Search Results (45)

Dang Gui (Radix Angelica sinensis), a classic Chinese medicinal herb, is renowned for nourishing blood, promoting blood circulation, regulating meridians, and relieving pain, and widely used clinically for anemia, cancer, rheumatoid arthritis, ulcerative colitis, and other diseases. Studies have confirmed that Dang Gui and its major bioactive components (e.g., polysaccharides, ferulic acid, (Z)-ligustilide) exert diverse pharmacological activities including immunomodulation, neuroprotection, and hepatoprotection. Based on a systematic literature search, this review summarizes the traditional applications and main chemical constituents of A. sinensis, with a focused analysis of its immunomodulatory effects. Evidence shows that A. sinensis exerts bidirectional immunoregulation by improving immune organ indices, promoting the proliferation and activation of immune cells, including T/B lymphocytes (T/B cells), macrophages, and regulating cytokine secretion. Furthermore, it reviews its immunomodulatory mechanisms in immune-related diseases (e.g., cancer, aplastic anemia, chronic pain), analyzes its quality control standards from regulatory and pharmacopeial perspectives and summarizes relevant safety research. This review comprehensively integrates the immunoregulatory effects and underlying mechanisms of A. sinensis, aiming to provide a scientific basis for its future research and clinical application. Full article

Background/Objectives: Primary dysmenorrhea is a common gynecological disorder characterized by painful uterine contractions. Danggui Buxue Decoction (DBD) is used to treat menstrual irregularities, but its mechanism in primary dysmenorrhea remains unclear. This study investigated the efficacy of DBD against dysmenorrhea and its calcium signaling-related mechanism. Methods: DBD components were analyzed by UPLC–Orbitrap MS. Isolated uterine muscle strips precontracted with oxytocin (OT, 50 ng/mL) or KCl (60 mM) were used to assess the effects of DBD and its active compounds (Quercetin, Formononetin, Ononin, Ferulic acid, Senkyunolide I, Calycosin, Ligustilide, Calycosin-7-O-β-D-glucoside). Ca²⁺-dependent experiments, intracellular calcium release assays, and inhibitor treatments (Nifedipine, 2-APB) were performed to evaluate the involvement of L-type calcium channels and the IP₃R pathway. A primary dysmenorrhea model induced by estradiol benzoate and oxytocin was used to assess the analgesic effects, histopathology, inflammatory factors, and IP₃/Ca²⁺-related proteins and genes following DBD and Quercetin treatment. Results: A total of 161 compounds were identified in DBD. DBD and its eight active constituents relaxed OT (50 ng/mL) or KCl (60 mM)-induced uterine contractions, with Quercetin, Calycosin, and Ligustilide showing particularly prominent relaxant activity. These three compounds suppressed extracellular calcium influx and intracellular calcium release through the blockade of L-type calcium channels and IP₃R. In vivo, DBD and Quercetin alleviated pain, reduced inflammation, and decreased uterine Ca²⁺ and IP₃ levels in dysmenorrhea mice. Conclusions: DBD and its active component Quercetin promote uterine relaxation by lowering Ca²⁺ levels, which is achieved through suppression of L-type calcium channels and the IP₃/Ca²⁺ pathway. This contributes to their therapeutic action against primary dysmenorrhea. Full article

Objective: The objective is to investigate and optimize the β-cyclodextrin inclusion process for volatile oils in Ligusticum Chuanxiong–Vinegar cyperus rotundus based on Quality by Design (QbD) principles. Methods: First, ligustilide and α-cyperone were selected as inclusion process indicator components using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS). Single-factor experiments were conducted to preselect the inclusion speed based on ligustilide and α-cyperone content as evaluation criteria. Subsequently, using the inclusion rates of ligustilide and α-cyperone as evaluation criteria, a factorial design was employed to investigate the inclusion temperature, inclusion time, and the volume ratio of β-cyclodextrin solution to essential oil, thereby optimizing the inclusion process parameters. Finally, the inclusion process parameters were validated, and the inclusion rates were determined. The obtained inclusion complexes were characterized by microscopic analysis, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). Furthermore, phase dissolution studies and molecular docking were employed for confirmation. Results: The optimal process parameters were determined as follows: encapsulation speed of 300 rpm, β-cyclodextrin solution excess of 6, encapsulation time of 2.5~3 h, and encapsulation temperature of 30~35 °C. The encapsulation rates for ligustilide and α-cyperone in the resulting inclusion complex were 63.15~64.74% and 71.33~76.89%, respectively. Structural characterization confirmed the formation of the inclusion complex. Conclusions: This inclusion process is reliable and provides a reference for preparing β-cyclodextrin inclusion complexes of volatile oils in formulations containing the Chuanxiong–Vinegar cyperus rotundus drug pair. Full article

Angelica sinensis is susceptible to blue mold caused by Penicillium polonicum during storage. The metabolic mechanisms of O₃ as a fungicide in controlling blue mold caused by P. polonicum in A. sinensis remain unclear. This study investigated the effects of O₃ treatment on the physiology, pathology, and functional active ingredients of A. sinensis and analyzed its impact on metabolites and metabolic pathways associated with P. polonicum infection. The results indicated that O₃ inhibited the occurrence of blue mold, maintained the content of ferulic acid and ligustilide, and suppressed the quality deterioration of A. sinensis. Metabolomics analysis revealed that O₃ enhances antioxidant capacity by up-regulating the tricarboxylic acid (TCA) cycle and increasing resistance to fungal invasion by up-regulating the phenylpropanoid biosynthesis pathway. Collectively, O₃ treatment improves the quality of postharvest A. sinensis, which provides a theoretical foundation for the application of O₃ in fresh postharvest storage for A. sinensis. Full article

Cancer remains one of the leading global health challenges, with increasing resistance to conventional therapies hindering treatment efficacy. Ligustilide, a bioactive compound derived from Ligusticum chuanxiong, has garnered attention for its multifaceted pharmacological properties, including anti-inflammatory, neuroprotective, and anticancer effects. This review comprehensively examines Ligustilide and its isomer, (Z)-Ligustilide, focusing on their anticancer potential across various cancer types. Ligustilide exerts its therapeutic effects through multiple mechanisms, including inhibition of cell proliferation, induction of apoptosis, and modulation of autophagy. Additionally, (Z)-Ligustilide has been shown to enhance drug sensitivity and modulate epigenetic regulation, providing a novel approach to overcoming chemoresistance. Despite promising preclinical results, the precise molecular mechanisms, pharmacokinetics, and bioavailability of Ligustilide remain under investigation. Future research should focus on optimizing its therapeutic applications, exploring its synergy with other chemotherapeutic agents, and assessing its potential in personalized cancer therapies. This review offers an in-depth analysis of Ligustilide’s anticancer mechanisms, its role in overcoming drug resistance, and its potential as a novel therapeutic strategy in cancer treatment. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by dysregulated immunity, skin barrier dysfunction, and cutaneous microbiome dysbiosis. While current therapies face limitations, Thuja sutchuenensis essential oil (TEO) shows promise due to its multi-target potential. We sought to explore the beneficial effects of TEO and delve into its mechanistic actions in a mouse model of AD. We combined network pharmacology with in vivo validation to evaluate the therapeutic efficacy and mechanisms of TEO in an AD model, and confirmed network-predicted targets in an in vitro inflammatory cell model. In AD mice, TEO alleviated pruritus and epidermal hyperplasia, suppressed systemic IL-4/TNF-α and IgE, and partially normalized serum ALB, LDL-C, and HDL-C. Microbial diversity increased after treatment, although potentially pathogenic taxa (Arthrobacter sp. and Corynebacterium mastitidis) remained enriched. Machine-learning analysis indicated the highest predicted metabolic activity in CK controls, whereas the AD and TEO groups showed elevated pathogenic phenotype scores. Network pharmacology prioritized active compounds [(E)-ligustilide, senkyunolide A, 3-butylisobenzofuran-1(3H)-one, butylated hydroxytoluene, Z-buthlidenephthalide, and β-Myrcene] and core targets (TNF, PTPRC, CCR5, JAK1), implicating T-cell receptor signaling, Staphylococcus aureus infection, and STAT3 pathways. Docking and molecular dynamics supported strong, stable binding of major constituents to JAK1, and Western blotting confirmed TEO-mediated inhibition of the JAK1/STAT3 axis. TEO effectively alleviates atopic dermatitis symptoms by modulating immune responses and enhancing microbial diversity. It targets key signaling pathways, such as JAK1/STAT3, highlighting its potential as a therapeutic option for AD. Full article

Curcumin (CUR), atractylodin (ATD), α-mangostin (αMG), ethyl-p-methoxycinnamate (EPMC), ligustilide (LIG), and β-eudesmol (BEU) are commonly used in Thai traditional medicine formulations. This study evaluated the cytotoxic effects of these compounds in HepG2 liver cancer cells and ReNcell VM neural progenitor cells using the resazurin assay, as well as their potential for hERG inhibition in hERG-overexpressing HEK293 cells, utilizing the automated patch-clamp technique. αMG and CUR significantly reduced HepG2 cell viability (IC₅₀ = 5.5 and 21 µM, respectively). In undifferentiated ReNcell VM cells, αMG was the most potent inhibitor of cell viability (IC₅₀ = 2.1 µM), followed by CUR (IC₅₀ = 21.1 µM), while in differentiated ReNcell VM cells, only αMG exhibited significant neurotoxicity (IC₅₀ = 6.0 µM). Other compounds showed no significant effects on these cells. ATD, BEU, LIG, and EPMC demonstrated low inhibition of hERG channels (IC₅₀ = 26.4, 33.4, 37.3, and 53 µM, respectively), while CUR and αMG displayed weak inhibitory effects (IC50 > 100 µM). αMG may have cytotoxic effects on hepatocytes and neurons at concentrations much higher than when used as medicine or food supplements. At regular clinical doses, αMG, ATD, BEU, EPMC, LIG, and CUR are unlikely to cause significant side effects. However, if these compounds are considered for drug development, their potential effects on hERG channels should be carefully assessed to avoid possible cardiotoxicity. Pharmacokinetics, both preclinical and clinical studies, are necessary to understand the relationship between the plasma concentration profile of EPMC and its potential risks for hepatotoxicity, neurotoxicity, cardiotoxicity, and drug interactions. Full article

This study developed a rapid, non-destructive method combining near-infrared (NIR) spectroscopy with chemometric techniques (OPLS-DA, ANN, and PLS) to accurately identify the geographic origin and quantify six key chemical components of V. thibetica rhizomes. The results demonstrated that the combination of NIR spectroscopy, OPLS-DA, and ANN successfully and accurately distinguished V. thibetica from three distinct origins. Additionally, combining partial least squares (PLS) and NIR spectroscopy, the contents of chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, umbelliferone (7-hydroxycoumarin), senkyunolide I, and ligustilide measured by HPLC-UV were used as reference values to predict the contents of the six chemical components in V. thibetica, and spectral preprocessing methods optimized the model. The correlation coefficients of the final quantitative model for the contents of the six components in V. thibetica were between 0.7852 and 0.9538, the root mean square error of calibration (RMSEC) was between 0.0027 and 0.2530, and the root mean square error of prediction (RMSEP) was between 0.0031 and 0.4240. The results suggest that NIR spectroscopy combined with OPLS-DA and ANN can be used as a rapid and accurate method to evaluate the quality of V. thibetica herbs. Full article

Background: Temozolomide (TMZ) is the first-line therapy for glioblastoma (GBM), but its clinical efficacy is limited by its short half-life, poor brain targeting, adverse side effects, and the development of drug resistance. Ligustilide (LIG) has been shown to enhance blood-brain barrier permeability and reduce P-glycoprotein activity, thereby potentiating the synergistic effect of TMZ against GBM. Methods: The dual-drug-loaded nanoparticles encapsulating both TMZ and LIG (TMZ/LIG-NPs) were prepared using Poly (d,l-lactic-co-glycolide)-monomethoxy poly (ethylene glycol) (PLGA-mPEG). The physicochemical properties of the NPs, including particle size and zeta potential, were characterized. Cellular uptake of NPs was evaluated using flow cytometry and fluorescence staining. The pharmacokinetic profile and cytotoxicity of TMZ/LIG-NPs were compared to those of free TMZ and a mixture of TMZ and LIG in rat and glioma cells, respectively. Results: The mean particle size of TMZ/LIG-NPs was 117.6 ± 0.7 nm, with a zeta potential of −26.5 ± 0.4 mV. Cellular uptake of NPs was significantly higher than that of free drug in U251 cells. Encapsulation of TMZ in NPs significantly increased its half-life by 1.62-fold compared to free TMZ and significantly improved its pharmacokinetic profile. Moreover, the storage stability of the TMZ/LIG-NPs solution was extended to one month. The toxicity of TMZ/LIG-NPs to glioma cells C6 and U251 was markedly enhanced compared to the mixture of TMZ and LIG. Conclusions: The development of TMZ/LIG-NPs using PLGA-mPEG effectively enhanced the stability and efficacy of both TMZ and LIG. This dual drug-loaded nanoparticle system represents a promising strategy for glioblastoma therapy. Full article

Lomatium is a genus of 98 species, widely distributed in western North America. This work presents a chemometric analysis of the essential oils of seven species of Lomatium (L. anomalum, L. dissectum var. dissectum, L. multifidum, L. nudicaule, L. packardiae, L. papilioniferum, and L. triternatum var. triternatum) from the intermountain western United States (Oregon and Idaho). The essential oils were obtained by hydrodistillation and analyzed by gas chromatographic methods. Lomatium packardiae essential oil can be characterized as limonene-rich, L. anomalum is a species rich in sabinene and α-pinene, and L. multifidum essential oils were rich in myrcene, while L. dissectum var. dissectum essential oils were dominated by octyl acetate and decyl acetate, L. papilioniferum essential oils from western Idaho had high p-cymene and 2-methyl-5-(1,2,2-trimethylcyclopentyl)phenol concentrations, while those from Oregon had relatively high β-phellandrene and sedanenolide levels. The essential oils of L. triternatum var. triternatum were too variable to confidently assign a chemical type. The major components in the L. nudicaule essential oils were β-phellandrene (16.0–45.7%), (Z)-ligustilide (5.6–47.1%), (E)-β-ocimene (3.3–9.9%), and δ-3-carene (0.2–12.6%). The enantiomeric distributions of α-pinene, camphene, sabinene, β-pinene, limonene, and linalool were also utilized to discriminate between the Lomatium taxa. There are not enough consistent data to properly characterize L. triternatum var. triternatum or the Oregon L. papilioniferum essential oils. Additional research is needed to confidently describe the chemotype(s) of these species. Full article

Atherosclerosis (AS) is one of the major catalysts of ischemic cerebrovascular disease, and the death and disease burden from AS and its cerebrovascular complications are increasing. Z-ligustilide (Z-LIG) is a key active ingredient in Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. In this paper, we first introduced LIG’s physicochemical properties and pharmacokinetics. Then, we reviewed Z-LIG’s intervention and therapeutic mechanisms on AS and its cerebrovascular complications. The mechanisms of Z-LIG intervention in AS include improving lipid metabolism, antioxidant and anti-inflammatory effects, protecting vascular endothelium, and inhibiting vascular endothelial fibrosis, pathological thickening, and plaque calcification. In ischemic cerebrovascular diseases complicated by AS, Z-LIG exerts practical neuroprotective effects in ischemic stroke (IS), transient ischemic attack (TIA), and vascular dementia (VaD) through anti-neuroinflammatory, anti-oxidation, anti-neuronal apoptosis, protection of the blood-brain barrier, promotion of mitochondrial division and angiogenesis, improvement of cholinergic activity, inhibition of astrocyte proliferation, and endoplasmic reticulum stress. This paper aims to provide a basis for subsequent studies of Z-LIG in the prevention and treatment of AS and its cerebrovascular complications and, thus, to promote the development of interventional drugs for AS. Full article

Angelica sinensis is a perennial herbaceous species mainly cultivated in the Gansu, Yunnan, and Qinghai provinces of China, and its dried roots have been widely used for nourishing blood and harmonizing vital energy, largely relying on its bioactive compounds (e.g., alkylphthalides, polysaccharides, and flavonoids). In recent years, viral diseases have been suspected to be present in A. sinensis in field cultivation. In order to reveal the infection status and causes, a survey and the identification of viral diseases and their influence on the yield and quality of A. sinensis were conducted in four different counties of Gansu province. The results showed viral disease rates of ca. 21% to 37% for potato virus Y (PVY) and tomato mosaic virus (ToMV), as well as ca. 2.8- to 8.9-fold decreases in root yield on a unit-area basis; meanwhile, the contents of the main bioactive compounds (i.e., ferulic acid, ligustilide, and polysaccharides) were significantly lower in the virus-infected plants (VIPs) compared with the virus-free plants (VFPs); there were significant positive relationships of the viral disease rate with planting density and expression levels of the PVY-coat protein (CP) and ToMV-CP genes (p < 0.01). The above-mentioned observations indicate that it is necessary and urgent to take measures (e.g., controlling plant density, rational rotation, and using virus-free seedlings) to prevent the spread of plant viruses. Full article

Chlormequat chloride (CCC), as a commonly used plant growth regulator in the production of rhizomatous medicinal herbs, can effectively control the bolting phenomenon in Angelica sinensis, significantly increasing the yield of underground rhizomes (medicinal part). However, its specific effects on the intrinsic quality of Angelica sinensis, especially medicinal components, require further investigation. The objective of this study is to conduct a thorough examination of CCC residue and its influence on the yield and medicinal components of Angelica sinensis. By spraying different concentrations of CCC on Angelica sinensis, we systematically monitored the final yield of Angelica sinensis Radix (ASR) in each treatment group and the residual concentration of CCC in ASR. Using UPLC-QTOF-MS technology, we conducted an in-depth analysis of the metabolic profile of ASR. Subsequently, UFLC-MS/MS was employed to accurately quantify the changes in the content of nine key active components in ASR. The results of this study indicate that the application of CCC significantly improves the yield of ASR, with the best effect observed at 0.1 g/L, resulting in a yield increase of 24.8%. Meanwhile, the residual amount of CCC in ASR is positively correlated with the application concentration, with the residual levels as high as 7.12 mg/kg in the high-concentration treatment group. Metabolomic analysis preliminarily identified 21 chemical components in ASR, including four organic acids and 13 phthalides. It is worth noting that the quantitative analysis results indicate significant changes in active components such as butylphthalide, Z-ligustilide, and ferulic acid after the application of CCC. Specifically, high-concentration CCC significantly increased the content of butylphthalide and levistolide A, while low-concentration CCC significantly promoted the accumulation of coniferyl ferulate and senkyunolide A, accompanied by a significant decrease in Z-ligustilide and ferulic acidy. In conclusion, while CCC use can increase yield, the associated increase in residues and imbalanced composition ratios may threaten the quality and safety of ASR. Therefore, it is crucial to control the amount of CCC used rationally to balance yield enhancement and quality assurance. Full article

Angelica sinensis is an alpine medicinal plant that has been widely used as a general blood tonic and gynecological indications over 2000 years, which depend on the bioactive metabolites (e.g., volatile oils, organic acids, and flavonoids). Although the accumulation of these metabolites is significantly affected by the environmental factors (e.g., altitude, temperature, and sunshine) as found in previous studies, the regulatory mechanism of different lights has not been clearly revealed. Here, growth parameters, contents of bioactive metabolites, and expression levels of related genes were examined when A. sinensis was exposed to different white-light (WL) and UV-B radiation treatments. The results showed that the differences in growth parameters (e.g., plant height, root length, and plant biomass) and leaf tissue characteristics (e.g., leaf thickness, stomatal density and shape, and chloroplast density) were observed under different light treatments. The contents of Z-ligustilide and ferulic acid elevated with the increase of WL (50 to 150 µmol·m²/s) and maximized under the combination of WL-100 and UV-B (107 µW/m², UV-107) radiation, while the total flavonoids and polysaccharides contents, as well as in vitro antioxidant capacity, elevated with the increasing of WL and UV-B. mRNA transcripts encoding for the biosynthesis of volatile oils, ferulic acid, flavonoids, and polysaccharides were found to be differentially regulated under the different WL and UV-B treatments. These morphological, anatomical, and transcriptional changes are consistent with the elevated bioactive metabolites in A. sinensis under the combination of WL and UV-B. These findings will provide useful references for improving bioactive metabolite production via the cultivation and bioengineering of A. sinensis. Full article

Lung cancer is a malignant tumor with one of the highest morbidity and mortality rates in the world. Approximately 80–85% of lung cancer is diagnosed as non-small lung cancer (NSCLC), and its 5-year survival rate is only 21%. Cisplatin is a commonly used chemotherapy drug for the treatment of NSCLC. Its efficacy is often limited by the development of drug resistance after long-term treatment. Therefore, determining how to overcome cisplatin resistance, enhancing the sensitivity of cancer cells to cisplatin, and developing new therapeutic strategies are urgent clinical problems. Z-ligustilide is the main active ingredient of the Chinese medicine Angelica sinensis, and has anti-tumor activity. In the present study, we investigated the effect of the combination of Z-ligustilide and cisplatin (Z-ligustilide+cisplatin) on the resistance of cisplatin-resistant lung cancer cells and its mechanism of action. We found that Z-ligustilide+cisplatin decreased the cell viability, induced cell cycle arrest, and promoted the cell apoptosis of cisplatin-resistant lung cancer cells. Metabolomics combined with transcriptomics revealed that Z-ligustilide+cisplatin inhibited phospholipid synthesis by upregulating the expression of phospholipid phosphatase 1 (PLPP1). A further study showed that PLPP1 expression was positively correlated with good prognosis, whereas the knockdown of PLPP1 abolished the effects of Z-ligustilide+cisplatin on cell cycle and apoptosis. Specifically, Z-ligustilide+cisplatin inhibited the activation of protein kinase B (AKT) by reducing the levels of phosphatidylinositol 3,4,5-trisphosphate (PIP₃). Z-ligustilide+cisplatin induced cell cycle arrest and promoted the cell apoptosis of cisplatin-resistant lung cancer cells by inhibiting PLPP1-mediated phospholipid synthesis. Our findings demonstrate that the combination of Z-Ligustilide and cisplatin is a promising approach to the chemotherapy of malignant tumors that are resistant to cisplatin. Full article