb, Ligusticum striatum DC. The structures of all the isolated compounds were determined from NMR, HRESIMS and X-ray diffraction spectroscopies. Additionally, a novel 3-step synthetic route was developed to synthesize ligusticumine C by substitution, thiolation and coupling, with an overall yield of 5.4%. The inhibitory activities of the isolated compounds against phosphatidylinositol 3-kinase (PI3K) were tested, of which, (3S)-butylphthalide, a characteristic component of L. striatum, showed a potent inhibitory effect on PI3Kα (IC50: 3.6 µg/mL).


Assuntos
Ligusticum , Plantas Medicinais , Ligusticum/química , Fosfatidilinositol 3-Quinases , Pirimidinas/química , Pirimidinas/farmacologia , Espectroscopia de Ressonância Magnética
16.
Poult Sci ; 102(3): 102430, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36621100

RESUMO

Ligusticum chuanxiong (CX) is a traditional Chinese medicine that is widely planted throughout the world. CX is one of the most important and commonly used drugs to enhance blood circulation. The preovulatory follicles in laying hens have a large number of blood arteries and meridians that feed the follicles' growth and maturation with nutrients, hormones, and cytokines. With the extension of laying time, preovulatory follicles angiogenesis decreased gradually. In this study, we studied the mechanism of CX on preovulatory follicles angiogenesis in late-phase laying hens. The results show that CX extract can increase the angiogenesis of preovulatory follicles (F1-F3) of late-phase laying hens. CX extract can promote vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation in preovulatory follicles theca layers, promote the proliferation, invasion and migration through PI3K/AKT and RAS/ERK signaling pathways in primary follicle microvascular endothelial-like cells (FMECs). In addition, CX extract can up-regulate the expression of hypoxia inducible factor α (HIF1α) in granulosa cells (GCs) and granulosa layers through PI3K/AKT and RAS/ERK signaling pathways, thereby promoting the secretion of vascular endothelial growth factor A (VEGFA). In conclusion, the current study confirmed the promoting effect of CX extract on the preovulatory follicles angiogenesis, which sets the stage for the design of functional animal feed for late-phase laying hens.


Assuntos
Ligusticum , Folículo Ovariano , Feminino , Animais , Folículo Ovariano/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Tecais/metabolismo , Galinhas/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células da Granulosa
17.
J Ethnopharmacol ; 301: 115764, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36183951

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum striatum DC., also known as Ligusticum chuanxiong Hort. (LCH), is widely used in China for its excellent effect in ischaemic stroke (IS) patients, and borneol (BO) has been confirmed to maintain the blood‒brain barrier (BBB) after stroke. They are often used as a combination in the prescriptions of IS patients. Although the advantage of their combined treatment in improving brain ischaemia has been verified, their synergistic mechanism on BBB maintenance is still unclear. AIM OF THE STUDY: This study was designed to evaluate the synergistic effect of maintaining the BBB between LCH and BO against IS and to further explore the potential mechanism. MATERIALS AND METHODS: After primary mouse brain microvascular endothelial cells (BMECs) were extracted and identified, the duration of oxygen-glucose deprivation (OGD) and the doses of LCH and BO were optimized. Then, the cells were divided into five groups: control, model, LCH, BO, and LCH + BO. Cell viability, injury degree, proliferation and migration were detected by CCK-8, LDH, EdU and wound-healing assays, respectively. Hoechst 33342 staining was adopted to detect the apoptosis rate, and western blotting was employed to observe the expressions of Bax, Bcl-2, caspase-3 and cleaved caspase-3. The TEER value and NaF permeability were measured to assess tight junction (TJ) function, while ZO-1, occludin and claudin-5 were also probed by western blotting. Moreover, the HIF-1α/VEGF pathway was observed to explore the underlying mechanism of BBB maintenance. In vivo, global cerebral ischaemia/reperfusion (GCIR) surgery was performed to establish an IS model. After treatment with LCH (200 mg/kg) and/or BO (160 mg/kg), histopathological structure and BMECs repair were observed by HE staining and immunohistochemistry of vWF. Meanwhile, TJ-associated proteins in vivo were also detected by western blotting. RESULTS: Basically, LCH and BO had different emphases. LCH significantly attenuated the vacuolar structure, nuclear pyknosis and neuronal loss of GCIR mice, while BO focused on promoting BMECs proliferation and angiogenesis and inhibiting the degradation of TJ-associated proteins in vivo after IS. Interestingly, their combination further enhanced these effects. OGD injury markedly reduced the viability, proliferation and migration of primary BMECs; decreased the ratio of Bcl-2/Bax, TEER value, and the expressions of ZO-1, occludin and claudin-5; induced LDH release and apoptosis; and increased the cleaved caspase-3/caspase-3 ratio and NaF permeability. Meanwhile, BO might be the main contributor to the combinative treatment in ameliorating OGD-induced damage of BMECs and degradation of TJ-related proteins, and the potential mechanism might be involved in upregulating the HIF-1α/VEGF signalling pathway. Although LCH showed no obvious improvement, it could enhance the therapeutic effect of BO. Interestingly, their combination even produced some new improvements, including the reduction of cleaved caspase-3 and increase in TEER value, none of which were exhibited in their monotherapies. CONCLUSIONS: LCH and BO exhibited complementary therapeutic features in alleviating cerebral ischaemic injury by inhibiting BMECs apoptosis, maintaining the BBB and attenuating the loss of neurons. LCH preferred to protect ischaemic neurons, while BO played a key role in protecting BMECs, maintaining the BBB and TJs by activating the HIF-1α/VEGF signalling pathway.


Assuntos
Isquemia Encefálica , Ligusticum , Acidente Vascular Cerebral , Animais , Camundongos , Proteína X Associada a bcl-2/metabolismo , Barreira Hematoencefálica , Isquemia Encefálica/metabolismo , Caspase 3/metabolismo , Claudina-5/metabolismo , Células Endoteliais , Glucose/metabolismo , Ocludina/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
J Integr Neurosci ; 22(6): 149, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38176927

RESUMO

BACKGROUND: Cerebral stroke is a leading cause of death and disability worldwide. Ligusticum Chuanxiong Hort. (LCH), a well-known Chinese herb, is widely used for the treatment of cerebral stroke. This study aimed to investigate the underlying mechanisms of LCH in cerebral stroke and develop a diagnostic model. METHODS: We employed network pharmacology analyses to identify the active compounds, targets, and underlying mechanisms of LCH for treating cerebral stroke. Molecular docking was performed to visualize the binding site between the core active compounds and hub targets. Furthermore, a diagnostic model for cerebral stroke was constructed based on transcriptomic analysis. RESULTS: Our findings revealed that LCH contains multiple active ingredients, including oleic acid and caffeic acid. Protein-protein interaction network analysis identified IL1B, CCL2, MAPK3, PTGS2, JUN, MMP9, TLR4, HIF1A, PPARA, FOS, PTEN, NFE2L2, TLR2, TIMP1, and SOD2 as the top 15 hub genes. Kyoto Encyclopedia of Genes and Genomes pathway analysis highlighted the enrichment of TNF and IL-17 signaling pathways. Molecular docking analysis demonstrated binding sites between oleic acid, caffeic acid, and MMP9, PPARP, PTEN, and TIMP1. The diagnostic model indicated that FOS, MMP9, PPARA, PTEN, TIMP1, and TLR2 serve as blood biomarkers for cerebral stroke. CONCLUSIONS: This study demonstrates that LCH alleviates the symptoms following cerebral stroke through interactions with the TNF and IL-17 signaling pathways. The findings contribute to a better understanding of the therapeutic mechanisms of LCH and offer insights into the development of a diagnostic model for cerebral stroke.


Assuntos
Interleucina-17 , Ligusticum , Metaloproteinase 9 da Matriz , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ácido Oleico , Receptor 2 Toll-Like , Perfilação da Expressão Gênica
19.
Molecules ; 27(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36364473

RESUMO

Ischemic stroke is a difficult-to-treat brain disease that may be attributed to a limited therapeutic time window and lack of effective clinical drugs. Nasal-brain administration is characterized by low systemic toxicity and is a direct and non-invasive brain targeting route. Preliminary studies have shown that the volatile oil of Chaxiong (VOC) has an obvious anti-ischemic stroke effect. In this work, we designed a nanoemulsion thermosensitive in situ gel (VOC-NE-ISG) loaded with volatile oil of Chaxiong for ischemia via intranasal delivery to rat brain treatment of cerebral ischemic stroke. The developed VOC-NE-ISG formulation has a suitable particle size of 21.02 ± 0.25 nm and a zeta potential of -20.4 ± 1.47 mV, with good gelling ability and prolonged release of the five components of VOC. The results of in vivo pharmacokinetic studies and brain targeting studies showed that intranasal administration of VOC-NE-ISG could significantly improve the bioavailability and had excellent brain-targeting efficacy of nasal-to-brain delivery. In addition, the results of pharmacodynamics experiments showed that both VOC-NE and VOC-NE-ISG could reduce the neurological deficit score of model rats, reducing the size of cerebral infarction, with a significant effect on improving ischemic stroke. Overall, VOC-NE-ISG may be a promising intranasal nanomedicine for the effective treatment of ischemic stroke.


Assuntos
Ligusticum , Nanopartículas , Óleos Voláteis , Acidente Vascular Cerebral , Compostos Orgânicos Voláteis , Animais , Ratos , Medicina Tradicional Chinesa , Óleos Voláteis/farmacologia , Compostos Orgânicos Voláteis/farmacologia , Géis/farmacologia , Administração Intranasal , Tamanho da Partícula , Encéfalo , Emulsões/farmacologia
20.
Biomed Pharmacother ; 156: 113888, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36272263

RESUMO

Acute lung injury (ALI), a clinical syndrome of acute respiratory failure due to acute lung inflammation, remains a substantial public health problem in the worldwide. Ligusticum Chuanxiong Rhizoma and Angelicae Sinensis Radix was herb-pair of the traditional Chinese medicine. Modern pharmacological studies have shown that volatile oil extracted from Chuanxiong Rhizome and Angelicae Sinensis Radix is identified as an important active ingredient, which has good antipyretic, analgesic and anti-inflammatory effects. However, whether their volatile oil combination (CA-VO), has effects on the prevention and treatment of ALI has not been reported yet. Due to poor water solubility and low oral bioavailability of CA-VO, CA -VO-loaded microemulsion (CA-VO-ME) was formulated to enhance its oral bioavailability. The physical properties of CA-VO-ME were characterized. The pharmacokinetic parameters and the effect on ALI were evaluated. The particle size, polydispersity index, zeta potential, and encapsulation efficiency of CA-VO-ME were 20.19 ± 0.08 nm, 0.091 ± 0.01, 36.33 ± 4.29%, and 93.75%, respectively. CA-VO-ME had a greater bioavailability (214%) than CA-VO. CA-VO-ME reduced the lipopolysaccharide (LPS)-induced increase in levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in vitro and/or in vivo. Moreover, CA-VO-ME treatment notably decreased the lung index, ameliorated histopathological changes and prolonged the survival of ALI mice. By comparison, CA-VO-ME exerted a better effect on ALI than CA-VO, suggesting that CA-VO-ME is a promising drug for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , Medicamentos de Ervas Chinesas , Ligusticum , Óleos Voláteis , Camundongos , Animais , Rizoma , Óleos Voláteis/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Lesão Pulmonar Aguda/tratamento farmacológico
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