Cadmium induced changes in rhizosphere microecology to enhance Cd intake by Ligusticum sinense cv. Chuanxiong.

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

LcSAO1, an Unconventional DOXB Clade 2OGD Enzyme from Ligusticum chuanxiong Catalyzes the Biosynthesis of Plant-Derived Natural Medicine Butylphthalide.

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

Comparison of Volatile Oil between the Ligusticum sinese Oliv. and Ligusticum jeholense Nakai et Kitag. Based on GC-MS and Chemical Pattern Recognition Analysis.

Ligustici Rhizoma et Radix (LReR) is the dried rhizomes and roots of Ligusticum sinese Oliv. (LS) or Ligusticum jeholense Nakai et Kitag. (LJ). However, in the market, LS and LJ are frequently confused with each other. Since the volatile oils are both the main active components and quality control indicators of LReR, a strategy combining gas chromatography-mass spectrometry (GC-MS) and chemical pattern recognition (CPR) was used to compare the volatile components of LJ and LS. Total ion chromatography (TIC) revealed that phthalides (i.e., neocnidilide) and phenylpropanoids (i.e., myristicin) could be thought of as the most critical components in the volatile oils of LJ and LS, respectively. In addition, the chemical components of the volatile oils in LJ and LS were successfully distinguished by hierarchical cluster analysis (HCA) and principal component analysis (PCA). Moreover, two quality markers, including myristicin and neocnidilide, with a very high discriminative value for the classification of LJ and LS, were found by orthogonal partial least squares discriminant analysis (OPLS-DA). The relative contents of myristicin and neocnidilide were 10.86 ± 6.18% and 26.43 ± 19.63% for LJ, and 47.43 ± 12.66% and 2.87 ± 2.31% for LS. In conclusion, this research has developed an effective approach to discriminating LJ and LS based on volatile oils by combining GC-MS with chemical pattern recognition analysis.

Elucidating the Novel Mechanism of Ligustrazine in Preventing Postoperative Peritoneal Adhesion Formation.

Postoperative peritoneal adhesion (PPA) is a major clinical complication after open surgery or laparoscopic procedure. Ligustrazine is the active ingredient extracted from the natural herb Ligusticum chuanxiong Hort, which has promising antiadhesion properties. This study is aimed at revealing the underlying mechanisms of ligustrazine in preventing PPA at molecular and cellular levels. Both rat primary peritoneal mesothelial cells (PMCs) and human PMCs were used for analysis in vitro. Several molecular biological techniques were applied to uncover the potential mechanisms of ligustrazine in preventing PPA. And molecular docking and site-directed mutagenesis assay were used to predict the binding sites of ligustrazine with PPARγ. The bioinformatics analysis was further applied to identify the key pathway in the pathogenesis of PPA. Besides, PPA rodent models were prepared and developed to evaluate the novel ligustrazine nanoparticles in vivo. Ligustrazine could significantly suppress hypoxia-induced PMC functions, such as restricting the production of profibrotic cytokines, inhibiting the expression of migration and adhesion-associated molecules, repressing the expression of cytoskeleton proteins, restricting hypoxia-induced PMCs to obtain myofibroblast-like phenotypes, and reversing ECM remodeling and EMT phenotype transitions by activating PPARγ. The antagonist GW9662 of PPARγ could restore the inhibitory effects of ligustrazine on hypoxia-induced PMC functions. The inhibitor KC7F2 of HIF-1α could repress hypoxia-induced PMC functions, and ligustrazine could downregulate the expression of HIF-1α, which could be reversed by GW9662. And the expression of HIF-1α inhibited by ligustrazine was dramatically reversed after transfection with si-SMRT. The results showed that the benefit of ligustrazine on PMC functions is contributed to the activation of PPARγ on the transrepression of HIF-1α in an SMRT-dependent manner. Molecular docking and site-directed mutagenesis tests uncovered that ligustrazine bound directly to PPARγ, and Val 339/Ile 341 residue was critical for the binding of PPARγ to ligustrazine. Besides, we discovered a novel nanoparticle agent with sustained release behavior, drug delivery efficiency, and good tissue penetration in PPA rodent models. Our study unravels a novel mechanism of ligustrazine in preventing PPA. The findings indicated that ligustrazine is a potential strategy for PPA formation and ligustrazine nanoparticles are promising agents for preclinical application.

The isolation, structural features and biological activities of polysaccharide from Ligusticum chuanxiong: A review.

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.

The molecular mechanism of Ligusticum wallichii for improving idiopathic pulmonary fibrosis: A network pharmacology and molecular docking study.

BACKGROUND: At present, there was no evidence that any drugs other than lung transplantation can effectively treat Idiopathic Pulmonary Fibrosis (IPF). Ligusticum wallichii, or Chinese name Chuan xiong has been widely used in different fibrosis fields. Our aim is to use network pharmacology and molecular docking to explore the pharmacological mechanism of the Traditional Chinese medicine (TCM) Ligusticum wallichii to improve IPF. MATERIALS AND METHODS: The main chemical components and targets of Ligusticum wallichii were obtained from TCMSP, Swiss Target Prediction and Phammapper databases, and the targets were uniformly regulated in the Uniprot protein database after the combination. The main targets of IPF were obtained through Gencards, OMIM, TTD and DRUGBANK databases, and protein interaction analysis was carried out by using String to build PPI network. Metascape platform was used to analyze its involved biological processes and pathways, and Cytoscape3.8.2 software was used to construct "component-IPF target-pathway" network. And molecular docking verification was conducted through Auto Dock software. RESULTS: The active ingredients of Ligusticum wallichii were Myricanone, Wallichilide, Perlolyrine, Senkyunone, Mandenol, Sitosterol and FA. The core targets for it to improve IPF were MAPK1, MAPK14, SRC, BCL2L1, MDM2, PTGS2, TGFB2, F2, MMP2, MMP9, and so on. The molecular docking verification showed that the molecular docking affinity of the core active compounds in Ligusticum wallichii (Myricanone, wallichilide, Perlolyrine) was <0 with MAPK1, MAPK14, and SRC. Perlolyrine has the strongest molecular docking ability, and its docking ability with SRC (-6.59 kJ/mol) is particularly prominent. Its biological pathway to improve IPF was mainly acted on the pathways in cancer, proteoglycans in cancer, and endocrine resistance, etc. CONCLUSIONS: This study preliminarily identified the various molecular targets and multiple pathways of Ligusticum wallichii to improve IPF.

Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy.

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl4)-induced fibrosis model. Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels, inflammatory cell infiltration and collagen deposition caused by CCl4. The increased expression of liver fibrosis markers, such as collagen 1, fibronectin, α-smooth muscle actin (α-SMA) and transforming growth factor-ß (TGF-ß), and inflammatory factors, such as chemokine (C-C motif) ligand 2 (MCP-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2 (ERK1/2)-protein kinase B (AKT) signaling pathways. Collectively, these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition, decreasing inflammatory reactions and bile acid accumulation, which provides insights into the mechanisms of herb-pair in improving liver fibrosis.

Physicochemical properties of polysaccharides from Ligusticum chuanxiong and analysis of their anti-tumor potential through immunoregulation.

We investigated the extraction, purification, physicochemical properties and biological activity of Ligusticum chuanxiong polysaccharides (LCXPs). Two polysaccharide fractions (Ligusticum chuanxiong [LCX]P-1a and LCXP-3a) were obtained by DEAE Sepharose™ Fast Flow and Sephacryl™S-300 high resolution column chromatography. The results showed that the molecular weight of LCXP-1a and LCXP-3a was 11.159 kDa and 203.486 kDa, respectively. LCXP-1a is composed of rhamnose, glucuronic acid, galacturonic acid, and glucose at a molar percentage of 0.52 : 1.88 : 1.06 : 95.36, But LCXP-3a has another molar percentage of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, arabinose, and fucose of 0.64 : 6.69 : 1.03 : 43.74 : 2.20 : 26.90 : 0.82 : 15.94 : 1.80. Both LCXP-1a and LCXP-3a could stimulate macrophages to produce NO, TNF-α, IL-6, and IL-12p70. Co-culturing macrophages and hepatocellular carcinoma cells showed that LCXP-1a and LCXP-3a inhibited the growth of HepG2 and Hep3B through immunoregulation. They arrested the cell cycle at the G0/G1 phase and promoted apoptosis. Moreover, there was no cytotoxicity to the hepatocyte cell line, LO2. We also noted that the immunomodulatory activity and anti-tumor activity of LCXP-3a were significantly better than those of LCXP-1a. Our data demonstrate that LCXP-3a is potentially a well-tolerated and effective immunomodulatory adjuvant cancer treatment.

Structural elucidation of an immunological arabinan from the rhizomes of Ligusticum chuanxiong, a traditional Chinese medicine.

In the present study, an immunological arabinan, LCP70-2A, was isolated from Ligusticum chuanxiong for the first time. The absolute molecular weight of LCP70-2A was determined to be 6.46 × 104 g/mol using the HPSEC-MALLS-RID method. The absolute configuration of arabinose in LCP70-2A was determined to be L-configuration. Physicochemical characterization revealed that LCP70-2A was a homogeneous polysaccharide and had a backbone of (1 â†’ 5)-linked α-L-Araf with terminal α-L-arabinose residues at position O-2 and O-3. Molecular conformation analysis showed that LCP70-2A was a branching polysaccharide with a compact coil chain conformation in 0.1 M NaCl solution. In addition, in vitro cell assays showed that LCP70-2A can activate macrophages by enhancing the phagocytosis and potentiating the secretion of immunoregulatory factors including NO, TNF-α, IL-6, and IL-1ß. Furthermore, LCP70-2A was proved to promote the production of ROS and NO using the zebrafish model, suggesting that LCP70-2A can be further developed as a candidate supplement for immunological enhancement.

Chemical constituents of Ligusticum chuanxiong and their anti-inflammation and hepatoprotective activities.

Ligusticum chuanxiong Hort is a famous health promoting plant cultivated in China, and widely consumed due to its various curative effects. To study the potential bioactive constituents from the rhizome of L. chuanxiong, a chemical investigation was thus performed. In present study, we report the isolation and identification of ten new compounds, including two coumarins (1-2), four lignans (3-6), and four phenols (7-10), along with five known compounds (11-15) from the rhizome of L. chuanxiong. The structures of these compounds were unambiguously established by HR-ESI-MS, UV, IR, CD, NMR spectral data and comparison to reported data. Meanwhile, the anti-inflammation and hepatoprotective activities of all these compounds were evaluated. The results show that compounds 5, 6 and 7 showed excellent inhibition of NO production in LPS-induced RAW 264.7 cells stronger than curcumin, and compounds 5, 7 and 9 exhibited greater hepatoprotective effect than that of bicyclol.

Fabrication of Ligusticum chuanxiong polylactic acid microspheres: A promising way to enhance the hepatoprotective effect on bioactive ingredients.

Ligusticum chuanxiong extract-polylactic acid sustained-release microspheres (LCE-PLA) are fabricated in this study for enhancing both duration and hepatoprotective efficacy of the main bioactive ingredients. LCE-PLA in vitro release, cytotoxicity and in vivo hepatoprotective effect were discussed to evaluate its efficiency and functionality. Results demonstrated that the optimal drug-loading rate and encapsulation efficiency of tetramethylpyrazine (TMP, the main active ingredient) were 8.19%, 83.72%, respectively. The LCE-PLA in vitro release of TMP showed prolong 5-fold and in vitro cytotoxicity declined 25.00% compared with naked LCE. After 6 weeks of in vivo intervention in high fat diet mice, both liver aspartate aminotransferase and alanine aminotransferase levels were higher in LCE-PLA group than LCE group. The above results indicated that TMP had a higher bioavailability of hepatoprotection when encapsulation of LCE-PLA was applied. The current study has provided a promising novel way to enhance the efficacy of short half-life ingredients.

Effects of Herbal Medicines on Pain Management.

Pain is an unpleasant sensory and emotional experience in many diseases and is often caused by intense or damaging stimuli. Pain negatively affects the quality of life and increases high health expenditures. Drugs with analgesic properties are commonly used to relieve pain, but these Western medications could be overwhelmed by side effects including tolerance and addiction. Herbal medicines may provide alternative measures for pain management. In this review paper, after introduction of Chinese medicine theory and treatment modality, emphasis is placed on the application of Chinese herbs and herbal formulations in pain management. Three of the most commonly used herbs, i.e., Corydalis yanhusuo, Ligusticum chuanxiong, and Aconitum carmichaeli, are reviewed. Subsequently, using this ancient medical remedy, Chinese herbal formulation in treating common medical conditions associated with pain, such as headache/migraine, chest pain, abdominal pain, low back pain, neuropathic pain, osteoarthritis, and cancer pain, is presented. Chinese herbal medicines could be considered as a complementary and integrative approach in the modern armamentarium in combating pain.

Ligusticum chuanxiong exerts neuroprotection by promoting adult neurogenesis and inhibiting inflammation in the hippocampus of ME cerebral ischemia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia, also known as stroke, can stimulate the proliferation and migration of endogenous neural stem cells (NSCS) in subventricular zone of the lateral ventricle and subgranularzone of the dentate gyrus in the adult hippocampus as a defense response to damage. However, the proliferation of endogenous NSCS is insufficient for central nervous system repair. Neurogenesis and anti-neuroinflammation are two important aspects for neuroprotection. Rhizome Ligusticum chuanxiong (LC), the dried rhizomes of Ligusticum striatum DC., has been widely used to treat stroke for over hundreds of years in Traditional Chinese Medicine. PURPOSE: of the study: Previous reports on pharmacological mechanism of LC mainly focus on the cerebral blood flow and thrombolysis. We aim to explore whether LC provides neuroprotective effect by increasing neurogenesis and inhibiting the IL-1ß, TNF-α and expressions of glial fibrillary acidic protein. MATERIALS AND METHODS: LC extract was delivered to microsphere-embolized (ME) cerebral ischemia Wister rats to examine its neuroprotection. Body weight, neurological scores, hematoxylin-eosin staining (HE), TUNEL assay were conducted for neurological damage. Neurogenesis was evaluated by assessing the expression of Doublecortin (DCX) and neurogenic differentiation1 (NeuroD1) through immunofluorescence staining. Western blot performed to measure the protein levels of growth associated protein-43(GAP-43), glial fibrillary acidic protein (GFAP). IL-1ß and TNF-α was detected by Elisa. RESULTS: LC alleviated pathomorphological change and apoptosis of neurons in the hippocampus caused by ME surgery. Furthermore, LC significantly increased the DCX in the DG of adult rat hippocampus at 14 days after surgery. A significant upregulation of GAP-43 compared to the ME after LC was administered. Besides, LC decreased pro-inflammatory cytokine (IL-1ß, TNF-α) and protein level of GFAP. CONCLUSION: The finding suggested that LC had the ability to protect neurons by promoting the endogenous proliferation of neuroblast and production of neural differentiation factor in rats after ischemia injury. Meanwhile, LC can anti-neuroinflammation, which is important for the treatment of neuron injury. Accordingly, LC perhaps a promising medicine for neuron damage therapy after cerebral ischemia.

Bioactivities of 3-Butylidenephthalide and n-Butylbenzene from the Essential Oil ofLigusticum jeholense against Stored-product Insects.

The essential oil extracted from roots and rhizomes of Ligusticum jeholense Nakai et Kitagawa was investigated for its chemical composition by GC-MS analysis, and evaluated for its contact toxicity and repellency against Tribolium castaneum and Lasioderma serricorne, along with some of its individual components. The essential oil was rich in aromatics (65.34%) with low molecular weight. Major components included sedanolide (33.95%), 3-butylidenephthalide (18.76%), spathulenol (8.90%) and myristicin (6.76%). The results of bioassays indicated that the essential oil of L. jeholense and 3-butylidenephthalide possessed significant repellent activities against T. castaneum at 2 and 4 h post-exposure. Meanwhile, 3-butylidenephthalide had potent contact toxicity against L. serricorne (LD50 = 13.64 µg/adult). The minor component n-butylbenzene in the oil was highly toxic to T. castaneum (LD50 = 23.99 µg/adult) and L. serricorne (LD50 = 7.86 µg/adult) in contact assays, but failed to repel these beetles at all testing concentrations. Spathulenol and myristicin exerted good insecticidal and repellent effects on the two target insects. This work suggests that the essential oil of L. jeholense has promising potential for development as natural insecticide or repellent to control pest damage in warehouses.

Bioactive butylphthalide derivatives from Ligusticum chuanxiong.

Seven new butylphthalide derivatives, ligusticumolide A-G (1-7), together with two known butylphthalide derivatives (8-9) were isolated from an ethanol extract of Ligusticum chuanxiong Hort. The structures of these derivatives were elucidated from analysis of 1D/2D NMR, UV, IR and HRESIMS data. The absolute configurations of these derivatives were determined by electronic circular dichroism (ECD) calculations and Mosher's method. Ligusticumolide A (1) and ligusticumolide B (2) are enantiomers that were obtained by chiral separation. Ligusticumolide C (3) and ligusticumolide D (4) are diastereomers. All of the compounds were evaluated for their hepatoprotective activity against N-acetyl-p-aminophenol-induced HepG2 cell injury. Compounds 4, 5, and 7-9 showed more significant hepatoprotective activity than that of the positive control drug (bicyclol) at a concentration of 10 µM (p < 0.01).

Nucleoside alkaloids with anti-platelet aggregation activity from the rhizomes of Ligusticum striatum.

Two new (1-2) and six known (3-8) nucleoside alkaloids were isolated from the rhizomes of Ligusticum striatum DC. Compounds 1 and 2 (liguadenosines A and B) were unusual N-10 substituted adenosine derivatives. Their structures were elucidated by extensive spectroscopic analyses and ECD calculation. Most of them significantly inhibited the abnormal increase in platelet aggregation induced by ADP at concentrations of 50 and 100 µM. Particularly, the inhibitory effect of 3 was equivalent to aspirin.

Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo.

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC50 values of 78.9 and 31.1 µM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 µM) compared to arbutin (20 µM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.

A systematic review on the rhizome of Ligusticum chuanxiong Hort. (Chuanxiong).

Chuanxiong Rhizome (called Chuanxiong, CX in Chinese), the dried rhizome of Ligusticum chuanxiong Hort, is an extremely common traditional edible-medicinal herb. As a widely used ethnomedicine in Asia including China, Japan and Korea, CX possesses ideal therapeutic effect on cardiovascular and cerebrovascular diseases, and is also used as a major ingredient in soups for regular consumption to benefit health. Based on the traditional perception, amounts of investigations on different aspects have been done for CX in the past decades. However, no literature systematic review about these achievements have been compiled. Herein, the aim of this review is to present the up-to-date information on the ethnobotany, ethnopharmacological uses, phytochemicals, pharmacological activities, toxicology of this plant to identify their therapeutic potential and directs future research opportunities. So far, about 174 compounds has been isolated and identified from CX, in which phthalides and alkaloids would be the main bioactive ingredients for its pharmacological properties, such as anti-cerebral ischemia, anti-myocardial ischemia, blood vessel protection, anti-thrombotic, anti-hypertensive, anti-atherosclerosis, anti-spasmodic, anti-inflammatory, anti-cancer, anti-oxidant, and anti-asthma effects. Even so, due to the incomplete standardized planting, unstable herbal quality, and outdated preparation techniques, the industrial progress of CX is still less developed.

Ferulic acid derivatives from Ligusticum chuanxiong.

Four new ferulic acid derivatives ligusticumacid A-C (1-3) and ligusticumaldehyde A (4), one new dimer ligusticumacid D (5), and two novel 8-8' lignans ligusticumacid E-F (6-7) were isolated from the rhizome of Ligusticum chuanxiong Hort. In particular, compounds 1-2, 5 were rarely phenylpropanoid phenolic acid dimers through different polymerization action in natural products. Their structures were established using UV, IR, HRESIMS, NMR data. The absolute configurations of 3 was determined by quantum ECD calculation and 4, 6-7 were determined by the ECD exciton chirality method. In addition, all compounds were evaluated for their neuroprotective effects on human neuroblastoma SH-SY5Y cell injury induced by H2O2. Compound 2 had a moderate neuroprotective activity and 7 had a weak neuroprotective activity on human neuroblastoma SH-SY5Y cell injury induced by H2O2 respectively.

Evaluation of antioxidant activities of ethanol extract from Ligusticum subjected to in-vitro gastrointestinal digestion.

The Rhizome of Ligusticum chuanxiong Hort, a traditional Chinese medicine, is widely used to treat cardiovascular diseases and attenuate oxidative stress. The main bioactive compounds including tetramethylpyrazine (TMP), polyphenols, ferulic acid have been reported to be responsible for these effects. This study was to evaluate the influence of Ligusticum chuanxiong extraction (LCE) in mimic gastrointestinal tract on antioxidant activity. The effects of gastric digestion group metabolic liquid on free radical scavenging followed as DPPH > ·O2- > ·OH, while the clearance effects of intestine digestion group expressed as ·O2-> ·OH > DPPH. Furthermore, the digested extraction promoted lower cellular antioxidant activity (CAA) with dose-response correlations. Gastrointestinal digestion increased the release of bound ferulic acids and polyphenols. Content of ferulic acid in gastric and intestinal metabolic solution increased from 6.07 mg/g to 9.33 mg/g and 14.17 mg/g. The free phenolic before and after digestion were 177.38 mg/g, 179.69 mg/g and 194.99 mg/g, respectively. The simulated gastrointestinal digestion of LCE promoted a significant increase in the free phenolic acids content, antioxidant activity and CAA.