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Aucubin
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Aucubin-loaded BSAMA/GelMA hydrogel accelerates diabetic wound healing via ROS scavenging

Zhixiang Mu,Yan Yang,Guanyao Zhang,Xiaobin Yang,Qingqing Dong,Jiaying Ma,Anlin Li,Ke Li,Jiajun Hu,Xuanxin Yang,Qiuqiu Mu,Xiaojie Wang

Diabetic wound healing remains challenging due to persistent hyperglycemia-driven reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. To address this, we engineered a photocurable hydrogel ( [email protected] ) composed of gelatin methacryloyl (GelMA) and bovine serum albumin methacryloyl (BSAMA) to encapsulate aucubin (Auc). Systematic evaluation of GelMA/BSAMA ratios identified the 1:1 formulation as optimal, exhibiting superior mechanical strength. The binding ability of BSAMA to Auc could realize sustained release. Furthermore, GelMA's MMP-9-responsive domains enabled accelerated Auc release in inflammatory microenvironments. The design integrates BSAMA's drug-binding capacity with GelMA's MMP-9 responsiveness to achieve spatiotemporal drug release. In vitro studies demonstrated that the hydrogel effectively scavenges ROS and restores mitochondrial membrane potential, thereby disrupting the ROS storm cycle. This antioxidative effect further suppressed the production of pro-inflammatory cytokines (IL-1β, IL-6) and the overexpression of MMP-9. In a type 2 diabetic rat model, the hydrogel accelerated full-thickness wound closure, with histological analysis revealing dense collagen deposition and enhanced angiogenesis. By synergistically integrating GelMA's MMP-9-triggered drug release with BSAMA's Auc-binding capacity, the hydrogel establishes a multifunctional platform that couples microenvironment-responsive drug delivery with anti-oxidative, anti-inflammatory, and pro-angiogenic functions, offering a promising solution for diabetic wound management.

研究领域: 生物材料 · 药剂学 · 伤口愈合 · 糖尿病研究 · 生物工程 · 纳米医学
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JOURNAL OF MOLECULAR LIQUIDS · 2022 · IF 6.633

Polarity-controlled deep eutectic solvents-based biphasic system for the selective separation of geniposidic acid and aucubin from Eucommia ulmoides male flowers

Yicong Wang,Leilei Liu,Zhijian Tan

Owing to their unique characteristics, deep eutectic solvents (DESs) have the potential to replace organic solvents in the extraction and separation of chemicals from natural sources. In this study, a novel biphasic system composed of hydrophilic and hydrophobic DESs was designed for the selective separation of geniposidic acid (GPA) and aucubin (AU) from Eucommia ulmoides male flowers. Fifteen DESs with different hydrophilicity/hydrophobicity were used to design the biphasic system. The biphasic system designed using tetrabutyl ammonium chloride-hexanoic acid and choline chloride- D, L -malic acid was found to be an optimal extraction system. The influence of the phase volume ratio, system concentration, water content in the DESs, equilibrium temperature, and pH of the phosphate buffer solution was investigated through single-factor experiments. Under optimal conditions, maximum extraction efficiencies were observed for GPA in the top phase ( E GPA  = 94.59%) and AU in the bottom phase ( E AU  = 80.41%). Further, density functional theory calculations indicated that H-bond interaction was the main factor influencing the selective separation of GPA and AU. This DES-based biphasic system is efficient and environmentally friendly and could be used in the separation of other homologues present in natural products.

研究领域: 植物化学 · 天然产物分离 · 环境科学
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY · 2023 · IF 2.9

Aucubin alleviates methotrexate-induced enteritis in rats by inducing autophagy

Tongao Yang,Wuying Lang,Yun Zhao,Yahan Yang,Hongli Liu,Sufen Li,Xianglong Li,Shuangqi Zhang,Haihua Zhang

One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti-inflammation, anti-apoptosis and anti-oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX-induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX-induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D-lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved-caspase 1, IL-18 and IL-1β. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy-related markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX-induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX-induced enteritis. However, 3-methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX-induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX-resulted enteritis.

研究领域: 药理学 · 免疫学 · 胃肠病学 · 分子生物学
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INDUSTRIAL CROPS AND PRODUCTS · 2022 · IF 6.449

Extraction and separation of flavonoids and iridoids from Eucommia ulmoides leaves using choline tryptophan ionic liquid-based aqueous biphasic systems

Runping Wang,Zaibo Yang,Wenzhi Lv,Zhijian Tan,Hongfu Zhang

The choline tryptophan ionic liquid (IL)-based aqueous biphasic system (ABS) was designed and applied to extract and separate flavonoids and iridoids from Eucommia ulmoides leaves. This ABS possessed a unique viscous layer enriching iridoids that can be directly removed at the interface between the IL-rich and salt-rich phases. The extraction yield of total flavonoids was optimized by RSM to obtain a predicted maximum of 2.91% at the IL concentration of 36.73%, liquid to solid ratio of 38, extraction temperature of 44 °C and extraction time of 105 min. The determined extraction yield of total flavonoids is 2.78% ± 0.12% under revised optimization conditions. The distribution coefficient K and extraction rate E of total flavonoids in the IL-rich phase reach the maximum of 129% and 98.53% at the K 3 PO 4 content of 26% in the ILABS, respectively. The HPLC analysis shows a high content of rutin in the flavonoids precipitate induced by water as an anti-solvent. Aucubin content reaches 15.19% in the intermediate viscous layer enriching iridoids. Hence, the designed process has the potential to be applied to the separation and enrichment of rutin and aucubin from other industrial crops.

研究领域: 植物化学 · 天然产物分离
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CHEMICAL PAPERS · 2023 ·Vol. 77 ·期 9 ·5357-5369 · IF 2.2

The simultaneous extraction and separation of hydrophobic and hydrophilic phytochemicals from Eucommia ulmoides seeds with green solvent CPME system

Duan Cong-Jia,Zhang Ying,Yu Lian,Chang Yuan-Hang,Xu Jian,Yue Gan-Lu,Han Xu,Wang Chen-Lu,Fu Yu-Jie

This work, an efficient method for simultaneous extraction and separation of different polarity phytochemicals from E. ulmoides seeds was developed with green solvent cyclopentyl methyl ether (CPME) system. Firstly, the green solvent CPME with optimal solubility for E. ulmoides seeds oil (EUO) was fast screened by Hansen solubility parameters (HSPs). Under optimum conditions: liquid–solid ratio of 20:1, ultrasound time of 60 min and ultrasound power of 60 W, 28.6% EUO and 6.4% aucubin (AU) were extracted by cyclopentyl methyl ether-ethyl alcohol (CPME-EtOH) system, which were 1.10- and 1.19-fold higher than that of traditional extraction. Meantime, the fatty acid composition and in vitro biological activity of EUO shown it had 86.99% unsaturated fatty acids and excellent antioxidant activity, non-cytotoxicity and lipid-lowering activity. Moreover, EUO had good physicochemical properties and met the standard of edible oil, which indicated EUO is a good oil source for medicine and food. Besides, the CPME that has been recycled six runs can still extract 25.6% EUO. In short, this study gave some guidance for simultaneous extraction and separation of hydrophobic oil and hydrophilic bioactive compounds from plant resources using green solvent instead of petrochemical solvents in food, pharmaceutical, cosmetic and other fields. Graphical abstract

CAS / MDL: 479-98-1 5614-37-9
研究领域: 植物化学 · 食品科学 · 药学
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ACS Omega · 2023 · IF 4.1

Extraction and Purification of Aucubin from Eucommia ulmoides Seed Draff in Natural Deep Eutectic Solvents Using Macroporous Resins

Yunhui Liao,Feng Chen,Haishan Tang,Wubliker Dessie,Zuodong Qin

Aucubin (AU) is an active ingredient that exerts strong antioxidant and anti-inflammatory effects in the treatment of several diseases. In order to improve the efficiency of resource utilization of traditional biomass waste, Eucommia ulmoides seed-draff (EUSD) waste biomass was used as the raw material, and a series of deep eutectic solvents were selected to evaluate the extraction efficiency of aucubin from EUSD. A response surface experiment was designed based on a single-factor experiment to optimize the extract conditions. The results showed that the best conditions for aucubin extraction were an HBD–HBA ratio of 2.18, a liquid–solid ratio of 46.92 mL/g, a water percentage of 37.95%, a temperature of 321.03 K, and an extraction time of 59.55 min. The maximum amount of aucubin was 156.4 mg/g, which was consistent with the theoretical value (156.8 mg/g). Then, the performance of 12 resins for adsorption and desorption was contrasted. The results revealed that HPD950 resin exhibited the best performance, with an adsorption capacity of 95.2% and a desorption capacity of 94.3%. Additionally, the pseudo-second-order model provided the best match to the kinetics data, the Langmuir model provided the best fit to the isotherm data, and adsorption was a beneficial, spontaneous, exothermic, and physical process. In the recyclability test, the HPD950 resin had great potential and excellent sustainability in aucubin recovery. In the antioxidant activity study, the aucubin extract exerted a strong antioxidant ability with scavenging capabilities for four free radicals. Furthermore, the antifungal activity study found that the aucubin extract exhibited a good antifungal effect against 5 tested pathogens. The research results can provide a theoretical basis for the extraction of high-value components from waste biomass by deep eutectic solvent and a certain application value for the development and utilization of natural aucubin products.

研究领域: 植物化学 · 天然产物开发 · 环境科学
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