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Protective effects of Dioscorea bulbifera and Zingiber officinale mixed extracts against glutamate-induced cell death in HT22 cells 黄薯蓣和生姜混合提取物对谷氨酸诱导HT22细胞死亡的保护作用
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-14 DOI: 10.1186/s13765-025-01026-5
Seung Woo Im, Won Min Jeong, Dong Yeol Lee, Tae Woo Oh

This study aimed to evaluate the neuroprotective effects of mixed extracts from Dioscorea bulbifera and Zingiber officinale (DBZO) against glutamate-induced excitotoxicity in HT-22 cells and to elucidate the associated molecular mechanisms. Neurotoxicity and protective effects were assessed using MTT and LDH assays, while cellular morphology was analyzed via microscopy. DBZO extract significantly restored axonal integrity disrupted by glutamate exposure. A DCFDA assay confirmed that DBZO reduced reactive oxygen species (ROS) generation in a concentration-dependent manner, underscoring its antioxidant capacity. Western blot analysis demonstrated that DBZO markedly decreased glutamate-induced neuronal death at 0.25 and 0.5 mg/mL. The observed neuroprotection was associated with the inhibition of the MAPK signaling cascade and the downregulation of apoptotic markers, including Caspase-3 and PARP. Moreover, DBZO activated the PI3K/Akt/mTOR survival pathway, enhancing neuronal viability. It also boosted antioxidant defenses by modulating Keap1 and NQO1 expression, thereby reducing oxidative damage. Collectively, these findings suggest that DBZO confers neuroprotection by regulating oxidative stress and apoptosis through NRf2/NQO-1 signaling. Due to its strong antioxidant and antiapoptotic properties.

Graphical Abstract

本研究旨在探讨黄药黄姜混合提取物(DBZO)对谷氨酸诱导的HT-22细胞兴奋性毒性的神经保护作用,并阐明相关分子机制。通过MTT和LDH检测评估神经毒性和保护作用,同时通过显微镜分析细胞形态。DBZO提取物可显著恢复因谷氨酸暴露而破坏的轴突完整性。DCFDA分析证实,DBZO以浓度依赖的方式减少活性氧(ROS)的产生,强调其抗氧化能力。Western blot分析显示,0.25和0.5 mg/mL DBZO可显著降低谷氨酸诱导的神经元死亡。观察到的神经保护作用与抑制MAPK信号级联和下调凋亡标志物(包括Caspase-3和PARP)有关。此外,DBZO激活PI3K/Akt/mTOR存活通路,增强神经元活力。它还通过调节Keap1和NQO1的表达来增强抗氧化防御,从而减少氧化损伤。综上所述,这些发现表明DBZO通过NRf2/NQO-1信号传导调节氧化应激和细胞凋亡,从而具有神经保护作用。由于其强大的抗氧化和抗凋亡特性。图形抽象
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引用次数: 0
Biosynthesis of three benzoic acid derivatives in Escherichia coli 三种苯甲酸衍生物在大肠杆菌中的生物合成
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-13 DOI: 10.1186/s13765-025-01024-7
Hyun-Ah Kim, Hyun Ji Kang, Joong-Hoon Ahn

Benzoic acid, an aromatic compound conventionally obtained from coal tar, can also be produced via microbial biotransformation. The shikimate pathway of Escherichia coli provides a route for the biosynthesis of aromatic acids, with its intermediates serving as valuable starting materials for the synthesis of benzoic acid derivatives. Here, we report the E. coli-based synthesis of three benzoic acid derivatives: 3,4-dihydroxybenzoic acid (protocatechuic acid, 3,4-DHBA), gallic acid (GA), and β-glucogallin. The enzyme QuiC was used to catalyze the conversion of 3-dehydroshikimate to 3,4-DHBA. For GA production, a screening of four pobA mutants was conducted to identify the most efficient mutant. A grape-derived uridine diphosphate-dependent glucosyltransferase (UDP-GT) was utilized for the glucosylation of GA to β-glucogallin. To improve the production titers of 3,4-DHBA and GA, a shikimate pathway gene module and a specifically engineered E. coli mutant were employed, resulting in the accumulation of 451.3 mg/L 3,4-DHBA and 123.4 mg/L GA. β-Glucogallin synthesis was achieved through a stepwise process, wherein one E. coli strain produced GA, and its clarified culture medium was subsequently used by a second E. coli strain for β-glucogallin formation. Optimization of the ratio between the GA-containing supernatant and the second cell culture led to a β-glucogallin yield of 118.5 mg/L.

苯甲酸是一种芳香化合物,通常从煤焦油中获得,也可以通过微生物转化生产。大肠杆菌的莽草酸途径为芳香酸的生物合成提供了一条途径,其中间体为苯甲酸衍生物的合成提供了有价值的起始原料。本文报道了以大肠杆菌为基础合成的三种苯甲酸衍生物:3,4-二羟基苯甲酸(原儿茶酸,3,4- dhba),没食子酸(GA)和β-胰高糖素。用QuiC酶催化3-脱氢莽草酸转化为3,4- dhba。对于GA的生产,筛选了四个pobA突变体,以确定最有效的突变体。利用葡萄衍生的尿苷二磷酸依赖葡萄糖基转移酶(UDP-GT)将GA糖基化为β-葡高糖素。为了提高3,4- dhba和GA的生产滴度,采用了一个shikimate通路基因模块和一个特异性工程的大肠杆菌突变体,使3,4- dhba和GA的积累量分别达到451.3 mg/L和123.4 mg/L。β-Glucogallin的合成是通过一个循序渐进的过程实现的,其中一个大肠杆菌菌株产生GA,然后将其澄清的培养基用于第二个大肠杆菌菌株形成β-Glucogallin。优化含ga的上清液与第二次细胞培养液的比例,β-葡聚糖产量为118.5 mg/L。
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引用次数: 0
Preparation, flavor compounds, and antioxidant activity of hawthorn fruit-derived maillard reaction products 山楂果美拉德反应产物的制备、风味化合物和抗氧化活性
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-12 DOI: 10.1186/s13765-025-01022-9
Fushen Wang, Shangrong Wang, Cunyong Qin, Jiaxin Li, Zhiping Zhang, Lingbo Ji, Xuewei Jia, Baojiang He, Lei Xing, Chunping Xu, Tianxiao Li

In this study, a new kind of hawthorn fruit-derived food flavor was developed through Maillard reaction. The reaction conditions were optimized using a combination of single-factor experiments and response surface methodology (RSM). The key flavor compounds were determined by gas chromatography-mass spectrometry (GC-MS) and relative odor activity values (ROAVs). Single-factor experiments indicated that the preferred conditions were glycine supplement amount of 5.0%, reaction temperature of 130 °C, and reaction time of 90 min, which were further optimized by RSM. GC-MS analysis demonstrated a remarkable 2.7-fold increase in total flavor compounds (TFCs) of Maillard reaction samples (MRSs) than those of enzymolysis extract of hawthorn. ROAV analysis indicated 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP), furfural, 2-methylbutyric acid, hexyl acetate, linalool, decanal, and α-ionone were the key flavor compounds of MRSs, which contributed to the sweetness, roasting, fruity, and acidic aromas. The antioxidant activity were obviously enhanced after Maillard reaction that could be associated with the yielded DDMP and 4-vinylphenol.

以山楂果为原料,通过美拉德反应制备了一种新型食品香精。采用单因素试验和响应面法(RSM)相结合的方法对反应条件进行优化。采用气相色谱-质谱联用(GC-MS)和相对气味活性值(ROAVs)测定了主要风味成分。单因素实验表明,甘氨酸添加量为5.0%,反应温度为130℃,反应时间为90 min为最佳条件,并通过RSM进一步优化。GC-MS分析表明,美拉德反应样品(MRSs)的总风味化合物(tfc)比酶解山楂提取物增加了2.7倍。ROAV分析表明,2,3-二氢-3,5-二羟基-6-甲基- 4h -吡喃-4-酮(DDMP)、糠醛、2-甲基丁酸、乙酸己酯、芳樟醇、癸醛和α-离子酮是MRSs的主要风味化合物,它们构成了MRSs的甜味、烘烤味、果味和酸性香气。美拉德反应后的抗氧化活性明显增强,这可能与DDMP和4-乙烯基酚有关。
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引用次数: 0
Correction: Assessment of iridoid profiles in the growth period of aerial parts of Pseudolysimachion rotundum var. subintegrum and their antioxidant and MUC5AC inhibitory potential 校正:评估圆形假毛囊亚整部分生长期环烯醚萜类化合物的分布及其抗氧化和MUC5AC抑制潜能
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-12 DOI: 10.1186/s13765-025-01023-8
Soobin Song, Doo-Young Kim, Seon Min Oh, So-Yeun Woo, Il-joo Kim, Mun-Ock Kim, Ji-Yoon Park, Namho Kim, Hae-Young Kim, Juhee Lee, Sang Yoon Kim, Bang Yeon Hwang, Hyung Won Ryu, Sei-Ryang Oh
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引用次数: 0
Characterization of the volatile profiles in Korean rice-matured spirits and premium whiskies using HS-SPME-Arrow-GC/MS 用HS-SPME-Arrow-GC/MS分析韩国稻熟酒和优质威士忌的挥发性成分
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-12 DOI: 10.1186/s13765-025-01020-x
Un Jung Chae, Ji Yoon Cha, Tae-Wan Kim, Hae Won Jang

Spirits exhibit distinct flavors based on variations in raw materials and production methods. This study aimed to evaluate the potential of Korean rice-matured distilled spirits as premium distilled spirits by comparing their volatile compounds with those of commercially available whiskies. Volatile compounds in 17 single malt whiskies (SM), 9 blended whiskies (BL), and 3 rice-matured distilled spirits (RM) were analyzed using gas chromatography/mass spectrometry (GC/MS) combined with headspace solid-phase microextraction arrow (HS-SPME-Arrow). Among the 77 identified volatile compounds, the concentrations of ethyl acetate, ethyl decanoate, and ethyl octanoate tended to increase as SM, BL, and RM matured, and may serve as key volatile compounds for distinguishing spirits. Additionally, ethanol, isoamyl alcohol, 2-methyl-1-butanol, isoamyl acetate, and phenylethyl acetate may function as volatile indicators for predicting the type and aging level of whisky. In this study, we evaluated volatile compounds in 29 spirits and identified eight key compounds that differentiate whisky types. Moreover, ethyl acetate and lactones, closely related to the flavor of whiskies, were remarkably higher in RMs compared to commercial whiskies. These findings could greatly contribute to the development of rice-matured spirits as high-quality Korean whisky and offer significant contributions to the classification of premium whiskies.

根据原料和生产方法的不同,烈酒呈现出不同的风味。本研究旨在通过将韩国稻熟蒸馏酒的挥发性化合物与市售威士忌的挥发性化合物进行比较,评估韩国稻熟蒸馏酒作为优质蒸馏酒的潜力。采用气相色谱/质谱法(GC/MS)结合顶空固相微萃取箭(HS-SPME-Arrow)对17种单一麦芽威士忌(SM)、9种混合威士忌(BL)和3种米熟蒸馏酒(RM)中的挥发性成分进行了分析。经鉴定的77种挥发性化合物中,随着SM、BL和RM的成熟,乙酸乙酯、癸酸乙酯和辛酸乙酯的浓度呈上升趋势,可以作为鉴别烈酒的关键挥发性化合物。此外,乙醇、异戊醇、2-甲基-1-丁醇、乙酸异戊酯和乙酸苯乙酯可以作为预测威士忌类型和陈年水平的挥发性指标。在这项研究中,我们评估了29种烈酒中的挥发性化合物,并确定了区分威士忌类型的8种关键化合物。此外,与威士忌风味密切相关的乙酸乙酯和内酯的均数比商业威士忌高得多。这一发现将对韩国高品质米酿威士忌的发展做出巨大贡献,并对优质威士忌的分类做出重大贡献。
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引用次数: 0
Rice bran supplementation exerts a protective effect against mitochondrial dysfunction associated with high-fat diet consumption in ovariectomized mice 在去卵巢小鼠中,米糠补充对与高脂肪饮食消耗相关的线粒体功能障碍具有保护作用
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-11 DOI: 10.1186/s13765-025-01016-7
Jisun Choi, Songhee Lee, Dongshin Yang, Minji Kim, Min Young Um, Sooim Shin

Obesity results from various factors, such as menopause, age, physical activity, genetics, and environmental factors. Notably, the risk of obesity in women, especially in the context of menopause, has increased with rising life expectancy. Therefore, preventing and treating menopause-related obesity is crucial. Rice bran, the brown outer layer of the rice kernel, is known to contain nutrients and bioactive compounds. Rice bran supplement (RBS), a byproduct of rice polishing, recognizably treats obesity; moreover, it is also known to increase mitochondrial function. To validate the effect of RBS on menopause-induced obesity, we administered RBS to ovariectomized mice as a menopause model. Ultimately, we aimed to evaluate the potential of RBS as an alternative candidate to hormone replacement therapy for treating menopause-induced obesity. RBS treatment significantly reduced body weight by 20% and retroperitoneal fat by 97% compared to the HFD group. Furthermore, mitochondrial enzyme activities as mitochondrial respiratory function in the brain increased on average by 102% compared to the HFD group and by average by 93% compared to the ND group, highlighting the therapeutic efficacy of RBS in ameliorating metabolic complications associated with menopause, without the use of hormone replacement therapy.

肥胖由多种因素引起,如更年期、年龄、体育活动、遗传和环境因素。值得注意的是,女性肥胖的风险随着预期寿命的延长而增加,尤其是在更年期的情况下。因此,预防和治疗更年期相关肥胖至关重要。米糠,米粒的棕色外层,已知含有营养物质和生物活性化合物。米糠补充剂(RBS)是大米抛光的副产品,可以治疗肥胖;此外,它还能增加线粒体功能。为了验证RBS对绝经性肥胖的影响,我们将RBS作为绝经模型给予卵巢切除的小鼠。最终,我们的目的是评估RBS作为激素替代疗法治疗绝经性肥胖的替代方案的潜力。与HFD组相比,RBS治疗显著降低了20%的体重和97%的腹膜后脂肪。此外,与HFD组相比,大脑中线粒体呼吸功能的线粒体酶活性平均增加了102%,与ND组相比平均增加了93%,突出了RBS在不使用激素替代疗法的情况下改善更年期相关代谢并发症的治疗效果。
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引用次数: 0
Novel pyran-based anti-inflammatory agents: design, synthesis, and mechanistic studies in LPS-stimulated macrophages 新型吡喃类抗炎药:lps刺激巨噬细胞的设计、合成和机制研究
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-09 DOI: 10.1186/s13765-025-01018-5
Mei Tong He, Sung Jin Kim, Viet Duc Le, Su Ji Min, Heesu Lee, Jae Wook Lee, Myoung-Sook Shin

This study investigated the anti-inflammatory effects of pyran derivatives, focusing on compound 19, in LPS-stimulated RAW264.7 macrophages. We screened 19 pyran derivatives for cytotoxicity and nitric oxide (NO) inhibition, and identified compound 19 as the most promising compound owing to its efficacy. Western blot analysis revealed that compound 19 significantly inhibited the expression of key inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in LPS-stimulated macrophages in a dose-dependent manner. Furthermore, compound 19 inhibited the phosphorylation of Akt at 12.5 μM, and suppressed JNK and ERK MAPK phosphorylation at both concentrations (12.5 and 6.25 μM), while p38 phosphorylation was not inhibited. These findings suggest that compound 19 exerts its anti-inflammatory action by modulating multiple signaling pathways involved in inflammatory responses. Our results demonstrate that compound 19 is a promising candidate for the development of novel anti-inflammatory agents.

本研究以化合物19为重点,研究吡喃衍生物对lps刺激的RAW264.7巨噬细胞的抗炎作用。我们筛选了19种吡喃衍生物的细胞毒性和一氧化氮(NO)抑制作用,并确定化合物19是最有希望的化合物。Western blot分析显示,化合物19显著抑制lps刺激的巨噬细胞中诱导型一氧化氮合酶(iNOS)和环氧化酶(COX)-2等关键炎症介质的表达,且呈剂量依赖性。此外,化合物19在12.5 μM浓度下抑制Akt的磷酸化,在12.5 μM和6.25 μM浓度下抑制JNK和ERK MAPK的磷酸化,而p38的磷酸化未被抑制。这些发现表明化合物19通过调节参与炎症反应的多种信号通路发挥其抗炎作用。我们的研究结果表明,化合物19是开发新型抗炎药的一个有希望的候选者。
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引用次数: 0
Metabolomic signatures of lactic acid bacteria: their growth rates and roles in enhancing kimchi quality 乳酸菌的代谢组学特征:它们的生长速度及其在提高泡菜品质中的作用
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-08 DOI: 10.1186/s13765-025-01025-6
So-Jeong Kim, Ji-Sue Lee, Vindya H. J. Hetti Arachchige, Eun-Hee Kim, Byung-Hee Ryu, Jung Sung Lee, Young-Shick Hong

Kimchi, a traditional Korean fermented food, undergoes spontaneous fermentation driven by lactic acid bacteria (LAB), which significantly influences its flavor, texture, and nutritional content. The quality of kimchi is largely determined by the metabolites produced during microbial metabolism, but the relationship between intra- and extra-cellular metabolism of LAB remains unclear. This study aimed to investigate the metabolism of various LAB strains isolated from kimchi, through metabolomic analysis of both their intra- and extra-cellular matrices, and to explore the role of their metabolism during kimchi fermentation. Hetero- and homo-fermentative characters of Leuconstoc and Lactiplantibacillus strains were characterized by production of extracellular mannitol and lactate, respectively. Notably, the rapid growth of Lactiplantibacillus strains was found to associated with a substantial uptake of extracellular glucose and aromatic amino acids, whereas the slow growth of Leuconostoc strains contributed to the production of most extracellular amino acids and a less uptake of extracellular glucose. Indeed, Lactiplantibacillus strains may regulate intracellular pH through the elimination of intracellular acidic amino acids, while Leuconostoc strains possibly protect themselves against osmotic stress by producing intracellular betaine. Moreover, kimchi fermented under slow fermentation conditions contained higher levels of mannitol and amino acids compared to fast fermentation condition, thereby enhancing its nutritional value and overall quality. This study highlights the links between the slow fermentation or metabolic distinction of LAB and the potential contribution to the improvement of fermented food quality.

泡菜是韩国传统的发酵食品,在乳酸菌(LAB)的推动下自发发酵,这对泡菜的味道、质地和营养成分产生了很大的影响。泡菜的品质在很大程度上取决于微生物代谢过程中产生的代谢物,但细胞内和细胞外代谢之间的关系尚不清楚。本研究旨在通过对不同酵母菌胞内和胞外基质的代谢组学分析,研究其在泡菜发酵过程中的代谢作用。Leuconstoc和Lactiplantibacillus菌株的异质和同质发酵特性分别通过胞外甘露醇和乳酸的产生来表征。值得注意的是,Lactiplantibacillus菌株的快速生长与细胞外葡萄糖和芳香氨基酸的大量摄取有关,而Leuconostoc菌株的缓慢生长有助于大多数细胞外氨基酸的产生和细胞外葡萄糖的较少摄取。事实上,Lactiplantibacillus菌株可能通过消除细胞内酸性氨基酸来调节细胞内pH,而Leuconostoc菌株可能通过产生细胞内甜菜碱来保护自己免受渗透胁迫。此外,与快速发酵相比,在缓慢发酵条件下发酵的泡菜含有更高水平的甘露醇和氨基酸,从而提高了其营养价值和整体品质。本研究强调了乳酸菌的缓慢发酵或代谢差异与发酵食品品质改善的潜在贡献之间的联系。
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引用次数: 0
Metabolic profiling and anti-neuroinflammatory effects of Liriope platyphylla extract in LPS-stimulated BV2 microglia 白桦提取物在lps刺激的BV2小胶质细胞中的代谢谱和抗神经炎作用
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-08-06 DOI: 10.1186/s13765-025-01015-8
Kwan-Woo Kim, Woo-Cheol Shin, Jin-Kyu Jang, Myoung-Jin Kim, Dahye Yoon, Young-Seob Lee, Dae Young Lee

Liriope platyphylla F. T. Wang & T. Tang (L. platyphylla) is a perennial member of the Liliaceae family, is predominantly found in East Asian regions such as Korea, Taiwan, and Japan. In this study, we investigated the neuroinflammation-modulating potential of an ethanol-based extract from L. platyphylla (LPE) using BV2 microglial cells activated by lipopolysaccharide (LPS). In addition, we examined which bioactive constituents in LPE contribute to its anti-neuroinflammatory effects by isolating and profiling the major compounds. Notably, treating LPE prior to LPS exposure led to a marked decrease in the synthesis of inflammatory mediators, including cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines such as IL-6, IL-1β, and tumor necrosis factor-α (TNF-α) in the microglia. Mechanistic studies revealed that suppressive effects of LPE are linked to the downregulation of LPS-triggered signaling pathways, specifically those involving Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), and the p38 and JNK branches of the mitogen-activated protein kinase (MAPK) cascade. Chemical analysis of the extract identified eight distinct compounds, with methylophiopogonone A (2) and methylophiopogonanone B (3) being primarily responsible for the observed anti-neuroinflammatory activity. Quantitative profiling by ultra-performance liquid chromatography coupled with quadrupole time of flight / mass spectrometry (QTOF/MS) indicated that these two bioactive constituents were present in the ethyl acetate fraction of LPE at concentrations of 0.0007 ± 0.0001 mg/g and 0.0197 ± 0.0009 mg/g, respectively. Collectively, these findings highlight the promise of LPE as a source for developing novel functional ingredients or herbal therapeutics targeting neuroinflammatory conditions.

Liriope platyphylla F. T. Wang & T. Tang (L. platyphylla)是百合科的多年生植物,主要分布在韩国、台湾和日本等东亚地区。在这项研究中,我们利用脂多糖(LPS)激活的BV2小胶质细胞,研究了白桦(L. platyphylla)乙醇提取物(LPE)的神经炎症调节潜力。此外,我们通过分离和分析主要化合物,研究了LPE中哪些生物活性成分有助于其抗神经炎作用。值得注意的是,在LPS暴露之前治疗LPE导致炎症介质的合成显著减少,包括环氧化酶-2 (COX-2)、一氧化氮(NO)、前列腺素E2 (PGE2)、诱导型一氧化氮合酶(iNOS)和促炎细胞因子,如IL-6、IL-1β和肿瘤坏死因子-α (TNF-α)。机制研究表明,LPE的抑制作用与lps触发的信号通路下调有关,特别是涉及toll样受体4 (TLR4)、核因子κB (NF-κB)以及丝裂原活化蛋白激酶(MAPK)级联的p38和JNK分支。化学分析鉴定出八种不同的化合物,其中甲基菲奥古酮A(2)和甲基菲奥古酮B(3)是观察到的抗神经炎症活性的主要原因。超高效液相色谱-四极杆飞行时间/质谱(QTOF/MS)定量分析表明,这两种生物活性成分分别以0.0007±0.0001 mg/g和0.0197±0.0009 mg/g的浓度存在于LPE的乙酸乙酯部位。总的来说,这些发现突出了LPE作为开发针对神经炎症疾病的新型功能成分或草药治疗的来源的希望。
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引用次数: 0
Omija (Schisandra chinensis) extract and soybean mixture to enhance memory function through the gut-brain axis: network pharmacology and in vivo validation of multi-target mechanisms 五味子提取物和大豆混合物通过肠-脑轴增强记忆功能:网络药理学和多靶点机制的体内验证
IF 2.7 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-07-30 DOI: 10.1186/s13765-025-01019-4
Yu Yue, Hye Jeong Yang, Myung-Sunny Kim, Ting Zhang, Chen Li, Min Jung Kim, Dai-Ja Jang, Sunmin Park

With the growing prevalence of memory impairment and limited treatment options, this study evaluated the cognitive-enhancing potential of an Omija (Schisandra chinensis (Turcz). Baill) 50% ethanol extract and soybean mixture (OSM). By integrating network pharmacology with in vivo validation, we aimed to elucidate the molecular mechanisms and therapeutic efficacy of OSM. Network pharmacology was used to identify core pathways and targets associated with the memory-enhancing effects of Omija (gomisin, schizandrin) and soybean. To validate these findings, scopolamine-induced memory-impaired rats (2 mg/kg/day for 8 weeks) through the parasympathetic nervous system (PNS) suppression were administered OSM (100, 250, or 750 mg/kg/day) or dextrin (positive control) alongside a high-fat diet. Behavioral, metabolic, and molecular evaluations were conducted. Network analysis identified key targets involved in neuroinflammation including interleukin (IL)-17 and nuclear factor Kappa B (NF-κB) signaling and neurotransmitter regulation (dopamine synapse), including acetylcholinesterase (AChE), prostaglandin-endoperoxide synthase-2 (PTGS2), glycogen-synthase kinase-3beta (GSK-3β), solute carrier family 6 member 3 (SLC6A3; dopamine transporter), and plasminogen activator (PLAU). In vivo, OSM at 250 and 750 mg/kg significantly improved memory performance across passive avoidance, Y-maze, Morris water maze, and novel object recognition tests. These improvements were associated with suppressed neuroinflammatory genes (NF-κB, PTGS2, TNF-α, IL-17, IL-1β), enhanced cholinergic and dopaminergic balance (reduced AChE activity, increased dopamine), improved glucose metabolism, and upregulated neurotrophic factor expression (brain-derived neurotrophic factor, ciliary neurotrophic factor). Furthermore, OSM enhanced hippocampal insulin signaling (increased phosphorylation of Akt and GSK-3β), improved intestinal morphology, and increased portal vein butyrate levels, suggesting modulation of the gut-brain axis. In conclusion, OSM enhances memory through multiple central (cholinergic, dopaminergic, neurotrophic) and peripheral (anti-inflammatory, metabolic) mechanisms via activating the gut-brain axis. These findings support OSM (250–750 mg/kg) as a promising candidate for cognitive enhancement potentially by inhibiting PNS suppression, warranting further clinical investigation.

Graphical abstract

随着记忆障碍的日益普遍和有限的治疗选择,本研究评估了五味子(Schisandra chinensis (Turcz))的认知增强潜力。50%乙醇提取物和大豆混合物(OSM)。通过网络药理学和体内验证相结合的方法,我们旨在阐明OSM的分子机制和治疗效果。利用网络药理学方法,确定了Omija (gomisin, schizandrin)和大豆增强记忆作用的核心通路和靶点。为了验证这些发现,通过抑制副交感神经系统(PNS),东莨菪碱诱导的记忆受损大鼠(2 mg/kg/天,持续8周)在高脂肪饮食的同时给予OSM(100、250或750 mg/kg/天)或糊精(阳性对照)。进行了行为、代谢和分子评价。网络分析确定了参与神经炎症的关键靶点,包括白细胞介素(IL)-17和核因子κB (NF-κB)信号传导和神经递质调节(多巴胺突触),包括乙酰胆碱酯酶(AChE)、前列腺素内过氧化物合成酶-2 (PTGS2)、糖原合成酶激酶-3β (GSK-3β)、溶质载体家族6成员3 (SLC6A3;多巴胺转运蛋白)和纤溶酶原激活物(PLAU)。在体内,250和750 mg/kg的OSM显著提高了被动回避、y迷宫、Morris水迷宫和新物体识别测试的记忆性能。这些改善与抑制神经炎症基因(NF-κB、PTGS2、TNF-α、IL-17、IL-1β)、增强胆碱能和多巴胺能平衡(AChE活性降低、多巴胺增加)、改善葡萄糖代谢和上调神经营养因子表达(脑源性神经营养因子、睫状体神经营养因子)有关。此外,OSM增强了海马胰岛素信号(Akt和GSK-3β磷酸化增加),改善了肠道形态,增加了门静脉丁酸水平,提示肠-脑轴的调节。综上所述,OSM通过激活肠-脑轴,通过多种中枢(胆碱能、多巴胺能、神经营养)和外周(抗炎、代谢)机制增强记忆。这些发现支持OSM (250-750 mg/kg)可能通过抑制PNS抑制来增强认知,值得进一步的临床研究。图形抽象
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Applied Biological Chemistry
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