Food & Function
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2014
·Vol. 6
·期 2
·584-589
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IF 2.907
Lianqi Huang,Xin Yang,Anlin Peng,Hui Wang,Xiang Lei,Ling Zheng,Kun Huang
Long-term hyperglycemia is a typical symptom of diabetes mellitus (DM) which can cause a high level of protein glycation and lead to the formation of advanced glycation end products (AGEs). The accumulation of AGEs in turn deteriorates DM and its complications. Insulin, the only hormone that directly decreases blood sugar in vivo, is vulnerable to glycation which causes the loss of its biological activity. In this study, we used a porcine insulin (PI)–methylglyoxal (MGO) model to investigate the inhibitory effect of leonurine (LN), a natural alkaloid extracted from Herba leonuri, on AGE formation. Assays including AGE-specific fluorescence, and fructosamine level and carbonyl group content determination showed that LN can dose-dependently suppress PI glycation. A significantly decreased cross-linking level on the glycated PI was also proven by SDS-PAGE electrophoresis. A further liquid chromatography-mass spectrometry study suggested that LN may inhibit PI glycation through trapping MGO and keeping it from reacting with PI. Our results thus indicate that LN is a promising anti-glycation agent for the prevention of diabetes and its complications via inhibiting AGE formation.
研究领域:
药理学
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糖尿病研究
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DOI
PubMed
高影响因子
Aging-US
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2019
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IF 5.515
Peng Chen,Fuchao Chen,Ben-hong Zhou
Aging is a complex physiological phenomenon associated with oxidative stress damage. The objective of this study was to investigate the potential effects of leonurine on D-galactose-induced aging in mice and its possible mechanisms. In this study, we first tested the antioxidant activity of leonurine in vitro . A subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of leonurine. The results showed that treatment with 150 mg·kg -1 leonurine could improve the mental condition, organic index, and behavioural impairment; significantly increase the activities of antioxidative enzymes including SOD, CAT, and T-AOC; and ameliorate the advanced glycation end product (AGE) level and histopathological injury. Furthermore, the Western blotting data revealed that leonurine supplementation noticeably modulated the suppression of the Nrf2 pathway and upregulated the downstream expression of HO-1 and NOQ1 in aging mice. Additionally, leonurine treatment activated Nrf2 nuclear translocation in both aging mice and normal young mice, and the expression levels of Nrf2 in normal young mice was higher than those in naturally aging mice. In conclusion, our findings suggest that leonurine is a promising agent for attenuating the aging process, and the underlying molecular mechanisms depend on activating the Nrf2 pathway.
研究领域:
老年学
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药理学
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分子生物学
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Li Zhang,Hui-Xia Li,Wu-Si Pan,Farhan Ullah Khan,Cheng Qian,Feng-Rong Qi-Li,Xiaojun Xu
Background and aims Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome and is characterized by steatosis, inflammation, and fibrosis. We aim to characterize the hepatoprotective effects of Leonurine hydrochloride (LH) and the possible pathway in a cell and rodent model of diet-induced steatohepatitis (NASH). Methods For in vitro studies, Palmitic acid (PA) and free fatty acid (FFA) induced HepG2 and HL7702 steatosis cell models were used. For in vivo studies, NASH was induced by feeding mice MCD diet. These mice received either placebo or LH at three different doses (50、100、200 mg/kg/day) for 6 weeks. Histological staining’s, and commercially available kits for ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively. Results After establishing NASH models, LH treatment improved lipid accumulation, hepatic contents of TG, TC, and expression levels of ALT and AST in dose-dependent manner. Also, LH improved MDA, SOD, and GSH expression levels. The results of RT-PCR and Western blotting showed that LH upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes expression level. Conclusions Our data reveal the promising role of Leonurine hydrochloride in the prevention and treatment of NASH, in vitro and in vivo . This effect may be partially mediated by the AMPK/SREBP1 pathway. These findings provide a novel therapeutic target for the clinical treatment of NASH.
研究领域:
药理学
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肝病学
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代谢性疾病
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PubMed
高影响因子
Natural Product Communications
·
2021
·
IF 0.986
Liping Liu,Cheng Wang,Xuemei Luo,Yuwen Wang,Fang Li
ObjectivemiRNAs as pharmaco-targets have been investigated in multifarious diseases. Our study aimed to determine whether leonurine was a potential cardioprotective agent by targeting miRNAs in hypoxia-stimulated mice and H9c2 cardiomyocytes.MethodsCell proliferation and apoptosis were examined by CCK-8 and TUNEL assay in hypoxia-stimulated rat H9c2 cardiomyocytes. miRNAs expression levels in cardiomyocytes in response to hypoxia stimulation were detected by RT-qPCR. Mice with myocardial injury were induced by chronic intermittent hypoxia stimulation.ResultsLeonurine alleviated hypoxia-induced cardiac hypertrophy in mice. Moreover, up-regulation of miR-31 and down-regulation of miR-210 in hypoxia-stimulated mice were reversed by leonurine administration. Leonurine exhibited cardioprotective activity in an vitro cell model of hypoxia-stimulated rat H9c2 cardiomyocytes, reflecting that the compound improved hypoxia-induced growth inhibition and apoptosis of cardiomyocytes. TUNEL assay revealed that transfection of miR-31 inhibitors or miR-210 mimics abrogated hypoxia-induced cardiomyocyte apoptosis. In contrast to that, miR-31 mimics or miR-210 inhibitors counteracted the anti-apoptotic effect of leonurine on hypoxia-treated rat H9c2 cardiomyocytes.ConclusionOur findings suggest that miR-31 and miR-210 as the upstream regulators of leonurine are involved in hypoxia-induced cardiomyocyte apoptosis. Leonurine can target miRNAs to protect against hypoxia-induced myocardial damage. miRNAs as potential drug targets may provide prospective therapeutic strategies for the treatment of myocardial damage.
研究领域:
心脏病学
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分子生物学
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药理学
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高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Yanmin Zhang,Jianqiang Hu,Yan Zhang,Xiaolin Yang,Weihua Tong,Xinxin Ci
Background The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a significant cause of kidney failure. Although the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) has been demonstrated to inhibit ferroptosis and alleviate cisplatin-induced AKI, the specific roles of Nrf2 and the alkaloid leonurine in modulating the AKI-CKD transition remain incompletely elucidated. Methods Murine and human proximal tubular epithelial cell models of the AKI-CKD transition were established using repeated low-dose cisplatin (RLDC) to investigate the roles of Nrf2 and leonurine in ferroptosis regulation and disease progression. Key results In mice, RLDC administration induced persistent tubular injury, ferroptosis, and progressive renal fibrosis. In HK-2 cells, RLDC triggered oxidative stress and ferroptosis. Although Nrf2 expression was transiently upregulated during the acute phase (4 weeks post-RLDC), it was downregulated by the chronic phase (8 weeks post-RLDC), correlating with impaired antioxidant capacity and exacerbated ferroptosis. Nrf2 knockout mice exhibited more severe oxidative damage, ferroptosis, and renal dysfunction following RLDC challenge. Pharmacological activation of Nrf2 by leonurine attenuated oxidative injury and ferroptosis and promoted tubular repair. Leonurine also suppressed the epithelial–mesenchymal transition and aberrant extracellular matrix deposition, ultimately mitigating renal fibrosis. The protective effects of leonurine were abolished in Nrf2 knockout mice. Conclusion These findings demonstrate that Nrf2 activation mitigates cisplatin-induced AKI-CKD transition by counteracting oxidative stress and ferroptosis, thereby attenuating renal fibrosis. Leonurine, as a potent Nrf2 activator, represents a promising therapeutic agent for preventing AKI-CKD transition.
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高影响因子
PHYTOTHERAPY RESEARCH
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2026
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IF 8.1
Pengru Wang,Xin Hu,Haiyan Pu,Junjie Bai,Lei Sun,Tingting Ma,Yichao Du,Wenguang Fu
Hepatic ischemia–reperfusion (I/R) injury complicates transplantation, resection, and shock, yet lacks effective pharmacotherapy. We evaluated Leonurine (SCM-198) as a hepatoprotective agent. Male C57BL/6 mice were pretreated with SCM-198 for 7 days, then subjected to hepatic I/R and sampled at the reperfusion endpoint. AML12 cells were pretreated with SCM-198 for 24 h, exposed to hypoxia/reoxygenation (H/R), and immediately analyzed. Injury, inflammation, apoptosis, and cell-cycle changes were assessed using assay kits, histology, IHC, WB, and qPCR; network pharmacology, docking, and MD simulations explored potential targets. SCM-198 sharply cut hepatic necrosis and serum transaminases, suppressed pro-inflammatory cytokines, reduced leukocyte infiltration, blocked apoptosis and restored cyclin D1/cyclin E1. In hypoxia-reoxygenation AML12 cells, it improved viability, limited oxidative stress and mirrored the anti-apoptotic effects. Network and dynamic simulation identified stable phosphoinositide 3-kinase (PI3K) binding, and the compound raised PI3K, protein kinase B and mammalian target of rapamycin phosphorylation; the PI3K inhibitor LY294002 abolished these changes. SCM-198 protects liver I/R by curbing inflammation, apoptosis, and cell-cycle arrest via PI3K/AKT/mTOR activation, offering a promising therapeutic candidate.
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高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Siyuan Shen,Gaojun Wu,Wu Luo,Weixin Li,Xiaobo Li,Chengyi Dai,Weijian Huang,Guang Liang
Background Hypertension is a common risk factor for heart failure, and excessive angiotensin II (Ang II) leads to hypertensive cardiac alterations such as hypertrophy, cardiac fibrosis, remodeling, and dysfunction. Leonurine is the major active alkaloid compound obtained from the traditional Chinese herbal medicine, Leonurus japonicus Houtt. The effects of leonurine on Ang II-induced hypertensive cardiac injury remain unknown. Hypothesis/Purpose In the present study, we investigated the cardioprotective effects of leonurine in Ang II-infused mice and explored the underlying mechanisms in cardiomyocytes. Methods Cardiac injury was induced by Ang II infusion in experimental mice with or without leonurine (at 10 or 20 mg/kg) treatment. H9c2 cells and neonatal rat primary cardiomyocytes were used to investigate the mechanisms through which leonurine exerts its protection effects. Results The results showed that leonurine significantly alleviated Ang II-induced cardiac hypertrophy, fibrosis, and inflammation in both mice and cultured cardiomyocytes. Echocardiography revealed that leonurine preserved cardiac function in mice. Further investigations revealed that leonurine inhibited the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways to reduce inflammatory response and injuries in Ang II-challenged cardiomyocytes. Inhibition of MAPKs and NF-κB in cardiomyocytes abolished the anti-inflammatory effects of leonurine. Conclusions Our study provides evidence that leonurine exerts protective effects against Ang II-induced hypertensive cardiac remodeling and dysfunction by inhibiting the MAPK and NF-κB pathways. Leonurine may be a promising agent for treating hypertensive heart failure.
研究领域:
心脏病学
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药理学
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分子生物学
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PubMed
高影响因子
INFLAMMATION
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2026
·Vol. 49
·期 1
·79
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IF 5.4
Hu Rui-Jie,Ying Xiao-Long,Zhang Cheng,Wang Xu,Zhan Chang-Sheng
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) constitutes a clinically complex urological condition defined by the persistence of pelvic pain and chronic inflammation. Emerging evidence underscores the critical involvement of macrophage-mediated immune dysregulation, particularly the dominance of pro-inflammatory M1 macrophages, in driving CP/CPPS pathogenesis. Leonurine, a bioactive alkaloid derived from leonuri, exhibits various pharmacological properties and has been shown to regulate macrophage polarization in rheumatoid arthritis. This study aimed to evaluate leonurine’s therapeutic efficacy in a murine experimental autoimmune prostatitis (EAP) model, established by subcutaneous injection of complete Freund’s adjuvant-emulsified prostate antigens. Leonurine administration in EAP mice markedly reduced prostatic inflammatory responses, mitigated chronic pain, and inhibited the expression of pro-inflammatory cytokines. Likewise, leonurine decreased inducible nitric oxide synthase (iNOS) expression levels, an established marker for M1 macrophage polarization. Leonurine has been found to suppress M1 polarization and decrease the secretion of M1-related cytokines (IL-1β and TNF-α) in immortalized bone marrow-derived macrophages (iBMDMs) under in vitro conditions. Mechanistic investigations demonstrated that leonurine mediates its therapeutic effects by modulating the TLR4/NF-κB signaling pathway in both macrophages and EAP models. Molecular docking and dynamics simulations demonstrated stable binding interactions between leonurine and key proteins involved in the TLR4/NF-κB signaling cascade. As a whole, these findings verify that leonurine relieves experimental autoimmune prostatitis (EAP) by regulating M1 macrophage polarization through the TLR4/NF-κB signaling cascade.
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高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2025
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IF 1.3
Ning Li,Xing-Long Dai,Gui-Xin Xiong,Wan-Li Meng,Jie Hao,Jie-Jie Hao
N-(4-Guanidinobutyl)-2-(4-hydroxyphenyl)-2-oxoacetamide (C1), a marine-derived leonurine analogue, was synthesized via a six-step route with 38% total yield. Biological evaluation demonstrated potent anticoagulant activity through significant prolongation of APTT (20 mM) and PT (5 mM). C1 dose-dependently (100–200 μM) suppressed LPS-induced NO production in RAW 264.7 macrophages without cytotoxicity and modulated phagocytosis. In LPS-induced acute lung injury rats, C1 reduced proinflammatory cytokines in BALF. These findings highlight C1’s dual anticoagulant and anti-inflammatory properties as a promising lead compound.
研究领域:
药物化学
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海洋药理学
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炎症研究
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心血管药理学
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药物发现
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产品关联
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PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2018
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IF 3.616
Yanzhuo Liu,Chenfan Duan,Honglei Chen,Chenlong Wang,Xiaoxiao Liu,Miao Qiu,Honglin Tang,Feng Zhang,Xiaoyang Zhou,Jing Yang
Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase-1 (mPGES-1)-derived eicosanoids play an essential role in human inflammatory disorders. Here, we investigated whether inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate (MSU) crystal-induced inflammation. Virtual screening assay and in vitro enzyme inhibition assay showed that leonurine was a potential inhibitor of COX-2, mPGES-1 and 5-LOX. Compared with COX-2 inhibitor celecoxib , leonurine (30 mg/kg) significantly decreased ankle perimeter, gait score and neutrophil number in synovial fluid in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, mPGES-1 and 5-LOX and production of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) in the synovial fluid macrophages. In addition, leonurine decreased representative M1 marker (iNOS and CD86) expression, NLRP3 inflammasome activation and M1 cytokine (TNF-α and IL-1β) production. In the in vitro cultured RAW264.7 and human monocyte-derived macrophages (MDMs), blockade of COX-2/mPGES-1 and 5-LOX by leonurine inhibited macrophage M1 polarization and NLRP3 inflammasome activation in response to MSU crystals, and thus down-regulated IL-1β and TNF-α with STAT1 and NF-κB inactivation. Conversely, these effects were partially abolished by overexpression of COX-2, mPGES-1, 5-LOX or STAT1. Furthermore, leonurine prevented a positive feedback loop between COX-2/mPGES-1/5-LOX and IL-1β/TNF-α in MSU crystal-induced inflammation. Together, simultaneous down-regulation of COX-2/mPGES-1 and 5-LOX by leonurine ameliorates MSU crystal-induced inflammation through decreasing IL-1β and TNF-α production. Our study may provide novel multi-target agents toward the arachidonic acid (AA) network for gouty arthritis therapy.
研究领域:
药理学
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免疫学
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风湿病学
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炎症性疾病
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
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IF 11
Zhen-Zhen Wang,Lihua Cao,Zhenzhu Zhao,Mengke Zhao,Yanyan Lu,Yanhui Zhu,Weijie Xie,Ping Li,Siqi Liu,Xuejiao Li,Kang Yang,Xiaobo Sun
TLR4 activation and the cascade of neutrophil extracellular trap (NET) formation exacerbate excessive inflammation and organ damage in the pathogenesis of acute lung injury (ALI), yet effective pharmacological interventions remain unavailable. Nanoaggregates derived from natural products offer promising avenue by leveraging synergistic anti-inflammatory effects. In this study, we surprisingly discovered that leonurine and ursolic acid spontaneously self-assemble into nanoparticles (LUNP) through non-covalent interactions, achieving a drug loading capacity of 100%. The LUNP platform exhibits superior biophysical properties, including enhanced mucus penetration, pH-responsive drug release, improved cellular uptake, and prolonged retention within inflamed lung tissue. Mechanistically, LUNP ameliorates ALI by dampening TLR4/MyD88/NF-κB-driven inflammatory activation, thereby remodeling the microenvironment to limit NOX4-PAD4-mediated NET formation. Notably, inhalational LUNP exhibits outstanding biosafety with minimal off-target distribution. Overall, this work introduces a synergistic self-assembled nanoplatform for precise pulmonary intervention in ALI, showcasing its ability to safely and effectively orchestrate the coordinated modulation of multiple pathological pathways. In summary, by inhibiting both TLR4 activation and NET formation, the synergistic LUNP platform offers an efficient, safe, and easily accessible therapeutic strategy for ALI, providing a promising solution for clinical translation.
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DOI
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2025
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IF 3
Song Peng,Yang-yang Sun,Qiangqiang Chu,Hua-dong Meng,Ming-wei Hao,Yan-bei Zhang
Background Leonurine (Leo) has antioxidant and anti-inflammatory activities. In this study, we investigated the effect of Leo in a rat model of lipopolysaccharide (LPS)-induced chronic obstructive pulmonary disease (COPD).Methods Rats with COPD were administered Leo, and the pulmonary function parameters, pathological changes, and inflammatory mediators in tissues were evaluated. The expression of IκBa, p65, JAK2, STAT3, p-IκBa, p-p65, p-JAK2 and p-STAT3 was measured using western blotting.Results Leo effectively improved the clinical manifestations of COPD by decreasing the pulmonary function parameters including peak expiratory flow and expiratory flow at 50% tidal volume, and improving pathological changes. Leo reduced lung inflammation and oxidative stress by reducing CD68+ cell infiltration, regulating Treg/Th17 cell differentiation, attenuating the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-17, increasing IL-10 secretion, and regulating malondialdehyde and glutathione peroxidase levels. In vitro experiments revealed that Leo exhibits similar inhibitory effects on Th17 cell differentiation and macrophage activation. Furthermore, Leo effectively protected against LPS-induced damage to bronchial airway epithelial cells by reducing reactive oxygen species production. Mechanistic investigations revealed Leo inhibits NF-κB transcriptional activity, downregulates the levels of p-p65, p-JAK2, and p-STAT3 without affecting their total protein levels.Conclusion Our results suggest that Leo exerts therapeutic effect against COPD. Leo inhibited tissue inflammation and oxidative stress in COPD rat models via inhibition of the NF-κB and JAK2/STAT3 signaling pathways.
研究领域:
呼吸医学
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药理学
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分子生物学
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炎症研究
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信号转导
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）