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JOURNAL OF MOLECULAR LIQUIDS · 2024 · IF 5.3

Inhibitory effect of caffeic acid and dihydrocaffeic acid on the formation of advanced glycation end products: Mechanism analysis based on intermolecular interaction

Yanqing Zhang,Lixia Yuan,Qiulu Wang,Xuejie Zhang,Yiyun Yang,Min Liu

The accumulation of advanced glycation end products (AGEs) generated from glycation reaction accelerates the development and deterioration of some diseases. Herein, the AGEs model of fructose-induced glycation of human serum albumin (HSA) was constructed and characterized. Both caffeic acid (CA) and dihydrocaffeic acid (DHCA) can inhibit the formation of AGEs, and the inhibitory effect of CA was more pronounced, as confirmed by fluorescence spectroscopy, gel electrophoresis, scanning electron microscopy, and carbonyl and thiol contents analysis. The binding of CA and DHCA to HSA was investigated by fluorescence spectroscopy and molecular docking. The primary inhibitory mechanism was the occupation of the glycation site LYS199 of HSA, and the more significant inhibitory effect of CA was related to its stronger binding affinity. Furthermore, the conformational changes caused by glycation and CA/DHCA binding were monitored using fluorescence, circular dichroism, and dynamic light scattering analysis. The results would help to elucidate the inhibitory mechanism of CA and DHCA on AGEs formation based on their different structures and inhibitory effects, and provide guidance for choosing natural inhibitors for diabetes.

CAS / MDL: 4091-99-0
研究领域: 生物化学 · 药理学 · 分子生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2011 · IF 2.816

Coffee Components Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in Vitro: Possible Link between Coffee Consumption and Diabetes Mellitus

Biao Cheng,Xinran Liu,Hao Gong,Lianqi Huang,Hong Chen,Xin Zhang,Chuanzhou Li,Muyang Yang,Bingjun Ma,Lihua Jiao,Ling Zheng,Kun Huang

Global epidemic studies have suggested that coffee consumption is reversely correlated with the incidence of type 2 diabetes mellitus (T2DM), a metabolic disease. The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of T2DM. Coffee extracts have three major active components: caffeine, caffeic acid (CA), and chlorogenic acid (CGA). In this study, the effects of these major coffee components, as well as dihydrocaffeic acid (DHCA) (a major metabolite of CGA and CA), on the amyloidogenicity of hIAPP were investigated by thioflavin-T based fluorescence emission, transmission electronic microscopy, circular dichroism, light-induced cross-linking, dynamic light scattering, and MTT-based cell viability assays. The results suggest that all components show varied inhibitory effects on the formation of toxic hIAPP amyloids, in which CA shows the highest potency in delaying the conformational transition of the hIAPP molecule with the most prolonged lag time, whereas caffeine shows the lowest potency. At a 5-fold excess molar ratio of compound to hIAPP, all coffee-derived compounds affect the secondary structures of incubated hIAPP as suggested by the circular dichroism spectra and CDPro deconvolution analysis. Further photoinduced cross-linking based oligomerization and dynamic light scattering studies suggested CA and CGA significantly suppressed the formation of hIAPP oligomers, whereas caffeine showed no significant effect on oligomerization. Cell protection effects were also observed for all three compounds, with the protection efficiency being greatest for CA and least for CGA. These findings suggest that the beneficial effects of coffee consumption on T2DM may be partly due to the ability of the major coffee components and metabolites to inhibit the toxic aggregation of hIAPP.

CAS / MDL: 331-39-5 327-97-9
研究领域: 生物化学 · 分子生物学 · 糖尿病研究
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Growth Factors-Loaded Temperature-Sensitive Hydrogel as Biomimetic Mucus Attenuated Murine Ulcerative Colitis via Repairing the Mucosal Barriers

Dingwei Li,Jianxun Shangguan,Fengnan Yu,Gaolong Lin,Hanxiao Pan,Mengjiao Zhang,Haoran Lin,Ben Chen,Helin Xu,Sunkuan Hu

The pathogenesis of ulcerative colitis (UC) is associated with the shedding of the gut mucus. Herein, inspired by the biological functions of mucus, growth factors-loaded in situ hydrogel (PHE-EK) was designed for UC treatment by integrating dihydrocaffeic acid-modified poloxamer as a thermosensitive material with hyaluronic acid (colitis-specific adhesive), epigallocatechin-3-gallate (antibacterial agent), and bioactive factors (KPV tripeptide and epidermal growth factor). PHE-EK presented good thermosensitive properties, as a flowable liquid at room temperature and gelled within 10 s when exposed to body temperature. PHE-EK hydrogel presented good mechanical strength with a strain of 77.8%. Moreover, PHE-EK hydrogel displayed antibacterial activity against Escherichia coli. Importantly, in vitro and in vivo adhesive tests showed that the PHE-EK hydrogel could specifically adhere to the inflamed colon via electrostatic interaction. When PHE-EK as a biomimetic mucus was rectally administrated to colitis rats, it effectively hindered the body weight loss, reduced the disease activity index and improved the colonic shorting. Moreover, the expression of pro-inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) at the laminae propria or epitheliums of the colon for colitis rats was substantially inhibited by PHE-EK. Besides, the colonic epitheliums were well rearranged, and the tight junction proteins (Zonula-1 and Claudin-5) between them were greatly upregulated after PHE-EK treatment. Collectively, PHE-EK might be a promising therapy for UC.

CAS / MDL: 989-51-5 7647-01-0
研究领域: 药学 · 生物医学工程 · 胃肠病学 · 材料科学
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