BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Heng Tang,Ke Ning,Boji Wu,Xuhong Wang,Jingyu He,Pingping Li,Lina Pan,Jiawen Zhang,Yi He,Shizhu Bian,Xingyu Ma,Jihang Zhang,Chuan Liu,Zhexue Qin,Houyuan Hu
Scutellarein (Sc), a natural flavonoid, holds potential for treating pulmonary arterial hypertension (PAH), yet its mechanisms remain unexplored. This study investigated Sc’s therapeutic effects and underlying pathways in PAH. In vivo experiments demonstrated that Sc significantly attenuated right ventricular hypertension, pulmonary arterial remodeling, αSMA expression, and vascular inflammation in PAH models. In vitro, Sc suppressed hypoxia-induced proliferation, migration, inflammation, and pyroptosis in human pulmonary artery smooth muscle cells (HPASMCs). Mechanistically, Sc activated the SIRT1/NAD + axis to restore mitochondrial homeostasis: it upregulated SIRT1 expression and elevated NAD + levels by promoting SIRT1-mediated deacetylation of nicotinamide nucleotide transhydrogenase (NNT), thereby enhancing NNT activity. Elevated NAD + further activated SIRT1, forming a self-reinforcing SIRT1/NNT/NAD + feedback loop that mitigated hypoxia-induced mitochondrial dysfunction. This study identifies Sc as a novel regulator of the SIRT1-dependent NNT deacetylation pathway, which stabilizes NAD + homeostasis to counteract HPASMCs dysregulation in PAH. These findings highlight Sc’s potential as a therapeutic candidate for PAH, offering insights into targeting mitochondrial-metabolic pathways for vascular remodeling diseases.
研究领域:
药理学
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心血管疾病
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分子生物学
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DOI
PubMed
高影响因子
Microbial Cell Factories
·
2024
·Vol. 23
·期 1
·1-14
·
IF 4.3
Song Yuping,Lv Hongfa,Xu Lei,Liu Zhiying,Wang Jianfeng,Fang Tianqi,Deng Xuming,Zhou Yonglin,Li Dan
Background Inorganic polyphosphate (polyP)-targeted polyphosphate kinase 1 (PPK1) has attracted much attention by virtue of its importance in bacterial pathogenicity and persistence, as well as its exclusive presence in microorganisms. However, only very few drugs have been found to be efficacious in inhibiting the Acinetobacter baumannii (A. baumannii) PPK1 protein.Results In this study, we identified Scutellarein (Scu), a potent PPK1 inhibitor that could significantly influence PPK1-regulated motility, biofilm formation, and bacterial persistence, which was further validated by the results of transcriptome analysis. Mechanistic explorations revealed that Scu achieved its enzyme inhibitory activity predominantly through direct engagement with the active center of PPK1. Moreover, the survival rate of Galleria mellonella larvae was increased by about 35% with 20 mg/kg of Scu treatment. The remarkable therapeutic benefits of Scu were also observed in the mouse pneumonia model, shown mainly by reduced bacterial colonization, pathological lesions, and inflammatory factors.Conclusion Our results revealed that Scu could attenuate the pathogenicity and persistence of A. baumannii by interfering with its important kinase PPK1.
研究领域:
微生物学
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药理学
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感染病学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2022
·Vol. 179
·期 20
·4792-4808
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IF 9.473
Yujing Wang,Liaoxi Tan,Kejun Jiao,Chu Xue,Qinglian Tang,Shan Jiang,Younan Ren,Hao Chen,Tarek Mohamed Abd El-Aziz,Khalid N. M. Abdelazeem,Ye Yu,Fang Zhao,Michael X. Zhu,Zhengyu Cao
Background and Purpose Atopic dermatitis (AD) is one of the most common chronic inflammatory cutaneous diseases with unmet clinical needs. As a common ingredient found in several medicinal herbs with efficacy on cutaneous inflammatory diseases, Scutellarein (Scu) has been shown to possess anti-inflammatory and anti-proliferative activities. We aimed to evaluate the therapeutic efficacy of Scu against AD and its underlying molecular mechanism. Experimental Approach Efficacy of Scu on AD was evaluated in 2,4-dinitrofluorobenzene (DNFB) and carvacrol-induced dermatitis mouse models. Cytokine mRNA and serum IgE levels were examined using qPCR and ELISA, respectively. Voltage clamp recordings were used to measure currents mediated by transient receptor potential (TRP) channels. In silico docking, site-direct mutagenesis, and covalent modification were used to explore the binding pocket of Scu on TRPV3. Key Results Subcutaneous administration of Scu efficaciously suppresses DNFB and carvacrol-induced pruritus, epidermal hyperplasia and skin inflammation in wild type mice but has no additional benefit in Trpv3 knockout mice in the carvacrol model. Scu is a potent and selective TRPV3 channel allosteric negative modulator with an apparent affinity of 1.18 μM. Molecular docking coupled with site-direct mutagenesis and covalent modification of incorporated cysteine residues demonstrate that Scu targets the cavity formed between the pore helix and transmembrane helix S6. Moreover, Scu attenuates endogenous TRPV3 activity in human keratinocytes and inhibits carvacrol-induced proliferative and proinflammatory responses. Conclusion and Implications Collectively, these data demonstrate that Scu ameliorates carvacrol-induced skin inflammation by directly inhibiting TRPV3, and TRPV3 represents a viable therapeutic target for AD treatment. Graphical
研究领域:
药理学
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皮肤病学
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分子生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2026
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IF 2.5
Yaling Cheng,Chen Liang,Zhou Qi,Binbin Zhang,Shiwen Guo
Glioma is the most common primary intracranial tumor and is characterized by poor prognosis and high invasiveness. Currently, treatment options remain limited. Accumulating evidence has demonstrated the efficacy of diverse natural compounds in cancer treatment. In this study, we evaluated the anticancer effects of scutellarein on gliomas and its underlying mechanisms. Cell proliferation, migration, invasion, and apoptosis were evaluated by CCK-8 assay, colony formation assay, wound healing assay, Transwell assay, and flow cytometry. Network pharmacology, transcriptomics, and western blotting were conducted to investigate the underlying mechanisms. The in vivo effect of scutellarein was evaluated using an intracranial xenograft model. Our results showed that scutellarein significantly inhibited proliferation, invasion, and migration of glioma cells. Furthermore, scutellarein induced glioma cell apoptosis by triggering oxidative stress. This was evidenced by the elevation of reactive oxygen species and malondialdehyde, alongside the suppression of superoxide dismutase and catalase activities. Network pharmacology and transcriptomic analyses suggested that scutellarein may target SRC, EGFR, and AKT1; and exerts its effects through the PI3K/AKT signaling pathway, which was subsequently verified by further experiments. Rescue experiments showed that activation of the PI3K/AKT signaling pathway markedly reversed scutellarein-induced apoptosis and oxidative stress. In an intracranial xenograft model, mice treated with scutellarein survived significantly longer. Moreover, no significant histological differences were observed in the hearts, lungs, spleens, livers, and kidneys of treated mice compared with the controls. In conclusion, our study demonstrates that scutellarein inhibits glioma proliferation, invasion, and migration by modulating the PI3K/AKT signaling pathway and inducing oxidative stress, showing promising therapeutic potential.
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PubMed
高影响因子
Cancer Nanotechnology
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2021
·Vol. 12
·期 1
·1-15
·
IF 5.095
Wang Jundong,Li Tianhao,Yue Chaochi,Zhong Sen,Yang Xiangdong,Li Jun,Li Yuanzhi
Background The problems associated with the poor water solubility of anticancer drugs are one of the most important challenges in achieving effective cancer therapy. The present study was designed to evaluate the effect of scutellarein on human colon cancer cells in vitro by using a target α v β3 novel scutellarein (Scu)-loaded niosome nanoparticle (β-CD-CL-Scu-cRGD). Results β-CD-CL-Scu-cRGD has a diameter of 140.2 nm and zeta potential of − 11.3 mV with constant physicochemical stability. The MTT assay showed both Scu and β-CD-CL-Scu-cRGD caused a decrease in cell proliferation and viability of LoVo, but β-CD-CL-Scu-cRGD showed better activity in vitro. Colony formation assay and flow cytometry assay showed that β-CD-CL-Scu-cRGD has a better effect on cell proliferation and apoptosis. In vivo, animal experimental results showed that β-CD-CL-Scu-cRGD can significantly inhibit tumor growth, and the bodyweight of mice decreases during the treatment of scutellarein and its derivatives. β-CD-CL-Scu-cRGD could inhibit the protein levels of Ki67 and αvβ3, thereby inhibiting tumor growth. Conclusions Although further in vitro and in vivo studies are necessary, our results suggested that β-CD-CL-Scu-cRGD could be an outstanding carrier to deliver Scu for potential therapeutic approaches into colon cancer.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
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DOI
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 12
·3225
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IF 3.098
Qianru Liu,Xican Li,Xiaojian Ouyang,Dongfeng Chen
To explore whether and how glucuronidation affects pyrogallol-type phytophenols, scutellarein and scutellarin (scutellarein-7-O-glucuronide) were comparatively investigated using a set of antioxidant analyses, including spectrophotometric analysis, UV-vis spectra analysis, and ultra-performance liquid chromatography coupled with electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis. In spectrophotometric analyses of the scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•), and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radicals (PTIO•) and the reduction of Cu2+ions, scutellarein showed lower IC50values than scutellarin. However, in•O2−-scavenging spectrophotometric analysis, scutellarein showed higher IC50value than scutellarin. The analysis of UV-Vis spectra obtained after the Fe2+-chelating reaction of scutellarin showed a typical UV-Vis peak (λmax= 611 nm), while scutellarein showed no typical peak. In UPLC-ESI-Q-TOF-MS/MS analysis, mixing of scutellarein with DPPH•yielded MS peaks (m/z678, 632, 615, 450, 420, 381, 329, 300, 288, 227, 196, 182, 161, and 117) corresponding to the scutellarein-DPPH adduct and an MS peak (m/z570) corresponding to the scutellarein-scutellarein dimer. Scutellarin, however, generated no MS peak. On the basis of these findings, it can be concluded that glucuronidation of pyrogallol-type phytophenol antioxidants has a dual effect. On the one hand, glucuronidation can decrease the antioxidant potentials (except for•O2−scavenging) and further lower the possibility of radical adduct formation (RAF), while on the other hand, it can enhance the•O2−-scavenging and Fe2+-chelating potentials.Keywords:scutellarein;scutellarin;pyrogallol-type phytophenol;structure-activity relationship;glucuronidation;antioxidant
研究领域:
植物化学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2014
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IF 1.357
Fen Wang,Bo Yang,Yulin Zhao,Xiali Liao,Chuanzhu Gao,Ruijian Jiang,Bin Han,Jian Yang,Man Liu,Rongguang Zhou
The inclusion complexation behavior of scutellarein (SCUE) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has been investigated in both solution and in the solid state. SCUE/HP-β-CD solid system was prepared by suspension method. The formation of SCUE/HP-β-CD complex in aqueous solution was demonstrated by fluorescence spectroscopy, and the Job plot showed a maximum at a molar fraction of 0.5, indicating 1:1 inclusion complexation between SCUE and HP-β-CD. However, SCUE/HP-β-CD inclusion complex was characterized by means of XRD, DSC, 1H, and two-dimensional NMR. Through the complexation between HP-β-CD and SCUE, the water solubility and antitumor activity of SCUE were obviously increased. This satisfactory water solubility and high antitumor activity of the SCUE/HP-β-CD complex will be potentially useful for its application on human colon cancer chemotherapies.
研究领域:
药学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 21
·7417
·
IF 4.6
Wei Yang,Wenping Wang,Song Cai,Peng Li,Die Zhang,Jinhua Ning,Jin Ke,Anguo Hou,Linyun Chen,Yunshu Ma,Wenbin Jin
Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated fromScutellaria altissimaL., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4′-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves’ amplitude. The most promising compound10eshowed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound10ewas able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound10eeven showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound10edid not block the hERG potassium channel which highly associated with cardiotoxicity.Keywords:antiarrhythmic;scutellarein derivatives;Nav1.5 channel blockers;Cav1.2 channel blockers;electrophysiology
研究领域:
药理学
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心脏病学
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药物化学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
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IF 8.1
Shuanggong Liu,Jie Zhao,Shuhang Dong,Yang Zhang,Yachao Zhao,Ning Ran,Guowei Yang,Changliang Peng,Xu Yang,Guangxu Song,Yingze Zhang,Dongjin Wu
Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain and is driven by oxidative stress, inflammation, and ferroptosis. While mitophagy regulates ferroptosis in other diseases, its role in IVDD remains unclear. The potential of scutellarein, a flavonoid with antioxidant properties, to treat IVDD has not yet been explored. Primary human nucleus pulposus (HNP) cells were treated with tert-butyl hydroperoxide (TBHP) to establish an in vitro IVDD model. Mitophagy was inhibited by cyclosporin A (CsA) treatment. Radiographic and histopathological analyses were performed in a rodent IVDD model. Key markers (IL-1β, ACSL4, GPX4, PINK1, LC3, and PI3K/mTOR) were assessed. Scutellarein preserved the NPC phenotype, reduced inflammation, and suppressed ferroptosis by activating PINK1/Parkin-mediated mitophagy. It restored mitochondrial function and inhibited the PI3K/AKT/mTOR pathway. In vivo, scutellarein attenuated IVDD progression; downregulated the expression of IL-1β and ACSL4; and upregulated the expression of collagen II, GPX4, PINK1, and LC3. Scutellarein mitigates IVDD by inducing mitophagy to inhibit ferroptosis and restore mitochondrial function, highlighting its therapeutic potential.
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PubMed
高影响因子
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