OBJECTIVE: Aloin, the main active component in Aloe vera (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism. METHODS: We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo. RESULTS: Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo. CONCLUSION This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization. Please cite this article as: Chen YN, Lu JY, Gao CF, Fang ZR, Zhou Y. Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis. J Integr Med. 2025; 23(2): 195-208.
Lung Neoplasms/metabolism* ; Humans ; Animals ; Cell Line, Tumor ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Macrophages/drug effects* ; Emodin/analogs & derivatives* ; Metallothionein/genetics* ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Receptors, Glucocorticoid/genetics*

To evaluate the hepatotoxicity risks of physcion on the basis of the bilirubin metabolism mediated by glucuronidation of UDP-glucuronosyltransferases 1A1(UGT1A1 enzyme). The monomers were added into the rat liver microsomes to test the hepatotoxicity by using bilirubin as UGT1A1 enzyme substrate, with apparent inhibition constant K_i as the evaluation index. Liver microsome incubation in vitro was adopted to initiate phase Ⅱ metabolic reaction and investigate the inhibitory effect of physcion. Then the phase Ⅰ and Ⅱ metabolic reactions were initiated to investigate the comprehensive inhibition of metabolites and prototype components. The results showed that when only the phase Ⅱ reaction was initiated, physcion directly acted on the UGT1A1 enzyme in a prototype form, exhibited weak inhibition and the inhibition type was mixed inhibition; When the phase Ⅰ and Ⅱ reactions were initiated simultaneously, the inhibitory effects of physcion on UGT1A1 enzyme became strong and the inhibition type was mixed inhibition, suggesting that physcion had phase Ⅰ and Ⅱ metabolic processes, and the metabolites had strong inhibitory effect on UGT1A1 enzyme. This experiment preliminarily proved that the metabolites of physcion may be the main components to induce hepatotoxicity.
Animals ; Chemical and Drug Induced Liver Injury ; Emodin ; analogs & derivatives ; toxicity ; Glucuronosyltransferase ; metabolism ; Kinetics ; Microsomes, Liver ; drug effects ; Rats

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-β-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg, i.p.) on sepsis. Cytokines including TNF-α, IL-1β and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg, i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 μg·mL) significantly decreased the TNF-α, IL-1β and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 μg·mL (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Emodin ; administration & dosage ; analogs & derivatives ; Glucosides ; administration & dosage ; Humans ; Interleukin-1beta ; genetics ; immunology ; Interleukin-6 ; genetics ; immunology ; Interleukin-8 ; genetics ; immunology ; Macrophages ; drug effects ; immunology ; Male ; Mice ; Mice, Inbred ICR ; RAW 264.7 Cells ; Rumex ; chemistry ; Sepsis ; drug therapy ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVETo explore the effect of a novel emodin derivative E19 on proliferation inhibition and apoptosis induction of human chronic myelogenous leukemia (CML) cell line K562 and imatinib-resistant CML cell line (K562/G01), and to clarify the involved mechanisms.

METHODSMTT and colony formation test were used to detect the cell proliferation. Apoptotic induction effects were examined by DAPI staining method and DNA ladder assay. Western blot was performed to detect the changes of P210(Bcr-Abl) protein.

RESULTSThe emodin derivative E19 could efficiently inhibit proliferation and induce apoptosis in K562 and K562/G01 cells. IC50 of K562 cells and IC50 of K562/G01 cells were (1.20 ± 0.19) µmol/L and (1.22 ± 0.16) µmol/L, respectively. DNA fragmentation in K562 cells and K562/G01 cells confirmed that the E19 induced apoptosis in dose-dependent manner. Western blot showed that emodin derivative inhibited phosphorylation of P210 protein in K562 cells and K562/G01 cells and down-regulated the expression level of P210 in dose- and time-dependent manners.

CONCLUSIONThe emodin derivative E19 can efficiently inhibit growth and induce apoptosis of K562 cells and K562/G01 cells, while the inhibition of phosphorylation of P210 protein and down-regulation of P210 protein expression may be involved in these processes.

Apoptosis ; drug effects ; Cell Proliferation ; Down-Regulation ; Drug Resistance, Neoplasm ; Emodin ; analogs & derivatives ; pharmacology ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; pharmacology ; K562 Cells ; drug effects ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; pathology ; Phosphorylation

Untargeted metabolomics analysis of rhubarb and stewed rhubarb samples shows that the determined samples clearly clustered in to two groups, indicating that the processing procedures caused changes in the composition and/or content of components in rhubarb. Ten components were identified by UHPLC-Q-TOF-MS/MS and references, which intensity declined in rhubarb after processing. Targeted metabolomics analysis of rhubarb and stewed rhubarb samples indicated that aloe-emodin, rhein, emodin and physcion were detected with lower intensity in stewed rhubarb samples than in rhubarb samples. Metabolomics analysis of rhubarb and stewed rhubarb indicated the various components of rhubarb changed after processing.
Anthraquinones ; analysis ; Chromatography, High Pressure Liquid ; Emodin ; analogs & derivatives ; analysis ; Food Handling ; methods ; Food Preservation ; methods ; Metabolomics ; methods ; Multivariate Analysis ; Principal Component Analysis ; Rheum ; chemistry ; metabolism ; Tandem Mass Spectrometry

OBJECTIVEThe stable quality of Chinese herbal medicines is a critical factor for their reliable clinical efficiency. An improved liquid-liquid extraction procedure and a liquid chromatographic method were developed to simultaneously analyze five anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) in a Chinese traditional hospital preparation, Fuyankang mixture, in order to quantitatively control its quality in a more effective way.

METHODSA more economical and repeatable extraction procedure based on conventional liquid-liquid extraction technique was developed and used to extract five marker components in Fuyankang mixture. These anthraquinones were separated in less than 20 min on a C18 column with methanol and 0.1% phosphoric acid (88:12, v/v) as mobile phase. The method was validated for specificity, precision, spiked recovery and stability.

RESULTSCompared to conventional liquid-liquid extraction, the improved liquid-liquid extraction was found to be more effective for simultaneous extraction of anthraquinones from an aqueous Chinese herbal preparation, especially for hydrophobic compounds. The improved extraction method was successfully applied to determine the content of five marker components in Fuyankang mixture by the means of reverse phase high-performance liquid chromatography.

CONCLUSIONThe improved extraction procedure may be suitable for routine quality control of Fuyankang mixture and other traditional preparations at city-level hospitals in China.

Anthraquinones ; analysis ; Chromatography, High Pressure Liquid ; methods ; Chromatography, Reverse-Phase ; methods ; Drugs, Chinese Herbal ; analysis ; Emodin ; analogs & derivatives ; analysis

The aim of this study was to explore the inhibitory effect of newly synthesised emodin derivatives on the proliferation of leukemia cell lines and to select the most effective one from these emodin derivatives for further research. Emodin derivatives were synthesized by modifying the structure of emodin. MTT method was used to detect the proliferative inhibition in leukemia cell lines treated with emodin derivatives. The results showed that the half inhibitory concentration (IC50) for K562 cells treated with emodin derivatives E10-19 for 48 h was 0.84 - 12.01 µmol/L. E19 displayed the best anti-proliferative activity, while E16 and E17 did not show effects on K562 cells. Emodin derivative E19 was chosen for treating U937, NB4, Molt-4 and CA-46 cells, their IC50 for 48 h were 0.85, 0.9, 0.76, 0.8 µmol/L respectively. The IC50 of E19 for LQ2 cells was 3.60 µmol/L, and the IC50 range of E19 for normal human peripheral blood mononuclear cells at 48 h was 4.01 - 4.78 µmol/L. It is concluded that emodin derivative E19 can strongly inhibit the growth of leukemia cells and its inhibiting effect on proliferation of leukemia cells has a certain specificity. The specific mechanism of E19 anti-leukemia effect should be further studied.
Cell Proliferation ; drug effects ; Emodin ; analogs & derivatives ; pharmacology ; Humans ; K562 Cells ; Leukemia ; pathology

OBJECTIVETo establish a quality evaluation method, quantitative analysis of multi-component with a single-marker (QAMS) to determine the contents of four rhubarb anthraquinones in Sanhuang tablets.

METHODEmodin was used as the internal reference substance, the relative correlation factors (RCF) of rhein, chrysophanol and physcion to emodin were calculated and evaluated. The contents of these four anthraquinones were determined by the external standard method and QAMS, respectively. Rationality, feasibility and repeatability of the QAMS method was verified by comparing the results obtained from the two different methods.

RESULTRCFs of rhein, chrysophanol and physcion to emodin against Sanhuang tablets were 1.13, 1.46 and 1.01, respectively, indicating good reproducibilities. The two methods did not show significant difference in results.

CONCLUSIONThe QAMS method can be used a new quality assessment model for quantity of anthraquinones in Sanhuang tablets.

Anthraquinones ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; Emodin ; analogs & derivatives ; analysis ; Reproducibility of Results ; Rheum ; chemistry ; Tablets ; Technology, Pharmaceutical ; methods

OBJECTIVETo detect absorbed bioactive compounds of the water extract whose pharmacodynamic effect was craniocerebral protection for quality control assessment.

METHODSAnthraquinones in water extract of rhubarb (WER), in cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI) and in ipsilateral cortex of TBI rats following oral WER were respectively explored by ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method developed in the present study. The effects of anthraquinones absorbed into injured cortex on superoxidase dismutase (SOD) activity in TBI rats were detected. The antioxidative anthraquinones absorbed into target organ were evaluated for quality control of WER.

RESULTSAnthraquinones in WER were aloe-emodin, rhein, emodin, chrysophanol, and physcion. Only the last anthraquinone was found in CSF and in ipsilateral cortex under this chromatographic condition. Physcion increased SOD activity in TBI rats significantly.

CONCLUSIONSPhyscion was the main active compound of rhubarb against craniocerebral injury via antioxidant pathway. According to our strategy, the exploration of physcion suggested the possibility of a novel quality control of WER in treating TBI injury.

Absorption ; drug effects ; Animals ; Anthraquinones ; cerebrospinal fluid ; chemistry ; Biological Products ; analysis ; cerebrospinal fluid ; chemistry ; Brain Injuries ; drug therapy ; pathology ; Chromatography, Liquid ; instrumentation ; methods ; Emodin ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Humans ; Limit of Detection ; Linear Models ; Male ; Plant Extracts ; chemistry ; Quality Control ; Rats ; Rats, Sprague-Dawley ; Reference Standards ; Reproducibility of Results ; Rheum ; chemistry ; Water ; chemistry

OBJECTIVETo study the chemical constituents of Dolomiaea souliei.

METHODVarious chromatographic techniques were adopted to separate the constituents, and the spectrum analysis was made to identify their structures.

RESULTSeventeen compounds were isolated and identified as: dehydrocostus lactone (1), costunolide (2), mokko lactone (3), santamarine(4), reynosin (5), 4alpha-hydroxy-4beta-methyldihydrocostol (6), sulfocostunolide A (7), beta-costic acid (8), beta-cyclocostunolide (9), vladinol A (10), ursolic acid (11), betulinic acid (12), betulin (13), dibutyl terephthalate (14), dibutyl phthalate (15), uridine (16), and emodin (17).

CONCLUSIONCompounds 6-9 and 12-17 were obtained from this genus for the first time, and compound 11 was obtained from this plant for the first time.

4-Butyrolactone ; analogs & derivatives ; chemistry ; Asteraceae ; chemistry ; Emodin ; chemistry ; Lactones ; chemistry ; Sesquiterpenes ; chemistry ; Triterpenes ; chemistry