Chuanxiong Research Articles

A Spray-Dried Self-Stabilizing Nanocrystal Emulsion of Traditional Chinese Medicine: Preparation, Characterization and ex vivo Intestinal Absorption

AbstractSalvia miltiorrhizae (Danshen, the rhizome of Salvia miltiorrhiza Bge.) and Chuanxiong rhizome (Chuanxiong, the rhizome of Ligusticum chuanxiong Hort.) are two traditional Chinese medicines that have been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, formulation development is difficult due to the complexity of the active ingredients, particularly the water-insoluble tanshinones and volatile oil of Chuanxiong rhizome, which cannot be absorbed via oral administration in conventional dosage forms. This study aimed to develop a self-stabilized nanocrystal emulsion co-loading the water-soluble, insoluble, and volatile active ingredients of Salvia miltiorrhizae and Chuanxiong rhizome to improve the bioavailability of the drugs. In this work, a high-pressure homogenization method was used to prepare a self-stabilizing nanocrystal emulsion. The emulsion was then spray-dried using hydroxypropyl-β-cyclodextrin. The dispersibility and storage stability of the spray-dried emulsion, the particle size and morphology of the emulsion droplets, and the drug content and phase distribution of the reconstituted emulsion were evaluated. An everted intestinal sac model was established, and high-performance liquid chromatography was used to determine the concentration of six active components (ferulic acid, salvianolic acid B, senkyunolide A, ligustilide, cryptotanshinone, and tanshinone IIA) and to assess the cumulative uptake amount of the drug and the apparent permeability coefficient. A mixture of the crude materials of tanshinones extract, total salvianolic acid, ferulic acid, and volatile oil of Ligusticum Chuanxiong was used as a control. The results showed that the spray-dried emulsion can be easily reconstituted into a uniform submicron emulsion with no significant changes in particle size, morphology, and microstructure of the emulsion droplets compared with the original emulsion before drying. The self-stabilizing nanocrystal emulsion significantly improved the intestinal absorption of water-insoluble components (tanshinone IIA, cryptotanshinone, and ferulic acid), and volatile oil components (senkyunolide A and ligustilide). Overall, the spray-dried self-stabilizing nanocrystal emulsion represents a potential oral formulation for Salvia miltiorrhiza and Chuanxiong rhizoma.

Exploring the mechanism of tetramethylpyrazine in the treatment of osteoarthritis based on network pharmacology

BackgroundOsteoarthritis (OA) is the most common joint disease, which mainly damages articular cartilage and involves the whole joint tissue. It has the characteristics of long course, repeated symptoms and high disability rate, and the incidence trend is gradually increasing. Tetramethylpyrazine (TMP) is the main alkaloid active substance in Ligusticum wallichii, a traditional Chinese medicine, which has the effect of promoting blood circulation and dredging collaterals, and has a good effect on the treatment of early OA, but its molecular mechanism has not been fully clarified so far. Based on network pharmacology, molecular docking simulation and animal experiments, this study explored the target and molecular mechanism of TMP in the treatment of OA.MethodsWe used PubChem, SwissTargetPrediction, and PharmMapper databases to predict the molecular structure and potential targets of TMP. GeneCards and DisGeNET databases were used to predict the relevant targets of OA. Apply UniProt database to convert targets into unified gene names, and proofread and remove duplicate gene names. The intersection targets of TMP and OA obtained on venny2.1.0 website were submitted to the STRING database to construct a PPI network. CytoScape 3.8.2 software was used to analyze the PPI network and obtain the sub-network modules and 10 key targets. The intersection targets of TMP and OA were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment using DAVID 6.8 database. The intersecting targets of TMP and OA, the biological process of GO enrichment, and KEGG signaling pathway were imported into Cytoscape 3.8.2 software to construct the TMP-target-pathway network diagram. Use molecular docking technology to simulate the interaction between TMP molecules and key targets, and predict the binding mode and binding ability. Animal models of rabbit knee osteoarthritis were prepared, and magnetic resonance imager (MRI) and fluorescence quantitative PCR (RT-qPCR) were used to observe the effect of TMP in treating OA as well as the expression of key target genes.Results585 potential targets of TMP, 3,857 potential targets of OA, and 49 intersecting targets of TMP and OA were obtained. The top 10 key target genes were obtained, in order of ranking: ALB, ESR1, IL10, CAT, F2, MPO, C3, CYP3A4, CYP2C9, ANXA1. GO and KEGG analysis implied that the key targets might act on OA by affecting endothelial cell permeability, peri-articular microcirculatory status, NETs production, activation of complement system and coagulation pathway, regulation of immune function of macrophages and T cells, and substance metabolism pathway in vivo, etc. The molecular mechanism might involve the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc. Molecular docking simulations showed that the binding energy of IL10 and ANXA1 to TMP was greater than -5Kal/mol, but the other key target proteins showed better binding to TMP, and the binding energy was less than -5 kcal/mol. Animal experiments showed that TMP had a significant therapeutic effect on OA. The TMP group had significantly reduced knee joint effusion and bone marrow damage compared to the OA group (p < 0.05). The qRT-PCR results showed that compared with the OA group, the mRNA expression of ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 in the TMP group increased (p < 0.05), while there was no significant difference in mRNA expression of ALB, IL-10, F2, MPO, etc. (p > 0.05).ConclusionTMP is effective in the treatment of OA, with multi-target and multi-pathway interactions. ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 may be potential targets for TMP treatment of OA. The molecular mechanism mainly involves the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc.

Effects of ensemble-forecasted key environmental factors on the distribution, active constituents, and transcription regulation in Ligusticum chuanxiong Hort.

Ligusticum chuanxiong Hort., with over 2000 years of medicinal use and cultivation history, is extensively used in clinical settings for treating heart disease, headache, dysmenorrhea, and amenorrhea. Constructing the geographic distribution pattern of L. chuanxiong and identifying the environmental factors limiting its range, as well as clarifying the effects of key environmental factors on the content of major active constituents and transcription regulation, could provide a scientific foundation for the conservation and effective management of this valuable medicinal resource. The results reveal that the predominant environmental factors influencing the distribution were the minimum temperature of the coldest month (Bio6) and solar radiation (Srad), with cumulative account for 87.46% of the importance. Correlation analysis further reveals significant negative correlations between Bio6 and the content of major active constituents in L. chuanxiong, with Srad exhibiting a negative correlation with these constituents. The gene differential expression analysis indicated that the expression levels of some genes associated with growth and active constituent biosynthesis pathways, such as RPT2_13888, UVR8_16871, CLPB3_3155, and 4CLL5_116, varied significantly among locations influenced by differing key environmental factors. Consequently, alterations in the environment were found to influence the gene expression levels within these pathways, resulting in variations in the content of active constituents. These findings contribute to an enhanced understanding of how environmental factors impact the distribution and quality of medicinal plants and offer a theoretical reference for the introduction, cultivation, quality improvement, resource utilization and management of L. chuanxiong. © 2024 Society of Chemical Industry.

Exploring Plant Growth-Promoting Traits of Endophytic Fungi Isolated from Ligusticum chuanxiong Hort and Their Interaction in Plant Growth and Development.

Endophytic fungi inhabit various plant tissues and organs without inducing evident disease symptoms. They can contribute positively to the growth of plants, bolster plants resilience to environmental and biological stresses, and facilitate the accumulation of secondary metabolites. These microbial resources possess significant developmental and utilization value in various applications. Hence, this study focused on exploring the plant growth-promoting (PGP) traits of 14 endophytic fungi from Ligusticum chuanxiong Hort (CX) and elucidating the effects and mechanisms that facilitate plant growth. According to PGP activity evaluation, the majority of strains demonstrated the capacity to produce IAA (78.57%), siderophores (50.00%), ammonia (35.71%), potassium solubilization (21.43%), nitrogen fixation (57.14%), and phosphate solubilization (42.86%). Further investigations indicated that the levels of IAA ranged from 13.05 to 301.43 μg/mL, whereas the soluble phosphorus levels ranged from 47.32 to 125.95 μg/mL. In cocultivation assays, it was indicated that Fusarium sp. YMY5, Colletotrichum sp. YMY6, Alternaria sp. ZZ10 and Fusarium sp. ZZ13 had a certain promoting effect on lateral root number and fresh weight of tobacco. Furthermore, ZZ10 and ZZ13 significantly enhanced the germination potential, germination index, and vigor index of tobacco seeds. The subsequent potted trials demonstrated that the four endophytic fungi exhibited an enhancement to growth parameters of tobacco to a certain extent. ZZ10 and ZZ13 treatment had the best promotion effect. Inoculation with YMY5 increased the chlorophyll a and total chlorophyll content. ZZ10 and ZZ13 treatment remarkably increased the net photosynthetic rate, soluble sugars and soluble protein content, catalase and peroxidase activities, and lowered malondialdehyde content in tobacco leaves. In addition, YMY5 remarkably elevated superoxide dismutase activities. ZZ13 upregulated the expression of growth-related gene. Among them, ZZ13 had a better growth-promoting effect. In conclusion, these endophytic fungi possessing multi-trait characteristics and the capacity to enhance plant growth exhibit promising potential as biofertilizers or plant growth regulators.

Effect of Suanzaoren on Perioperative Analgesia, Hemodynamics and Postoperative Delirium

Hip fracture is not only accompanied by severe pain, but also impair body tissue and organ functions in patients, particularly in elderly individuals who have reduced tolerance and are prone to organ damage after experiencing a hip fracture. Surgery is the primary clinical approach for treating hip fractures. However, both the fracture trauma and surgical procedure can result in significant pain during the perioperative period, leading to abnormal hemodynamic fluctuations and an increased risk of postoperative delirium. Therefore, it is crucial to select an appropriate intervention method to facilitate the postoperative rehabilitation of hip fracture patients. Traditional Chinese Medicine (TCM) acknowledges that surgery will have different degrees of impact on muscles and bones, Qi and blood. Suanzaoren Decoction contains suanzaoren, anemarrhena asphodeloides, ligusticum chuanxiong and other TCM. The effective components of these TCM, such as spinosin, sarsasapogenin, and tetramethylpyrazine, have been proved to have analgesic effects. This study demonstrates, through clinical trials, that Suanzaoren Decoction exerts a positive influence on promoting the postoperative rehabilitation of hip fracture patients by reducing postoperative pain, stabilizing hemodynamic indexes, improving inflammatory state, and shortening the duration of postoperative delirium (all P <0.05). The fact that Suanzaoren Decoction can effectively promote the postoperative rehabilitation of hip fracture patients may be related to the anti-inflammatory, analgesic and neuroprotective effects of the effective ingredients in the prescription, such as spinosin, sarsasapogenin and tetramethylpyrazine. Therefore, this study believes that Suanzaoren Decoction+ERAS intervention program represents an optimal approach for hip fracture surgery patients within the perioperative period.

Z-ligustilide alleviates atherosclerosis by reconstructing gut microbiota and sustaining gut barrier integrity through activation of cannabinoid receptor 2

BackgroundZ-Ligustilide (ZL) is an essential phthalide found in Ligusticum chuanxiong Hort, a commonly used traditional Chinese medicine for treating atherosclerosis (AS) clinically. ZL has been shown to be effective in treating AS. However, the underlying mechanism of ZL against AS and its potential targets remain elusive. PurposeThe purpose of this research was to assess the influence of ZL on AS and explore the role of the gut microbiome in mediating this effect. MethodsA well-established AS mouse model, apolipoprotein E deficient (ApoE-/-) mice was used to examine the effects of ZL on AS, inflammation, and the intestinal barrier. To analyze the changes in gut microbial community, we employed the 16S rRNA gene sequencing. Antibiotic cocktail and fecal microbiota transplantation (FMT) were employed to clarify the contribution of the gut microbiota to the anti-AS effects of ZL. The mechanism through which ZL provided protective effects on AS and the intestinal barrier was explored by untargeted metabolomics, as well as by validating the involvement of cannabinoid receptor 2 (CB2R) in mice and Caco-2 cells. ResultsOral administration of ZL inhibited the development of atherosclerotic lesions, improved plaque stability, inhibited the increase in serum and atherosclerotic inflammation, and improved intestinal barrier function. Fecal bacteria from ZL-treated mice induced similar beneficial effects on AS and the intestinal barrier. We used 16S RNA gene sequencing to reveal a significant increase in Rikenella abundance in both ZL-treated mice and ZL-FMT mice, which was associated with the beneficial effects of ZL. Further function prediction analysis of the gut microbiota and CB2R antagonist intervention experiment in mice and Caco-2 cells showed that the activation of CB2R resulted in the enhancement of the intestinal barrier by ZL. Furthermore, the analysis of metabolomic profiling revealed the enrichment of capsaicin upon ZL treatment, which induced the activation of CB2R in human colon epithelial cells. ConclusionOur study is the first to demonstrate that oral treatment with ZL has the potential to alleviate AS by reducing inflammation levels and enhancing the intestinal barrier function. This mechanism relies on the gut microbiota in a CB2R-dependent manner, suggesting promising strategies and ideas for managing AS. This study provides insights into a novel mechanism for treating AS with ZL.

Rapid screening of xanthine oxidase inhibitors from Ligusticum wallichii by using xanthine oxidase functionalized magnetic metal-organic framework.

In this study, xanthine oxidase was immobilized for the first time using a novel magnetic metal-organic framework material (Fe3O4-SiO2-NH2@MnO2@ZIF-8-NH2). A ligand fishing method was established to rapidly screen XOD inhibitors from Ligusticum wallichii based on the immobilized XOD. Characterization and properties of the immobilized enzyme revealed its excellent stability and reusability. A ligand was screened from Ligusticum wallichii and identified as ligustilide by ultra-high performance liquid chromatography tandem mass spectrometry. The IC50 value of ligustilide was determined to be 27.70 ± 0.13μM through in vitro inhibition testing. Furthermore, molecular docking verified that ligustilide could bind to amino acid residues at the active site of XOD. This study provides a rapid and effective method for thepreliminary screening of XOD inhibitors from complex natural products and has great potential for further discovery of anti-hyperuricemic compounds.

Potential mechanistic linkages of Naoluotong granules on the remission of atherosclerosis by multidimensional analysis

BackgroundNaoluotong granules (NLTGs) are a medicinal formula derived from traditional Chinese medicine, which have been demonstrated to be effective in slowing down the progression of atherosclerosis (AS) through clinical practice and animal experiments. By means of multidimensional analysis, the relevant mechanism of NLTGs in delaying the progression of atherosclerosis was studied, which is conducive to its widespread adoption. Materials and methodsIn this study, data from network pharmacology and GEO database were comprehensively analysed to identify differentially expressed core cluster genes (DECCGs). Subsequently, multilevel analyses were applied to investigate the potential mechanistic linkages and causal associations of NLTGs in delaying atherosclerosis. ResultsEight DECCGs positively correlated with atherosclerosis risk were identified, with Polygonatum sibiricum (Huangjing), Hirudo nipponica (Shuizhi), and Ligusticum chuanxiong (Chuanxiong) as the core drug pairs. Senkyunone, Wallichilide, and Aurantiamide were the core components. The prediction model using principal components (PC) demonstrated high accuracy and clinical relevance. The mechanisms were strongly associated with the PI3K-Akt signaling pathway, as well as the polarization of Macrophages M0 and the balanced regulation of M1/M2 types. Ultimately, elevated expression of CTSB was causally associated with increased risk of cerebral atherosclerosis (OR = 1.313; 95 % CI = 1.024–1.685; P = 0.032). ConclusionsEmploying multidimensional analysis, we identified core pairs, components, and targets of NLTGs. Our multilevel analysis of DECCGs enabled the construction of a clinical prediction model, highlighting CTSB as a risk target for AS. Additionally, we unveiled NLTGs' mechanisms closely tied to the polarization and regulation of macrophage, facilitating subsequent research and application.

SIRT1 activation by Ligustrazine ameliorates migraine via the paracrine interaction of microglia and neurons

BackgroundNeuroinflammation with associated oxidative stress aggravates the pathogenesis and progression of migraine. Ligustrazine (LGZ) is a key component from traditional edible-medicinal herb Ligusticum chuanxiong Hort., and has the effects of anti-platelet aggregation, expanding small arteries, improving microcirculation and promoting blood circulation and removing blood stasis in clinic. Hypothesis/PurposeThis study aims to investigate the pharmacological effect and mechanism of LGZ in migraine. Study Design/MethodsA mouse model of migraine was induced by nitroglycerin (NTG), and LPS/IFN-γ stimulated microglial cell model was conducted to investigate neuroinflammation, the paracrine interactions between microglia and neurons were determined by the co-culture system, and the effect of LGZ on stability of SIRT1 protein was measured by cellular thermal shift assay (CETSA). Whilst, the SIRT1 inhibitor EX527 was used alone or co-treatment with LGZ in vitro or in vivo. ResultsLGZ significantly attenuated migraine-like behaviors in NTG-induced mice, and ameliorated neuroinflammation and related oxidative damage in brain tissue, but co-treatment with SIRT1 inhibitor EX527 abolished the protective effects of LGZ. Mechanistically, LGZ mitigated neuroinflammation by upregulating SIRT1 expression and subsequently inhibiting the activation of NF-κB pathway in microglia. CETSA indicated that LGZ significantly maintained the stability of SIRT1 protein in microglia. While, in the co-culture system, culture medium from LPS/IFN-γ-treated microglia exacerbated neuronal damage and oxidative stress, which was suppressed by treating LPS/IFN-γ-induced microglia with LGZ, this effect might be related to the activation of Nrf2 signals in neurons. Notably, SIRT1 inhibitor EX527 abrogated the effects of LGZ both in vitro and in vivo. ConclusionConsequently, SIRT1 might be an important pharmacological target of LGZ, which attenuates migraine associated neuroinflammation and oxidative stress by interfering the crosstalk between microglia and neurons, thereby relieving migraine.

Exploring the bioactive substances and mechanisms of Ligusticum chuanxiong Hort. treating acute lung injury based on combined network pharmacological, phytochemical, and pharmacological investigations

Exploring the bioactive substances and mechanisms of Ligusticum chuanxiong Hort. treating acute lung injury based on combined network pharmacological, phytochemical, and pharmacological investigations

Stabilised pathway and its anti-oxygen/glucose deprived activity about ligustilide, as a pharmacodynamic marker for Angelica sinensis (Oliv) Diles or Ligusticum chuanxiong Hort

The inherent structural instability and very low bioavailability of ligustilide (Lig) lead to the limited application of the clinical neuroprotection. We developed a stabilised method for Lig, which involved a chemical synthesis between cyclopropylamine and the active phthalides extract included Lig from Angelica sinensis (Oliv) Diles or Ligusticum chuanxiong Hort, which generated correspond phthalide derivatives by nucleophilic additive and substituted reaction. During this process, four phthalide derivatives have been obtained and two compounds (3 and 4) stands out as an unprecedented dimeric phthalide entity. This research has meticulously delineated the stabilised pathway and polymerisation mechanics of Lig or its derivatives, an oxygen/glucose deprived PC12 cells experiment model utilised to screen the anti-stroke activity of this isolated Lig derivatives and the results supported this chemical transformation could achieve the stabilised goal of Lig and improved its anti-oxygen/glucose deprived activity.

Sedative-Hypnotic Effect and Mechanism of Carbon Nanofiber Loaded with Essential Oils of Ligusticum chuanxiong (Ligusticum chuanxiong Hort.) and Finger Citron (Citrus medica L. var. sarcodactylis) on Mice Models of Insomnia.

(1) Background: Insomnia is a neurological illness that poses a significant threat to both physical and mental health. It results in the activation of neuroglial cells, heightened neuroinflammation, oxidative stress, and disruptions in the Hypothalamic-Pituitary-Adrenal (HPA) axis. Ligusticum Chuanxiong (CX) and Finger citron (FC) are frequently utilized botanicals for addressing sleeplessness. Both herbs possess notable anti-inflammatory properties in their volatile oils. However, their effectiveness is hindered by the nasal mucosal irritation and instability they exhibit. (2) Methods: This study involved the preparation of a nanofiber composite system using carbon nanofiber (CNF) suspensions containing essential oils of Ligusticum chuanxiong-Finger citron (CXEO-FCEO-CNF). The effects and mechanisms of these essential oils in improving insomnia were investigated using an insomnia mouse model after encapsulation. (3) Results: The CXEO-FCEO-CNF had an average particle size of 103.19 ± 1.64 nm. The encapsulation rates of essential oils of Ligusticum chuanxiong (CXEO) and essential oils of Finger citron (FCEO) were 44.50% and 46.15%, respectively. This resulted in a considerable improvement in the stability of the essential oils over a period of 30 days. The essential oils effectively decreased the irritation of the nasal mucosa following encapsulation. Furthermore, CXEO-FCEO-CNF enhanced voluntary activity and sleep in mice with insomnia, notably boosted the activity of superoxide dismutase (SOD), reduced the concentration of lipoxidized malondialdehyde (MDA), decreased the levels of hormones associated with the HPA axis, and regulated the levels of neurotransmitters, resulting in a beneficial therapeutic outcome. CXEO-FCEO-CNF contains a total of 23 active ingredients, such as alpha-Asarone, (E)-methyl isoeugenol, and Senkyunolide. These ingredients primarily work by modulating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling system to decrease oxidative stress and inflammatory reactions. (4) Conclusions: This study presented initial evidence that the combination of CXEO and FCEO in nanofiber formulations effectively reduces the nasal mucosal irritation and instability of essential oils. Furthermore, it demonstrated the potential anti-neuroinflammatory and therapeutic effects of these formulations in treating insomnia. Overall, this study provides a theoretical foundation for developing new essential oil formulations derived from herbs.

Rules of medication for leucorrhea in ancient books of traditional Chinese medicine based on latent structure model and association rules

Objective: To analyze syndrome differentiation and medication rules for leucorrhea in ancient books of traditional Chinese medicine (TCM) based on the “Chinese Medical Code” using the latent structure model. Methods: The formulations for leucorrhea were searched in the Chinese Medical Code (software), based on which an Excel sheet was created to conduct frequency analysis and construct a matrix of high-frequency medications. The high-frequency medications for leucorrhea were then analyzed using the Latent 5.0 software and a latent structure model. With SPSS Modeler and Latent 5.0 as the main analysis methods, Chinese medications with a frequency >1.00% were investigated using the latent structure model and association rules, and the medication rules in treating leucorrhea with TCM were dissected based on the data of frequency. Results: For 373 kinds of Chinese medicines retrieved from 236 TCM prescriptions, the total medication frequency was 2522. Chinese Angelica (Angelicae Sinensis Radix), White Peony Root (Paeoniae Radix Alba), Indian Buead Tuckahoe (Poria), Common Oyster Shell (Ostreae Concha), and Largehead Atractylodes Rhizome (Atractylodis Macrocephalae Rhizoma) were high-frequency medicines for leucorrhea. Tonic, heat-clearing, and qi-regulating medicines had a high frequency of usage. According to a formula-based analysis of the evidence, the main syndromes of leucorrhea included liver qi affecting the spleen pattern, damp heat accumulation pattern, liver qi stagnation pattern, liver-stomach disharmony pattern, yin deficiency of the liver and kidney pattern, and spleen deficiency with dampness pattern, which are generally in line with the etiology and pathogenesis of leucorrhea, namely pathogenic dampness as the detrimental factor together with spleen-kidney dysfunction. However, in ancient books, emphasis was laid out on the regulation of the liver. This study determined 31 association rules for treating leucorrhea, where the primary compatible medicines contained Chinese Angelica (Angelicae Sinensis Radix)-Nutgrass Galingale Rhizome (Cyperus rotundus), Chinese Angelica (Angelicae Sinensis Radix)-Szechwan Lovage Rhizome (Ligusticum chuanxiong Hort.), White Peony Root (Paeoniae Radix Alba)-Szechwan Lovage Rhizome (Ligusticum chuanxiong Hort.), White Peony Root (Paeoniae Radix Alba)-Adhesive Rehmannia Root Tuber (Rehmanniae Radix) and Tangerine Peel (Citri Reticulatae Pericarpium)-Ternate Pinellia (Rhizoma Pinelliae). Conclusion: The medication rules targeting leucorrhea in the Chinese Medical Code were mainly represented by the regulation of qi and blood, as well as the 3 internal organs—the kidney, spleen, and liver.

Evaluation of the Pharmaceutical Activities of Chuanxiong, a Key Medicinal Material in Traditional Chinese Medicine.

Szechwan lovage rhizome (SLR, the rhizome of Ligusticum chuanxiong Hort., Chuanxiong in Chinese transliteration) is one Chinese materia medica (CMM) commonly used to activate blood circulation and remove blood stasis. SLR is applicable to most blood stasis syndromes. It has significant clinical efficacy in relation to human diseases of the cardiocerebrovascular system, nervous system, respiratory system, digestive system, urinary system, etc. Apart from China, SLR is also used in Singapore, Malaysia, the European Union, and the United States of America. However, the current chemical markers in pharmacopeia or monography for the quality assessment of SLR are not well characterized or specifically characterized, nor do they fully reflect the medicinal efficacy of SLR, resulting in the quality of SLR not being effectively controlled. CMM can only have medicinal efficacy when they are applied in vivo to an organism. The intensity of their pharmaceutical activities can more directly represent the quality of CMM. Therefore, the chemical constituents and pharmacological actions of SLR are reviewed in this paper. In order to demonstrate the medicinal efficacy of SLR in promoting blood circulation and removing blood stasis, bioassay methods are put forward to evaluate the pharmaceutical activities of SLR to improve hemorheology, hemodynamics, and vascular microcirculation, as well as its anti-platelet aggregation and anticoagulation properties. Through comprehensive analyses of these pharmaceutical properties, the quality and therapeutic value of SLR are ascertained.

Ligusticum chuanxiong Hort.: a review of its phytochemistry, pharmacology, and toxicology.

Conioselinum anthriscoides (H. Boissieu) Pimenov & Kljuykov, also known as Ligusticum chuanxiong Hort. is a perennial Umbelliferae herb, whose dried rhizome commonly called Chuanxiong Rhizoma. Chuanxiong Rhizoma is widely used in TCM, especially for cardiocerebrovascular and gynecological diseases. However, these studies are scattered and there is no review that can centralize the results of these studies. The authors summarized this review by collecting research results on the chemical, pharmacological, and toxicological of Chuanxiong Rhizoma published in various publications over the past 20 years. The purpose of this review is to summarize the current experimental studies on Chuanxiong Rhizoma and explore its mechanism of action. Web of Science, PubMed, CBM, CNKI, Medline, Embase, Elsevier, Springer, Wiley Online Library, Scholar, and other databases were searched, and nearly one hundred experimental studies were collected to summarize this review. Chuanxiong Rhizoma is composed of essential oil, terpenes, alkaloids, polysaccharide, organic acids, ceramides, and cerebrosides. It has the functions of promoting blood circulation, removing blood stasis, antibacterial, antiviral, and calming the mind to sleep. Now it can be used to treat cardiocerebrovascular and gynecological diseases, neurodegenerative disease, psoriasis, rectal cancer, osteoporosis, and osteoarthritis. In the past 20 years, a large number of research data have confirmed that Chuanxiong Rhizoma contains rich effective metabolites, has huge medicinal potential, and has a wide range of effective treatments.

Ligustilide alleviates oxidative stress during renal ischemia-reperfusion injury through maintaining Sirt3-dependent mitochondrial homeostasis

BackgroundRenal ischemia-reperfusion (I/R) injury is an inevitable complication during renal transplantation and is closely related to patient prognosis. Mitochondrial damage induced oxidative stress is the core link of renal I/R injury. Ligustilide (LIG), a natural compound extracted from ligusticum chuanxiong hort and angelica sinensis, has exhibited the potential to protect mitochondrial function. However, whether LIG can ameliorate renal I/R injury requires further investigation. Delving deeper into the precise targets and mechanisms of LIG's effect on renal I/R injury is crucial. PurposeThis study aimed to elucidate the specific mechanism of LIG's protective effect on renal I/R injury. MethodsIn this study, an in vivo model of renal ischemia-reperfusion (I/R) injury was developed in mice, along with an in vitro model of hypoxia-reoxygenation (H/R) using human proximal renal tubular epithelial cells (HK-2). To assess the impact of LIG on renal injury, various methods were employed, including serum creatinine (Cr) and blood urea nitrogen (BUN) testing, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) for kidney injury molecule-1 (KIM-1). The effects of LIG on oxidative stress were examined using fluorescent probes dihydroethidium (DHE) and dichlorodihydrofluorescein diacetate (DCFH-DA), TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and flow cytometry. Additionally, the influence of LIG on mitochondrial morphology and function was evaluated through transmission electron microscopy (TEM), Mito Tracker Red CMXRos staining, adenosine triphosphate (ATP) concentration assays, and JC-1 staining. The potential mechanism involving LIG and Sirt3 was explored by manipulating Sirt3 expression through cell transfection. ResultsThe results showed that LIG could provide protective function for mitochondria to alleviate oxidative stress induced by renal I/R. Further mechanistic studies indicated that LIG maintained mitochondrial homeostasis by targeting Sirt3. ConclusionOur findings demonstrated that LIG alleviated oxidative stress during renal I/R injury through maintaining Sirt3-dependent mitochondrial homeostasis. Overall, our data raised the possibility of LIG as a novel therapy for renal I/R injury.

Targeting non-classical autophagy-dependent ferroptosis and the subsequent HMGB1/TfR1 feedback loop accounts for alleviating solar dermatitis by senkyunolide I

Given the substantial risks associated with ultraviolet B (UVB) radiation-induced solar dermatitis, enhancing current strategies to combat UVB regarding skin diseases is imperative. The cross-talk between ferroptosis and inflammation has been proven to be an essential factor in UVB-induced solar dermatitis, whereas detailed process of how their interaction contributes to this remains unclear. Therefore, further investigation of ferroptosis-mediated processes and identification of corresponding inhibitory approaches hold promise for repairing skin damage. Senkyunolide I (Sen I), a bioactive component mainly extracted from the traditional Chinese medicinal plants, Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, has demonstrated efficacy in combating oxidative stress and inflammation. In this study, we utilized UVB-irradiated HaCaT cells as an in vitro model and C57BL/6J mice as an in vivo model of solar dermatitis. Our findings revealed the pivotal roles of autophagy and ferroptosis in inducing skin inflammation, particularly emphasizing the activation of ferroptosis through macroautophagy. Surprisingly, this mechanism operated independently of ferritinophagy, a classical autophagy-driven ferroptosis pathway. Instead, our results highlighted Transferrin Receptor 1 (TfR1), tightly controlled by autophagy, as a crucial mediator of ferroptosis execution and amplifier of subsequent lethal signals. Furthermore, extracellular High Mobility Group Box 1 protein (HMGB1), released following UVB-induced ferroptotic cells from activated autophagic flux, initiated a feedback loop with TfR1, propagating ferroptosis to neighboring cells and exacerbating damage. Remarkably, Sen I administration showed a significant protective effect against UVB damage in both in vitro and in vivo models by interrupting this cascade. Consequently, we have illuminated a novel therapeutic pathway post-UVB exposure and identified Sen I as a potent natural molecule that safeguarded against UVB-induced solar dermatitis by suppressing the autophagy-ferroptosis-HMGB1-TfR1 axis, highlighting a new frontier in photoprotection.

Rapid and Non-Destructive Geographical Origin Identification of Chuanxiong Slices Using Near-Infrared Spectroscopy and Convolutional Neural Networks

Ligusticum Chuanxiong, a perennial herb of considerable medicinal value commonly known as Chuanxiong, holds pivotal importance in sliced form for ensuring quality and regulating markets through geographical origin identification. This study introduces an integrated approach utilizing Near-Infrared Spectroscopy (NIRS) and Convolutional Neural Networks (CNNs) to establish an efficient method for rapidly determining the geographical origin of Chuanxiong slices. A dataset comprising 300 samples from 6 distinct origins was analyzed using a 1D-CNN model. In this study, we initially established a traditional classification model. By utilizing the Spectrum Outlier feature in TQ-Analyst 9 software to exclude outliers, we have enhanced the performance of the model. After evaluating various spectral preprocessing techniques, we selected Savitzky–Golay filtering combined with Multiplicative Scatter Correction (S-G + MSC) to process the raw spectral data. This approach significantly improved the predictive accuracy of the model. After 2000 iterations of training, the CNN model achieved a prediction accuracy of 92.22%, marking a 12.09% improvement over traditional methods. The application of the Class Activation Mapping algorithm not only visualized the feature extraction process but also enhanced the traditional model’s classification accuracy by an additional 7.41% when integrated with features extracted from the CNN model. This research provides a powerful tool for the quality control of Chuanxiong slices and presents a novel perspective on the quality inspection of other agricultural products.

Metabolomics integrated with mass spectrometry imaging reveals novel action of tetramethylpyrazine in migraine

Migraine as a common neurological disorder still lacks effective therapies. Tetramethylpyrazine (TMP) is the main bioactive component from Ligusticum chuanxiong hort., a traditional edible-medicinal herb. This study aimed to investigate the action of TMP on migraine by metabolomics with mass spectrometry imaging (MSI) analysis and molecular exploring, including random forest model analysis, KEGG enrichment analysis and metabolite-metabolite interaction network analysis. The results indicated that 26 key representative metabolic biomarkers were identified, especially γ-glu-cys, which were highly related to glutathione (GSH) metabolism. MSI found the abundance of eleven endogenous metabolites were modulated by TMP, particularly glucose, the most important energy metabolism molecule, and GSH were increased that maintains intracellular redox balance, which was consistent with activation of Nrf2 signals by TMP. These findings provide insights into the effectiveness of metabolomics integrated with MSI in explaining the metabolic mechanisms of TMP, and afford valuable information for healthy development of TMP in migraine.

Yixin-Fumai granules modulate autophagy through the PI3K/AKT/FOXO pathway and lead to amelioration of aging mice with sick sinus syndrome

ObjectiveBy employing network pharmacology alongside molecular docking techniques, we can delve into the intricate workings of Yixin-Fumai granules (YXFMs) and their impact on sick sinus syndrome (SSS) within wrinkles mice. Specifically, we aim to understand how YXFMs enhance autophagy through the PI3K/AKT/FOXO path.MethodsThe active ingredients and medicinal uses of Ginseng, ligusticum wallichii, Ophiopogon, Schisandra, salvia, and astragalus were compiled using the BATMAN-TCM database. We also used Genecards, OMIM, and Disgenet files to identify the disease goals. A hierarchical diagram of “disease-drug-key targets” was generated using the Cytoscape programs. In addition, we established a target protein interaction (PPI) network using the STRING database. Then, the Cluster Profiler R package was used to conduct GO functional enrichment evaluation and KEGG pathway enrichment analyses of the targets. Based on the PPI system, we chose the top communicating targets and substances over molecular docking. In vivo studies were performed to validate these selections further. The mouse model was induced to study the damaged sinoatrial node (SAN) in mice with lower heart rates due to age-related changes. Electrocardiogram and Masson staining assessments were performed to obtain the results. The transmission electron microscope was used to assess the autophagy level of SAN cells. Western blot was employed to analyze the impact of YXFMs on protein expression in the PI3K/AKT/FOXO signaling process throughout SSS therapy in aging mice.ResultsOne hundred forty-two active ingredients, 1858 targets, 1226 disease targets, and 266 intersection targets were obtained. The key targets of the PPI network encompassed TP53, AKT1, CTNNB1, INS, and TNF, among others. According to GO functional analysis, the mechanism underlying YXFMs in SSS treatment may primarily be associated with the control of ion transport across membranes, cardiac contraction, regulation of blood circulation, and other biological processes. Based on the results of KEGG pathway enrichment analysis, it was determined that they were mainly enriched in multiple pathways of signaling such as the PI3K-Akt signaling route, MAPK signaling process, AGE-RAGE signaling path, FOXO signaling path, HIF-1 signaling process, and several other paths. Molecular docking demonstrated that five compounds had excellent binding to the key candidate target proteins AKT1 and INS. Through the in vivo studies, we noticed notable effects when administering YXFMs. These effects included the suppression of aging-induced SSS, a decrease in the R-R interval, a rise in heart rate, a reduction in fibrosis, a boost in the autophagy process level, and a spike in the levels of expression of key protein molecules in the PI3K/AKT/FOXO signaling path.ConclusionThis research has made preliminary predictions about the potential of YXFMs in treating SSS. It suggests that YXFMs may have the ability to target key proteins and critical paths associated with the condition. Further testing has been conducted to discover new findings and evidence of ideas for tackling SSS triggered by aging.