Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cells via regulating cellular free fatty acid sensitivity

The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury.Label retaining cells(LRCs)expressing SRY-box transcription factor 9(SOX9)promote epithelial repair by replenishing LGR5 t intestinal stem cells(ISCs).While,LRCs are also considered precursor cells for enteroendocrine cells(EECs)which exacerbate mucosal damage in inflammatory bowel disease(IBD).The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain unclear.In this study,we investigated the effects of a natural anthraquinone called aloe emodin(derived from the Chinese herb rhubarb)on mucosal healing in IBD models.Our findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9t LRCs,thereby promoting mucosal healing.Furthermore,we discovered that aloe emodin acted as an antagonist of free fatty acid receptors(FFAR1),suppressing the FFAR1-mediated Gbg/serine/threonine-protein kinase(AKT)pathway and promoting the translocation of forkhead box protein O1(FOXO1)into the nucleus,ultimately resulting in the intervention of differentiation fate.These findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway.

Unique Azolyl Acylhydrazonyl Hybridization of Aloe Emodins to Access Potential Antibacterial Agents

A type of unique azole-hybridized acylhydrazonyl aloe emodins(AAEs)were developed as new antibacterial agents for combating bacterial infections.Some target AAEs showed strong antibacterial activities,especially,tetrazolylthioether AAE 27a exhibited broad antibacterial spectrum with 16-256 folds and 8-64 folds more active antibacterial efficacy than the reference drugs aloe emodin and norfloxacin,respectively.Tetrazolylthioether AAE 27a also gave low hemolysis and cytotoxicity,as well as favorable bioavailability.Preliminary mechanism explorations revealed that tetrazolylthioether AAE 27a could cause bacterial membrane depolarization and damage the cell membrane,resulting in nucleic acid leakage.Moreover,compound 27a could intercalate into DNA to impede its replication and form supramolecular 27a-DNA gyrase complex to disturb the function of DNA gyrase.These findings would provide valuable insights for the further exploration of azolyl acylhydrazonyl aloe emodins as new potential antibacterial candidates.

Antibacterial and Alkali-responsive Cationic Waterborne Polyurethane Based on Modification of Aloe Emodin

Cationic water-based polyurethane(CWPU)was synthesized to explore aloe-emodin modifies to obtain CWPU materials with better comprehensive performance.It provides a simple way to synthesize antibacterial waterborne polyurethane,which is to introduce the end-blocking group of herbal extracts into the structure.It contains synergistic antibacterial effect of herbal antibacterial and quaternary ammonium ion on Escherichia coli.It makes the material resist the erosion of bacterial,and increase the service life of materials.When the pH value of the environment changes,the UV absorbance of the aloe-emodin modified cationic water-based polyurethane(AE-CWPU)also changes.Therefore,within a certain detection range,AE-CWPU has great applications in the field of smart response materials.The modified thermodynamic properties have been improved,and the mechanical properties basically maintained the maximum stress,and the elongation at break was reduced.

Selective Solid-phase Extraction of Aloe Emodin from Aloe by Molecularly Imprinted Polymers

The extraction and separation of aloe emodin were optimized via selective molecularly imprinted solid-phase extraction. Molecularly imprinted polymer was prepared from the functional monomer, methacrylic acid and a mixture of ethanol/dodecanol（90/10, volume ratio） as porogen. It overcomes the common problems of imprin- ting biological polar compounds and shows high selectivity compared favorably with those of non-imprinted polymer and commercially available C18 and silica cartridges in similar aloe emodin tests. Good linearity was obtained be- tween 0.002 and 2.5 mg/mL（r2=0.998） with relative standard deviations below 3.3%.

Effect of Aloe Emodin on Proliferation of Vascular Smooth Muscle Cells after Arterial Injury

Objective: To study the effect of Aloe emodin (AE), an active ingredient of Rhubarb,on the kinetics of proliferation of smooth muscular cells (SMCs) cultured in vitro after rabbit iliac arterial injury. Methods: Forty-eight hours after de-endothelialization (balloon endothelial denudation), the iliac arteries of the Japanese white rabbits were isolated and the smooth muscle cells were cultured primarily.AE was added to culture medium containing 10% fetal calf serum (FCS ). The cultures were pulse-labeled with 3H-TdR and TdR uptake into VSMC were measured and the cell cycle of the cultures were analyzed by using flow cytometer. Results: Compared with control, when the concentration gradient ranged from 10 - 1 to 10-5 g/L, the amount (cpm,count per minute) of 3H-TdR uptake into SMCs has significant differences (P < 0. 05 )and 10 -1 and 10 -2 g/L AE showed strong inhibitory effects on TdR uptake into VSMC and the percentage of inhibition [% inhibition =(cpm without AE-cpm with AE)/cpm without AE] was more than 90%. AE displayed concentration dependent inhibitory effects. The percentage of cells in G0/G1 phase was increased, but the percentage of cells in S phase was decreased in AE group, the transition of SMC cycle phase from G0 to S was blocked.Conclusion: AE is a strong inhibitor to the proliferation of SMCs and the pharmacological action of AE may reduce SMC proliferation in vivo and decrease intimal hyperplasia of restenosis.Original article on CJIM(Chin) 1998; 18(7): 420