BIOORGANIC CHEMISTRY
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2025
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IF 4.7
Wenhao Zhou,Yijie Cai,Xilei Wang,Yijun Tu,Jiejuan Jiang,Jianqing Yu
Alantolactone (AL) and isoalantolactone (IAL) are the bioactive components of Inula racemosa Hook. f. and constitute a significant portion in this herb. These two compounds are widely utilized in pharmaceuticals, cosmetics, agriculture and other fields due to their extensive biological activities, exhibiting remarkable market potential. However, their current acquirement remains primarily reliant on traditional Chinese medicine, which makes it necessary to optimize the extraction process. Additionally, the minor components, particularly sesquiterpenes, are often overlooked due to the high contents of AL and IAL, which makes their chemical components still unclear. This study developed an HPLC detection method and optimized an ultrasound-assisted extraction process with response surface methodology (RSM), achieving optimal parameters: liquid-solid ratio of 15.34: 1, 88.92 % ethanol, and 49.21 °C. Furthermore, to identify the minor components, a novel combination of Feature-based Molecular Networking (FBMN), Network Annotation Propagation (NAP), and ClassyFire was employed. The results revealed that the minor sesquiterpenes still accounted for a high proportion. Systematic separation yielded 22 sesquiterpenes, including three novel compounds ( 1 – 3 ) and 19 known ones ( 4 – 22 ). Biological evaluation demonstrated that some compounds exhibited stronger cytotoxicity than AL and IAL against HepG2, SKOV3 and HeLa cells, and compound 14 showed the best cytotoxicity via apoptosis induction. Moreover, four compounds exhibited synergistic effects with cisplatin (CDDP) on SKOV3 cells. Compounds 14 and 15 displayed potent anti-inflammatory effects with IC 50 < 3 μM. These findings indicated that the neglected part still contain bioactive sesquiterpenes, deserving for further exploration.
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高影响因子
CNS Neuroscience & Therapeutics
·
2025
·Vol. 31
·期 7
·e70502
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IF 5
Xin Shu,Xinxin Zou,Jingxuan Zhang,Xu Fang,Xinyu Wang,Hui Wu,Xuan He,Dujuan Sha
Background Neuroinflammation is an important factor in ischemic stroke. Dehydrocostus lactone (DHC) plays an anti-inflammatory role in certain diseases. However, the role of DHC in neuroinflammation after ischemic stroke remains unclear. Methods DHC was administered to lipopolysaccharide (LPS)-treated BV2 cells and a middle cerebral artery occlusion (MCAO) model to detect the levels of inflammatory factors using quantitative real-time PCR, western blotting, and behavioral tests. Morphological changes in microglia were observed using immunofluorescence. The Swiss Target Prediction database was used to predict the target of DHC. Finally, a specific inhibitor of the target protein was used to investigate its potential synergistic role in neuroinflammation, both with and without being combined with DHC. Results The expression of inflammation-related factors both in vivo and in vitro was improved by DHC, and the neurological deficits in mice after MCAO were improved in the DHC administration group. In addition, the Swiss Target Prediction showed that CYP2A6 was a target of DHC. Specifically, the combination of DHC with the CYP2A6 inhibitor showed that DHC exerts anti-inflammatory effects in a CYP2A6-dependent manner. Conclusion Mechanistically, DHC inhibited neuroinflammation by binding to the target CYP2A6. Our study suggests that DHC is a promising new strategy for treating ischemic stroke.
研究领域:
神经生物学
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药理学
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免疫学
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生物化学
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高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Miaomiao Sun,Honghong Zhan,Xiaoliang Long,Ali M. Alsayed,Zhe Wang,Fancheng Meng,Guowei Wang,Jingxin Mao,Zhihua Liao,Min Chen
Background Irinotecan (CPT-11) is used as chemotherapeutic drug for treatment of colorectal cancer. However, without satisfactory treatments, its gastrointestinal toxicities such as diarrhea and intestinal inflammation severely restrained its clinical application. Roots of Aucklandia lappa Decne. are used as traditional Chinese medicine to relieve gastrointestinal dysfunction and dehydrocostus lactone (DHL) is one of its main active components. Nevertheless, the efficacy and mechanism of DHL against intestinal mucositis remains unclear. Purpose The present study aimed to investigate the protective effects of DHL on CPT-11-induced intestinal mucositis and its underlying mechanisms. Methods The protective effect of DHL was investigated in CPT-11-induced mice and lipopolysaccharide (LPS)+CPT-11 induced THP-1 macrophages. Body weight, diarrhea score, survival rate, colon length, and histopathological changes in mice colon and jejunum were analyzed to evaluate the protective effect of DHL in vivo . And DHL on reducing inflammatory response and regulating TLR4/NF‐κB/NLRP3 pathway in vivo and in vitro were explored. Moreover, DHL on the interaction between TLR4 and MD2 was investigated. And silencing TLR4 targeted by siRNA was performed to validate the mechanisms of DHL on regulating the inflammation. Results DHL prevented CPT-11-induced intestinal damage, represented by reducing weight loss, diarrhea score, mortality rate and the shortening of the colon. Histological analysis confirmed that DHL prevented intestinal epithelial injury and improved the intestinal barrier function in CPT-11 induced mice. Besides, DHL significantly downregulated the level of inflammatory cytokines by inhibiting TLR4/NF-κB/NLRP3 signaling pathway in CPT-11-induced mice and LPS+CPT-11-induced THP-1 macrophages. In addition, DHL blocked TLR4/MD2 complex formation. Molecular docking combined with SIP and DARTS assay showed that DHL could bind to TLR4/MD2 and occludes the hydrophobic pocket of MD2. Furthermore, Silencing TLR4 abrogated the effect of DHL on LPS+CPT-11 induced inflammatory response in THP-1 macrophages. Additionally, DHL ameliorate the CPT-11-induced intestinal mucositis without affecting the anti-tumor efficacy of CPT-11 in the tumor xenograft mice. Conclusion This study found that DHL exhibited the anti-inflammatory effects in CPT-11-induced intestinal mucositis by inhibiting the formation of TLR4/MD2 complex and then regulation of NF-κB/NLRP3 signaling pathway. DHL is potentially served as a novel strategy of combined medication with CPT-11.
研究领域:
药理学
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免疫学
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肿瘤学
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胃肠病学
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高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Jingwen Guo,Yuanzhi He,Jiaqi Li,Min Lin,Yihan Wu,Jiayi Yang,Zehui He,Long Meng,Zhi Wang,Qing Xia,Chunyun Zhu,Yongtai Zhang,Nianping Feng
Ulcerative colitis (UC), a chronic disease characterized by continuous damage to the intestinal mucosa and inflammation in the colon, comprises a series of gastrointestinal reactions and is difficult to cure. Here, we have designed a nanotherapeutic strategy combining pharmacotherapy with physical protection, which is achieved by constructing a green nanocarrier named cyclodextrin-based nanosponges (CDNSs) and encapsulating the insoluble drug parthenolide (PTL). CDNSs were transformed into a hydrogel driven by water, releasing the anti-inflammatory agent PTL and forming a sticky barrier in the position of the ulcer lesion to confront pathogenic bacteria at the same time. Notably, the resulting PTL-loaded CDNS (PTL@CDNS) had improved the solubility and intestinal cellular uptake of PTL. The orally delivered transformable PTL@CDNS via a colon-specific capsule significantly relieved UC in rats by enhancing the regulation of c-kit and STAT6 pathways as well as normalizing inflammatory cytokines, including IL-4, IL-6, IL-10, IL-13, nitric oxide, malondialdehyde, and TNF-α, with excellent biocompatibility. To sum up, transformable PTL@CDNSs were demonstrated as a promising strategy for in situ treatment of mucosal ulcers including UC.
研究领域:
药学
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生物医学工程
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消化系统疾病
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高影响因子
Food Chemistry-X
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2022
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IF 6.443
Xinyu Yang,Ru Zhao,Mengxia Wei,Huiyan Gu,Jialei Li,Lei Yang,Tingting Liu
An improved method denoted as salting out-solvent-free microwave rotary distillation (SOSFMRD) was successfully developed for the extraction of essential oils from fresh magnolia ( Oyama sieboldii ) leaves, in which we achieved the rotation of the reaction material by means of a rotating motor to subject the material to uniform microwave irradiation. Magnesium chloride was selected as the salting-out agent through a comparative study on the salting-out effects of different anions and cations of metal salts. The variables of SOSFMRD were systematically optimized. Under the obtained optimization conditions, the essential oil yield was 21.68 ± 1.02 mL/kgDW. Gas chromatography–mass spectrometry analysis showed that the main chemical constituent of O. sieboldii essential oil was dehydrocostuslactone, the content of which reached 30.23 ± 1.27 %. Compared with the other conventional methods, this method has a high yield and low energy consumption, which can effectively reduce impact on the environment.
研究领域:
化学工程
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植物化学
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环境科学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Chunlei Wei,Lingjiao Wu,Yuyi Wu,Chunyi Xu,Huiling Hu,Zhanguo Wang
Ethnopharmacological relevance As a representative local medicinal herb produced in China, Vladimiriae Radix (VR) has been proven to exert hepatoprotective and choleretic effects, with particular therapeutic efficacy in cholestatic liver injury (CLI), as demonstrated by the VR extract (VRE). However, the quality markers (Q-markers) of VRE for the treatment of CLI remain unclear. Aim of the study A new strategy based on the core element of “efficacy" was proposed, using a combination of spectrum-effect relationship, pharmacokinetics, and molecular docking methods to select and confirm Q-markers of VRE. Material and methods First, the HPLC fingerprinting of 10 batches of VRE was studied, and the in vivo pharmacological index of anti-CLI in rats was determined. The spectrum-effect relationship was utilized as a screening method to identify the Q-markers of VRE. Secondly, Q-markers were used as VRE pharmacokinetic markers to measure their concentrations in normal and CLI rat plasma, and to analyze their disposition. Finally, molecular docking was utilized to predict the potential interaction between the identified Q-markers and crucial targets of CLI. Results The fingerprints of 10 batches of VRE was established. The in vivo pharmacological evaluation of rats showed that VRE had a significant therapeutic effect on CLI. The spectrum-effect correlation analysis showed that costunolide (COS) and dehydrocostus lactone (DEH) were the Q-markers of VRE anti-CLI. The pharmacokinetic results showed that AUC (0-t) , C max , CL Z/F , and V Z/F of COS and DEH in CLI rats had significant differences ( P < 0.01). They were effectively absorbed into the blood plasma of CLI rats, ensuring ideal bioavailability, and confirming their role as Q-markers. Molecular docking results showed that COS, DEH had good affinity with key targets (FXR, CAR, PXR, MAPK, TGR5, NRF2) for CLI treatment (Binding energy < −4.52 kcal mol −1 ), further verifying the correctness of Q-marker selection. Conclusions In this study, through the combination of experimental and theoretical approaches from the aspects of pharmacodynamic expression, in vivo process rules, and interaction force prediction, the therapeutic effect of VRE and Q-markers (COS、DEH) were elucidated. Furthermore, a new idea based on the principle of “efficacy" was successfully proposed for screening and evaluating Q-markers.
研究领域:
民族药理学
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药理学
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分析化学
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分子生物学
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JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Jun Li,Ming Li,Ke Ye,Qixin Jiang,Mi Wang,Xiaodong Wen,Jie Yang
Ethnopharmacological relevance Xian-He-Cao-Chang-Yan formula (XHCF) is consisting of six crude drugs including Agrimoniae Herba, Coptidis Rhizoma , Aucklandiae Radix, Cicadae Periostracum, Acori Tatarinowii Rhizoma, and Platycodonis Radix at the ratio of 5:1.5:1.5:1.5:1.5:1. It has been used to improve syndromes of ulcerative colitis (UC) for many years. Aim of the study This study was designed to study the bioactive ingredients and therapeutic mechanisms of XHCF. Materials and methods The chemical profile of XHCF was characterized by UHPLC-QTOF-MS/MS. The effects and mechanisms of XHCF on UC were investigated in colitis mice induced by dextran sulfate sodium (DSS) and LPS-stimulated RAW 264.7 cells. Results A total of 103 compounds were characterized in XHCF. XHCF could effectively improve acute colitis induced by DSS. More importantly, XHCF significantly decreased M1 macrophage markers (CD11c, IL-6 and IL-1β) whereas increased M2 macrophage markers (CD206) in colitis mice, suggesting it could regulate macrophage polarization. Furthermore, the levels of HK2 and lactic acid in colon tissues were significantly reduced by XHCF, indicating that XHCF could inhibit glycolysis. It also down-regulated HK2 expression in macrophages challenged by LPS. In addition, XHCF enhanced the phosphorylation of AMPK both in vivo and in vitro , suggesting the involvement of AMPK in XHCF function. Conclusions XHCF ameliorated DSS-induced colitis in mice via inhibition of M1 macrophage polarization, probably by the modulation of macrophage metabolic reprogramming via AMPK, contributing to its anti-inflammatory activity. The synergistic actions of multiple ingredients might be responsible for the therapeutic benefits of XHCF on UC.
研究领域:
药理学
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免疫学
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胃肠病学
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中医
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高影响因子
Analytical Methods
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2016
·Vol. 8
·期 23
·4727-4735
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IF 1.915
Chaojun He,Xiangmeng Guo,Yumin Yang,Yanfu Xie,Fengyang Ju,Wenbo Guo
Aroma volatiles from zijuan and pu-erh green teas were extracted by headspace solid-phase microextraction (HS-SPME). They were then characterized and identified using gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS). The conditions of HS-SPME, including fiber selection and optimization of sampling conditions, have been previously investigated. Under optimal conditions, 51 and 42 aroma-active compounds were detected and characterized in zijuan and pu-erh green tea samples, respectively. Alcohols, ketones, and hydrocarbons were qualitatively the most dominant aroma-active compounds in zijuan and pu-erh green teas. The aroma-active compounds with similar sensory descriptors were grouped into the same category, and the sum of individual aroma intensity values within each category showed that the “floral” aroma, “woody” aroma, and “fruity” aroma in both zijuan and pu-erh green teas were the major aroma categories. These aroma notes were closely related to the characteristics of green tea aroma and its sensory perception.
研究领域:
食品科学
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分析化学
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茶叶科学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Liqian Chen,Xinghong Zhou,Yijian Deng,Ying Yang,Xiaohu Chen,Qinghong Chen,Yanyan Liu,Xiuqiong Fu,Hiu Yee Kwan,Yanting You,Wen Jin,Xiaoshan Zhao
Ethnopharmacological relevance Zhenwu Decoction (ZWD) is a traditional Chinese medicine (TCM) formula which has wide scope of indications related to Yang deficiency and dampness retention in TCM syndrome. Cardiac hypertrophy can induce similar symptoms and signs to the clinical features of Yang deficiency and dampness retention syndrome. ZWD can increase the left ventricular ejection fraction, reduce cardiac hypertrophy of patients with chronic heart failure. However, its underlying pharmacological mechanism remains unclear. Aim of the study The study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms. Materials and methods The potential targets and pathways of ZWD in cardiac hypertrophy were highlighted by network pharmacology and validated by mechanistic and functional studies. Results Our network pharmacology analysis suggests that the protective effects of ZWD on cardiac hypertrophy are related to cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Subsequent animal studies showed that ZWD significantly ameliorated cardiac function decline, cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. To explore the underlying mechanisms of action, we performed Western blotting, immunohistochemical analysis, and detection of inflammatory response and oxidative stress. Our results showed that ZWD activated the soluble guanylate cyclase (sGC) - cGMP - PKG signaling pathway. The sGC inhibitor ODQ that blocks the sGC-cGMP-PKG signaling pathway in zebrafish abolished the protective effects of ZWD, suggesting sGC-cGMP-PKG is the main signaling pathway mediates the protective effect of ZWD in cardiac hypertrophy. In addition, three major ingredients from ZWD, poricoic acid C, hederagenin and dehydrotumulosic acid, showed a high binding energy with prototype sGC. Conclusion ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.
研究领域:
药理学
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心脏病学
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中医药
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网络药理学
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高影响因子
危险品化学品经营许可证（带存储）