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Cholangiocarcinoma (CCA) is one of the most aggressive cancers with a poor prognosis. Current treatment strategies involve hepatobiliary surgery, chemotherapy, radiotherapy, and supportive care; however, the success of these treatments remains limited. Therefore, this study investigated the potential of Atractylodes lancea (Thunb) D.C. (AL) in limiting the progress of CCA by targeting the expression of cancer-related genes involved in immune responses and circulating tumor cells. The study was part of Phase 2A clinical trial in advanced-stage intrahepatic iCCA (iCCA) patients: Group 1 (n = 16) received low-dose AL (capsule formulation of the standardized extract of AL: CMC-AL) with standard supportive care, Group 2 (n = 16) received high-dose AL with standard supportive care, and Group 3 (n = 16) received standard supportive care alone. Venous whole blood samples (EDTA, 5 ml) were collected from each patient on Day 1 and Day 90 and the non-CCA subjects (n = 16) on Day 1. Fifty-nine samples (48 and 11 samples for Day 1 and Day 90, respectively) were processed for total RNA isolation. Gene expression was evaluated using reverse transcription followed by a PCR array. Regardless of dosage, gene expression patterns in the AL-treated groups closely resembled those of the healthy subjects. Specifically, cancer-associated genes, including VEGF-A , NR4A3 , Ki-67 , and EpCAM , were significantly down-regulated. Additionally, the expression levels of immune-related genes were modulated in AL-treated patients. The treatment groups exhibited lower levels of the pro-inflammatory cytokine IL-6 , increased expression of the anti-inflammatory cytokine IL-10, and cell-mediated immune-related molecules such as CTLA4 and PFR1 . These findings suggest the potential of AL for iCCA treatment. However, additional studies are required to confirm the correlation between gene and protein expression profiles, as well as CTCs profile.

Background A recent phase 2A clinical study of Atractylodes lancea (Thunb.) DC. (AL) in patients with advanced-stage intrahepatic cholangiocarcinoma (iCCA) demonstrated significant reduction of the risk of tumor progression and mortality with a dose ranging from 1,000 to 2,000 mg. The present study aimed to determine the potential dosage regimen of AL for further phase 2B clinical study. Methods Plasma-concentration time profiles of total AL bioactivity and clinical efficacy in patients with advanced-stage iCCA were obtained from Phase 2 A study. The population pharmacokinetic (pop-PK) model was developed. The pop-PK model and Monte-Carlo (MC) simulation, in conjunction with maximum concentration of AL (C max ) as a cut-off criterion, was performed and validated with clinical data. The optimal model was used to simulate further dosage regimens and clinical efficacy of AL. Results The pop-PK properties of total AL bioactivity were best described by a compartmental model with zero-order absorption (without delay) and linear clearance. None of the investigated covariates improved model accuracy.The developed pop-PK with MC simulations following once-daily dosing of 1,000 mg and 2,000 mg adequately predicted the clinical efficacy (tumor progression and mortality). The once-daily dose of 2,500 mg is recommended for further phase 2B clinical study due to its relatively high efficacy on tumor progression inhibition (73%) and mortality rate reduction (71%) without excessive number of the administered capsules (23 capsules) and low risk of toxicities (<5%). Conclusions The applied pop-PK model with MC simulation, along with the appropriate cut-off pharmacokinetic parameters, can be used as a potential tool for supporting dosage prediction and selection for clinical studies, and thus reducing the rate of drug development failures. Trial registration www.thaiclinicaltrials.org , WHO ICTRP search, TCTR20210129007 , Registed 29 January 2021.

Atractylodes lancea is an important source of traditional Chinese medicines. Sesquiterpenoids are the key active compounds in A. lancea, and their presence determines the quality of the material. Hairy hoot (HR) culture is a potential method to produce medicinally active compounds industrially; however, the induction and metabolic profiling of A. lancea HR have not been reported. We found that optimal induction of A. lancea HR was achieved by Agrobacterium rhizogenes strain C58C1 using the young leaves of tissue culture seedlings in the rooting stage as explants. Ultra-performance liquid chromatography-tandem mass spectrometric analyses of the chemical compositions of HR and normal root (NR) led to the annotation of 1046 metabolites. Over 200 differentially accumulated metabolites were identified, with 41 found to be up-regulated in HR relative to NR and 179 down-regulated in HR. Specifically, atractylodin levels were higher in HR, while the levels of β-eudesmol and hinesol were higher in NR. Metabolic pathway analyses showed a significant difference in metabolites of the shikimate acid pathway between HR and NR. Five A. lancea compounds are potential biomarkers for evaluation of HR and NR quality. This study provides an important reference for the application of HR for the production of medicinally active compounds.Key points• We established an efficient protocol for the induction of HR in A. lancea• HR was found to have a significantly higher amount of atractylodin than did NRs• Metabolic pathway analyses showed a significant difference in metabolites of the shikimate acid pathway between HR and NR

Atractylodes macrocephala (A.M.) is a traditional Chinese medicinal and edible herb renowned for its spleen-tonifying, dampness-resolving, diuretic, and antiperspirant properties. Its primary bioactive constituents are terpenoids, which have demonstrated anti-inflammatory, antitumor, and immunomodulatory activities. However, transcriptomic studies focusing on terpenoid biosynthesis in A.M. from different geographical origins remain limited. To investigate the molecular mechanisms underlying differential sesquiterpenoid production, we performed transcriptome sequencing on samples collected from four distinct regions in China. Sesquiterpenoid biosynthesis predominantly proceeds through the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways. Comparative analysis revealed four key enzyme-encoding genes—HMGCR, ISPF, GCPE, and FDPS—whose differential expression patterns were further validated by quantitative real-time PCR (qRT-PCR). Samples from Shaanxi exhibited the highest upregulation of biosynthetic genes and the greatest enrichment of terpene-related metabolites, suggesting enhanced pharmacological potential. In contrast, samples from Fujian, Anhui, and Hebei displayed relatively lower activity, with only FDPS upregulated in the Hebei sample. High-performance liquid chromatography (HPLC) quantification confirmed regional differences in the levels of major terpenoids—including atractylodin, atractylenolide I, and atractylenolide III—which correlated well with the observed gene expression profiles. This study compared conspecific A.M. from different geographical regions and further revealed that the variation in terpenoid metabolites is closely related to environmental factors. These findings provide a theoretical basis for the further discovery of functional genes and offer important implications for the quality control of A.M.

Atractylenolides, comprising atractylenolide I, II, and III, represent the principal bioactive constituents of Atractylodes macrocephala, a traditional Chinese medicine. These compounds exhibit a diverse array of pharmacological properties, including anti-inflammatory, anti-cancer, and organ-protective effects, underscoring their potential for future research and development. Recent investigations have demonstrated that the anti-cancer activity of the three atractylenolides can be attributed to their influence on the JAK2/STAT3 signaling pathway. Additionally, the TLR4/NF-κB, PI3K/Akt, and MAPK signaling pathways primarily mediate the anti-inflammatory effects of these compounds. Atractylenolides can protect multiple organs by modulating oxidative stress, attenuating the inflammatory response, activating anti-apoptotic signaling pathways, and inhibiting cell apoptosis. These protective effects extend to the heart, liver, lung, kidney, stomach, intestine, and nervous system. Consequently, atractylenolides may emerge as clinically relevant multi-organ protective agents in the future. Notably, the pharmacological activities of the three atractylenolides differ. Atractylenolide I and III demonstrate potent anti-inflammatory and organ-protective properties, whereas the effects of atractylenolide II are infrequently reported. This review systematically examines the literature on atractylenolides published in recent years, with a primary emphasis on their pharmacological properties, in order to inform future development and application efforts.

The rhizome of Atractylodes lancea (RAL) is a well-known Chinese herbal medicine (CHM) that has been applied in clinical settings for thousands of years. In the past two decades, cultivated RAL has gradually replaced wild RAL and become mainstream in clinical practice. The quality of CHM is significantly influenced by its geographical origin. To date, limited studies have compared the composition of cultivated RAL from different geographical origins. As essential oil is the primary active component of RAL, a strategy combining gas chromatography-mass spectrometry (GC-MS) and chemical pattern recognition was first applied to compare the essential oil of RAL (RALO) from different regions in China. Total ion chromatography (TIC) revealed that RALO from different origins had a similar composition; however, the relative content of the main compounds varied significantly. In addition, 26 samples obtained from various regions were divided into three categories by hierarchical cluster analysis (HCA) and principal component analysis (PCA). Combined with the geographical location and chemical composition analysis, the producing regions of RAL were classified into three areas. The main compounds of RALO vary depending on the production areas. Furthermore, a one-way analysis of variance (ANOVA) revealed that there were significant differences in six compounds, including modephene, caryophyllene, γ-elemene, atractylon, hinesol, and atractylodin, between the three areas. Hinesol, atractylon, and β-eudesmol were selected as the potential markers for distinguishing different areas by orthogonal partial least squares discriminant analysis (OPLS-DA). In conclusion, by combining GC-MS with chemical pattern recognition analysis, this research has identified the chemical variations across various producing areas and developed an effective method for geographic origin tracking of cultivated RAL based on essential oils.

Atractylodes macrocephala Koidz. has been used as an invigorating spleen drug for eliminating dampness and phlegm in China. According to recent researches, different processing methods may affect the drug efficacy, so we collected A. macrocephala from the Zhejiang Province, produced with different processing methods, crude A. macrocephala (CA) and bran-processed A. macrocephala (BA), then analyzed its essential oils (EOs) by GC/MS. The results showed 34 components representing 98.44% of the total EOs of CA were identified, and 46 components representing 98.02% of the total EOs of BA were identified. Atractylone is the main component in A. macrocephala. Compared with CA, BA has 46 detected compounds, 28 of which were identical, and 6 undetected compounds. Pharmacodynamic results revealed that the EOs of CA and atractylone exhibited more effective anticancer activity in HepG2, MCG803, and HCT-116 cells than the EOs of BA; while the EOs of BA exhibited simple antiviral effect on viruses H3N2, both the EOs and atractylone show anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in ANA-1 cells.

This study aimed to evaluate the stability and quality enhancement of Acorus tatarinowii and Atractylodes lancea volatile oils (ATaAL-VO) and their β -cyclodextrin encapsulated and Pickering emulsion forms under ozone exposure. Under an ozone environment, ATaAL-VO were subjected to three treatments: raw oil, β -cyclodextrin encapsulated oil, and pickering emulsion. Peroxide values were quantified. GC-MS was employed to identify compositional variances, while t-tests were used to identify compounds with significant quantitative differences. PCA charts were generated using OmicShare, and line diagrams were created with Rmisc and reshape2. OmicShare was also utilized to construct Upset diagrams for filtering qualitative differential compounds, and charts illustrating newly formed and disappeared qualitative differential compounds were composed. Principal compounds’ box diagrams were crafted through reshape2 and ggplot2. The β -cyclodextrin and pickering emulsion groups exhibited lower oxidation levels compared to the original oil group after ozone exposure. The pickering emulsion and β -cyclodextrin encapsulation groups both demonstrated a marked improvement in the stability of the majority of volatile components. The stability and quality of ATaAL-VO can be markedly enhanced through β -cyclodextrin encapsulation or Pickering emulsion preparation, with the latter offering distinct advantages.

Atractylodes chinensis (DC.) Koidz. (AK) is a kind of medicinal plant in the Asteraceae family, and its dried rhizomes have the functions of drying dampness, strengthening the spleen, dispelling wind and cold, and brightening the eyes. However, there remains insufficient development and utilization of other portions of the plant. To reveal the chemical characteristics and bioactivity potential of different AK parts, this study adopted UPLC-QE-MS/MS-based widely targeted metabolomics to analyze the metabolic components in ethanol extracts of AK rhizomes, fibrous roots, stems and leaves, flowers, and seeds. We then compared the antioxidant activities of these AK parts. The results showed that the highest ethanol extraction rate was from the rhizomes, while the flowers showed the strongest antioxidant activity. A total of 165 metabolites were categorized into seven major categories that included organic acids, flavonoids, and coumarins. Among these, organic acids were found with higher content in stems and leaves, fibrous roots, and seeds, while flavonoids were higher in flowers. This study explored the chemical composition and preliminary bioactivities of different AK parts based on widely targeted metabolomics. The results confirmed that the non-medicinal AK parts have high utilization values, and provided a scientific basis for the further development and utilization of this promising medicinal plant.

Polysaccharides derived from Atractylodes chinensis (DC.) Koidz. (ACP), a traditional Chinese medicine, were extracted and analyzed for their structural characteristics and anti-gouty nephropathy (GN) activity. Sprague-Dawley (SD) rats were divided into six groups: control, model, positive control, and three treatment groups (ACP-60-L, ACP-60-M, and ACP-60-H). Treatment significantly reduced inflammatory responses and renal damage, as evidenced by decreased levels of uric acid (UA), creatinine (Cr), and blood urea nitrogen (BUN), alongside modulation of NOD-like receptor protein 3 (NLRP3) expression in renal tissues. ACP-60 was fractionated into three polysaccharides, including ACP-60-A (Mw 9.18 kDa), ACP-60-B (Mw 58.21 kDa), and ACP-60-C (Mw 109.01 kDa) using DEAE-52 cellulose column chromatography. Monosaccharide analysis revealed that ACP-60-A predominantly comprised fructose (Fru) and glucose (Glc), ACP-60-B contained rhamnose (Rha), galactose (Gal), Fru, and mannose (Man), and ACP-60-C included Man, Gal, Rha and xylose (Xyl). In vitro studies using HK-2 cells confirmed the anti-GN activity of all three fractions, with ACP-60-A demonstrating the highest efficacy. Structural elucidation of ACP-60-A identified its main glycosidic linkages as a →1)-β-Fruf-(2→ backbone with α-Glcp-(1→ and β-Fruf-(2→ branches. The underlying mechanism of ACP-60-A’s anti-GN activity is associated with inhibition of the NLRP3 inflammasome signaling pathway, suppression of downstream inflammatory factor release, and downregulation of NLRP3, ASC, and Caspase-1 protein expression. Further studies demonstrated that the superior activity of ACP-60-A is attributable to its lower molecular weight, specific monosaccharide composition, and unique glycosidic bond arrangement. ACP-60-A shows potential for increased anti-GN efficacy through purification or modification, laying the groundwork for developing novel therapeutic agents for GN.