JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Wei Zhang,Mengjiao Wang,Huijie Song,Chengfeng Gao,Dongmei Wang,Huiming Hua,Yingni Pan,Xiaoqiu Liu
Ethnopharmacological relevance Evodiae Fructus (EF), the traditional Chinese medicine , has been typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It is a mild toxicity herb-medicine listed in Sheng Nong's Herbal Classic . Recently, EF was reported to have toxicity or no toxicity in some investigations. Toxicity and approaches to reducing toxicity of EF are of great interest. Limonin (LIM), a major triterpenoid component of EF, also had various pharmacological activities such as anti-inflammatory, anticancer, and antioxidant effects. However, little attention was paid to the role of LIM in EF-induced hepatotoxicity. Aim of study The study aimed to address the problem of controversial hepatotoxicity of EF, evaluate the role of CYP3A4 inducer/inhibitor in EF-induced hepatotoxicity and disclose the effect of LIM in EF-induced hepatotoxicity. Materials and methods The chemical compositions and hepatotoxicity of small flower EF (SEF), medium flower EF (MEF), big flower EF (BEF) and the “organ knock-out” samples (the shell and seed part of BEF) were investigated. Simultaneously, C57BL-6 mice were randomly divided into four groups, which were given orally administered BEF, BEF in combination with dexamethasone (DEX), BEF in combination with ketoconazole (KTC), and BEF in combination with LIM, respectively. Results In this study, more alkaloids and less LIM were detected in BEF compared with the compounds in SEF and MEF. Furthermore, we found that BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in SEF and MEF groups. In addition, no LIM was detected in the shell part of BEF and five alkaloids were not detected in the seed part of BEF. Correspondingly, the shell part of BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in the seed part of BEF group. It was also found that the BEF-induced hepatotoxicity was remarkably exacerbated when the mice were pretreated with DEX whereas the BEF-induced hepatotoxicity could be reversed by pretreatment with KTC or LIM. Conclusions Based on the results in this study, the misuse of BEF but not SEF and MEF could produce hepatotoxicity. The hepatotoxicity difference of different categories of EF might be associated with the relative contents of alkaloids and LIM. In addition, the results demonstrated that CYP3A4 inducer aggravated BEF-induced hepatotoxicity and LIM attenuated its hepatotoxicity.
研究领域:
民族药理学
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毒理学
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药理学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
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IF 8.5
Di Sun,Yifan Liu,Zihui Jin,Bo Xu,Yaqi Jin,Qiyang Zhao,Yue He,Jing Li,Yaohai Zhang,Yongliang Cui
Limonin is an intensely bitter and highly oxidized tetracyclic triterpenoid secondary metabolite, which is abundant in the Rutaceae and Meliaceae, especially in Citrus. In order to detect limonin content in complex substrates such as citrus and traditional Chinese medicine, monoclonal antibodies specifically recognizing limonin were prepared and an indirect competitive enzyme-linked immunosorbent assay (icELISA) was established. The median inhibition concentration (IC 50 ) was 5.40 ng/mL and the linear range was 1.25–23.84 ng/mL. The average recoveries from citrus peel and pulp samples were 95.9%–118.8% and 77.5%–113.1%, respectively. Moreover, the contents of limonin in 6 citrus samples and 4 herbal samples were analyzed by icELISA and UPLC-MS, and the results of the two methods were consistent. This validation is sufficient to demonstrate that the developed immunoassay is applicable for the detection of limonin in citrus and herbal samples and has the advantage of high efficiency, sensitivity, and convenience.
研究领域:
分析化学
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免疫学
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食品科学
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生药学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2019
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IF 3.858
Yikun Liu,Wei Zhou,Zhenkun Mao,Zilin Chen
Evodiae Fructus is used as a traditional Chinese medicine for the treatment of several kinds of diseases with its bioactive constituents. In this study, a capillary electrochromatography-mass spectrometry (CEC-MS) method was developed to determine three bioactive compounds including evodiamine, rutaecarpine and limonin in Evodiae Fructus fruit. Home-developed monolithic columns with methyl-vinylimidazole functionalized organic polymer monolilth as stationary phases were used in CEC-MS with excellent separation selectivity and high efficiency. The CEC-MS methods provided 4–16 folds improvement of LODs when compared with CEC-UV method. The conditions, which could affect separation efficiency and detection sensitivity, were optimized. Under optimum conditions, baseline separation with high detection sensitivity was obtained. The method showed good linearity (R 2 >0.99) of 0.8–160 μg mL −1 with low limits of detection of 0.15-0.31 μg mL −1 . Relative standard deviations of migration time and relative peak areas were <13.89%. Recoveries of evodiamine, rutaecarpine and limonin in Evodiae Fructus fruit were tested and calculated, which ranged from 102% to 113%. Finally, the three bioactive compounds in Evodiae Fructus herb samples from different regions were analyzed and studied. It has been demonstrated that the developed method has great potential for quality control of Evodiae Fructus herb.
研究领域:
中药分析
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分析化学
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药学
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DOI
高影响因子
Food & Function
·
2015
·Vol. 6
·期 11
·3540-3549
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IF 2.791
Aihua Zhang,Huiyu Wang,Hui Sun,Yue Zhang,Na An,Guangli Yan,Xiangcai Meng,Xijun Wang
Limonin has been found to possess significant anti-inflammatory properties in animal tests and with, human cells, however, its precise metabolism mechanism has not been well explored. The aim of this study was to investigate the anti-inflammatory effects of limonin in a nonbacterial prostatitis (NBP) animal model. Global metabolite profiling was performed by ultra-high-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC/ESI-TOFMS) and in conjunction with multivariate data analysis and pathway analysis which were integrated to explore differentiating metabolites and clarify the mechanism of limonin against capsaicin-induced NBP. Limonin has a potential protective function revealed by the metabolic profiling of limonin-treated rats located closer to the normal group. Twenty potential biomarker candidates and several key metabolic pathways contributing to the treatment of NBP were discovered and identified. Among the pathways, the related glycine, serine and threonine metabolism, glycerophospholipid metabolism were acutely perturbed. The changes in metabolites were restored to their base-line levels after limonin treatment, which might be through regulating the perturbed pathways to the normal state. The results indicate that changed biomarkers and pathways may provide evidence and insight into limonin action mechanisms and enable us to increase research productivity toward metabolomics in therapeutical assessment and drug discovery.
研究领域:
药理学
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代谢组学
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炎症研究
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PubMed
高影响因子
International Journal of Biological Sciences
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2023
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IF 9.2
Xianke Zhou,Yadie Xiang,Dier Li,Menghua Zhong,Xue Hong,Yuan Gui,Wenjian Min,Yudan Chen,Xi Zeng,Haili Zhu,Youhua Liu,Shijia Liu,Peng Yang,Fanfan Hou,Dong Zhou,Haiyan Fu
Acute kidney injury (AKI) is a refractory clinical syndrome with limited effective treatments. Amid AKI, activation of the extracellular signal-regulated kinase (ERK) cascade plays a critical role in promoting kidney repair and regeneration. However, a mature ERK agonist in treating kidney disease remains lacking. This study identified limonin, a member of the class of compounds known as furanolactones, as a natural ERK2 activator. Employing a multidisciplinary approach, we systemically dissected how limonin mitigates AKI. Compared to vehicles, pretreatment of limonin significantly preserved kidney functions after ischemic AKI. We revealed that ERK2 is a significant protein linked to the limonin's active binding sites through structural analysis. The molecular docking study showed a high binding affinity between limonin and ERK2, which was confirmed by the cellular thermal shift assay and microscale thermophoresis. Mechanistically, we further validated that limonin promoted tubular cell proliferation and reduced cell apoptosis after AKI by activating ERK signaling pathway in vivo . In vitro and ex vivo , blockade of ERK abolished limonin's capacity of preventing tubular cell death under hypoxia stress. Our results indicated that limonin is a novel ERK2 activator with strong translational potential in preventing or mitigating AKI.
研究领域:
药理学
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肾病学
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分子生物学
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临床研究
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PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Wei-yun Zhang,Jin-song Liao,Jun-ru Qi
Despite the well-established role of calcium in pectin gelation, the regulatory mechanisms by which Ca 2+ concentration governs the microstructure and functionality of emulsion gels derived from citrus pectin remain poorly understood. This study bridges this knowledge gap by employing citrus pectin with distinct fine structures to fabricate emulsion gel system via Ca 2+ -mediated cross-linking, systematically elucidating the influence of Ca 2+ on gel microstructure, rheology, and stability. The results demonstrated that low-methoxyl pectin (LMP) formed a dense gel network through Ca 2+ cross-linking. In contrast, the structure of high-methoxyl pectin (HMP) emulsion gels was stabilized predominantly by hydrophobic interactions. An increased ratio of rhamnogalacturonan I (RGI) side chains enhanced hydrogen bonding interactions, though excessive Ca 2+ (10 mM) induced localized over-crosslinking in LM.HRGI, increasing droplet size and reducing homogeneity. In vitro digestion experiments revealed that LM.HRGI-based emulsion gels facilitated rapid limonin release in the colon (release rate constant k = 0.54 min −1 ), whereas HMP-based gels showed sustained intestinal release ( k = 0.17 min −1 ). The encapsulation efficiency of limonin reached 85.24 % in optimally formulated LM.LRGI-based emulsion gels (5 mM Ca 2+ ). The study established a quantitative structure-gel property-delivery behavior relationship model, demonstrating that the multivariate fine structure of pectin dictates the digestion fate of loaded bioactives, providing a foundational principle for the engineering of functional foods and precise design of nutraceutical delivery systems.
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PubMed
高影响因子
Foods
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2025
·Vol. 15
·期 1
·
IF 5.1
Limin Wang,Qianfei Jia,Yuxi Qin,Shufen Li,Zijian Wu
This study aimed to fabricate an active film incorporating limonin (LM) and resveratrol (RES) within a zein/shellac (ZS) matrix for use in strawberry preservation. Zein/shellac composite films embedded with varying concentrations of LM (0–4%w/w) and RES were successfully fabricated using coaxial electrospinning. The prepared films were comprehensively characterized for their mechanical properties, water vapor permeability (WVP), antioxidant capacity (DPPH, ABTS, FRAP), and antibacterial efficacy againstE. coliandS. aureus. Mechanical properties and WVP results revealed that the ZSLM4R film exhibited an elongation at break (EBA) of 28.91%, tensile strength (TS) of 0.93 MPa, elastic modulus (EM) of 40.76 MPa, and a WVP of 1.55 g mm/m2. h. kPa. Furthermore, LM and RES increased the antioxidant properties of the composite film. ZSLM4R’s free radical scavenging activities against DPPH and ABTS were 68.14% and 89.69%, respectively. The composite film also demonstrated strong antibacterial efficacy againstE. coliandS. aureus. When applied to strawberries, ZSLM4R packaging effectively extended the fruit’s shelf life compared to the unwrapped and commercial polyethylene (PE) controls. These obtained results indicate that LM/RES-incorporated zein/shellac composites are a promising eco-friendly packaging alternative for preserving perishable fresh produce and extending its shelf life.
研究领域:
食品科学与技术
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高分子材料
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活性包装
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采后保鲜
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食品安全
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Jie Chen,Dexian Li,Xiaohu Chen,Qiuxing He,Anna Zuo,Baizhao Peng,Ying Yang,Chuanghai Wu,Qinghong Chen,Zihao Jiang,Ziwei Li,Wen Fang,Jingxin Lin,Hiu Yee Kwan,Xiaomin Sun,Lin Zhou,Xiaoshan Zhao
Limonin alleviates hyperuricemia-induced cognitive impairment and neuroinflammation in UOX −/− rat models. • Limonin exerts neuroprotective effects by inhibiting microglial activation and subsequent neuronal apoptosis. • Limonin modulates the HIF-1α/iNOS pathway to exert anti-inflammatory and neuroprotective effects. Background Hyperuricemia (HUA), a highly prevalent metabolic disorder, is increasingly linked to cognitive impairment. Limonin (LIM), a natural compound with anti-inflammatory and neuroprotective properties, has the therapeutic benefits, but its underlying mechanisms remain unclear. Purpose This study aimed to investigate the therapeutic effect and mechanism of LIM on HUA-induced cognitive impairment. Methods A rat model of HUA-induced cognitive impairment was established using urate oxidase gene knockout (UOX −/− ) rat. Uric acid (UA) levels of serum and cerebrospinal fluid (CSF) were measured to confirm hyperuricemia. Cognitive function was assessed using morris water maze test, while neuronal morphology and synaptic integrity were evaluated via Nissl staining and synaptic plasticity biomarkers. Microglial activation and polarization were examined through double immunofluorescence staining of CD86/IBA1 and ARG1/IBA1, inflammatory and oxidative stress markers were quantified using ELISA, qRT-PCR and Western blot. In vitro , BV2 microglial cells were stimulated with UA to model activation and inflammatory responses. HT22 neuronal cells were co-cultured using conditioned medium to assess apoptosis via TUNEL assay and expression of apoptosis-related biomarkers. RNA sequencing was performed to identify key signaling pathways modulated by LIM, and the findings were validated through targeted gene overexpression or inhibition experiments. Results The UOX −/− rat model successfully recapitulated HUA-induced cognitive impairment, as evidenced by elevated UA levels, alongside significant cognitive deficits. LIM treatment ameliorated these cognitive impairments, attenuated neuropathological alterations, modulated microglial M1/M2 polarization, and reduced neuroinflammation and oxidative damage. In vitro , LIM suppressed UA-induced microglial activation and inflammatory response, while also rescuing neuronal apoptosis in HT22 cells. RNA sequencing revealed involvement of the HIF-1 pathway. HIF-1α inhibitor YC-1 enhanced LIM's effects, whereas HIF-1α activator DMOG reversed them, suggesting that the modulation of the HIF-1α/iNOS pathway contributes to redox homeostasis and neuroinflammation. Conclusion LIM ameliorates HUA-induced cognitive impairment by suppressing microglial activation and neuroinflammation, which is associated with the inhibition of the HIF-1α/iNOS signaling pathway, underscoring its therapeutic potential. Download: Download high-res image (110KB) Download: Download full-size image
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Danyang Chen,Xiangbo Ma,Jingjing Zhu,Yong Wang,Shuai Guo,Jianglei Qin
Self-healing hydrogels have shown great application potential in drug delivery for anti-tumor therapy and tissue engineering. In this research, Doxorubicin (DOX) was coupled onto the oxidized pectin (pec-Ald) to prepare DOX grafted pec-AD and used to fabricate self-healing hydrogel for lung cancer therapy combined with novel herbal medicine extract limonin targeting lung cancer cells. The hydrogel was prepared with P(NIPAM 195 - co -AH 54 ) cross-linking and the hydrazone bond cross-linked hydrogel showed good mechanical property and self-healing behavior. With pectin composition , the hydrogel was still biodegradable catalyzed by enzyme and in vivo. The hydrogel formed fast fit for injectable application and the hydrogel itself showed moderate lung cancer inhibition activity. With limonin loading, the hydrogel showed synergistic lung cancer therapy with the tumor growth greatly inhibited. The covalent coupling of DOX and loaded limonin in the hydrogel decreased in vivo toxicity and the hydrogel degraded on time. With biodegradability and improved lung cancer therapy efficiency, this DOX grafted self-healing hydrogel could find great potential application in cancer therapy in near future.
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PubMed
高影响因子
Analytical Methods
·
2025
·
IF 2.6
Tian Zhang,Chenxi Guo,Lu Yang,Lei Liu,Di Sun,Xinqi Long,Qi Wu,Qiyang Zhao,Yaohai Zhang,Jing Li,Yongliang Cui,Yue He
The detection of limonin, a bitter compound in citrus samples, is crucial for maintaining product quality, safety, and marketability, and ultimately benefits both producers and consumers. In this assay to effectively modify the monoclonal antibody on gold nanobipyramids (AuNBP), we replaced the original hexadecyltrimethylammonium bromide coating (CTAB) with SH-PEG2000-NHS. Then AuNBP were modified with a limonin-specific monoclonal antibody (mAb) to create the AuNBP@mAb immunoprobe. We present a novel plasmonic AuNBP-based lateral flow immunoassay (LFIA) for colorimetric and photothermal assay of limonin. The limit of detection for the colorimetric mode of AuNBP is 4.8 ng/mL. The limit of detection for the photothermal mode of AuNBP is 3.8 ng/mL .Validation experiments using citrus samples demonstrate the robustness and reliability of the LFIA in real-world applications. Comparative analysis with ultra-high performance liquid chromatography tandem mass spectrometry confirms the accuracy of our LFIA.
研究领域:
食品科学
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Nawei Zhang,Yang Xu,Xiao Jia,Xiao Li,Jingnan Ren,Siyi Pan,Gang Fan,Jinchu Yang
BACKGROUND Citrus products often suffer from delayed bitterness, which is generated from the conversion of non-bitter precursors (limonoate A-ring lactone, LARL) to limonin under the catalysis of limonin D-ring lactone hydrolase (LDLH). In this study, LDLH was isolated and purified from sweet orange seeds, and a rapid and accurate high-performance liquid chromatography method to quantify LARL was developed and applied to analyze the activity and enzymatic properties of purified LDLH. RESULTS Purified LDLH (25.22 U mg −1 ) showed bands of 245 kDa and 17.5 kDa molecular weights in native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate PAGE analysis respectively. After a 24 h incubation under strongly acidic (pH 3) or strongly alkaline (pH 9) conditions, LDLH still retained approximately 100% activity. Moreover, LDLH activity was not impaired by thermal treatment at 50 °C for 120 min. Enzyme inhibition assays showed that LDLH was inactivated only after ethylenediaminetetraacetic acid treatment, and other enzyme inhibitors showed no significant effect on its activity. In addition, the LDLH activity of calcium ion (Ca 2+ ) intervention was 108% of that in the blank group, and that of zinc ion (Zn 2+ ) intervention was 71%. CONCLUSION LDLH purified in this study was a multimer containing 17.5 kDa monomer with a wide pH tolerance range (pH 3–9) and excellent thermal stability. Moreover, LDLH might be a metallopeptidase, and its activity was stimulated by Ca 2+ and significantly inhibited by Zn 2+ . These findings improve our understanding of LDLH and provide some important implications for reducing the bitterness in citrus products in the future. © 2024 Society of Chemical Industry.
研究领域:
植物科学
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生物化学
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食品科学
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酶学
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DOI
PubMed
高影响因子
Microorganisms
·
2021
·Vol. 9
·期 5
·969
·
IF 4.128
Yi Li,Runan Zhao,Yan Li,Zhiqin Zhou
Penicillium italicum, the cause of citrus blue mold, is a pathogenic fungus that seriously affects the postharvest quality of citrus fruit and causes serious economic loss. In this study, a eugenol nanoemulsion containing limonin, an antimicrobial component from citrus seeds, was prepared using a high-pressure microfluidizer and the antifungal activity of the nanoemulsions againstP. italicumwas evaluated based on the conidial germination rate, mycelial growth, and scanning electron microscopy analysis. The results showed that the minimum inhibitory concentration and the inhibition rate of limonin-loaded eugenol nanoemulsion was 160 μg/mL and 59.21%, respectively, which was more potent than that of the limonin-free eugenol emulsion. After treatment with the nanoemulsions, the integrity of theP. italicumcell membrane was disrupted, the cell morphology was abnormal, and the leakage of nucleic acid and protein was observed. In addition, the challenge test on citrus fruits revealed that the limonin-loaded eugenol emulsion inhibited citrus infection for longer periods, with an infection rate of 29.2% after 5 days. The current research shows that nanoemulsions containing limonin and eugenol have effective antifungal activity againstP. italicum, and may be used as a substitute for inhibiting blue mold in citrus fruits.Keywords:eugenol nanoemulsion;citrus blue mold;limonin;Penicillium Italicum;antifungal activity
研究领域:
植物病理学
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食品科学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）