Angelica glauca Edgew., a high-altitude Himalayan medicinal plant, is an important source of bioactive essential oil rich in phthalide derivatives. The present study investigated the influence of environmental conditions and extraction parameters on essential oil yield and chemical composition, with particular emphasis on Z-ligustilide. Essential oils obtained from roots collected across different altitudes revealed marked variations in yield and phytochemical profile, with plants growing at 3500-3800 m producing the highest concentration of Z-ligustilide (75.2%). The optimised essential oil exhibited broad-spectrum antimicrobial activity against both Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Candida species. Molecular docking studies further supported its therapeutic potential by demonstrating strong interactions with microbial target proteins, with binding affinities reaching approximately -6.9 kcal/mol. The predicted mechanisms of antimicrobial action include membrane disruption, interference with ATP production, and inhibition of biofilm formation, indicating a multi-target mode of action. Overall, these findings demonstrate that altitude-driven phytochemical variation combined with optimised extraction significantly enhances the quality and biological efficacy of A. glauca root oil, highlighting its potential as a natural antimicrobial agent for pharmaceutical and nutraceutical applications.

Vascular cognitive impairment (VCI) is a vast disease with chronic cerebral hypoperfusion (CCH) being the major driver. In our previous study, we have verified that Da ChuanXiong (DCX) formula could alleviate VCI, and obviously upregulate the decreased cerebral blood flow, indicating its potential benefits on vascular remodeling. This study aims to explore the pro-angiogenic and vasodilatory effects of DCX formula after CCH injuries, and clarify its pharmacodynamic substances and potential mechanisms. The rat model of CCH was established by bilateral common carotid artery occlusion. CD31[+] immunofluorescent staining and quail chorioallantoic membrane (qCAM) experiments were conducted to assess the angiogenic effect of DCX. Isolated vascular ring experiments and NO assay in qCAM were performed to evaluate the vasodilatory effect of DCX. Then we analyzed the chemical components absorbed in the blood of DCX under CCH conditions by UPLC-Q-TOF/MS, and further combined network pharmacology, molecular docking to predict the potential mechanisms and effective components. Western blot was performed in CCH rats to verify the possible mechanisms and in vitro pharmacodynamic verification experiment was conducted for innovative active ingredients in DCX. Our results revealed that DCX obviously increased the number of CD31[+] cells in the hippocampus and brain cortex of CCH rats, and significantly increased the vascular areas in qCAM. DCX significantly dilated the pre-constricted vascular ring and increased NO contents in qCAM. Besides, Senkyunolide A, Butylphthalide, Ferulic acid, Senkyunolide I, Levistilide A, Ligustilide, Senkyunolide H and Gastrodin were identified as the 8 major blood-absorbed compounds of DCX under CCH condition. Next, network pharmacology and molecular docking revealed NOS3 and PI3K/Akt signaling as the critical targets and pathway of DCX improving vascular remodeling against CCH injuries, which was further validated by western blot. Moreover, we firstly discovered that Senkyunolide A and Senkyunolide H could obviously promote cell migration and enhance the tube formation ability of HUVECs in vitro. Taken together, DCX formula effectively enhanced the angiogenesis and vasodilation via activating PI3K/Akt/eNOS signaling, which might be the important pathways for DCX promoting vascular remodeling against CCH injuries. Notably, Senkyunolide A and Senkyunolide H were firstly identified as innovative components responsible for the pro-angiogenic effects of DCX.

Ligustilide, a major bioactive phthalide in Angelica sinensis and Ligusticum chuanxiong, is pharmacologically potent but chemically labile. Its transformation behavior under stress conditions remains incompletely characterized. Herein, we employed an integrated high resolution liquid chromatography-mass spectrometry (LC-MS) and solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) approach to profile degradation products of ligustilide after thermal-oxidative stress (80 °C, air). Thirty transformation products were tentatively identified by LC-MS, including 11 monomers, 18 dimers, and 1 trimer, with 17 previously unreported degradation products that could not be matched in the SciFinder database, and volatile degradation fragments (e.g., butanal and phthalic anhydride) were tentatively identified by SPME-GC-MS. Based on the identification results, a comprehensive transformation network of ligustilide was constructed. Subsequently, the degradation of ligustilide under different stress conditions was studied by ultra-high performance liquid chromatography (UPLC), suggesting oxidative transformation as the predominant pathway and tentatively identifying distinct routes induced by acidic conditions and Fe[3+]. Degradation kinetics indicated rapid initial loss consistent with bimolecular reactions such as oxidation and dimerization. This work provides a comprehensive transformation network of ligustilide and advances the mechanistic understanding of its degradation behavior under multiple stress conditions.

The present study investigated the chemical composition, antimicrobial, insecticidal, and food preservation potential of Ligusticum chuanxiong CO2 oil (LCCO) standardised to a ligustilide content of ≥35%. The volatile composition of LCCO was characterised by GC-MS and found to be dominated by cis-ligustilide (63.3%), senkyunolide (15.8%), 3-butylidenephthalide (5.4%), and trans-neocnidilide (4.9%). In vitro antimicrobial activity was evaluated by disc diffusion and broth microdilution against six bacterial and five yeast reference strains. The largest inhibition zones were observed against Enterococcus faecalis (14.33 mm) and Staphylococcus aureus (13.67 mm). MIC50 values ranged from 0.064 mg/mL (Yersinia enterocolitica) to 3.492 mg/mL (Candida tropicalis), while MIC90 values ranged from 0.151 to 3.800 mg/mL. In situ vapour-phase antimicrobial activity was evaluated on pear, banana, white radish, and carrot at concentrations of 62.5-500 µL/L, demonstrating a clear concentration-dependent inhibitory effect across all tested food matrices and microorganisms. Insecticidal activity against Callosobruchus maculatus and Megabruchidius dorsalis was confirmed under fumigation conditions, with LC50 values of 17.50% and 20.99% and LC90 values of 83.10% and 87.60%, respectively. The effect of LCCO, applied alone and in combination with vacuum packaging, on the microbiological quality of fresh white radish was evaluated over 28 days of refrigerated storage at 4 °C. The combined treatment resulted in the lowest total viable count (2.75 log CFU/g) and coliform bacteria count (2.58 log CFU/g) on day 28. A total of 404 bacterial isolates were identified using MALDI-TOF MS Biotyper, comprising 22 species. Acinetobacter pittii was the predominant species (33%), followed by Pantoea agglomerans (7%) and Serratia nematodiphila (7%). No Pseudomonas species were recovered from the EO vacuum treatment. Overall, these findings demonstrate the potential of LCCO, particularly in combination with vacuum packaging, as a natural antimicrobial agent for the postharvest preservation of fresh white radish.

This study developed an efficient and sustainable extraction process for extracting ferulic acid (FA) and ligustilide (LIG) from Angelica sinensis Radix (ASR) using green natural deep eutectic solvents (NADESs) by machine learning optimization. After screening, L-proline/methylurea was identified as the optimal NADES system, and the genetic algorithm optimized back-propagation neural network (GA-BPNN) model demonstrated superior predictive performance over traditional methods (MSE = 1.7 × 10[5], R[2] = 0.9860). Under the optimized conditions (NADES volume fraction 67.44%, ultrasonic time 25.556 min, ultrasonic temperature 59.791 ℃, and solid-liquid ratio 7.610 mg/mL), the predicted extraction yield was 0.149, which closely matched the experimental yield of 0.151. Shapley Additive Explanations (SHAP) analysis further indicated that the NADES volume fraction was the most critical factor affecting extraction efficiency. Animals' experiments demonstrated that both FA and LIG significantly ameliorated neurological deficits and reduced cerebral infarct volume in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. To further elucidate the underlying antioxidant mechanism, Mendelian randomization (MR) analysis was employed, revealing a significant causal relationship between FA and superoxide dismutase (SOD) expression (P = 0.0265), but no significant association with heme oxygenase-1 (HO-1); LIG showed no significant association with either. These findings were corroborated in MCAO/R mice, FA administration significantly increased SOD levels in plasma. Collectively, the GA-BPNN-guided NADES combined with ultrasound assisted extraction (UAE) strategy significantly enhanced the extraction of bioactive compounds from ASR. Moreover, the integrated approach combining MR analysis with in vivo experiments provided converging evidence supporting the underlying specific antioxidant mechanism mediated by FA.

Angelica sinensis (Oliv.) Diels (A. sinensis), commonly known as Danggui, is a chemically complex medicinal plant widely used in East Asian medicine and reported to exert anti-inflammatory, antioxidant, immunomodulatory, hematopoietic, neuroprotective, vasoprotective, metabolic, and tissue-repair effects. This narrative translational review evaluates literature published up to May 2026 and reappraises A. sinensis through a constituent-specific and exposure-relevant framework, focusing on phthalides, ferulic acid-related phenolic acids, polysaccharides, and representative preparations. Phthalides are mainly associated with neurovascular protection, mitochondrial homeostasis, autophagy/mitophagy regulation, and anti-apoptotic responses, but their translational relevance is constrained by chemical instability and low oral exposure. Ferulic acid and related phenolic acids are more consistently linked to inflammatory attenuation, redox regulation, epithelial barrier protection, and metabolic stress responses; however, many in vitro studies use concentrations exceeding plausible free systemic exposure. Polysaccharides are most strongly associated with hematopoietic support, immune modulation, gut microbiota regulation, metabolic homeostasis, and microenvironmental remodeling, although structural heterogeneity limits cross-study comparability. Direct clinical evidence for single-herb A. sinensis remains limited, and most clinical signals derive from multi-herb formulas. Overall, this review highlights the importance of distinguishing constituent-specific mechanisms, exposure plausibility, and attribution directness when evaluating the translational potential of A. sinensis.

An analytical method to detect Angelica root constituents described in the Japanese Pharmacopoeia (scopoletin and ligustilide), Korean Pharmacopoeia (nodakenin, decursin, and decursinol angelate), Pharmacopoeia of the People's Republic of China (ferulic acid and ligustilide), and furocoumarins (psoralen, xanthotoxin, and bergapten) using liquid chromatograph-mass spectrometer with photodiode array detector was examined and applied to a dietary supplement containing Angelica Gigas Root. All target analytes were separated in reversed-phase mode using a phenylhexyl column at a column temperature of 45℃. Two detection wavelengths (250 and 340 nm) were set, and instrument detection limits (S/N ≥ 3) for all analytes were between 0.03 and 0.1 μg/mL. For confirmation of each compound, the mass spectrometer's selected ion monitoring conditions were optimized. The analytes, ferulic acid, nodakenin, psoralen, xanthotoxin, bergapten, decursin, and decursinol angelate, were detected in the dietary supplement via this analytical method.

In this study, Magnetic Hydrogen-bonded Organic Frameworks (MHOFs) were utilized for the first time to immobilize thrombin (THR) via physical adsorption, enabling efficient screening of THR inhibitors from Paeoniae Radix Rubra (Chishao, CS) and its herbal pair with Chuanxiong Rhizoma (CS-CX). Co-immobilization of THR and magnetic nanoparticles (MNPs) within HOF crystals yielded a biocomposite MNPs-THR@BioHOF-1, characterized by SEM, FTIR, XRD, and VSM. The HOF markedly improved THR's loading capacity (138 ± 0.12 μg/mg), immobilization efficiency (91.70 ± 0.08%), specific activity (53.19 ± 0.25 U/g), and stability (notable resistance to heat and organic solvents). Using UPLC-MS/MS, four THR inhibitors-albiflorin, benzoylpaeoniflorin, Z-ligustilide, and senkyunolide A-were rapidly identified from CS and CS-CX extracts, with IC50 values of 318.30 ± 2.32, 516.70 ± 1.90, 767.43 ± 13.75, and 713.43 ± 5.12 μM, respectively. Molecular docking further elucidated their binding interactions with THR. These results demonstrate that HOF-based enzyme immobilization is a promising strategy for rapid screening of active constituents in traditional Chinese medicine (TCM).

Fluorescein isothiocyanate (FITC)-labeled cyclooxygenase-2 (COX-2) immobilized chitosan (CS) coated Fe3O4 (FITC-COX-2-CS@Fe3O4, FCICFs) nanocomposites were accurately prepared by solvothermal and crosslinking methods, and employed as drug discovery platforms and fluorescent tracers to specifically screen and evaluate the activity of potential COX-2 inhibitors derived from Yaobitong capsules (YBTC). The FCICFs nanocomposites demonstrated a significant capacity for the selective recognition of positive compounds from artificial mixtures, indicating their substantial utility. Under optimal conditions, the prepared nanocomposites screened fourteen potential COX-2 inhibitors from YBTC, which were identified by UHPLC-MS/MS as tetrahydrocolumbamine, protopine, trahydocoptisine, yuanhunine, rotundine, tetrahydroberberine, thalictrimine, palmatine, dehydrocorydaline, mudanpioside D, astringin, nodakenin, paeoniflorin sulfite and ligustilide. The molecular docking analysis demonstrated a strong binding affinity between 14 small molecule ligands and the COX-2. Furthermore, the screened compounds exhibited significantly enhanced inhibitory activity against COX-2 compared to the YBTC crude extract. Fluorescence cell imaging results indicated that the screened compounds effectively inhibited synovial cell proliferation, suggesting their potential therapeutic efficacy in the treatment of rheumatoid arthritis (RA). The proposed methodology, integrating highly specific screening with in-situ visual imaging, established a robust platform for the efficient and selective screening of plant-derived biologically active molecules.

Angelica sinensis (Oliv.) Diels (A. sinensis), a perennial herb with a medicinal history spanning over two millennia, is widely recognized for its effects in nourishing blood, promoting circulation, regulating menstruation, and alleviating pain. As demonstrated by over 1572 articles published since 2016, research in this field has advanced rapidly. However, the most recent comprehensive review dates back to 2016, and lacks systematic coverage of pharmacological mechanisms, structure-activity relationships (SARs), and modern applications. As a result, much of the relevant knowledge has been fragmented across disciplines. This review addresses these gaps by providing a systematic synthesis of the botany, traditional uses, phytochemistry, pharmacology, safety, and applications of A. sinensis. Over 290 chemical constituents, which can be broadly categorized into volatile oils, organic acids, polysaccharides, phenylpropanoids, and flavonoids, have been identified from A. sinensisto date. Representative bioactive compounds, such as Z-ligustilide (Z-lig), ferulic acid, and angelica coumarin A, contribute significantly to its diverse biological activities. This review offers an in-depth, mechanism-based summary of its pharmacological properties, and places a particular emphasis on the SARs of key bioactive constituents. The scope of the review is further expanded to include emerging applications in functional foods, skincare, agriculture, and animal husbandry industries. This review integrates multidisciplinary advances to establish a comprehensive and mechanistically grounded framework. This framework aims in turn to guide evidence-based utilization, foster innovative applications, and support the sustainable global development of A. sinensis as a medicinal and functional resource. However, several challenges remain in current research. These include insufficient standardization of cultivation practices, limited high-quality clinical evidence, and the lack of internationally recognized quality standards. Future research should prioritize multicenter clinical trials, the elucidation of biosynthetic pathways, and the establishment of international quality standards in order to promote the sustainable global development of A. sinensis.