Rhizoma Chuanxiong Research Articles

Combination of platelet bio-specific extraction and high-performance liquid chromatography with diode-array detection/liquid chromatography-mass spectrometry method for analyzing platelet-targeted compounds in rhizoma chuanxiong

Context: Platelet is an important pharmacological target as it participates in complex processes of coagulation and hemostasis. Excessive platelet aggregation is responsible for the formation of pathogenic thrombi in patients with atherothrombotic disease. Objective: To expedite the search for platelet-targeted active candidates in Rhizoma Chuanxiong (root of Ligusticum chuanxiong Hort [Umbelliferae]). Materials and Methods: Rhizoma Chuanxiong ethyl acetate extract (EAE) was obtained by refluxing extraction method. A platelet bio-specific extraction combined with high-performance liquid chromatography with diode-array detection/liquid chromatography-mass spectrometry (HPLC-DAD/LC-MS) approach was employed to screen and identify the platelet-targeted compounds in Chuanxiong EAE, and the results were confirmed by in vitro antiplatelet aggregation test using turbidimetry method. Finally, HPLC-DAD analysis was employed for the quantitative determination of these hit compounds in Chuanxiong EAE. Results: A total of five hit components were tentatively detected and identified by HPLC-DAD/LC-MS, two of which, senkyunolide A and (Z)-ligustilide, were confirmed their antiplatelet activity by in vitro platelet aggregation experiment (both with IC50 <3 μg/mL, 2.42 μg/mL [12.60 μM] and 2.97 μg/mL [15.63 μM], respectively). Meanwhile, the quantitative results indicated that those two strongest inhibitors are the main components in Chuanxiong EAE (87.891 ± 1.668 mg/g and 109.058 ± 1.383 mg/g, respectively). Conclusion: Senkyunolide A and (Z)-ligustilide are the main active antiplatelet compounds in Rhizoma Chuanxiong EAE. The proposed platelet bio-specific extraction combined with HPLC-DAD/LC-MS method is of value for the discovering potential bioactive components in natural products.

Development and Validation for Rapid Analysis of Five Bioactive Components in Rhizoma Chuanxiong by Ultra-Performance Convergence Chromatography

Development and Validation for Rapid Analysis of Five Bioactive Components in Rhizoma Chuanxiong by Ultra-Performance Convergence Chromatography

­­­­ Wine-Processed Chuanxiong Rhizoma Combined with Aumolertinib for the Treatment of Brain Metastasis in Non-Small Cell Lung Cancer

­­­­ Wine-Processed Chuanxiong Rhizoma Combined with Aumolertinib for the Treatment of Brain Metastasis in Non-Small Cell Lung Cancer

Research Progress on the Pharmacological Mechanism of Chuanxiong Rhizome in the Treatment of Migraine

Migraine is a common clinical cause of primary neurovascular headache, which is closely related to psychosocial factors and has a great impact on people's daily life. The pathogenesis of migraine is diverse, and the more mature mechanisms include vascular theory, neuronal theory, inflammatory mediator theory, neurotransmitter theory, neurotrophic factor, central sensitization and activation of the limbic system of the thalamus, and dopaminergic system-related gene theory. Chinese medicine believes that headache can occur when the evil of the six leucorrhea attacks the top of the body, stagnating the evil qi and blocking the clear yang, or when internal injuries lead to the reversal of qi, and blood, stagnation of the meridians, and loss of nourishment for the brain. Chuanxiong, as a common clinical herb, has the function of promoting blood circulation, dispelling wind, and relieving pain. Based on the pattern of medication used in the treatment of migraine during the Song, Jin, and Yuan dynasties, it was found that Chuanxiong was used very frequently in the treatment of headaches, headwinds, first wind, and migraine. In addition, modern pharmacological studies have found that the main components of Chuanxiong Ligusticum include tetramethylpyrazine (Chuanxiongzin), ferulic acid, volatile oil, ligustilide, chuanxiong lactone and alkyl phenyl peptides such as butenolide and that Chuanxiong Ligusticum has analgesic, anti-inflammatory, antioxidant, anti-tumor, anti-coagulant, anti-depressant, anti-aging, anti-atherosclerosis, cytoprotective, and cardiac function improving effects. In conclusion, Chuanxiong has great research potential in the treatment of migraine. In this paper, we mainly classify and summarize the effects of Chuanxiong in the treatment of migraine and provide a scientific basis for the application of Chuanxiong in the treatment of migraine.

Exploring the Potential Mechanism of Chuanxiong Rhizoma Treatment for Migraine Based on Systems Pharmacology.

Migraine is a disease whose aetiology and mechanism are not yet clear. Chuanxiong Rhizoma (CR) is employed in traditional Chinese medicine (TCM) to treat various disorders. CR is effective for migraine, but its active compounds, drug targets, and exact molecular mechanism remain unclear. In this study, we used the method of systems pharmacology to address the above issues. We first established the drug-compound-target-disease (D-C-T-D) network and protein-protein interaction (PPI) network related to the treatment of migraine with CR and then established gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results suggest that the treatment process may be related to the regulation of inflammation and neural activity. The docking results also revealed that PTGS2 and TRPV1 could directly bind to the active compounds that could regulate them. In addition, we found that CR affected 11 targets that were more highly expressed in the liver or heart but were the lowest in the whole brain. It also expounds the description of CR channel tropism in TCM theory from these angles. These findings not only indicate that CR can be developed as a potential effective drug for the treatment of migraine but also demonstrate the application of systems pharmacology in the discovery of herbal-based disease therapies.

Key Phytochemicals and Biological Functions of Chuanxiong Rhizoma Against Ischemic Stroke: A Network Pharmacology and Experimental Assessment.

Presently, the treatment options for ischemic stroke (IS) are limited due to the complicated pathological process of the disease. Chuanxiong Rhizome (CR), also known as Conioselinum anthriscoides “Chuanxiong” (rhizome), is the most widely used traditional Chinese medicine for treating stroke. This study aimed to uncover the key phytochemicals and biological functions of CR against IS through a network pharmacology approach combining with IS pathophysiology analysis. We employed permanent unilateral common carotid artery ligation to construct a mouse model of global cerebral ischemia and found that cerebral ischemia injuries were improved after 7 days of gavage treatment of CR (1,300 mg/kg/day). CR exerts protective effects on neurons mainly by acting on targets related to synaptic structure, synaptic function, neuronal survival and neuronal growth. A total of 18 phytochemicals from CR based on UHPLC-MS/MS that corresponded to 85 anti-IS targets. Coniferyl ferulate, neocnidilide and ferulic acid were identified as the key phytochemicals of CR against IS. Its brain protective effects involve anti-inflammatory, anti-oxidative stress, and anti-cell death activities and improves blood circulation. Additionally, the two most important synergistic effects of CR phytochemicals in treating IS are prevention of infection and regulation of blood pressure. In brain samples of Sham mice, L-tryptophan and vanillin were detected, while L-tryptophan, gallic acid, vanillin and cryptochlorogenic acid were detected in IS mice by UHPLC–MS/MS. Our findings provide a pathophysiology relevant pharmacological basis for further researches on IS therapeutic drugs.

Mechanism of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on SIRT1 autophagy pathway of endothelial cell senescence induced by hydrogen peroxide

This study aims to explore the effect of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Chuanxiong Rhizoma(hereinafter referred to as GNS) on the SIRT1-autophagy pathway of endothelial cell senescence induced by hydrogen peroxide(H_2O_2). To be specific, vascular endothelial cells were classified into the blank control group(control), model group(model), model + DMSO group(DMSO), resveratrol group(RESV), and GNS low-dose(GNS-L), medium-dose(GNS-M), and high-dose(GNS-H) groups. They were treated with H_2O_2 for senescence induction except the control. After intervention of cells in each group with corresponding drugs for 24 h, cell growth status was observed under an inverted microscope, and the formation of autophagosome under the transmission electron microscope. In addition, the changes of microtubule-associated protein 1 light chain 3β(LC3 B) were detected by immunofluorescence staining. The autophagy flux was tracked with the autophagy double-labeled adenovirus(mRFP-GFP-LC3) fusion protein. Dansylcadaverine(MDC) staining was employed to determine the autophagic vesicles, and Western blot the expression of sirtuin 1(SIRT1), ubiquitin-binding protein p62, and LC3Ⅱ. After H_2O_2 induction, cells demonstrated slow growth, decreased adhesion ability, raised number of SA-β-gal-stained blue ones, a certain number of autophagosomes with bilayer membrane and secondary lysosomes in the cytoplasm, and slight rise of autophagy flux level. Compared with the model group, GNS groups showed improved morphology, moderate adhesion ability, complete and smooth membrane, decreased SA-β-gal-stained blue cells, many autophagosomes, autophagic vesicles, and secondary lysosomes in the cytoplasm, increased autophagolysosomes, autophagy flux level, and fluorescence intensity of LC3 B and MDC, up-regulated expression of SIRT1 and LC3Ⅱ, and down-regulated expression of p62, suggesting the improvement of autophagy level. GNS can delay the senescence of vascular endothelial cells. After the intervention, the autophagy flux and related proteins SIRT1, LC3Ⅱand p62 changed significantly, and the autophagy level increased significantly. However, EX527 weakened the effect of Chinese medicine in delaying vascular senescence. GNS may delay the senescence of vascular endothelial cells through the SIRT1 autophagy pathway.

Identification of active components in Xuefu Zhuyu Decoction based on targets of blood-activating function

As a classic prescription for promoting blood circulation to remove blood stasis, Xuefu Zhuyu Decoction(XFZYD) is widely used in clinical practice and has notable curative effect. Based on the key targets of activating blood circulation, this study identified the active components of XFZYD to reveal the material basis. The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD. The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription. The efficacy of the prescription can embody key pharmacological and high-content components. In this study, anti-platelet aggregation activity was used to characterize the effect of activating blood, and the in vivo experiments were conducted to verify the accuracy of the active components. A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood. Ligustrazine, acteoside, naringin, etc. were selected as the potential active components for activating blood in XFZYD. The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma, Rehmanniae Radix, Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, and Carthami Flos was 9.82%±5.11%. Compared with that in the control group, the platelet aggregation induced by adenosine diphosphate(ADP) was significantly inhibited in the test group(P&lt;0.01), which verified the accuracy of the active components. This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.

Screening of Potential Thrombin and Factor Xa Inhibitors from the Danshen-Chuanxiong Herbal Pair through a Spectrum-Effect Relationship Analysis.

In this study; a spectrum–effect relationship analysis combined with a high-performance liquid chromatography–mass spectrometry (LC–MS) analysis was established to screen and identify active components that can inhibit thrombin and factor Xa (THR and FXa) in Salviae Miltiorrhizae Radix et Rhizoma–Chuanxiong Rhizoma (Danshen–Chuanxiong) herbal pair. Ten potential active compounds were predicted through a canonical correlation analysis (CCA), and eight of them were tentatively identified through an LC–MS analysis. Furthermore; the enzyme inhibitory activity of six available compounds; chlorogenic acid; Z-ligustilide; caffeic acid; ferulic acid; tanshinone I and tanshinone IIA; were tested to verify the feasibility of the method. Among them; chlorogenic acid was validated to possess a good THR inhibitory activity with IC50 of 185.08 µM. Tanshinone I and tanshinone IIA are potential FXa inhibitors with IC50 of 112.59 µM and 138.19 µM; respectively. Meanwhile; molecular docking results show that tanshinone I and tanshinone IIA; which both have binding energies of less than −7.0 kcal·mol−1; can interact with FXa by forming H-bonds with residues of SER214; GLY219 and GLN192. In short; the THR and FXa inhibitors in the Danshen–Chuanxiong herbal pair have been successfully characterized through a spectrum–effect relationship analysis and an LC–MS analysis.

Natural inspired ligustrazine-based SLC-0111 analogues as novel carbonic anhydrase inhibitors

Ligustrazine is the principle bioactive alkaloid in the widely-used Chinese herb Chuan Xiong rhizome. Herein, a series of novel derivatives has been designed as human carbonic anhydrases inhibitors (hCAIs) starting from the natural product Ligustrazine inserted as a tail instead of the 4-fluorophenyl tail of SLC-0111, a front-runner selective hCA IX inhibitor currently in clinical trials as antitumor/antimetastatic agent. Other derivatives were designed via incorporation of different linkers, of amide and ester type, or incorporation of different zinc anchoring groups such as secondary sulfamoyl and carboxylic acid functionalities. The newly designed molecules were prepared following different synthetic pathways, and were assessed for their inhibitory actions against four isoforms: the widespread cytosolic (hCA I and II), and the transmembrane tumor-related (hCA IX and XII). The primary sulfonamides efficiently inhibited the target hCA IX and hCA XII in the nanomolar range (KIs: 6.2–951.5 nM and 3.3–869.3 nM, respectively). The most selective hCA IX inhibitors 6c and 18 were assessed for their potential anticancer effects, and displayed anti-proliferative activity against MCF-7 cancer cell line with IC50s of 11.9 and 36.7 μM, respectively. Molecular modelling studies unveiled the relationship between structural features and inhibitory profiles against the off-target hCA II and the target, tumor-related isoforms hCA IX and XII.

Mechanism of volatile oil from Chuanxiong (Chuanxiong Rhizoma) - Suhexiang (Styrax) - Bingpian (Borneolum) in treating angina pectoris based on network pharmacology and its protective effects on myocardial damage in rats

ObjectiveTo explore the pharmacodynamic material basis and mechanism of action of volatile oil from Chuanxiong (Chuanxiong Rhizoma) - Suhexiang (Styrax) - Bingpian (Borneolum) (hereinafter referred to as C-S-B volatile oil) in treating angina pectoris based on network pharmacology and to detect its protective effects against rat myocardial damage. MethodsGas chromatography-mass spectrometry (GC-MS) was used to determine the constituents of volatile oils from Chuanxiong (Chuanxiong Rhizoma), Suhexiang (Styrax), and Bingpian (Borneolum), and the targets of the three main constituents were found predicted and screened using the PharmMapper server, and GeneCards and CooLGeN databases. The STRING database and Cytoscape software were used to draw the protein-protein interaction (PPI) network, RStudio software was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genome and Genome (KEGG) pathways, and Cytoscape software was used to construct the component-target-pathway-disease network. The rat model of myocardial injury was established by intraperitoneal injection of a large dose of isoprenaline hydrochloride. After continuous intervention with C-S-B volatile oil for 14 d, the ejection fraction (EF) and short axis shortening rate (FS) of the left ventricle were detected. The indices of myocardial damage were detected after hematoxylin-eosin (HE) staining. ResultsFifteen volatile oil components from the C-S-B formula were identified. There are 470 targets of these volatile oil components and 401 angina-related genes. There are 28 core targets, including CHRM4, ADRA1A, FGFR1, CHRM2, CYP2A6, CHRM5, CHRM1, CHRM3, HDAC2, and MPO, etc.. The results of the KEGG analysis indicated that the C-S-B formula probably interferes with the following pathways: neuroactive ligand-receptor interactions, calcium signaling, cytochrome P450 metabolism of heteropoietin, among others. The results of animal experiments showed that the C-S-B formula essential oil could significantly improve the following myocardial indices in rats with myocardial injury: EF, FS, left ventricular end-systolic diameter (LVIDs), left ventricular end-diastolic diameter (LVIDd), and stroke volume (SV), and all the differences were statistically significant (P < 0.01). ConclusionThe mechanism of action of volatile oil components in the C-S-B formula in treating angina pectoris was analyzed using multi-component, multi-target and multi-pathway systems, which has laid a foundation for further revealing its mechanism of action. Animal experiments have shown that the volatile oil of the C-S-B formula can improve EF, FS, and other indices of myocardial damage in a rat model, thus relieving myocardial damage caused by heart hyperactivity, improving cardiac function, and protecting against myocardial damage.

Effects of Buyang Huanwu Decoction on neurovascular units after cerebral ischemia: a review

Buyang Huanwu Decoction, a representative prescription in traditional Chinese medicine(TCM) for tonifying Qi and activating blood, has been proved to be effective in preventing and treating acute cerebral infarction(ACI). It consists of Astragali Radix, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Pheretima, Chuanxiong Rhizoma, Carthami Flos, and Persicae Semen, possessing multiple active ingredients. The neurovascular unit is a functionally and structurally interdependent multicellular complex composed of neurons-glial cells-blood vessels. It plays an important role in the pathological changes of cerebral ischemia and the permeability variation of the blood-brain barrier. In recent years, Buyang Huanwu Decoction has been found to protect the integrity of neurovascular units and improve the permeability of the blood-brain barrier, thereby alleviating stroke and other diseases caused by cerebral ischemia. This paper collated and summarized the protective effects of Buyang Huanwu Decoction on neurovascular units.

Effect of acupoint application of Zhanjin Huoxue formula combined with local cold compress on swelling and pain after knee arthroscopy in patients with knee osteoarthritis

To compare the effect between acupoint application of Zhanjin Huoxue formula combined with local cold compress and simple local cold compress on swelling and pain after knee arthroscopy in patients with knee osteoarthritis (KOA). A total of 62 KOA patients with knee swelling after knee arthroscopy were randomly divided into an observation group and a control group, 31 cases in each group. In the control group, cold compress was adopted after surgery, 3 times a day. On the basis of the treatment as the control group, acupoint application of Zhanjin Huoxue formula (angelicae sinensis radix, chuanxiong rhizome, cinnamon twig, poria, etc.) was applied at Liangqiu (ST 34), Xuehai (SP 10), Zusanli (ST 36), Fenglong (ST 40), Sanyinjiao (SP 6), Yinlingquan (SP 9), Yanglingquan (GB 34), Xuanzhong (GB 39) on the affected side in the observation group, 4 h each time, 2 times a day. The treatment was given 7 days in both groups. Before treatment and 1,3,5 and 7 days into treatment, the pain visual analogue scale (VAS) score and swelling value of knee joint (2 cm above the patella upper pole, patella midline, 5 cm below the patella lower pole) were compared in the two groups. The VAS scores 3, 5 and 7 days into treatment were lower than those before treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The swelling values of 2 cm above the patella upper pole 3, 5 and 7 days into treatment were lower those before treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The swelling values of patella midline 1, 3, 5 and 7 days into treatment were lower than those before treatment in the two groups (P<0.05), and except for 1 day into treatment, those in the observation group were lower than the control group (P<0.05). The swelling values of 5 cm below the patella lower pole 1 day into treatment in the observation group and 3, 5 and 7 days into treatment in the two groups were lower those before treatment (P<0.05), and except for 1 day into treatment, those in the observation group were lower than the control group (P<0.05). The total effective rate in the observation group was 93.5% (29/31), which was higher than 74.2% (23/31) in the control group (P<0.05). Acupoint application of Zhanjin Huoxue formula combined with cold compress could effectively improve the knee joint swelling and pain after arthroscopy in KOA patients, and the curative effect is better than simple cold compress.

Puerarin-Chuanxiong oil submicron emulsion combining medicine and adjuvant

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.

Chuanxiong Rhizoma inhibits brain metastasis of lung cancer through multiple active ingredients acting on multiple targets, pathways and biological functions

To explore the molecular mechanism mediating the inhibitory effect of Chuanxiong Rhizoma against brain metastasis of lung cancer using network pharmacology methods and molecular docking. The chemical components of Chuanxiong Rhizoma and their targets were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The relevant targets for brain metastasis of lung cancer were screened using the GeneCards database. Clusterpro-filerR package was used to perform GO and KEGG enrichment analysis. Cytoscape and STRING database were used to construct the "active ingredient-target-disease" network and protein-protein interaction (PPI) network of Chuanxiong Rhizoma. The core components of Chuanxiong Rhizoma and their targets in the treatment of lung cancer brain metastasis were screened based on the topological parameters, and the results were verified using molecular docking and in Chuanxiong extract- treated human lung cancer PC9 cells by detecting the core target with Western blotting. Forty-eight active ingredients of Chuanxiong Rhizoma including (Z)-ligustilide, butylphthalide, oleic acid, and myricetone were screened, which target 49 proteins including INS, BDNF, FOS, VEGFA, PTGS2, ESR1, MAPK14, and PTGS1. These proteins participated in 57 biological functions such as nuclear receptor activity, ligand activation, and transcription factor activity, involving 40 signaling pathways such as prolactin signaling pathway, breast cancer, and etrogen signaling. The results of molecular docking showed that myricetone, butylphthalide, 4-hydroxy-3 butylphthalide, (Z)-ligustilide, and ligustalide-E, among others, had strong affinities to 7 cores targets including BDNF, FOS, PTGS2, and MAPK14. In PC9 cells, treatment with Chuanxiong Rhizoma extract resulted in significant reductions in the phosphorylation levels of PI3K, Akt and VEGF (P < 0.01). Chuanxiong Rhizoma contains multiple active ingredients against brain metastasis lung cancer, and these ingredients act on multiple targets involving multiple signal pathways and biological functions.

Ethyl ferulate protects against lipopolysaccharide-induced acute lung injury by activating AMPK/Nrf2 signaling pathway.

Ethyl ferulate (EF) is abundant in Rhizoma Chuanxiong and grains (e.g., rice and maize) and possesses antioxidative, antiapoptotic, antirheumatic, and anti-inflammatory properties. However, its effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is still unknown. In the present study, we found that EF significantly alleviated LPS-induced pathological damage and neutrophil infiltration and inhibited the gene expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in murine lung tissues. Moreover, EF reduced the gene expression of TNF-α, IL-1β, IL-6, and iNOS and decreased the production of NO in LPS-stimulated RAW264.7 cells and BMDMs. Mechanistic experiments revealed that EF prominently activated the AMPK/Nrf2 pathway and promoted Nrf2 nuclear translocation. AMPK inhibition (Compound C) and Nrf2 inhibition (ML385) abolished the beneficial effect of EF on the inflammatory response. Furthermore, the protective effect of EF on LPS-induced ALI was not observed in Nrf2 knockout mice. Taken together, the results of our study suggest that EF ameliorates LPS-induced ALI in an AMPK/Nrf2-dependent manner. These findings provide a foundation for developing EF as a new anti-inflammatory agent for LPS-induced ALI/ARDS therapy.

Herbal textual research on Chuanxiong Rhizoma in Chinese classical prescriptions

Fourteen classical prescriptions in the Catalog of 100 Ancient Classical Prescriptions(First Batch) promulgated in 2018 contain Chuanxiong Rhizoma, which reveals the high medicinal value and wide application of Chuanxiong Rhizoma. This paper systematically reviews the ancient herbal books and modern literature to explore the name, origin, genuine producing area, medicinal part, harvesting, and processing of Chuanxiong Rhizoma, thus facilitating the development of classical prescriptions containing Chuan-xiong Rhizoma. It is confirmed that Chuanxiong Rhizoma, formerly known as &quot;Xiongqiong&quot; in Chinese, was first called &quot;Chuanxiong&quot; in late Tang Dynasty, which has been gradually accepted as its official name due to the rise of the status of Chuanxiong Rhizoma produced in Sichuan. The main original plant of Chuanxiong Rhizoma in past dynasties has always been deemed to be Ligusticum chuan-xiong(Umbellifera), whose rhizome serves as the medicinal part. In general, it is best harvested in summer but the harvesting time can vary with different growth environments. Since the Song Dynasty, Sichuan province has been recognized as the genuine producing area of Chuanxiong Rhizoma in light of the high yield and good quality. It is suggested that Chuanxiong Rhizoma from Sichuan be used preferentially in the development of classical prescriptions. There are multiple processing methods of Chuanxiong Rhizoma recorded in ancient medical classics, and the raw(after purifying and slicing) or wine-processed or stir-fried Chuanxiong Rhizoma is still in use today. In the development of classical prescriptions containing Chuanxiong Rhizoma, Chuanxiong Rhizoma is advised to be processed in accordance with current processing standards if the specific processing method is described in the medical classics. If not, the raw Chuanxiong Rhizoma is preferred and then processed following the processing standards of Chuanxiong Rhizoma decoction pieces in Chinese Pharmacopoeia.

Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P&lt;0.01), increased cold spray scores(P&lt;0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P&lt;0.05), dwindled tumor necrosis factor(TNF-α)(P&lt;0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P&lt;0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P&lt;0.05) and CRE-M enabled the decrease in cold spray scores(P&lt;0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P&lt;0.05), and the levels of Glu in the extracellular fluids of SDH(P&lt;0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P&lt;0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P&lt;0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

The mechanisms of Chuanxiong Rhizoma in treating spinal cord injury based on network pharmacology and experimental verification.

BackgroundChuanxiong Rhizoma (CR) is a common traditional Chinese medicine (TCM) that has been widely used in the treatment of spinal cord injury (SCI). However, the underlying molecular mechanism of CR is still largely unknown. This study was designed to explore the bioactive components and the mechanism of CR in treating SCI based on a network pharmacology approach and experimental validation.MethodsFirst, the active compounds and related target genes in CR were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the corresponding target genes of SCI were collected by the Therapeutic Target Database (TTD) and GeneCards database. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, GO function and KEGG enrichment analysis of the targets were analyzed using DAVID tools. Subsequently, the AutoDock software for molecular docking was adopted to verify the above network pharmacology analysis results between the active components and key targets. Finally, an SCI rat model animal validation experiment was assessed to verify the reliability of the network pharmacology results.ResultsThere were 7 active ingredients identified in CR and 246 SCI-related targets were collected. Then, 4 core nodes (ALB, AKT1, MAPK1, and EGFR) were discerned via construction of a PPI network of 111 common targets. The KEGG enrichment analysis results indicated that the Ras signaling pathway, estrogen signaling pathway, and vascular endothelial growth factor (VEGF) signaling pathway were enriched in the development of SCI. The results of molecular docking demonstrated that the effects of CR have a strong affinity with the 4 pivotal targets. Experimental validation in a rat model showed that CR could effectively improve the recovery of motor function and mechanical pain threshold after SCI.ConclusionsIn summary, it revealed the mechanism of CR treatment for SCI involve active ingredients, targets and signaling pathways, providing a scientific basis for future investigations into the mechanism underlying CR treating for SCI.

Mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on intervention of cerebral ischemia based on network pharmacology-molecular docking

Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.