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CHEMICAL ENGINEERING JOURNAL · 2026 · IF 12.5

Lycii Fructus-derived extracellular vesicles-like particles attenuate sodium iodate-induced retinal injury by transporting bioactive cargo molecules

Pan Huang,Xiao-Bo Zhang,Jia-Qi Li,Guan-Wen He,Ying Chen,Ling-Yun Yang,Zai-Long Chi

LF-EVLPs treatment ameliorates retinal injury in mice. • LF-EVLPs mitigates oxidative stress, inflammation and complement factors in retinal injury. • LF-EVLPs exert retinal protective effects through the synergistic actions of multiple active ingredients. Oxidative stress and inflammation are major contributors to the development of age-related macular degeneration (AMD), which is one of the retinal degeneration (RD) diseases that are characterized by progressive damage to photoreceptors and retinal pigment epithelium (RPE) cells. This condition can ultimately lead to blindness. Lycii Fructus can clear liver heat, improve vision, and protect the optic nerve. Thus, the aim of this study was to investigate whether nanovesicles derived from Lycii Fructus (LF) can alleviate retinal damage. LF extracellular vesicle-like particles (EVLPs) were isolated from fresh Lycii Fructus . Intravitreal injection of LF-EVLPs resulted in significant retinal protective effects, such as the preservation of RPE cell morphology and junctional integrity, enhanced photoreceptor survival, improved retinal thickness, and restored visual function, in sodium iodate-induced retinal injury mice. Moreover, LF-EVLPs reduced retinal ROS levels and suppressed glial cell activation. Further experiments demonstrated that LF-EVLPs exert neuroprotective effects by modulating the NF-κB signalling pathway and suppressing the aberrant activation of proinflammatory cytokines ( IL-1β and TNF-α ) and complement factors ( C3, C4b, and C5 ). Through an integrated analysis of LF-EVLPs components and the retinal proteome, we identified 12 components and 17 target genes. We confirmed that the active ingredients caffeic acid phenethyl ester (CAPE), a derivative of caffeic acid, and nicotinamide (NAM) exhibit neuroprotective effects in sodium iodate-induced retinal injury mice. Our research provides new insight into neuroretinal protection, for which plant-derived EVLPs may be a promising therapeutic approach. LF-EVLPs preserve the structural and functional integrity of the retina by delivering bioactive constituents and attenuating oxidative stress, modulating the NF-κB pathway, suppressing inflammatory responses, and regulating the complement system after retinal injury. Download: Download high-res image (133KB) Download: Download full-size image

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Biomolecules · 2025 ·Vol. 15 ·期 7 ·918 · IF 4.8

Caffeic Acid Phenethyl Ester Alleviates Alcohol-Induced Inflammation Associated with Pancreatic Secretion and Gut Microbiota in Zebrafish

Menghui Lin,Xiaogang Guo,Xinyu Xu,Chao Chang,Thanh Ninh Le,Haiying Cai,Minjie Zhao

Caffeic acid phenethyl ester (CAPE) is identified to be an efficacious bioactive polyphenol in propolis for ameliorating glucose and lipid metabolism disorders and inflammation. In this study, an alcohol-induced zebrafish inflammation model was established. CAPE treatments at different concentrations (0.04, 0.2, and 1.0 μg/mL) were administered to alcohol-exposed zebrafish to investigate the underlying mechanisms of alleviating alcohol-induced liver inflammation using transcriptomic analysis and 16S rRNA gene sequencing methods. The results indicated that CAPE decreased the expressions of TNF-α and IL-1β and significantly increased the expression of IL-10 (p< 0.0001). Based on the KEGG enrichment analysis of transcriptomic sequencing, CAPE effectively alleviated the inflammation in zebrafish mainly through pancreatic secretion, complement and coagulation cascades, and protein digestion and absorption. Molecular docking supported the potential of CAPE in targeting cholecystokinin (CCK) A Receptor (CCKAR) and mediating the regulation of pancreatic secretion and related inflammation pathways. Moreover, intestinal microbiota analysis demonstrated that CAPE could improve the alcohol-induced microbiota disorder. Additionally, there was a significant correlation between the key genes related to lipid and sterol metabolism among the KEGG-enriched pathways and the specific intestinal microbial communities in zebrafish. Flavobacterium from Bacteroidota was significantly positively correlated withCEL1,CEL2, andLPIN(p< 0.01), which suggested that the anti-inflammatory function of CAPE was closely associated with the intestinal microbiota improvement. In conclusion, our findings demonstrated that CAPE could ameliorate liver inflammation in alcohol-induced zebrafish, which was mainly associated with the regulation of pancreatic secretion and intestinal microbiota disorder. This study emphasized the anti-inflammatory mechanisms of CAPE based on targeting the pancreatic secretion pathway, which will broaden the application of natural antioxidants in improving metabolic and inflammatory problems.

CAS / MDL: 104594-70-9
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE · 2022 ·Vol. 50 ·期 5 ·1-14 · IF 5.314

Caffeic acid phenethyl ester attenuates osteoarthritis progression by activating NRF2/HO‑1 and inhibiting the NF‑κB signaling pathway

Weichao Sun,Wei Xie,Dixi Huang,Yinxing Cui,Jiaji Yue,Qifei He,Luoyong Jiang,Jianyi Xiong,Wei Sun,Qian Yi

Osteoarthritis (OA) is the most common degenerative disease affecting the joints, and inflammation appears to play a critical role in the initiation and progression of OA. Caffeic acid phenethyl ester (CAPE), a natural flavonoid compound, has anti‑inflammatory and antioxidant functions. However, its anti‑inflammatory effects on OA and the underlying mechanisms of action of CAPE in the treatment of OA remain elusive. Therefore, the present study investigated the anti‑inflammatory effects of CAPE on IL‑1β‑stimulated chondrocytes in vitro and surgically induced rat models of OA in vivo. In vitro, CAPE reduced the expression of inducible nitric oxide synthase and cyclooxygenase‑2 in IL‑1β‑stimulated chondrocytes, as well as the extracellular secretion of nitric oxide and prostaglandin E2 in the cell culture supernatants. In addition, CAPE attenuated the degradation of extracellular matrix by increasing the expression of aggrecan and collagen II, and decreasing the expression of MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motif‑5. Furthermore, CAPE attenuated NF‑κB signaling and activated the nuclear factor erythroid 2‑related factor 2/heme oxygenase‑1 signaling pathway in IL‑1β‑stimulated chondrocytes. In vivo, CAPE protected cartilage from destruction and delayed the progression of OA in rats. Taken together, the findings of the present study indicated that CAPE may be a potential therapeutic agent for the prevention or treatment of OA.

CAS / MDL: 104594-70-9
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2022 ·Vol. 34 ·期 1 ·155-165 · IF 3.348

Thermosensitive acetylated carboxymethyl chitosan gel depot systems sustained release caffeic acid phenethyl ester for periodontitis treatment

Chengjun Peng,Guichun Wang,Yuxiao Wang,Maomao Tang,Xiaodong Ma,Xiangwei Chang,Jian Guo,Shuangying Gui

Periodontitis is a chronic inflammatory disease of tooth support tissues leading to progressive destruction of periodontal soft tissues as well as alveolar bone, and can be treated with anti-inflammatory and bone-protective agents to prevent disease progression. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound with anti-inflammation, anti-oxidation and bone tissue repair efficacy. In this work, we synthesized a thermosensitive hydrogel matrix of acetylated carboxymethyl chitosan (A-CC), and firstly applied for periodontal local drug delivery. The biocompatible CAPE-loaded A-CC hydrogel (CAPE-A-CC) has the advantages of forming a drug depot in situ, sustained release and precisely improving the drug concentration in the lesion sites compared with traditional systemic administration. In addition, CAPE-A-CC could significantly inhibit the expression of inflammatory cytokines of TNF-α, IL-1β, IL-6, and IL-17 in macrophages, and increased the expression of alkaline phosphatase (ALP) in human periodontal ligament stem cells (hPDLSC) related to osteogenesis. This study develops a novel in situ thermosensitive hydrogel delivery system to improve the therapeutic potential of natural active ingredient for periodontitis therapy.

CAS / MDL: 104594-70-9
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2021 · IF 3.205

High-throughput subzero-temperature assisted homogenous liquid-liquid extraction for the fast sample preparation of multiple phenolic compounds in propolis

Fengjie Yu,Jianing Zhang,Yunmin Tao,Chunping Du,Wenchao Yang,Wenbin Chen,Xijuan Tu

In the present study, a high-throughput homogenous liquid-liquid extraction method was developed for fast sample preparation of multiple phenolic compounds in propolis. This method was proposed based on cooling samples array in subzero temperature to induce phase separation of ACN-H 2 O extractant. Due to the high-throughput ability, optimization of extraction parameters was rapidly achieved by using a 5 × 4 × 3 samples array. In addition, multiple arrays were investigated for evaluating the analytical performance of the high-throughput method, which indicated that limits of detection and quantification were ranged from 0.04 to 0.35 µg/mL and 0.12 to 1.05 µg/mL, respectively. Recoveries and precisions in inter-day high-throughput studies were in the range of 90.55–105.50% and 2.58–4.30%, respectively. Comparing with the conventional liquid extraction method, this ecofriendly high-throughput method presented remarkable advantages in reducing sample and chemical consumption, as well as saving labor and time cost. The proposed method might provide a valuable strategy for the design of high-throughput extraction procedures.

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ARCHIVES OF VIROLOGY · 2021 ·Vol. 166 ·期 9 ·2443-2450 · IF 2.574

Icariin, Formononetin and Caffeic Acid Phenethyl Ester Inhibit Feline Calicivirus Replication In Vitro

Cui Zhanding,Wang Qian,Li Dengliang,Zhao Shihui,Zhang Qian,Tan Yuxin,Gong Qianwen,Liu Ting,Shao Jiang,Zhang Shuang,Huang Hailong,Wang Junzheng,Pei Zhihua,Dong Hao,Wang Kai,Hu Guixue,Li Zhiyong

Cats infected with feline calicivirus (FCV) often display oral ulcers and inflammation of the upper respiratory tract, which can lead to death in severe cases. Antiviral therapy is one of the most effective ways to control FCV infection. Natural compounds in Chinese herbal medicines and medicinal plants provide abundant resources for research on antiviral drugs. In this study, we found that icariin (ICA), formononetin (FMN) and caffeic acid phenethyl ester (CPAE) show low cytotoxicity towards F81 cells, that the three natural compounds have apparent antiviral effects on FCV in vitro , and that they can inhibit different FCV strains. Then, we found that ICA and FMN mainly function in the early stage of FCV infection, while CAPE can function in both the early and late stages of FCV infection. Finally, we found that ICA has an antagonistic effect on FMN and CAPE in FCV infection, and FMN has a synergistic effect with CAPE against FCV infection. Our results showed that ICA, FMN and CAPE may be potential drug candidates for FCV-induced diseases.

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ELECTROPHORESIS · 2020 ·Vol. 42 ·期 6 ·742-748 · IF 3.081

An integrated microfluidics for assessing the anti-aging effect of caffeic acid phenethylester in Caenorhabditis elegans

Beibei Zhang,Liping Zhuang,Duanping Sun,Yinbao Li,Zuanguang Chen

Aging is a fundamental and fascinating process. Anti-aging research tried to find the mysteries about the human lifespan. To investigate the longevity-extending role of caffeic acid phenethylester (CAPE) and reveal the possible regulation mechanism, the long-term cultivation under well-defined environments, real-time monitoring, and live imaging is highly desired. In this paper, a well-designed microfluidic device was proposed to analyze the anti-aging effect of CAPE in Caenorhabditis elegans . With the combined use of multiple functional units, including micro-pillar, worm responder, a branching network of distribution channels, and microchambers, the longitudinal measurements of the exact number of worms throughout the whole lifespans is possible. Meanwhile, the brief cooling function of temperature-controllable system can achieve temporary and repeated immobilization of nematodes for fluorescence imaging. Our research data showed that CAPE can increase the survival of worms under normal and stress condition, including heat stress and paraquat-induced oxidative stress. The further studies revealed the anti-aging mechanism of CAPE. This proposed strategy and device would be a useful platform to facilitate future anti-aging studies and the finding of new lead compounds.

CAS / MDL: 104594-70-9
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2020 · IF 4.872

Caffeic acid phenethyl ester against cadmium induced toxicity mediated by CircRNA modulates autophagy in HepG2 cells

Rili Hao,Feng Li,Xinyu Song,Xintong Tan,Dongxiao Sun-Waterhouse,Dapeng Li

Cadmium pollution and poisoning are serious environmental and pharmacological concerns, and effective drugs can alleviate or offset cadmium-induced toxicity are badly needed. In this study, Caffeic acid phenethyl ester (CAPE), a major active component of propolis, showed protective effect against CdCl 2 -induced toxicology by suppressing autophagy in HepG2 cells. CircRNAs are increasingly perceived as vital regulators in the process of autophagy. However, it remain unclear whether circRNAs are involved in CAPE's protection against CdCl 2 -induced autophagy. Under this context, the roles of CircRNA (hsa_circ_0040768) in CAPE's protection against CdCl 2 -induced damage were investigated by PCR and Western blot. Results showed that CAPE significantly ( P  < 0.05) increased cell viability via inhibiting CdCl 2 -induced autophagy, and this process was regulated by hsa_circ_0040768/MAP1LC3B axis. Overexpressing hsa_circ_0040768 led to reduced cell viability and increased autophagy in CAPE-treated HepG2 cells exposed to CdCl 2 . In contrast, silencing hsa_circ_0040768 showed similar protective effect to CAPE. These results show for the first time the involvement of the hsa_circ_0040768/MAP1LC3B axis in the CAPE's protection against CdCl 2 -induced autophagy, and provide novel insights into the pathogenesis and potential prevention/treatment of cadmium-associated diseases.

CAS / MDL: 104594-70-9
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FOOD AND CHEMICAL TOXICOLOGY · 2020 · IF 4.679

Caffeic acid phenethyl ester reversed cadmium-induced cell death in hippocampus and cortex and subsequent cognitive disorders in mice: Involvements of AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis

Rili Hao,Xinyu Song,Feng Li,Xintong Tan,Dongxiao Sun-Waterhouse,Dapeng Li

Exposure to nonbiodegradable cadmium (Cd) causes many health problems including the damage to the nervous system. This study aimed to increase knowledge about its neurotoxic effects and the neuroprotective potential of caffeic acid phenethyl ester (CAPE, a polyphenol abundant in honeybee propolis). In mice, CAPE (10 μmol/kg/day body weight) attenuated significantly learning and memory deficits induced by CdCl 2 (1.5 mg/kg/day body weight). For the CdCl 2 -treated mice, CAPE increased crossing number in open field test, decreased the alternation in Y-maze test, and increased the latency time and error number in step down test. CAPE also inhibited CdCl 2 -initiated Aβ accumulation and activation of pro-inflammatory factors and microglia in the brains. Therefore, CAPE could be a food-derived neuroprotective agent against Cd-induced neurotoxicity and neurodegenerative disorders, through attenuating neuronal apoptosis and neuroinflammation via the AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis.

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ACS Synthetic Biology · 2023 · IF 4.7

Yeast Metabolic Engineering for Biosynthesis of Caffeic Acid-Derived Phenethyl Ester and Phenethyl Amide

Zi-Chen Jia,Duo Liu,Hai-Di Ma,Yu-Hui Cui,Hui-Min Li,Xia Li,Ying-Jin Yuan

Caffeic acid (CA)-derived phenethyl ester (CAPE) and phenethyl amide (CAPA) are extensively investigated bioactive compounds with therapeutic applications such as antioxidant, anti-inflammatory, and anticarcinogenic properties. To construct microbial cell factories for production of CAPE or CAPA is a promising option given the limitation of natural sources for product extraction and the environmental toxicity of the agents used in chemical synthesis. We reported the successful biosynthesis of caffeic acid in yeast previously. Here in this work, we further constructed the downstream synthetic pathways in yeast for biosynthesis of CAPE and CAPA. After combinatorial engineering of yeast chassis based on the rational pathway engineering method and library-based SCRaMbLE method, we finally obtained the optimal strains that respectively produced 417 μg/L CAPE and 1081 μg/L CAPA. Two screened gene targets of ΔHAM1 and ΔYJL028W were discovered to help improve the product synthesis capacity. This is the first report of the de novo synthesis of CAPA from glucose in an engineered yeast chassis. Future work on enzyme and chassis engineering will further support improving the microbial cell factories for the production of CA derivatives.

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MOLECULES · 2019 ·Vol. 24 ·期 3 ·442 · IF 3.06

Comparison of the Partition Efficiencies of Multiple Phenolic Compounds Contained in Propolis in Different Modes of Acetonitrile–Water-Based Homogenous Liquid–Liquid Extraction

Wenbin Chen,Xijuan Tu,Dehui Wu,Zhaosheng Gao,Siyuan Wu,Shaokang Huang

Homogeneous liquid–liquid extraction (HLLE) has attracted considerable interest in the sample preparation of multi-analyte analysis. In this study, HLLEs of multiple phenolic compounds in propolis, a polyphenol-enriched resinous substance collected by honeybees, were performed for improving the understanding of the differences in partition efficiencies in four acetonitrile–water-based HLLE methods, including salting-out assisted liquid–liquid extraction (SALLE), sugaring-out assisted liquid–liquid extraction (SULLE), hydrophobic-solvent assisted liquid–liquid extraction (HSLLE), and subzero-temperature assisted liquid–liquid extraction (STLLE). Phenolic compounds were separated in reversed-phase HPLC, and the partition efficiencies in different experimental conditions were evaluated. Results showed that less-polar phenolic compounds (kaempferol and caffeic acid phenethyl ester) were highly efficiently partitioned into the upper acetonitrile (ACN) phase in all four HLLE methods. For more-polar phenolic compounds (caffeic acid,p-coumaric acid, isoferulic acid, dimethoxycinnamic acid, and cinnamic acid), increasing the concentration of ACN in the ACN–H2O mixture could dramatically improve the partition efficiency. Moreover, results indicated that NaCl-based SALLE, HSLLE, and STLLE with ACN concentrations of 50:50 (ACN:H2O,v/v) could be used for the selective extraction of low-polarity phenolic compounds. MgSO4-based SALLE in the 50:50 ACN–H2O mixture (ACN:H2O,v/v) and the NaCl-based SALLE, SULLE, and STLLE with ACN concentrations of 70:30 (ACN:H2O,v/v) could be used as general extraction methods for multiple phenolic compounds.Keywords:salting-out assisted liquid–liquid extraction;sugaring-out assisted liquid–liquid extraction;hydrophobic-solvent assisted liquid–liquid extraction;subzero-temperature assisted liquid–liquid extraction;phenolic compounds

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PHYTOMEDICINE · 2018 · IF 3.61

Caffeic acid phenethyl ester synergistically enhances the antifungal activity of fluconazole against resistant Candida albicans

Lingmei Sun,Kai Liao,Chengcheng Hang

Background Owing to the increased morbidity and mortality associated with invasive fungal infections , treatments with a combination of antifungal agents are often considered. Caffeic acid phenethyl ester (CAPE), a major active component of propolis, possesses many biological activities , including antibacterial, antiviral, antioxidant, anti-inflammatory, and anticancer effects. Purpose This study aimed to evaluate the interaction between CAPE and fluconazole (FLC) against Candida albicans . Methods Microdilution checkerboard and time-kill assays were employed to evaluate the in vitro interaction between CAPE and FLC. The data obtained from the checkerboard tests were analyzed by the fractional inhibitory concentration index (FICI).The antifungal activity of the CAPE and FLC combination was evaluated in vivo in a Caenorhabditis elegans model of infection. Results We observed that when used in combination, CAPE acted synergistically with FLC against FLC-resistant clinical isolates of C. albicans . In addition, the CAPE-FLC combination significantly extended the longevity and reduced fungal burden in C. elegans when compared with treatment with FLC or CAPE alone. Conclusion These results indicate that the use of CAPE and FLC in combination has considerable therapeutic potential against resistant C. albicans .

CAS / MDL: 104594-70-9
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