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Xanthohumol attenuates TXNIP-mediated renal tubular injury in vitro and in vivo diabetic models. 黄腐酚在体外和体内糖尿病模型中减轻txnip介导的肾小管损伤。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2025-01-03 DOI: 10.1007/s11418-024-01863-6
Yan Zhang, Runzhou Pan, Zhang Shou, Yongcai Zhao

Thioredoxin-interacting protein (TXNIP), as a pivotal protein in the cellular stress response, plays a significant role in the progression of diabetic nephropathy (DN). Consequently, therapeutic strategies aimed at targeting TXNIP may offer novel interventions for patients with DN. Our study is to explore the therapeutic potential of targeting TXNIP in mitigating renal tubular injury induced by hyperglycemia. Cell viability and apoptosis of renal tubular epithelial cells (RTECs) were evaluated using CCK-8, Annexin V/7-AAD, and TUNEL staining after exposure to normal glucose (NG; 5 mM), high glucose (HG; 30 mM), or treatment with TXNIP inhibitors (Xanthohumol, Xan). Furthermore, histochemical staining was utilized to assess the morphological changes in the kidney. Xan was determined to be a potential inhibitor of TXNIP due to its low binding energy value of - 7.433 kcal/mol. Both genetic inhibition of TXNIP using sh-RNA and pharmacological inhibition with Xan were found to reverse HG-induced RTEC apoptosis and inflammatory response. In diabetic mice, administration of Xan resulted in significant improvements in pathological features such as tubular atrophy, tubular injury score, and collagen deposition in the tubulointerstitium. Additionally, treatment with Xan effectively reduced the up-regulation of TXNIP protein expression caused by hyperglycemia. In conclusion, Xan, as a bioactive natural product, has been shown to attenuate hyperglycemia-induced renal tubular injury in both in vitro and in vivo models, potentially through the inhibition of TXNIP expression. Xan has the potential to serve as a therapeutic compound for the treatment of DN.

硫氧还蛋白相互作用蛋白(TXNIP)作为细胞应激反应中的关键蛋白,在糖尿病肾病(DN)的进展中起着重要作用。因此,针对TXNIP的治疗策略可能为DN患者提供新的干预措施。我们的研究是探讨靶向TXNIP减轻高血糖所致肾小管损伤的治疗潜力。采用CCK-8、Annexin V/7-AAD和TUNEL染色法观察正常葡萄糖(NG;5 mM),高葡萄糖(HG;30mm),或用TXNIP抑制剂(黄腐酚,Xan)治疗。此外,采用组织化学染色评估肾脏的形态学变化。由于Xan的结合能较低,为- 7.433 kcal/mol,因此被确定为TXNIP的潜在抑制剂。sh-RNA基因抑制TXNIP和Xan药物抑制TXNIP均可逆转hg诱导的RTEC细胞凋亡和炎症反应。在糖尿病小鼠中,给药Xan可显著改善病理特征,如小管萎缩、小管损伤评分和小管间质胶原沉积。此外,Xan治疗有效降低了高血糖引起的TXNIP蛋白表达上调。综上所述,Xan作为一种具有生物活性的天然产物,在体外和体内模型中都被证明可以减轻高血糖诱导的肾小管损伤,可能是通过抑制TXNIP的表达。Xan有潜力作为治疗DN的治疗性化合物。
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引用次数: 0
Red ginseng prevents niraparib-induced myelosuppression in C57BL/6 mice via inhibiting p53-mediated upregulation of p21 and p27. 红参通过抑制 p53 介导的 p21 和 p27 上调,防止尼拉帕利诱导的 C57BL/6 小鼠骨髓抑制。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-12-30 DOI: 10.1007/s11418-024-01866-3
Huiyan Liao, Xiangdan Hu, Shenming Chen, Zhaofeng Fan, Jing Xiao

Myelosuppression is a serious and common complication of targeted therapy for cancer patients, and there are few studies exploring the efficacy of natural drugs in this condition. Niraparib is a widely used targeted therapy for the treatment of advanced ovarian cancer. As a poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib significantly improves progression-free and overall survival in patients. We aimed to explore the potential effect of red ginseng (RG) on niraparib-induced myelosuppression and to further reveal its possible molecular mechanism. Female C57BL/6 mice were divided into control, tumor, model, and RG groups (n = 6). After receiving ID8 ovarian cancer cell inoculation, the mice received niraparib treatment (80 mg/kg) for 3 days. Meanwhile, RG groups (100 and 200 mg/kg) were intragastrically treated with RG extract for 7 days. Compared with the model group, RG extract increased the counts of peripheral blood cells and enhanced the hematopoietic function of bone marrow. Furthermore, RG extract increased the colony yield of hematopoietic progenitor cells (HPCs), facilitated DNA damage repair, alleviated the G0/G1 phase cell cycle arrest, and significantly reversed the increased expression levels of p53, p21, and p27, while stimulating cyclinE1 expression levels. These findings indicate that RG might have therapeutic potential on niraparib-induced myelosuppression, which encourages further clinical trials. This study is the first to explore the efficacy and mechanism of RG in preventing myelosuppression induced by niraparib.

骨髓抑制是肿瘤患者靶向治疗的一个严重而常见的并发症,目前很少有研究探讨天然药物在这种情况下的疗效。尼拉帕尼是一种广泛用于治疗晚期卵巢癌的靶向疗法。作为一种聚(adp -核糖)聚合酶(PARP)抑制剂,尼拉帕尼可显著改善患者的无进展生存期和总生存期。本研究旨在探讨红参对尼拉帕尼诱导的骨髓抑制的潜在作用,并进一步揭示其可能的分子机制。雌性C57BL/6小鼠分为对照组、肿瘤组、模型组和RG组(n = 6)。小鼠接种ID8卵巢癌细胞后,给予尼拉帕尼(80 mg/kg)治疗3 d。同时,RG组(100、200 mg/kg)灌胃RG提取物7 d。与模型组比较,RG提取物使大鼠外周血细胞计数增加,骨髓造血功能增强。此外,RG提取物增加造血祖细胞(HPCs)的集落产量,促进DNA损伤修复,缓解G0/G1期细胞周期阻滞,显著逆转p53、p21和p27的表达水平升高,同时刺激cyclinE1的表达水平。这些发现表明RG可能对尼拉帕尼诱导的骨髓抑制有治疗潜力,这鼓励了进一步的临床试验。本研究首次探讨RG预防尼拉帕尼诱导的骨髓抑制的疗效及机制。
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引用次数: 0
Ten new resin glycosides, ipoalbins I-X, from Ipomoea alba seeds. 从益波木种子中提取的10个新树脂苷——益波白蛋白I-X。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-12-27 DOI: 10.1007/s11418-024-01868-1
Nodoka Misuda, Mizuki Watanabe, Hirotaka Nishikawa, Shin Yasuda, Hiroyuki Miyashita, Kazumi Yokomizo, Hitoshi Yoshimitsu, Ryota Tsuchihashi, Masafumi Okawa, Junei Kinjo, Masateru Ono

Ipomoea alba L. (Convolvulaceae) is an annual vine native to tropical America that is cultivated primarily for ornamental purposes. Its seeds are used in traditional medicine as a laxative, and young shoots are consumed as food. In this study, ten new resin glycosides, ipoalbins I (1)-X (10), were isolated from I. alba seeds. The structures of 1-10 were determined based on spectroscopic data. All compounds had intramolecular cyclic ester structures (jalapins). The sugar moieties in 1-10 were partially acylated by organic acids, including isobutyric, (E)-2-methylbut-2-enoic, and 2S-methyl-3S-hydroxybutyric acids. Notably, one of these compounds has a rare jalapin structure characterized by an ester linkage between the carboxyl group of the aglycone moiety and the hydroxyl group of an organic acid attached to the sugar moiety. In contrast, other compounds exhibited typical macrolactone structures. Furthermore, the cytotoxic activity of 1-10 against HL-60 human promyelocytic leukemia cells and their antiviral activity against herpes simplex virus type 1 (HSV-1) were evaluated. All tested compounds, except 3, were comparable to or slightly less cytotoxic than cisplatin, the positive control. In addition, all the compounds showed anti-HSV-1 activity; notably, 5 showed an EC50 value lower than that of acyclovir, the positive control. However, the selectivity indices of these compounds were lower than that of acyclovir.

(旋花科)是一种一年生藤本植物,原产于热带美洲,主要用于观赏用途。它的种子在传统医学中被用作泻药,幼芽被当作食物食用。本研究从白桦种子中分离到了10个新的树脂苷,ipoalbins I (1)-X(10)。根据光谱数据确定了1-10的结构。所有化合物均具有分子内环状酯结构(jalapins)。其中1-10的糖部分被异丁酸、(E)-2-甲基丁-2-烯酸和2s -甲基- 3s -羟基丁酸等有机酸部分酰化。值得注意的是,其中一种化合物具有罕见的jalapin结构,其特征是在糖苷元部分的羧基和连接到糖部分的有机酸的羟基之间具有酯连接。相反,其他化合物表现出典型的内酯结构。此外,研究了1-10对HL-60人早幼粒细胞白血病细胞的细胞毒活性和对1型单纯疱疹病毒(HSV-1)的抗病毒活性。除3种外,所有被测化合物的细胞毒性与阳性对照顺铂相当或略低。所有化合物均具有抗hsv -1活性;其中5株的EC50值低于阳性对照阿昔洛韦。但这些化合物的选择性指标均低于阿昔洛韦。
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引用次数: 0
Optimizing post-harvest processing conditions for Angelica acutiloba roots in Hokkaido: storage temperature and duration. 北海道当归根采后加工条件优化:贮藏温度与贮藏时间。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-12-20 DOI: 10.1007/s11418-024-01867-2
Satoko Sasaki, Satoshi Yokota, Yohei Sasaki

The traditional post-harvest processing method of Angelica acutiloba roots, which involves hanging the roots outdoors after being harvested, is known to promote the conversion of starch in roots into sucrose, thereby increasing sweetness. At the same time, this method increases the dilute ethanol-soluble extract (DEE) content in A. acutiloba roots to meet the standard set by the Japanese Pharmacopoeia 18th edition. However, in Hokkaido, where A. acutiloba has been cultivated in recent years, it is a challenge to practice this traditional post-harvest processing method owing to the risk of freezing. Therefore, it is necessary to determine post-harvest processing conditions to increase DEE content in A. acutiloba roots in Hokkaido. In this study, we cultivated seedlings in plug trays and the open field in Hokkaido and stored the harvested products at various temperatures and durations to determine changes in DEE content. DEE content immediately after harvest was 20.5% in roots from plug-tray seedlings and 27.8% in roots from seedlings cultivated in the open field. DEE content in roots stored at 0 °C increased slowly over 5 weeks, whereas that in roots stored at 20 °C increased rapidly. We found a strong correlation between DEE content and sucrose content, but not (Z)-ligustilide content. Our findings on the post-harvest processing conditions for roots revealed that the optimal post-harvest processing conditions are storage at 0 °C for at least two weeks during which DEE content increases stably, similar to the traditional method.

传统的采收后加工方法是在采收后将当归的根悬挂在室外,这种方法可以促进根中的淀粉转化为蔗糖,从而增加甜味。同时,该方法提高了木耳根中稀醇溶物(DEE)的含量,达到日本药典第18版的标准。然而,在北海道,近年来种植了金针菇,由于有冷冻的风险,这种传统的采收后加工方法对实践来说是一个挑战。因此,有必要确定采收后的加工条件,以提高北海道针叶根中的DEE含量。在本研究中,我们在北海道的塞盘和开阔地培养幼苗,并将收获的产品在不同温度和时间下储存,以确定DEE含量的变化。收获后即刻DEE含量为塞盘苗20.5%,露天栽培苗27.8%。0℃贮藏5周,DEE含量增长缓慢,而20℃贮藏5周,DEE含量增长迅速。我们发现DEE含量与蔗糖含量有较强的相关性,而(Z)- liguslide含量则没有相关性。结果表明,采后处理条件与传统方法相似,最佳的采后处理条件是在0°C下保存至少2周,在此期间DEE含量稳定增加。
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引用次数: 0
Ellagic acid prevents ovariectomy-induced bone loss and attenuates oxidative damage of osteoblasts by activating SIRT1. 鞣花酸通过激活SIRT1来防止卵巢切除术引起的骨质流失和减轻成骨细胞的氧化损伤。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-12-19 DOI: 10.1007/s11418-024-01859-2
Liwei Guo, Pengcheng Wei, Shijie Li, Lulu Zhou, Yunjie Yan, Duan Li

Oxidative stress has been implicated as a causative factor for the development and progression of osteoporosis(OP). Ellagic acid (EA), a natural polyphenol, presents anti-oxidative and anti-inflammatory properties. However, EA's role and molecular mechanism in osteoblasts have not yet been elucidated. In this study, exogenous supplementation with EA restored the osteoporotic bone defects in ovariectomized (OVX)-induced osteoporotic mice. Also, EA inhibited the H2O2-induced apoptosis of primary osteoblasts, prevented the production of reactive oxygen species, and restored the bone-forming potential of osteoblasts. Furthermore, EA was revealed to activate Sirtuin1 (SIRT1) and its downstream Nrf2/Heme Oxygenase 1 (HO-1) signaling pathway, and EX527 (a SIRT1 inhibitor) partially counteracted the effect of EA on bone loss. The findings suggest that EA protects against osteoporotic bone loss by activating SIRT1 and its downstream Nrf2/HO-1 signaling pathway, providing novel insights into the potential of EA as a treatment agent for osteoporosis-related bone metabolism diseases.

氧化应激被认为是骨质疏松症(OP)发生和发展的一个致病因素。鞣花酸(EA)是一种天然多酚,具有抗氧化和抗炎特性。然而,EA在成骨细胞中的作用和分子机制尚未阐明。在这项研究中,外源性补充 EA 可恢复卵巢切除(OVX)诱导的骨质疏松小鼠的骨质疏松性骨缺损。此外,EA 还能抑制 H2O2 诱导的原发性成骨细胞凋亡,防止活性氧的产生,并恢复成骨细胞的成骨潜能。此外,EA还能激活Sirtuin1(SIRT1)及其下游的Nrf2/Heme氧化酶1(HO-1)信号通路,而EX527(一种SIRT1抑制剂)能部分抵消EA对骨质流失的影响。研究结果表明,EA通过激活SIRT1及其下游的Nrf2/HO-1信号通路来防止骨质疏松性骨丢失,为EA作为骨质疏松相关骨代谢疾病的治疗药物提供了新的见解。
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引用次数: 0
Huanglian decoction prevents and treats radiation-induced intestinal injury in lung cancer by regulating endoplasmic reticulum stress 黄连汤通过调节内质网应激预防和治疗辐射性肺癌肠损伤。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-12-05 DOI: 10.1007/s11418-024-01860-9
Liang-liang Shi, Ya-ping Chen, Hao-ming Guo, Xue-peng Wang, Yang-yang Li, Shuai-zhe Wang, Shang-zu Zhang, Qi-hong Zhuo, Yong-qi Liu, Ben-jun Wei, Li-ying Zhang

Radiotherapy is a primary treatment method for lung cancer, and radiation-induced lung injury has been widely studied. However, the lung and intestines are closely related, and patients receiving lung radiotherapy often experience gastrointestinal reactions. Huanglian Decoction has proven effective in treating intestinal diseases, but its role in radiation-induced intestinal injury in lung cancer has not yet been demonstrated. The study investigated the potential protective mechanisms of Huanglian Decoction against radiation-induced intestinal injury in lung cancer. In vivo experiments were conducted to examine the morphological changes. Changes in endoplasmic reticulum stress-related proteins were assessed using electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. In vitro studies involved the overexpression of TRPA1 protein in NCM460 cells via lentiviral vectors. Tumor-bearing mice exhibited severe damage to both lung and colon tissues following radiotherapy, with elevated levels of IL-33, increased expression of ST2L and TRPA1 in colon tissues, higher levels of endoplasmic reticulum stress-related proteins, and the presence of apoptosis and inflammatory responses. Huanglian Decoction reduced radiation-induced intestinal injury by lowering IL-33 levels, which in turn reduced endoplasmic reticulum stress response in colon tissues. In TRPA1-overexpressing NCM460 cells, Huanglian Decoction decreased TRPA1 expression levels and significantly alleviated endoplasmic reticulum stress response. Conclusively, the results indicate that Huanglian Decoction alleviates radiation-induced intestinal endoplasmic reticulum stress by reducing IL-33 levels, subsequently inhibiting the expression of ST2L and TRPA1 in colon tissues. This demonstrates the protective effect of Huanglian Decoction on the intestines during lung cancer radiotherapy, highlighting its promising clinical application in radiation protection.

Graphical Abstract

放射治疗是肺癌的主要治疗方法,放射性肺损伤已被广泛研究。然而,肺和肠是密切相关的,接受肺部放疗的患者经常会出现胃肠道反应。黄连汤对肠道疾病的治疗已被证实有效,但其在肺癌放射性肠道损伤中的作用尚未得到证实。本研究探讨黄连汤对放射性肺癌肠损伤的潜在保护机制。通过体内实验观察其形态学变化。内质网应激相关蛋白的变化通过电子显微镜、免疫组织化学、免疫荧光和Western blotting进行评估。体外研究通过慢病毒载体在NCM460细胞中过表达TRPA1蛋白。荷瘤小鼠放疗后肺和结肠组织均出现严重损伤,IL-33水平升高,结肠组织中ST2L和TRPA1表达增加,内质网应激相关蛋白水平升高,细胞凋亡和炎症反应出现。黄连汤通过降低IL-33水平减轻辐射引起的肠道损伤,从而降低结肠组织内质网应激反应。在TRPA1过表达的NCM460细胞中,黄连汤降低TRPA1表达水平,显著缓解内质网应激反应。综上所述,黄连汤通过降低IL-33水平,进而抑制结肠组织中ST2L和TRPA1的表达,缓解辐射诱导的肠内质网应激。这证明了黄连汤在肺癌放疗期间对肠道的保护作用,突出了其在放射防护方面的临床应用前景。
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引用次数: 0
Meroterpenoids with BACE1-inhibitory activity from the fruiting bodies of Suillus bovinus and Boletinus cavipes 牛肉菇和牛肉菇子实体中具有bace1抑制活性的牛肉菇萜类化合物。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-11-30 DOI: 10.1007/s11418-024-01862-7
Takamasa Yamaguchi, Hiroaki Sasaki, Genki Yatsu, Kiyotaka Koyama, Kaoru Kinoshita

Alzheimer disease (AD) is the most common type of dementia and accounts for the largest proportion of dementia cases. The amyloid cascade hypothesis is known for the pathogenesis of AD, in which excessive accumulation of amyloid-β (Aβ) leads to the formation of senile plaques and ultimately to AD. Inhibition of β-secretase (BACE1) may contribute to the treatment of AD by suppressing Aβ production. In this study, we isolated and characterized the activity of new and known BACE1-inhibiting compounds from two mushrooms of the Boletales order, Suillus bovinus and Boletinus cavipes, using a BACE1-inhibitory activity-guided separation approach. Three compounds (13) were isolated from Suillus bovinus CHCl3 extract and three compounds (4–6) were isolated from Boletinus cavipes CHCl3 extract. Compound 1 was a new compound. The structures were elucidated using MS, IR, and NMR. Compounds 16 showed BACE1-inhibitory activity (IC50; 21.2, 17.8, 1.0, 1.6, 23.7, and 22.8 μM, respectively). To examine the structure–activity relationship, we also evaluated the activity of geranylgerniol, farnesol, 2,5-dihydroxy-1,4-benzoquinone and mesaconic acid. These compounds showed no activity, and these results indicate that chain terpenes alone do not show BACE1-inhibitory activity, but only when mesaconic acid or a quinone with a hydroxyl group is bound. In addition, the mode of inhibition of 2 and 3 were competitive and 4 was uncompetitive inhibition, respectively, as determined by analysis of Lineweaver–Burk and Dixon plots.

Graphical abstract

阿尔茨海默病(AD)是最常见的痴呆症类型,占痴呆症病例的最大比例。淀粉样蛋白级联假说被认为是AD的发病机制,其中淀粉样蛋白-β (Aβ)的过度积累导致老年斑的形成,最终导致AD。抑制β分泌酶(BACE1)可能通过抑制Aβ的产生来促进AD的治疗。在本研究中,我们采用bace1抑制活性引导分离的方法,从两种Boletales目蘑菇,Suillus bovinus和Boletinus cavipes中分离出新的和已知的bace1抑制化合物,并对其活性进行了表征。从牛毛菇CHCl3提取物中分离到3个化合物(1 ~ 3),从牛毛菇CHCl3提取物中分离到3个化合物(4 ~ 6)。化合物1是一个新化合物。用质谱、红外光谱和核磁共振对其结构进行了鉴定。化合物1-6显示bace1抑制活性(IC50;分别为21.2、17.8、1.0、1.6、23.7、22.8 μM)。为了检验其构效关系,我们还对香叶香叶醇、法尼醇、2,5-二羟基-1,4-苯醌和间松香酸的活性进行了评价。这些化合物没有表现出活性,这些结果表明链萜烯单独不表现出抑制bace1的活性,而只有当与mesaconic酸或带有羟基的醌结合时才表现出抑制bace1的活性。Lineweaver-Burk和Dixon图分析表明,2和3的抑制模式为竞争性抑制,4的抑制模式为非竞争性抑制。
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引用次数: 0
Inhibition of amyloid β aggregation and BACE1, and protective effect on SH-SY5Y cells, by p-terphenyl compounds from mushroom Thelephora aurantiotincta 香菇对三苯基化合物对β淀粉样蛋白聚集和BACE1的抑制作用及对SH-SY5Y细胞的保护作用
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-11-29 DOI: 10.1007/s11418-024-01865-4
Shuntaro Hirabayashi, Koji Fujihara, Takehito Saito, Hiroaki Sasaki, Shin Koike, Yuki Ogasawara, Kiyotaka Koyama, Kaoru Kinoshita

The number of patients with Alzheimer’s disease (AD) is expected to increase as the population ages. The amyloid cascade hypothesis is proposed as the pathogenic mechanism of AD. We report the isolation and structural determination of three new p-terphenyl compounds, thelephantin P (1), thelephantin Q (2), and thelephantin R (3), with four known compounds (47), from the fruiting bodies of Thelephora aurantiotincta Corner. We evaluated Aβ aggregation and BACE1 inhibitory activities and neuroprotective activities of these isolated compounds. Compound 1 was shown to be multi-inhibitors for AD. Compound 1 had an IC50 = 12.9 μM (Aβ), 6.3 μM (BACE1), and EC50 = 8.0 μM (neuroprotection), respectively. Therefore, these compounds are potential therapeutic agents for AD.

Graphical Abstract

随着人口的老龄化,阿尔茨海默病(AD)患者的数量预计会增加。淀粉样蛋白级联假说被认为是AD的发病机制。本文报道了从金象菌(theelephora aurantiotincta Corner)子实体中分离并鉴定了3个新的对terphenyl化合物:象素P(1)、象素Q(2)和象素R(3),以及4个已知化合物(4-7)。我们评估了这些分离化合物的Aβ聚集和BACE1抑制活性以及神经保护活性。化合物1被证明是AD的多重抑制剂。化合物1的IC50 = 12.9 μM (Aβ), 6.3 μM (BACE1), EC50 = 8.0 μM (neuroprotection)。因此,这些化合物是潜在的阿尔茨海默病治疗剂。
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引用次数: 0
Two novel butyrolactone lignan dimers from leaves of Castanopsis chinensis and their anti-inflammatory activities 两种新的栲叶丁内酯木脂素二聚体及其抗炎活性。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-11-29 DOI: 10.1007/s11418-024-01864-5
Ya-Feng Wang, Ping Lin, Nao Pang, Zhang-Bin Liu, Bing-Yuan Yang, Rui-Jie He, Yong-Lin Huang

Castanopsis genus (Fagaceae) were rich in plant polyphenols and often used as medicinal plants. In this study, two new lignan dimer compounds with anti-inflammatory activity and four known compounds were isolated and identified from 80% methanolic extract of Castanopsis chinensis leaves. The structure determination supported by computational chemistry and extensive spectroscopic analysis. Two new lignan dimer compounds significantly inhibited LPS-induced NO production in RAW 264.7 cells at 10 µM without cytotoxicity.

Graphical abstract

蓖麻属(壳斗科)富含植物多酚,常被用作药用植物。本研究从Castanopsis chinensis叶片80%甲醇提取物中分离鉴定了2个新的具有抗炎活性的木脂素二聚体化合物和4个已知化合物。计算化学和广泛的光谱分析支持了结构的确定。两种新的木脂素二聚体化合物在10µM条件下显著抑制lps诱导的RAW 264.7细胞NO生成,且无细胞毒性。
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引用次数: 0
Pharmacokinetics of seven major components in Aβ1-42-treated rats after oral administration of an aqueous extract of Curculiginis Rhizoma and Epimedii Folium 莪术、淫羊藿水提物经a β1-42处理后大鼠体内7种主要成分的药代动力学研究。
IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-11-29 DOI: 10.1007/s11418-024-01861-8
Junzuo Zheng, Jun Wang, Linlin Chen, Xuelian Jiang, Xuesong Zhang, Wenqi Ai, Yuman Xie, Ping Wang, Zhou Lan, Xiaoping Ding

Alzheimer’s disease (AD) is the main cause of dementia. Aβ-mediated neuroinflammation plays a crucial role in the development of AD. Curculiginis Rhizoma and Epimedii Folium, frequently used in combination for their synergistic effects, have shown promise for cognitive improvement and anti-inflammatory properties in previous studies. This study, for the first time, investigates the pharmacokinetic profile of seven key compounds in the aqueous extract of Curculiginis Rhizoma and Epimedii Folium (CREF) in both normal and Aβ1-42-treated rats. A validated high-performance liquid chromatography–tandem triple quadrupole mass (HPLC–QQQ-MS) method was used to simultaneously quantify curculigoside, orcinol glucoside, icariin, epimedin B/C, baohuoside I, and magnoflorine in rat plasma. Results revealed significant increases in AUC0-∞ and Cmax values for curculigoside, orcinol glucoside, epimedin B, icariin, and magnoflorine in Aβ1-42-treated rats compared to normal rats, accompanied by decreased plasma clearance (CL). These findings suggest that the pathological condition induced by Aβ1-42 significantly affects the pharmacokinetic characteristics of components in CREF, potentially leading to increased bioavailability in a cognitive impairment model. This discovery provides a novel perspective for exploring the mechanism of CREF’s therapeutic effects on cognitive impairment.

Graphical abstract

阿尔茨海默病(AD)是痴呆症的主要原因。a β介导的神经炎症在AD的发展中起着至关重要的作用。curcuriginis Rhizoma和淫羊藿(Epimedii Folium)经常被联合使用,因为它们具有协同作用,在以前的研究中已经显示出改善认知和抗炎特性的希望。本研究首次对莪术和淫羊藿(CREF)水提物中7个关键化合物在正常和a β1-42处理大鼠体内的药动学特征进行了研究。采用高效液相色谱-串联三重四极杆质谱(HPLC-QQQ-MS)方法同时定量大鼠血浆中的莪术皂苷、酢浆草醇糖苷、淫羊藿苷、淫羊藿苷B/C、保火皂苷I和木兰花碱。结果显示,与正常大鼠相比,a β1-42处理的大鼠对莪术苷、酢浆草醇糖苷、淫羊藿苷B、淫羊藿苷和木兰花碱的AUC0-∞和Cmax值显著升高,并伴有血浆清除率(CL)降低。这些发现表明,a - β1-42诱导的病理状态显著影响CREF中成分的药代动力学特征,可能导致认知障碍模型中生物利用度增加。这一发现为探索CREF治疗认知障碍的机制提供了新的视角。
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Journal of Natural Medicines
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