Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages

Gao, Yuan; Liu, Fen; Fang, Lei; Cai, Runlan; Zong, Chuanjie; Qi, Yun

doi:10.1371/journal.pone.0096741

Cited by 110Flavonoids in Medical ResearchPhytochemistry and Biological ActivitiesBioactive natural compounds

Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages

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Gao, Yuan, Liu, Fen, Fang, Lei, Cai, Runlan, Zong, Chuanjie, Qi, Yun·2014·PLoS ONE

DOI 10.1371/journal.pone.0096741PMC PMC4011752

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Abstract

Genkwanin is one of the major non-glycosylated flavonoids in many herbs with anti-inflammatory activities. Although its anti-inflammatory activity in vivo has been reported, the potential molecular mechanisms remain obscure. In this study, by pharmacological and genetic approaches, we explore the anti-inflammatory effects of genkwanin in LPS-activated RAW264.7 macrophages. Genkwanin potently decreases the proinflammatory mediators, such as iNOS, TNF-α, IL-1β and IL-6, at the transcriptional and translational levels without cytotoxicity, indicating the excellent anti-inflammatory potency of genkwanin in vitro. Mechanism study shows that genkwanin significantly suppresses the p38- and JNK-mediated AP-1 signaling pathway and increases the mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression at the posttranscriptional level. We also confirmed that microRNA-101 (miR-101) is a negative regulator of MKP-1 expression. Moreover, regardless of miR-101-deficient cells or miR-101-abundant cells, the suppression effects of genkwanin on supernatant proinflammatory mediators' levels are far less than that in respective negative control cells, suggesting that genkwanin exerts anti-inflammatory effect mainly through reducing miR-101 production. However, genkwanin can't affect the level of phospho-Akt (p-Akt), indicating that the phosphorylation of Akt may be not responsible for the effect of genkwanin on miR-101 production. We conclude that genkwanin exerts its anti-inflammatory effect mainly through the regulation of the miR-101/MKP-1/MAPK pathway.

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The absolute level of IL6 detected fell in the middle range of reported levels in inflammatory contexts and above reported ranges post-exercise and diet-induced obesity.
“The absolute level of IL6 we detected fell in the middle range of reported levels (50 pg/mL to 200 ng/mL) in inflammatory contexts and above reported ranges post-exercise and diet-induced obesity (30-100 pg/mL) (Chowdhury et al.; Gao et al., 2014; Greenhill et al., 2011; Masuda et al., 2013; Osuchowski et al., 2006; Remick et al., 2005; Vida et al.; Wang et al., 2017; Yan et al., 2015).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Gao et al., 2014

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[1]The State Commission of Chinese Pharmacopoeia (2010) Pharmacopoeia of People's Republic of China. Part I. Beijing: Chemical Industry Press. p148.

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Traditional Use, Phytochemical Profiles and Pharmacological Properties of Artemisia Genus from Central Asia
Нурлыбекова, А. К., Kudaibergen, A., Kazymbetova, A., Amangeldi, M., Baiseitova, A., Ospanov, M., Aisa, H. A., Ye, Y., Ibrahim, M. A., & Jenis, J. (2022) · Molecules · doi:10.3390/molecules27165128 · Cited by 58 · see citing works
Propolis and Its Gastroprotective Effects on NSAID-Induced Gastric Ulcer Disease: A Systematic Review
Ruiz-Hurtado, P. A., Garduño‐Siciliano, L., Domínguez-Verano, P., Balderas-Cordero, D., Gorgua-Jiménez, G., Canales-Álvarez, O., Canales-Martinez, M. M., & Rodríguez-Monroy, M. A. (2021) · Nutrients · doi:10.3390/nu13093169 · Cited by 56 · see citing works
Antitumor and immunomodulatory activity of genkwanin on colorectal cancer in the APC Min/+ mice
Wang, X., Song, Z., He, X., Zhang, R., Zhang, C.-F., Li, F., Wang, C., & Yuan, C. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.09.006 · Cited by 55 · see citing works
A novel antagonist of p75NTR reduces peripheral expansion and CNS trafficking of pro-inflammatory monocytes and spares function after traumatic brain injury
Lee, S., Mattingly, A. J., Lin, A., Sacramento, J. A., Mannent, L., Castel, M., Canolle, B., Delbary-Gossart, S., Ferzaz, B., Morganti, J. M., et al. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0544-4 · Cited by 55 · see citing works
“Elevated TNFα production is a hallmark of proinflammatory stimulation [69–71].”
Background
Genkwanin: An emerging natural compound with multifaceted pharmacological effects
Menyiy, N. E., Aboulaghras, S., Bakrim, S., Moubachir, R., Taha, D., Khalid, A., Abdalla, A. N., Algarni, A. S., Hermansyah, A., Ming, L. C., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115159 · Cited by 54 · see citing works
“…[85], Mentha piperita [95], and Callicarpa americana [96], Asteraceae family including Gochnatia pulchra [29], Vernonia fasciculata [31], Artemisia ssp. [51,53,61], and Moquiniastrum floribundum [97], or Thymelaeaceae family involving Daphne ssp. [3,4,29 – 33], and Aquilaria ssp. [50,51,57].”
Influential
Obacunone causes sustained expression of MKP‐1 thus inactivating p38 MAPK to suppress pro‐inflammatory mediators through intracellular MIF
Gao, Y., Hou, R., Liu, F., Liu, H., Fei, Q., Han, Y., Cai, R., Peng, C. Y., & Qi, Y. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26248 · Cited by 53 · see citing works
“The activity of iNOS was assayed as we previously described.(28) 2.”
BackgroundMethodInfluential
Herbacetin inhibits inducible nitric oxide synthase via JNK and nuclear factor-κB in LPS-stimulated RAW264.7 cells
Li, L., Sapkota, M., Kim, S.-W., & Soh, Y. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.08.032 · Cited by 51 · see citing works
An ethanol extract of the rhizome of Atractylodes chinensis exerts anti-gastritis activities and inhibits Akt/NF-κB signaling
Hossen, M. J., Chou, J., Li, S., Fu, X., Yin, C., Guo, H., Amin, A., Chou, G., & Yu, Z. (2018) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2018.09.015 · Cited by 50 · see citing works
Identification of potential anticancer phytochemicals against colorectal cancer by structure-based docking studies
Qawoogha, S. S., & Shahiwala, A. (2020) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2020.1715431 · Cited by 45 · see citing works
“11 Genkwanin Daphne genkwa Anti-inflammatory, genkwanin potently decreases the proinflammatory mediators, such as iNOS, TNF-a, IL-1b, and IL-6 [45].”
Background
Phytochemicals targeting JAK/STAT pathway in the treatment of rheumatoid arthritis: Is there a future?
Kour, G., Choudhary, R., Anjum, S., Bhagat, A., Bajaj, B. K., & Ahmed, Z. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114929 · Cited by 43 · see citing works
MicroRNA-101a regulates microglial morphology and inflammation
Saika, R., Sakuma, H., Noto, D., Yamaguchi, S., Yamamura, T., & Miyake, S. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0884-8 · Cited by 42 · see citing works
Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer
Yin, H., Yin, C.-M., Ouyang, T., Sun, S., Chen, W., Yang, X.-L., He, X. H., & Zhang, C.-F. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s292417 · Cited by 42 · see citing works
The macrophage polarization by miRNAs and its potential role in the treatment of tumor and inflammation (Review)
Wang, C., Wang, X., Zhang, D., Sun, X., Wu, Y., Wang, J., Li, Q., & Jiang, G. (2023) · Oncology Reports · doi:10.3892/or.2023.8627 · Cited by 43 · see citing works
“Gao et al (195) demonstrated that the miR‑101/MKP‑1/ mitogen‑activated protein kinase pathway plays a potential anti‑inflammatory target.”
Background
The anti-inflammatory effects of an ethanolic extract of the rhizome of Atractylodes lancea, involves Akt/NF-κB signaling pathway inhibition
Hossen, M. J., Amin, A., Fu, X., Chou, J., Wu, J., Wang, X., Chen, Y., Wu, Y., Li, J., Yin, C., et al. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114183 · Cited by 41 · see citing works
Genkwanin nanosuspensions: a novel and potential antitumor drug in breast carcinoma therapy
Li, Y., Hong, J., Li, H., Qi, X., Guo, Y., Han, M., & Wang, X. (2017) · Drug Delivery · doi:10.1080/10717544.2017.1384519 · Cited by 36 · see citing works
“Previous evidence indicated that GKA has various pharmacological effects including antitussive, expectorant, anti-inflammatory (Gao et al., 2014), antibacterial (Cottiglia et al., 2001; Martini et al., 2004), antiplasmodial (Kraft et al., 2003), chemopreventive (Suh et al., 1995), and radical…”
Background
The pharmacological mechanism of Huashi Baidu Formula for the treatment of COVID-19 by combined network pharmacology and molecular docking
Cai, Y., Zeng, M., & Chen, Y. (2021) · Annals of Palliative Medicine · doi:10.21037/apm-20-1759 · Cited by 35 · see citing works
“Genkwanin can inhibit proinflammatory transmission to prevent the cytokine storm caused by SARS-CoV-2 infection via targeting the miR-101/MKP-1/MAPK pathway (56).”
Background
Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Daphne gnidium: A review
Khouchlaa, A., Menyiy, N. E., Guaouguaou, F., Baaboua, A. E., Charfi, S., Lakhdar, F., Omari, N. E., Taha, D., Shariati, M. A., Ребезов, М. Б., et al. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114124 · Cited by 33 · see citing works
Dietary Flavone Tectochrysin Exerts Anti‐Inflammatory Action by Directly Inhibiting MEK1/2 in LPS‐Primed Macrophages
Hou, R., Han, Y., Fei, Q., Gao, Y., Qi, R., Cai, R., & Qi, Y. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201700288 · Cited by 30 · see citing works
Genkwanin suppresses MPP+-induced cytotoxicity by inhibiting TLR4/MyD88/NLRP3 inflammasome pathway in a cellular model of Parkinson’s disease
Li, Q., Zhang, P., & Cai, Y. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.08.018 · Cited by 30 · see citing works
Mannitol Stress Directs Flavonoid Metabolism toward Synthesis of Flavones via Differential Regulation of Two Cytochrome P450 Monooxygenases in Coleus forskohlii
Awasthi, P., Gupta, A. P., Bedi, Y. S., Vishwakarma, R. A., & Gandhi, S. G. (2016) · Frontiers in Plant Science · doi:10.3389/fpls.2016.00985 · Cited by 30 · see citing works
“Genkwanin imparts this anti-inflammatory property to herbs through inhibition of proinflammatory mediators mainly via regulation of miR101/MKP-1/MAPK pathway in LPS-activated macrophages (Gao et al., 2014).”
Background
Hepatoprotective Potential of Genkwanin Against Aflatoxin B1-Induced Biochemical, Inflammatory and Histopathological Toxicity in Rats
Ijaz, M. U., Ishtiaq, A., Ehsan, N., Imran, M., & Zhu, G. (2022) · Pakistan Veterinary Journal · doi:10.29261/pakvetj/2022.048 · Cited by 29 · see citing works
“Genkwanin (GNK; 5,4′-dihydroxy-7-methoxy flavone) is a bioactive non-glycosylated flavonoid, which was primarily isolated from Daphne genkwa in 1932 with reported immunomodulatory, anti-oxidative and anti-inflammatory activities (Gao et al., 2014).”
Ilexgenin A, a novel pentacyclic triterpenoid extracted from Aquifoliaceae shows reduction of LPS-induced peritonitis in mice
Sun, W., Liu, C., Zhang, Y., Qiu, X., Zhang, L., Zhao, H., Rong, Y., & Sun, Y. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.01.019 · Cited by 27 · see citing works
“The activation of JNK, p38, and ERK1/2 protein are known to play critical roles in the modulation of NF-κB activity (Gao et al., 2014; Qi et al., 2012; Xu et al., 2014; Zhou et al., 2012).”
Influential
RETRACTED: Long non-coding RNA Mirt2 prevents TNF-α-triggered inflammation via the repression of microRNA-101
Han, Y., Kang, C., Kang, M., Quan, W., Gao, H., & Zhong, Z. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105878 · Cited by 27 · see citing works
Retracted
Investigating the association between the tissue expression of miRNA‐101, JAK2/STAT3 with TNF‐α, IL‐6, IL‐1β, and IL‐10 cytokines in the ulcerative colitis patients
Voshagh, Q., Anoshiravani, A., Karimpour, A., Goodarzi, G., Tehrani, S. S., Tabatabaei‐Malazy, O., & Panahi, G. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1224 · Cited by 25 · see citing works
“Gao et al. 33 demonstrated miRNA ‐ 101 as a pro ‐ inflammatory and proapoptotic miRNA that suppresses and inhibits the expression of MKP1 and increases TNF ‐ α , IL ‐ 6, and IL ‐ 1 β levels in response to the effect of pro ‐ inflammatory lipopolysaccharides.”
Background
Inhibitory effect of flavonoid xanthomicrol on triple‐negative breast tumor via regulation of cancer‐associated microRNAs
Attari, F., Keighobadi, F., Abdollahi, M. R., Arefian, E., Lotfizadeh, R., Sepehri, H., & Farimani, M. M. (2020) · Phytotherapy Research · doi:10.1002/ptr.6940 · Cited by 25 · see citing works
“Flavonoids utilize different mechanisms to exert their effects on the target cells, including enhancement of mitochondrial membrane permeability, regulation of the MAPK pathway, and apoptosis induction (Gao et al., 2014).”
Background
A network pharmacology approach to uncover the key ingredients in Ginkgo Folium and their anti-Alzheimer’s disease mechanisms
Zeng, P. H., Fang, M., Zhao, H., & Guo, J. (2021) · Aging · doi:10.18632/aging.203348 · Cited by 25 · see citing works
“GK can inhibit proinflammatory signaling through regulation of the miR-101/MKP-1/MAPK pathway in active macrophages [45].”
Inhibition of the Akt/NF-κB pathway is involved in the anti-gastritis effects of an ethanolic extract of the rhizome of Atractylodes macrocephala
Amin, A., Hossen, M. J., Fu, X., Chou, J., Wu, J., Wang, X., Chen, Y., Wu, Y., Yin, C., Dou, X., et al. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115251 · Cited by 24 · see citing works
Flavonoids of Haloxylon salicornicum (Rimth) prevent cisplatin-induced acute kidney injury by modulating oxidative stress, inflammation, Nrf2, and SIRT1
Ramadan, S. A., Kamel, E. M., Ewais, M. A., Khowailed, A. A., Hassanein, E. H. M., & Mahmoud, A. M. (2023) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-25694-2 · Cited by 24 · see citing works
“The radical scavenging, antioxidant, and ani-inflammatory properties of genkwanin, isorhamnetin, myricetin, and quercetin and its galactoside hyperoside and glycoside quercitrin found in HSE have been well documented (Gao et al. 2014; Gong et al. 2020; Hassan et al. 2017; Li et al. 2016; Tan et al. 2020; Zhang et al.…”
Background
Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine
Yang, X., Chen, H., Chen, Y., Birnbaum, Y., Liang, R., Ye, Y., & Qian, J. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000494168 · Cited by 23 · see citing works
Recent research progress of Cirsium medicinal plants in China
Wei, L., Wu, B., Liangjie, T., Li, G., Chen, H., & Yin, X. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114475 · Cited by 22 · see citing works
Nasunin inhibits the lipopolysaccharide-induced pro-inflammatory mediator production in RAW264 mouse macrophages by suppressing ROS-mediated activation of PI3 K/Akt/NF-κB and p38 signaling pathways
Komatsu, W., Itoh, K., Akutsu, S., Kishi, H., & Ohhira, S. (2017) · Bioscience Biotechnology and Biochemistry · doi:10.1080/09168451.2017.1362973 · Cited by 22 · see citing works
Anti-Inflammatory Activity and Mechanism of Isookanin, Isolated by Bioassay-Guided Fractionation from Bidens pilosa L.
Xin, Y., Choi, S.-J., Roh, K., Cho, E., Ji, H., Weon, J. B., Park, D., Whang, W. K., & Jung, E. (2021) · Molecules · doi:10.3390/molecules26020255 · Cited by 21 · see citing works
“To investigate whether these signaling pathways are involved in the isookanin effects, we performed Western blot analysis for MAPKs (Extracellular Signal-Regulated Kinases 1/2 (ERK1/2), c-jun NH2-terminal kinase (JNK), and p38 MAPK).”
BackgroundInfluential
Daphne genkwa flower extract promotes the neuroprotective effects of microglia
Gupta, D. P., Park, S. H., Lee, Y., Lee, S., Lim, S.-J., Byun, J., Cho, I., & Song, G. J. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154486 · Cited by 20 · see citing works
miR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2
Chen, Q., Li, X., Kong, L., Xu, Q., Wang, Z., & Lv, Q. (2019) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmz154 · Cited by 21 · see citing works
Antioxidant, anti-inflammatory, and anti-apoptotic effects of genkwanin against aflatoxin B1-induced testicular toxicity
Ijaz, M. U., Ishtiaq, A., Tahir, A., Alvi, M. A., Rafique, A., Wang, P., & Zhu, G. (2023) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2023.116750 · Cited by 20 · see citing works
Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence
Li, M., Yu, X., Chen, X., Jiang, Y., Zeng, Y., Ren, R., Nie, M., Zhang, Z., Bao, Y., & Kang, H. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112101 · Cited by 20 · see citing works
A systems pharmacology perspective to decipher the mechanism of action of Parangichakkai chooranam, a Siddha formulation for the treatment of psoriasis
Sundarrajan, S., & Arumugam, M. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.12.135 · Cited by 20 · see citing works
A periodic review of chemical and pharmacological profiles of Tubiechong as insect Chinese medicine
Xie, J., Dapeng, Z., Liu, C., & Wang, L. (2021) · RSC Advances · doi:10.1039/d1ra05425b · Cited by 19 · see citing works
Metabolism studies on hydroxygenkwanin and genkwanin in human liver microsomes by UHPLC-Q-TOF-MS
Lin, Y. Y., Liang, C., Diao, X., Cheng, X., Liao, M., & Zhang, L. (2017) · Xenobiotica · doi:10.1080/00498254.2017.1319991 · Cited by 19 · see citing works
“antioxidant and immunomodulatory activity (Gao et al., 2014; Wang et al., 2013, 2015), there were few reports with respect to the metabolism of HYGN and GN in vitro.”
Background
Macrophage migration inhibitory factor antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy
Zhou, Y., Zhao, L., Mei, F., Hong, Y.-P., Xia, H., Zuo, T., Ding, Y., & Wang, W. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8672 · Cited by 18 · see citing works
“Since the P38MAPK and NF‐κB signaling pathways play key roles in the induction of several inflammatory diseases (34,35), next we investigated if ISO‐1 exerts its anti‐inflammatory activities by affecting the two pathways in lung injury induced by APIP.”
Background
Phytochemistry and teratogenic potential of Mimosa tenuiflora (willd.) poir. (Fabaceae) in ruminants: A systematic review
Bezerra, J. J. L., Pinheiro, A. A. V., & Lucena, R. B. (2021) · Toxicon · doi:10.1016/j.toxicon.2021.03.010 · Cited by 18 · see citing works
miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease
Luo, M., Pang, Y., Li, J., Yi, L., Wu, B., Tian, Q., He, Y., Wang, M., Xia, L., He, G., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.10.015 · Cited by 17 · see citing works
The Role of Flavonoids in Inhibiting IL-6 and Inflammatory Arthritis
Mahmoud, A. M., Sayed, A. M. M., Ahmed, O. S., Abdel‐Daim, M. M., & Hassanein, E. H. M. (2022) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026622666220107105233 · Cited by 16 · see citing works
Metabolic engineering in Streptomyces albidoflavus for the biosynthesis of the methylated flavonoids sakuranetin, acacetin, and genkwanin
Pérez‐Valero, Á., Ye, S., Magadán‐Corpas, P., Villar, C. J., & Lombó, F. (2023) · Microbial Cell Factories · doi:10.1186/s12934-023-02247-3 · Cited by 15 · see citing works
“In different pharmacological studies, this compound showed antibacterial, antiplasmodial, radical scavenging, and chemopreventive activities, among others [35].”
Background
Saccharum Alhagi polysaccharide-1 and -2 promote the immunocompetence of RAW264.7 macrophages inï¿½vitro
Li, G., Xiang, Y., Zhao, J., & Chang, J. (2018) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2018.5818 · Cited by 14 · see citing works
“, Nanjing, China) as previously reported (15-17).”
Use of nPSi-βCD Composite Microparticles for the Controlled Release of Caffeic Acid and Pinocembrin, Two Main Polyphenolic Compounds Found in a Chilean Propolis
Guzmán-Oyarzo, D., Plaza, T., Recio‐Sánchez, G., Abdalla, D. S. P., Salazar, L. A., & Hernández‐Montelongo, J. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics11060289 · Cited by 14 · see citing works
“These activities are attributed to its polyphenols rich composition, molecules that present different biological properties: relaxing [10], antioxidant [11], antithrombotic [12], antiangiogenic [13], anti-inflammatory [14], anti-carcinogenic [15], among others.”
Wikstroemia: A Review on its Phytochemistry and Pharmacology
Huan, D. Q., Hợp, N. Q., & Son, N. T. (2023) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201024666230606122116 · Cited by 13 · see citing works
LncRNA Riken Attenuated Sevoflurane-Induced Neuroinflammation by Regulating the MicroRNA-101a/MKP-1/JNK Pathway
Hou, Q., Li, S., Zhang, B., Chu, H., Ni, C., Fei, X., & Zheng, H. (2021) · Neurotoxicity Research · doi:10.1007/s12640-021-00443-w · Cited by 13 · see citing works
Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi Bioss
Zamani, S.-S., Hossieni, M., Etebari, M., Salehian, P., & Ebrahimi, S. A. (2016) · DARU Journal of Pharmaceutical Sciences · doi:10.1186/s40199-016-0161-x · Cited by 13 · see citing works
Integrated chemical and biological characterization of Hypericum perforatum extract using LC-MS/MS and in vitro functional assays
Güzel, M. A., Kolaç, T., Menevşe, İ. N., Dündar, M., Zengin, R., Güzel, A., & Yılmaz, U. (2026) · Scientific Reports · doi:10.1038/s41598-026-36793-8 · Cited by 12 · see citing works
“The pharmacological relevance of this compound has been well-documented, with studies demonstrating its anti-inflammatory potential 31 , antibacterial activity 32 , chemopreventive properties 33 , and significant anti-tumour effects 34,35 .”
Controlled Release of Caffeic Acid and Pinocembrin by Use of nPSi-βCD Composites Improves Their Antiangiogenic Activity
Guzmán-Oyarzo, D., Hernández‐Montelongo, J., Rosas, C., Leal, P., Weber, H. L., Marysol Alvear, Z., & Salazar, L. A. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030484 · Cited by 12 · see citing works
“and morphogenic differentiation [28]; anti-inflammatories [29]; and anticarcinogenics [30].”
Background
RETRACTED: Sinomenine inhibits lipopolysaccharide-induced inflammatory injury by regulation of miR-101/MKP-1/JNK pathway in keratinocyte cells
Liu, S., Man, Y., & Zhao, L. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.02.086 · Cited by 11 · see citing works
Retracted
Genkwanin Prevents Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Induced Bone Loss
Fu, X., Sun, X., Zhang, C., Lv, N., Guo, H., Xing, C., Lv, J., Wu, J., Zhu, X., Liu, M., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.921037 · Cited by 11 · see citing works
Anti-atherosclerosis mechanisms associated with regulation of non-coding RNAs by active monomers of traditional Chinese medicine
Liu, G., Tan, L., Zhao, X., Wang, M., Zhang, Z., Zhang, J., Gao, H., Liu, M., & Qin, W. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1283494 · Cited by 10 · see citing works
Traditional Chinese medicine in chronic rhinosinusitis: Mechanisms and postoperative recovery
Zhang, X.-H., Sun, Q., Zhao, L., Chen, L., & Li, W. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156658 · Cited by 11 · see citing works
Therapeutic effects of natural polyphenols on colorectal adenomas: Focus on preclinical studies (Review)
Ma, F., Lin, Y., Ni, Z., Chen, T., & Wang, X. (2023) · Oncology Reports · doi:10.3892/or.2023.8549 · Cited by 10 · see citing works
“GKA has favorable anti‐inflammatory activity in lipopolysaccharide (LPS)‐activated macrophages by regulating miR‐101/MKP‐1/MAPK pathway (45).”
Background
Flavonoid diversity and roles in the lipopolysaccharide-mediated inflammatory response of monocytes and macrophages.
Rullah, K., Shamsudin, N. F., Koeberle, A., Tham, C., Aluwi, M. F. F. M., Leong, S., Jantan, I., & Lam, K. (2024) · Future Medicinal Chemistry · doi:10.4155/fmc-2023-0174 · Cited by 8 · see citing works
Characterization and Structural Analysis of Genkwanin, a Natural Product from Callicarpa americana
Porras, G., Bacsa, J., Tang, H., & Quave, C. L. (2019) · Crystals · doi:10.3390/cryst9100491 · Cited by 10 · see citing works
“Previous pharmacological studies have found that Genkwanin has a variety of pharmacological effects, including anti-tussive, expectorant, anti-bacterial [26,27], anti-plasmodial [28], free radical scavenging activity [29] and especially anti-inflammatory [30] and anti-cancer properties [31,32].”
Background
Protective effect of genkwanin against lipopolysaccharide-induced acute lung injury in mice with p38 mitogen-activated protein kinase and nuclear factor-κB pathway inhibition
Ni, Y., Shen, H., Chen, S., & Kuan, Y. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.105271 · Cited by 10 · see citing works
Caragana rosea Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways
Mitra, A., Ahuja, A., Rahmawati, L., Kim, H. G., Woo, B. Y., Hong, Y. D., Hossain, M. A., Zhang, Z., Kim, S.-Y., Lee, J., et al. (2021) · Molecules · doi:10.3390/molecules26216660 · Cited by 9 · see citing works
“For genkwanin, researchers reported that it possesses anti-inflammatory activity mainly through the regulation of the miR-101/MKP1/MAPK pathway in vitro [50] and has antitumor activity against cancer [51].”
Background
Cytochrome P450s: Blueprints for Potential Applications in Plants
Naveed, A., Li, H., & Liu, X. (2018) · Journal of Plant Biochemistry & Physiology · doi:10.4172/2329-9029.1000204 · Cited by 8 · see citing works
Integration of transcriptome and metabolome provides insights into metabolites and pathways associated with antiproliferative activity of cannabis flower extracts
Liu, Y., Li, S., Shen, M., Guo, F., Li, M., Cai, S., Huang, J., Wu, J., Li, X., Peng, L., et al. (2024) · Industrial Crops and Products · doi:10.1016/j.indcrop.2024.120239 · Cited by 7 · see citing works
Identification of Molecular Targets and Potential Mechanisms of Yinchen Wuling San Against Head and Neck Squamous Cell Carcinoma by Network Pharmacology and Molecular Docking
Zhang, B., Liu, G., Wang, X., & Hu, X. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.914646 · Cited by 7 · see citing works
“It exerted an antiinflammatory effect by the regulation of the miR-101/MKP-1/ MAPK signaling pathway and the downregulation of proinflammatory mediators such as TNF-a, IL-1B, and IL-6 (Gao et al., 2014).”
Background
ANTI-AMYLOIDOGENIC EFFECT OF MiR-101 IN EXPERIMENTAL ALZHEIMER’S DISEASE
Sokolik, V. V. (2019) · Biotechnologia Acta · doi:10.15407/biotech12.03.041 · Cited by 7 · see citing works
Canscora lucidissima, a Chinese folk medicine, exerts anti-inflammatory activities by inhibiting the phosphorylation of ERK1/2 in LPS-activated macrophages
Fei, Q., Zhang, X.-Y., Qi, R.-J., Huang, Y., Han, Y., Li, X., Cai, R., Gao, Y., & Qi, Y. (2019) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-019-2783-2 · Cited by 7 · see citing works
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Additional file 10 of Metabolic engineering in Streptomyces albidoflavus for the biosynthesis of the methylated flavonoids sakuranetin, acacetin, and genkwanin
Pérez‐Valero, Á., Ye, S., Magadán‐Corpas, P., Villar, C. J., & Lombó, F. (2024) · Figshare · doi:10.6084/m9.figshare.26640097
Additional file 12 of Metabolic engineering in Streptomyces albidoflavus for the biosynthesis of the methylated flavonoids sakuranetin, acacetin, and genkwanin
Pérez‐Valero, Á., Ye, S., Magadán‐Corpas, P., Villar, C. J., & Lombó, F. (2024) · Figshare · doi:10.6084/m9.figshare.26640103
Additional file 2 of Metabolic engineering in Streptomyces albidoflavus for the biosynthesis of the methylated flavonoids sakuranetin, acacetin, and genkwanin
Pérez‐Valero, Á., Ye, S., Magadán‐Corpas, P., Villar, C. J., & Lombó, F. (2024) · Figshare · doi:10.6084/m9.figshare.24564273
Additional file 6 of Metabolic engineering in Streptomyces albidoflavus for the biosynthesis of the methylated flavonoids sakuranetin, acacetin, and genkwanin
Pérez‐Valero, Á., Ye, S., Magadán‐Corpas, P., Villar, C. J., & Lombó, F. (2024) · Figshare · doi:10.6084/m9.figshare.26640079

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Authors: Gao, Y., Liu, F., Fang, L., Cai, R., Zong, C., & Qi, Y.
Affiliations: Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author: Qi, Yun
ORCID: Gao, Yuan
Liu, Fen
Fang, Lei
Qi, Yun
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2014-05-06
Volume: 9
Issue: 5
Pages: e96741
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0096741
PMC: PMC4011752
OpenAlex: W2035643839
Cited by: 110
References: 61
Citations by year: 2026: 4 · 2025: 5 · 2024: 15 · 2023: 15 · 2022: 14 · 2021: 16 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 5 · 2015: 4
FWCI: 4.13
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: National Natural Science Foundation of China (81173645, 2014ZX09201022-006, 81274163, 2012ZX09301002-001)
Ministry of Science and Technology of the People's Republic of China (81274163, 2012ZX09301-002, 2014ZX09201022-006, 2012ZX09301-002-001)
Topics: Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
Keywords: genkwanin, anti-inflammatory activity, macrophages, lipopolysaccharide stimulation, miR-101, MKP-1, MAPK signaling, AP-1 signaling, p38 MAPK, JNK, inflammatory cytokines, inducible nitric oxide synthase, post-transcriptional regulation, Akt
MeSH terms: Animals, Anti-Inflammatory Agents, Cell Line, Lipopolysaccharides, Macrophages, Nitric Oxide, Phosphorylation, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Up-Regulation, Oligonucleotides, Antisense, Inflammation Mediators, Mitogen-Activated Protein Kinases, MicroRNAs, Flavones, Mice, Nitric Oxide Synthase Type II, Interleukin-1beta, Dual Specificity Phosphatase 1

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Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages

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