Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

Ligustilide, a phthalide compound extracted from Umbelliferae plants such as Angelica sinensis and Ligusticum chuanxiong, has been proven to possess various pharmacological activities, such as anti-inflammatory, anti-tumor, anti-atherosclerosis, anti-ischemic stroke injury, and anti-Alzheimer's disease properties. In recent years, it has shown great potential, particularly in the treatment of locomotor system diseases. Studies have shown that ligustilide has significant therapeutic effects on various locomotor system diseases, including osteoporosis, osteoarthritis, femoral head necrosis, osteosarcoma, and muscle aging and injury. Its mechanisms of action include enhancing the differentiation ability of osteoblasts(OBs), inhibiting the formation ability of osteoclasts(OCs), downregulating inflammatory factors, promoting the synthesis of extracellular matrix(ECM), improving local blood supply to the femoral head, balancing lipid metabolism, inhibiting the proliferation and migration of osteosarcoma cells, inducing cell cycle arrest, enhancing glucose utilization in skeletal muscle, and regulating autophagy and apoptosis. However, its clinical application is severely limited by drawbacks such as structural instability, poor water solubility, and low bioavailability. Currently, formulation techniques such as dripping pills, micropills, inclusion complexes, and liposomes are being used to improve its stability and water solubility, thereby enhancing its therapeutic efficacy. This article summarized the effects, mechanisms of action, and pharmacokinetics of ligustilide monomers and preparations in the treatment of locomotor system diseases in China and abroad in recent years, aiming to provide reference and guidance for further development and application of ligustilide in this field.
Humans ; 4-Butyrolactone/pharmacology* ; Animals ; Drugs, Chinese Herbal/chemistry* ; Angelica sinensis/chemistry* ; Osteoporosis/metabolism* ; Ligusticum/chemistry*

Chuanxiong Rhizoma is a traditional Chinese medicinal material mainly produced in Sichuan and Chongqing of China. In recent years, the cadmium content in Chuanxiong Rhizoma produced in most of the genuine producing areas has exceeded the standard, which makes Chuanxiong Rhizoma difficult to be exported. To solve the problem of excessive cadmium content in soil, this study employed the MaxEnt model to simulate the potential geographic distribution of Ligusticum chuanxiong and evaluate important environmental factors, and re-plan its ecologically suitable areas based on the mineral distribution characteristics and soil cadmium pollution status. The results showed that the places suitable for L. chuanxiong growing covered an area of 335 523.69 km~2, mainly in central and eastern Sichuan, southern Shaanxi and most parts of Chongqing. Among them, the highly suitable areas of L. chuanxiong were mainly concentrated in Chengdu, Ya'an, Deyang, and Mianyang. Solar radiation, annual precipitation, and annual range of temperature were evaluated as important variables affecting the distribution of L. chuanxiong, with the contribution rates of 62.3%, 13.3%, and 6.8%, respectively. In addition, Qionglai county, Chongqing county, Mianyang city(Youxian district and Fucheng district), Qingchuan county, and Xinjin county were classified into the first-class ecologically suitable zone, covering a total area of 2 768.87 km~2. The se-cond-class ecologically suitable zone was even wider, involving such counties as Tongjiang county, Renshou county, Jianyang county, and Nanjiang county, and the total area reached 43 616.92 km~2. The re-planning of the ecologically suitable areas for L. chuanxiong has provided strong data support for the cultivation and resource development of L. chuanxiong and also new ideas for solving the problem of excessive cadmium content in L. chuanxiong.
Cadmium/toxicity* ; Environmental Pollution ; Ligusticum ; Rhizome ; Soil

As an environment-friendly agriculture, ecological agriculture of Chinese materia medica(CMM) is being implemented in all parts of the country. Due to the stronger dependence on natural environmental conditions, ecological agriculture of CMM shows obvious regional differences in production practice. More mature CMM ecological planting patterns representative of each region were collected. It was found that common types of patterns in various regions of the country mainly included intercropping,intercropping,rotation planting mode, undergrowth planting mode, wild tending planting mode and landscape ecological planting mode. Based on the Construction Plan of National Dao-di Herbs Production Base(2018-2025) and Chinese Medicine Division, this paper systematically sorts out the pattern of ecological planting of CMM in the 8-avenue medicinal materials production areas according to the varieties and regions. The specific pattern of ecological planting of CMM included the ginseng undergrowth planting pattern in northeastern China, the bionics wild ecological planting of the Forsythia suspensa in northern China, the Fritillaria thunbergii-rice rotation in eastern China, the imitation wild planting pattern under the Polygonatum cyrtonema in central China, the planting pattern of the Fructus amomi under forest in southern China, the Ligusticum chuanxiong-rice rotation pattern in the Southwest, wild tending of Glycyrrhiza uralensis in the Northwest, and rhubarb imitation wild planting pattern in Qinghai-Tibet area. Finally, it is expected to provide reference for the screening and popularization of ecological planting patterns of other CMMs in various distribution areas.
China ; Drugs, Chinese Herbal ; Ligusticum ; Materia Medica ; Medicine, Chinese Traditional ; Tibet

Aiming at the phenomenon of heavy metal Cd exceeding the standard of Chuanxiong medicinal materials,the accumulation of 12 inorganic elements,including heavy metals,in Ligusticum chuanxiong was studied in this paper. It was found that the contents and distribution of most inorganic elements in the stems and leaves of L. chuanxiong were higher than those in the rhizomes at seedling and shooting stages. The content of most elements in rhizome reached the highest at harvest stage,and the distribution ratio of some elements in rhizome was higher than that in stem and leaf at harvest stage. But rhizome,stem and leaf of L. chuanxiong have relatively stable absorption capacity and enrichment effect on different elements,and are less affected by growth period and position. Rhizomes and stems and leaves of L. chuanxiong were enriched with Cd,and stems and leaves also accumulated Pb at seedling stage and stem stage. The absorption capacity of Pb in stems and leaves of L. chuanxiong was higher than that of rhizomes,and the ability of absorbing Cd was less than that of rhizomes at harvest time. The total uptake of Cd and Pb by L. chuanxiong decreased with the prolongation of growth time,but the proportion of Cd and Pb in rhizome increased,so that the content of Cd and Pb increased with the prolongation of growth time.
Cadmium ; analysis ; Drugs, Chinese Herbal ; chemistry ; Ligusticum ; chemistry ; Metals, Heavy ; analysis ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rhizome ; chemistry

Quality constant is a kind of grading evaluation method of traditional Chinese medicine pieces based on the combination of traditional knowledge and modern quality control. This method has been successfully applied in the grading evaluation of Glycyrrizae Radix et Rhizome pieces and traditional Chinese medicine pieces,and with a positive influence in the industry. With Dachuanxiong Formula for example,different grades of Ligusticum chuanxiong and Gastrodia elata pieces formed high-quality,moderate and qualified Dachuanxiong Formula on the basis of the grading evaluation of the pieces,and the pharmacodynamics method was used to evaluate its efficacy. The results showed that the maximum vascular diastolic rates of Dachuanxiong Formula in the three grades were( 80. 3±5. 2) %,( 67. 0±6. 1) %and( 60. 3±6. 5) %,and the strength of pharmacodynamics was positively correlated with the grade of L. chuanxiong and G. elata pieces.The quality constant technique can objectively and quantitatively classify single decoctions,and has important correlations and prompts for the efficacy of traditional Chinese medicine prescriptions composed of these pieces,with important significance in promoting hierarchical management of the industry,implementing better price for high quality and defining high quality and superior effect.
Drugs, Chinese Herbal ; standards ; Gastrodia ; chemistry ; Glycyrrhiza ; chemistry ; Ligusticum ; chemistry ; Medicine, Chinese Traditional ; Plant Roots ; chemistry ; Quality Control ; Rhizome ; chemistry

The method of classifying the quality grade of traditional Chinese medicine slices with cross section model quality constant was applied to the grade evaluation of Ligusticum chuanxiong pieces,and a reasonable grade standard of L. chuanxiong pieces was established. The purpose is to classify the 15 batches of L. chuanxiong pieces by combining the advantages of traditional grading with modern quality control indicators. By measuring the natural morphological parameters,processing parameters and the intrinsic content of ferulic acid,an important active ingredient,of the 15 batches of L. chuanxiong pieces collected from different manufacturers and different batches of different medicinal materials markets,we can synthesize the results. The mass constants and percentage mass constants are calculated and analyzed based on the above data. The results showed that the quality constants of 15 batches of L. chuanxiong pieces collected ranged from 0.53-3.00; if the percentage mass constants were more than 80%,50%-80% was second-class pieces,and the rest were third-class pieces,the evaluation results were as follows: the quality constants of first-class L. chuanxiong pieces were more than 2.40,the quality constants of second-class L. chuanxiong pieces should be 1.70-2.40,and the quality constants of third-class L. chuanxiong pieces should be less than 1.70. In this paper,the method of dividing the quality constants of the top blade model into different grades is further applied and practiced,which proves that the method is scientific,reasonable and multi-adaptable. At the same time,it enriches the research data of the grade evaluation of L. chuanxiong pieces,provides a useful reference for the promotion of the grade evaluation of L. chuanxiong pieces,and lays an experimental foundation for the next research of the subject group.
Drugs, Chinese Herbal ; standards ; Ligusticum ; chemistry ; Medicine, Chinese Traditional ; Quality Control

Ligustrazine is an important active ingredient of the traditional Chinese medicine Chuanxiong Rhizoma, but its content is a controversial topic. The endophytes of medicinal plants have the ability to produce the same active substances as the host, so this report focused on the endophytic Bacillus subtilis, to study the origin of ligustrazine in Chuanxiong Rhizoma preliminarily by inoculating the isolated endophytic B. subtilis to the Chuanxiong Rhizoma medium for solid state fermentation. Tissue grinding method was used to isolate the endogenetic B. subtilis. The morphological features, conventional physiological and biochemical reactions and 16S rRNA molecular techniques were combined to identify the endogenetic strains. Then, the strains that grew well in the medicinal matrix of Chuanxiong Rhizoma were screened out for further fermentation studies. The solid-state fermentation was performed at 37 °C for 30 d using Chuanxiong Rhizoma fermentation medium (40 g Chuanxiong Rhizoma powder, 100 mL sterile water, 121 °C, sterilization for 25 minutes). UPLC was used to detect the contents of ligustrazine, acetoin in the Chuanxiong Rhizoma fermentation medium and Chuanxiong Rhizoma. All the five strains were Gram-positive and had spores. Phylogenetic analysis of the 16S rRNA sequence showed that the endophytes were B. subtilis. The results of UPLC showed that ligustrazine was detected in the Chuanxiong Rhizoma fermentation medium inoculated with endogenetic B. subtilis LB3, LB3-2-1, LB4, LB5 and LB6-2, while not detected neither in blank Chuanxiong Rhizoma fermentation medium nor in Chuanxiong Rhizoma. This study showed that the endogenetic B. subtilis of Ligusticum chuanxiong Hort. can make use of Chuanxiong Rhizoma fermentation medium to produce ligustrazine. Endogenetic B. subtilis has a certain correlation with the accumulation of ligustrazine in Rhizoma Chuanxiong. We speculate that the ligustrazine may be derived from the catabolism of endogenetic B. subtilis in Ligusticum chuanxiong.
Bacillus subtilis ; Endophytes ; Fermentation ; Ligusticum ; chemistry ; microbiology ; Phylogeny ; Pyrazines ; analysis ; RNA, Ribosomal, 16S ; Rhizome ; chemistry

To explore the effective ingredients and mechanism of Ligusticum wallichii in treating brain ischemia. Four brain ischemia-related target proteins were selected in the joint screening for the 45 component in L. wallichii reported in literatures based on molecular docking by reference to the corresponding drugs in the market. According to the docking results, multiple components in L. wallichii, such as phthalides, were superior to the corresponding drugs in the market, suggesting that they may be the major effective components in L. wallichii for treating brain ischemia. The method can be used to study the material base and molecular mechanism of traditional Chinese medicines.
Brain Ischemia ; drug therapy ; Ligusticum ; chemistry ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Nitric Oxide Synthase Type II ; antagonists & inhibitors ; Peroxidase ; antagonists & inhibitors ; Phytotherapy ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors

To observe the effect of Ligusticum wallichii-containing serum on the expressions of Toll-like receptor 4 and myeloid differentiation factor 88 in hepatic stellate cells. Clean-grade SD rats were randomly divided into 5 groups and orally given L. wallichii decoction, colchicine and normal saline for 7 d to prepare L. wallichii-containing serums. Except for the blank group, all of the remaining groups were stimulated with LPS 1 mg x L(-1) for 24 h. After being intervened, the L. wallichii-containing serums were cultured in 5% CO2 incubator at 37 degrees C for 24 hours. The expression of TLR4 and MyD88 were detected by RT-PCR and Western blot. After HSC was stimulated with LPS, TLR4 and MyD88 mRNA and protein expressions were significantly higher than the blank control group (P < 0.01). After being intervened with L. wallichii-containing serum, TLR4 and MyD88 mRNA and protein expressions were notably lower than the model group (P < 0.05 or P < 0.01). In conclusion, L. wallichii-containing serum could regulate the TLR4 signaling pathway and show the anti-fibrosis effect by inhibiting the expression of TLR4 and MyD88 in LPS-induced HSCs.
Animals ; Female ; Hepatic Stellate Cells ; drug effects ; metabolism ; Ligusticum ; Lipopolysaccharides ; pharmacology ; Liver Cirrhosis, Experimental ; drug therapy ; Myeloid Differentiation Factor 88 ; genetics ; physiology ; Phytotherapy ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; genetics ; physiology