REVIEW
The molecular mechanisms underlying anti-inflammatory effects of galangin in different diseases
Emad H. M. Hassanein,
Mostafa S. Abd El-Maksoud,
Islam M. Ibrahim,
Esraa K. Abd-alhameed,
Hanan S. Althagafy,
Nesma M. Mohamed,
Samir A. Ross,
Corresponding Author
Emad H. M. Hassanein
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt
Correspondence
Emad H. M. Hassanein, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt.
Email: [email protected]
Contribution: Conceptualization, Project administration, Writing - review & editing
Search for more papers by this authorMostafa S. Abd El-Maksoud
Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt
Contribution: Formal analysis, Investigation, Software, Writing - original draft
Search for more papers by this authorIslam M. Ibrahim
Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt
Contribution: Data curation, Formal analysis, Resources, Writing - original draft
Search for more papers by this authorEsraa K. Abd-alhameed
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt
Contribution: Formal analysis, Visualization, Writing - review & editing
Search for more papers by this authorHanan S. Althagafy
Department of Biochemistry, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia
Contribution: Data curation, Formal analysis, Validation, Writing - original draft
Search for more papers by this authorNesma M. Mohamed
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Asyut, Egypt
Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Assiut, Asyut, Egypt
Contribution: Data curation, Investigation, Resources, Writing - review & editing
Search for more papers by this authorSamir A. Ross
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi, USA
Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi, USA
Contribution: Supervision
Search for more papers by this authorEmad H. M. Hassanein,
Mostafa S. Abd El-Maksoud,
Islam M. Ibrahim,
Esraa K. Abd-alhameed,
Hanan S. Althagafy,
Nesma M. Mohamed,
Samir A. Ross,
Corresponding Author
Emad H. M. Hassanein
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt
Correspondence
Emad H. M. Hassanein, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt.
Email: [email protected]
Contribution: Conceptualization, Project administration, Writing - review & editing
Search for more papers by this authorMostafa S. Abd El-Maksoud
Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt
Contribution: Formal analysis, Investigation, Software, Writing - original draft
Search for more papers by this authorIslam M. Ibrahim
Faculty of Pharmacy, Al-Azhar University, Asyut, Egypt
Contribution: Data curation, Formal analysis, Resources, Writing - original draft
Search for more papers by this authorEsraa K. Abd-alhameed
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt
Contribution: Formal analysis, Visualization, Writing - review & editing
Search for more papers by this authorHanan S. Althagafy
Department of Biochemistry, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia
Contribution: Data curation, Formal analysis, Validation, Writing - original draft
Search for more papers by this authorNesma M. Mohamed
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Asyut, Egypt
Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Assiut, Asyut, Egypt
Contribution: Data curation, Investigation, Resources, Writing - review & editing
Search for more papers by this authorSamir A. Ross
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi, USA
Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi, USA
Contribution: Supervision
Search for more papers by this authorAbstract
When used as an alternative source of drugs to treat inflammation-associated diseases, phytochemicals with anti-inflammatory properties provide beneficial impacts. Galangin is one of the most naturally occurring flavonoids. Galangin has many biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antimicrobial, anti-obesity, antidiabetic, and anti-genotoxic activities. We observed that galangin was well tolerated and positively impacted disease underlying inflammation for the renal, hepatic, central nervous system, cardiovascular, gastrointestinal system, skin, and respiratory disorders, as well as ulcerative colitis, acute pancreatitis, retinopathy, osteoarthritis, osteoporosis, and rheumatoid arthritis. Galangin anti-inflammatory effects are mediated mainly by suppressing p38 mitogen-activated protein kinases, nuclear factor-kappa B, and nod-like receptor protein 3 signals. These effects are confirmed and supported by molecular docking. Clinical translational research is required to accelerate the bench-to-bedside transfer and determine whether galangin can be utilised as a safe, natural source of pharmaceutical anti-inflammatory medication for humans.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
This article contains all of the data generated or evaluated throughout the research.
REFERENCES
- Abd El-Ghafar, O. A. M., Hassanein, E. H. M., Ali, F. E. M., Omar, Z. M. M., Rashwan, E. K., Mohammedsaleh, Z. M., & Sayed, A. M. (2022). Hepatoprotective effect of acetovanillone against methotrexate hepatotoxicity: Role of Keap-1/Nrf2/ARE, IL6/STAT-3, and NF-κB/AP-1 signaling pathways. Phytotherapy Research, 36(1), 488–505. https://doi.org/10.1002/ptr.7355
- Abdel-Wahab, B. A., Ali, F. E. M., Alkahtani, S. A., Alshabi, A. M., Mahnashi, M. H., & Hassanein, E. H. M. (2020). Hepatoprotective effect of rebamipide against methotrexate-induced hepatic intoxication: Role of Nrf2/GSK-3β, NF-κβ-p65/JAK1/STAT3, and PUMA/Bax/Bcl-2 signaling pathways. Immunopharmacology and Immunotoxicology, 42(5), 493–503. https://doi.org/10.1080/08923973.2020.1811307
- Abdel-Wahab, B. A., Walbi, I. A., Albarqi, H. A., Ali, F. E. M., & Hassanein, E. H. M. (2021). Roflumilast protects from cisplatin-induced testicular toxicity in male rats and enhances its cytotoxicity in prostate cancer cell line. Role of NF-κB-p65, cAMP/PKA and Nrf2/HO-1, NQO1 signaling. Food and Chemical Toxicology, 151, 112133. https://doi.org/10.1016/j.fct.2021.112133
- Abramoff, B., & Caldera, F. E. (2020). Osteoarthritis: Pathology, diagnosis, and treatment options. The Medical Clinics of North America, 104(2), 293–311. https://doi.org/10.1016/j.mcna.2019.10.007
- Abukhalil, M. H., Althunibat, O. Y., Aladaileh, S. H., Al-Amarat, W., Obeidat, H. M., Al-Khawalde, A. A. A., Hussein, O. E., Alfwuaires, M. A., Algefare, A. I., Alanazi, K. M., Al-Swailmi, F. K., Arab, H. H., & Mahmoud, A. M. (2021). Galangin attenuates diabetic cardiomyopathy through modulating oxidative stress, inflammation and apoptosis in rats. Biomedicine & Pharmacotherapy, 138, 111410. https://doi.org/10.1016/j.biopha.2021.111410
- Afolayan, A. J., & Meyer, J. J. (1997). The antimicrobial activity of 3,5,7-trihydroxyflavone isolated from the shoots of Helichrysum aureonitens. Journal of Ethnopharmacology, 57(3), 177–181. https://doi.org/10.1016/s0378-8741(97)00065-2
- Ahmed, A. R., & Hombal, S. M. (1984). Cyclophosphamide (Cytoxan). A review on relevant pharmacology and clinical uses. Journal of the American Academy of Dermatology, 11(6), 1115–1126. https://doi.org/10.1016/s0190-9622(84)80193-0
- Aladaileh, S. H., Abukhalil, M. H., Saghir, S. A. M., Hanieh, H., Alfwuaires, M. A., Almaiman, A. A., Bin-Jumah, M., & Mahmoud, A. M. (2019). Galangin activates Nrf2 signaling and attenuates oxidative damage, inflammation, and apoptosis in a rat model of cyclophosphamide-induced hepatotoxicity. Biomolecules, 9(8), 346. https://doi.org/10.3390/biom9080346
- Aladaileh, S. H., Al-Swailmi, F. K., Abukhalil, M. H., & Shalayel, M. H. (2021). Galangin protects against oxidative damage and attenuates inflammation and apoptosis via modulation of NF-κB p65 and caspase-3 signaling molecules in a rat model of diabetic nephropathy. Journal of Physiology and Pharmacology, 72(1), 35–44. https://doi.org/10.26402/jpp.2021.1.04
- Alfwuaires, M. A. (2021). Galangin mitigates oxidative stress, inflammation, and apoptosis in a rat model of methotrexate hepatotoxicity. Environmental Science and Pollution Research International, 29(14), 20279–20288. https://doi.org/10.1007/s11356-021-16804-z
- Ali, F. E. M., Hassanein, E. H. M., El-Bahrawy, A. H., Omar, Z. M. M., Rashwan, E. K., Abdel-Wahab, B. A., & Abd-Elhamid, T. H. (2021). Nephroprotective effect of umbelliferone against cisplatin-induced kidney damage is mediated by regulation of NRF2, cytoglobin, SIRT1/FOXO-3, and NF-kB-p65 signaling pathways. Journal of Biochemical and Molecular Toxicology, 35(5), e22738. https://doi.org/10.1002/jbt.22738
- Allen, I. C., Scull, M. A., Moore, C. B., Holl, E. K., McElvania-TeKippe, E., Taxman, D. J., Guthrie, E. H., Pickles, R. J., & Ting, J. P. (2009). The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity, 30(4), 556–565. https://doi.org/10.1016/j.immuni.2009.02.005
- Aloud, A. A., Veeramani, C., Govindasamy, C., Alsaif, M. A., El Newehy, A. S., & Al-Numair, K. S. (2017). Galangin, a dietary flavonoid, improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats. Redox Report, 22(6), 290–300. https://doi.org/10.1080/13510002.2016.1273437
- Andrade, L. A. M., Delgado, A. T., Corona, L. F. P., Moreno, O. S., Rodríguez, D. F., Erazo, O. R. R., Duarte, E. V., Gomez, J. D. J. C., Rodriguez, R. C., Araujo, N. A., & Carmona, O. A. N. (2017). Acute pancreatitis, actualization and evidence based management. Archives of Clinical Gastroenterology, 3(1), 1–8.
10.17352/2455-2283.000028 Google Scholar
- Andrade, R. J., Chalasani, N., Björnsson, E. S., Suzuki, A., Kullak-Ublick, G. A., Watkins, P. B., Devarbhavi, H., Merz, M., Lucena, M. I., Kaplowitz, N., & Aithal, G. P. (2019). Drug-induced liver injury. Nature Reviews Disease Primers, 5(1), 58. https://doi.org/10.1038/s41572-019-0105-0
- Arif, H., Rehmani, N., Farhan, M., Ahmad, A., & Hadi, S. M. (2015). Mobilization of copper ions by flavonoids in human peripheral lymphocytes leads to oxidative DNA breakage: A structure activity study. International Journal of Molecular Sciences, 16(11), 26754–26769. https://doi.org/10.3390/ijms161125992
- Armas, L. A., & Recker, R. R. (2012). Pathophysiology of osteoporosis: New mechanistic insights. Endocrinology and Metabolism Clinics of North America, 41(3), 475–486. https://doi.org/10.1016/j.ecl.2012.04.006
- Aso, S., Matsui, H., Fushimi, K., & Yasunaga, H. (2019). Systemic glucocorticoids plus cyclophosphamide for acute exacerbation of idiopathic pulmonary fibrosis: A retrospective nationwide study. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases, 36(2), 116–123. https://doi.org/10.36141/svdld.v36i2.7181
- Babitt, J. L., & Lin, H. Y. (2011). The molecular pathogenesis of hereditary hemochromatosis. Seminars in Liver Disease, 31(3), 280–292. https://doi.org/10.1055/s-0031-1286059
- Bakr, A. G., Hassanein, E. H. M., Ali, F. E. M., & El-Shoura, E. A. M. (2022). Combined apocynin and carvedilol protect against cadmium-induced testicular damage via modulation of inflammatory response and redox-sensitive pathways. Life Sciences, 311(Pt A), 121152. https://doi.org/10.1016/j.lfs.2022.121152
- Banks, P. A., Bollen, T. L., Dervenis, C., Gooszen, H. G., Johnson, C. D., Sarr, M. G., Tsiotos, G. G., & Vege, S. S. (2013). Classification of acute pancreatitis—2012: Revision of the Atlanta classification and definitions by international consensus. Gut, 62(1), 102–111. https://doi.org/10.1136/gutjnl-2012-302779
- Bauernfeind, F. G., Horvath, G., Stutz, A., Alnemri, E. S., MacDonald, K., Speert, D., Fernandes-Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., Hornung, V., & Latz, E. (2009). Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Journal of Immunology, 183(2), 787–791. https://doi.org/10.4049/jimmunol.0901363
- Bedoui, Y., Guillot, X., Sélambarom, J., Guiraud, P., Giry, C., Jaffar-Bandjee, M. C., Ralandison, S., & Gasque, P. (2019). Methotrexate an old drug with new tricks. International Journal of Molecular Sciences, 20(20), 5023. https://doi.org/10.3390/ijms20205023
- Benković, G., Bojić, M., Maleš, Ž., & Tomić, S. (2019). Screening of flavonoid aglycons' metabolism mediated by the human liver cytochromes P450. Acta Pharmaceutica, 69(4), 541–562. https://doi.org/10.2478/acph-2019-0039
- Bergeron, C., Tulic, M. K., & Hamid, Q. (2010). Airway remodelling in asthma: From benchside to clinical practice. Canadian Respiratory Journal, 17(4), e85–e93. https://doi.org/10.1155/2010/318029
- Berneburg, M., Plettenberg, H., & Krutmann, J. (2000). Photoaging of human skin. Photodermatology, Photoimmunology & Photomedicine, 16(6), 239–244. https://doi.org/10.1034/j.1600-0781.2000.160601.x
- Biedermann, T., Skabytska, Y., Kaesler, S., & Volz, T. (2015). Regulation of T cell immunity in atopic dermatitis by microbes: The Yin and Yang of cutaneous inflammation. Frontiers in Immunology, 6, 353. https://doi.org/10.3389/fimmu.2015.00353
- Boismal, F., Serror, K., Dobos, G., Zuelgaray, E., Bensussan, A., & Michel, L. (2020). Skin aging: Pathophysiology and innovative therapies. Medical Science, 36(12), 1163–1172. https://doi.org/10.1051/medsci/2020232
10.1051/medsci/2020232 Google Scholar
- Bordbar, M., Shakibazad, N., Fattahi, M., Haghpanah, S., & Honar, N. (2018). Effect of ursodeoxycholic acid and vitamin E in the prevention of liver injury from methotrexate in pediatric leukemia. The Turkish Journal of Gastroenterology, 29(2), 203–209. https://doi.org/10.5152/tjg.2018.17521
- Bourgonje, A. R., Feelisch, M., Faber, K. N., Pasch, A., Dijkstra, G., & van Goor, H. (2020). Oxidative stress and redox-modulating therapeutics in inflammatory bowel disease. Trends in Molecular Medicine, 26(11), 1034–1046. https://doi.org/10.1016/j.molmed.2020.06.006
- Bowman, T., Garcia, R., Turkson, J., & Jove, R. (2000). STATs in oncogenesis. Oncogene, 19(21), 2474–2488. https://doi.org/10.1038/sj.onc.1203527
- Bowry, A. D., Lewey, J., Dugani, S. B., & Choudhry, N. K. (2015). The burden of cardiovascular disease in low- and middle-income countries: Epidemiology and management. The Canadian Journal of Cardiology, 31(9), 1151–1159. https://doi.org/10.1016/j.cjca.2015.06.028
- Calle, E. E., & Kaaks, R. (2004). Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nature Reviews Cancer, 4(8), 579–591. https://doi.org/10.1038/nrc1408
- Chaihongsa, N., Maneesai, P., Sangartit, W., Potue, P., Bunbupha, S., & Pakdeechote, P. (2021). Galangin alleviates vascular dysfunction and remodelling through modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats. Life Sciences, 285, 119965. https://doi.org/10.1016/j.lfs.2021.119965
- Choi, J. K., & Kim, S. H. (2014). Inhibitory effect of galangin on atopic dermatitis-like skin lesions. Food and Chemical Toxicology, 68, 135–141. https://doi.org/10.1016/j.fct.2014.03.021
- Chung, K. F. (2006). Cytokines as targets in chronic obstructive pulmonary disease. Current Drug Targets, 7(6), 675–681. https://doi.org/10.2174/138945006777435263
- Cildir, G., Low, K. C., & Tergaonkar, V. (2016). Noncanonical NF-κB signaling in health and disease. Trends in Molecular Medicine, 22(5), 414–429. https://doi.org/10.1016/j.molmed.2016.03.002
- Coulombe, P., & Meloche, S. (2007). Atypical mitogen-activated protein kinases: Structure, regulation and functions. Biochimica et Biophysica Acta, 1773(8), 1376–1387. https://doi.org/10.1016/j.bbamcr.2006.11.001
- Danese, S., & Fiocchi, C. (2011). Ulcerative colitis. The New England Journal of Medicine, 365(18), 1713–1725. https://doi.org/10.1056/NEJMra1102942
- Deng, W., Abliz, A., Xu, S., Sun, R., Guo, W., Shi, Q., Yu, J., & Wang, W. (2016). Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin. Molecular Medicine Reports, 14(4), 3525–3534. https://doi.org/10.3892/mmr.2016.5678
- Deng, X., Le, H., Wan, T., Weng, M., & Tan, Y. (2022). Galangin alleviates rheumatoid arthritis in rats by downregulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. Bioengineered, 13(4), 11192–11201. https://doi.org/10.1080/21655979.2022.2062969
- Dlouhy, A. C., & Outten, C. E. (2013). The iron metallome in eukaryotic organisms. Metal Ions in Life Sciences, 12, 241–278. https://doi.org/10.1007/978-94-007-5561-1_8
- Duan, W., & Wong, W. S. (2006). Targeting mitogen-activated protein kinases for asthma. Current Drug Targets, 7(6), 691–698. https://doi.org/10.2174/138945006777435353
- Eichenfield, L. F., Tom, W. L., Chamlin, S. L., Feldman, S. R., Hanifin, J. M., Simpson, E. L., Berger, T. G., Bergman, J. N., Cohen, D. E., Cooper, K. D., Cordoro, K. M., Davis, D. M., Krol, A., Margolis, D. J., Paller, A. S., Schwarzenberger, K., Silverman, R. A., Williams, H. C., Elmets, C. A., … Sidbury, R. (2014). Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis. Journal of the American Academy of Dermatology, 70(2), 338–351. https://doi.org/10.1016/j.jaad.2013.10.010
- Elia, P. P., Tolentino, Y. F., Bernardazzi, C., & de Souza, H. S. (2015). The role of innate immunity receptors in the pathogenesis of inflammatory bowel disease. Mediators of Inflammation, 2015, 936193. https://doi.org/10.1155/2015/936193
- Fang, D., Xiong, Z., Xu, J., Yin, J., & Luo, R. J. B. (2019). Chemopreventive mechanisms of galangin against hepatocellular carcinoma: A review. Biomedicine & Pharmacotherapy, 109, 2054–2061.
- Feldman, A. S., He, Y., Moore, M. L., Hershenson, M. B., & Hartert, T. V. (2015). Toward primary prevention of asthma. Reviewing the evidence for early-life respiratory viral infections as modifiable risk factors to prevent childhood asthma. American Journal of Respiratory and Critical Care Medicine, 191(1), 34–44. https://doi.org/10.1164/rccm.201405-0901PP
- Felson, D. T. (2004). Risk factors for osteoarthritis: Understanding joint vulnerability. Clinical Orthopaedics and Related Research, 427, S16–S21. https://doi.org/10.1097/01.blo.0000144971.12731.a2
- Feuerstein, J. D., Moss, A. C., & Farraye, F. A. (2019). Ulcerative colitis. Mayo Clinic Proceedings, 94(7), 1357–1373. https://doi.org/10.1016/j.mayocp.2019.01.018
- Fong, D. S., Aiello, L. P., Ferris, F. L., 3rd, & Klein, R. (2004). Diabetic retinopathy. Diabetes Care, 27(10), 2540–2553. https://doi.org/10.2337/diacare.27.10.2540
- Franchi, L., Eigenbrod, T., & Núñez, G. (2009). Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. Journal of Immunology, 183(2), 792–796. https://doi.org/10.4049/jimmunol.0900173
- Fu, Q., Gao, Y., Zhao, H., Wang, Z., & Wang, J. (2018). Galangin protects human rheumatoid arthritis fibroblast-like synoviocytes via suppression of the NF-κB/NLRP3 pathway. Molecular Medicine Reports, 18(4), 3619–3624. https://doi.org/10.3892/mmr.2018.9422
- Gaestel, M. (2008). Specificity of signaling from MAPKs to MAPKAPKs: kinases' tango nuevo. Frontiers in Bioscience, 13, 6050–6059. https://doi.org/10.2741/3136
- Gamad, N., Malik, S., Suchal, K., Vasisht, S., Tomar, A., Arava, S., Arya, D. S., & Bhatia, J. (2018). Metformin alleviates bleomycin-induced pulmonary fibrosis in rats: Pharmacological effects and molecular mechanisms. Biomedicine & Pharmacotherapy, 97, 1544–1553. https://doi.org/10.1016/j.biopha.2017.11.101
- Gerges, S. H., Tolba, M. F., Elsherbiny, D. A., & El-Demerdash, E. (2020). The natural flavonoid galangin ameliorates dextran sulphate sodium-induced ulcerative colitis in mice: Effect on toll-like receptor 4, inflammation and oxidative stress. Basic & Clinical Pharmacology & Toxicology, 127(1), 10–20. https://doi.org/10.1111/bcpt.13388
- Gong, J., Zhang, Z., Zhang, X., Chen, F., Tan, Y., Li, H., Jiang, J., & Zhang, J. (2018). Effects and possible mechanisms of Alpinia officinarum ethanol extract on indomethacin-induced gastric injury in rats. Pharmaceutical Biology, 56(1), 294–301. https://doi.org/10.1080/13880209.2018.1450426
- Groner, B., & von Manstein, V. (2017). Jak stat signaling and cancer: Opportunities, benefits and side effects of targeted inhibition. Molecular and Cellular Endocrinology, 451, 1–14. https://doi.org/10.1016/j.mce.2017.05.033
- Gross, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschläger, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V., Mocsai, A., Tschopp, J., & Ruland, J. (2009). Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature, 459(7245), 433–436. https://doi.org/10.1038/nature07965
- Hagar, H. H., Almubrik, S. A., Attia, N. M., & Aljasser, S. N. (2020). Mesna alleviates cerulein-induced acute pancreatitis by inhibiting the inflammatory response and oxidative stress in experimental rats. Digestive Diseases and Sciences, 65(12), 3583–3591. https://doi.org/10.1007/s10620-020-06072-1
- Haque, M. A., Jantan, I., & Harikrishnan, H. (2018). Zerumbone suppresses the activation of inflammatory mediators in LPS-stimulated U937 macrophages through MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways. International Immunopharmacology, 55, 312–322. https://doi.org/10.1016/j.intimp.2018.01.001
- Harikrishnan, H., Jantan, I., Haque, M. A., & Kumolosasi, E. (2018). Phyllanthin from Phyllanthus amarus inhibits LPS-induced proinflammatory responses in U937 macrophages via downregulation of NF-κB/MAPK/PI3K-Akt signaling pathways. Phytotherapy Research, 32(12), 2510–2519. https://doi.org/10.1002/ptr.6190
- Hassanein, E. H. M., Abd El-Ghafar, O. A. M., Ahmed, M. A., Sayed, A. M., Gad-Elrab, W. M., Ajarem, J. S., Allam, A. A., & Mahmoud, A. M. (2020). Edaravone and acetovanillone upregulate Nrf2 and PI3K/Akt/mTOR signaling and prevent cyclophosphamide cardiotoxicity in rats. Drug Design, Development and Therapy, 14, 5275–5288. https://doi.org/10.2147/dddt.S281854
- Hassanein, E. H. M., Abdel-Wahab, B. A., Ali, F. E. M., Abd El-Ghafar, O. A. M., Kozman, M. R., & Sharkawi, S. M. Z. (2021). Trans-ferulic acid ameliorates cisplatin-induced testicular damage via suppression of TLR4, P38-MAPK, and ERK1/2 signaling pathways. Environmental Science and Pollution Research International, 28(31), 41948–41964. https://doi.org/10.1007/s11356-021-13544-y
- Hassanein, E. H. M., Ahmed, M. A., Sayed, A. M., Rashwan, E. K., Abd El-Ghafar, O. A. M., & Mahmoud, A. M. (2021). Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR-4/NF-κB, and JAK1/STAT3 signaling in cyclophosphamide-intoxicated rats. Journal of Biochemical and Molecular Toxicology, 35(11), e22889. https://doi.org/10.1002/jbt.22889
- Hassanein, E. H. M., Kamel, E. O., Gad-Elrab, W. M., Ahmed, M. A., Mohammedsaleh, Z. M., & Ali, F. E. M. (2023). Lansoprazole attenuates cyclophosphamide-induced cardiopulmonary injury by modulating redox-sensitive pathways and inflammation. Molecular and Cellular Biochemistry, 1–17. https://doi.org/10.1007/s11010-023-04662-x
- Hassanein, E. H. M., Mohamed, W. R., Ahmed, O. S., Abdel-Daim, M. M., & Sayed, A. M. (2022). The role of inflammation in cadmium nephrotoxicity: NF-κB comes into view. Life Sciences, 308, 120971. https://doi.org/10.1016/j.lfs.2022.120971
- Hassanein, E. H. M., Sayed, G. A., Alzoghaibi, A. M., Alammar, A. S., Abdel-Wahab, B. A., Abd El-Ghafar, O. A. M., Mahdi, S. E., Atwa, A. M., Alzoghaibi, M. A., & Mahmoud, A. M. (2022). Azithromycin mitigates cisplatin-induced lung oxidative stress, inflammation and necroptosis by upregulating SIRT1, PPARγ, and Nrf2/HO-1 signaling. Pharmaceuticals, 16(1), 52. https://doi.org/10.3390/ph16010052
- Henry, L. J. K., Ramar, M. K., Palanisamy, S., Natesan, S., & Kandasamy, R. (2020). Mechanistic investigation of PPARgamma-facilitated anti-asthmatic effects of Galangin (Norizalpinin): Insights from in silico and in vivo analyses. Biochemical and Biophysical Research Communications, 526(3), 833–840. https://doi.org/10.1016/j.bbrc.2020.03.158
- Heo, M. Y., Sohn, S. J., & Au, W. W. (2001). Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate. Mutation Research, 488(2), 135–150. https://doi.org/10.1016/s1383-5742(01)00054-0
- Honda, K., Marquillies, P., Capron, M., & Dombrowicz, D. (2004). Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. The Journal of Allergy and Clinical Immunology, 113(5), 882–888. https://doi.org/10.1016/j.jaci.2004.02.036
- Huang, X., Pei, W., Ni, B., Zhang, R., & You, H. (2021). Chondroprotective and antiarthritic effects of galangin in osteoarthritis: An in vitro and in vivo study. European Journal of Pharmacology, 906, 174232. https://doi.org/10.1016/j.ejphar.2021.174232
- Huang, Y. C., Tsai, M. S., Hsieh, P. C., Shih, J. H., Wang, T. S., Wang, Y. C., Lin, T.-H., & Wang, S. H. (2017). Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. Toxicology and Applied Pharmacology, 329, 128–139. https://doi.org/10.1016/j.taap.2017.05.034
- Huh, J. E., Jung, I. T., Choi, J., Baek, Y. H., Lee, J. D., Park, D. S., & Choi, D. Y. (2013). The natural flavonoid galangin inhibits osteoclastic bone destruction and osteoclastogenesis by suppressing NF-κB in collagen-induced arthritis and bone marrow-derived macrophages. European Journal of Pharmacology, 698(1–3), 57–66. https://doi.org/10.1016/j.ejphar.2012.08.013
- Huh, J. E., Lee, W. I., Kang, J. W., Nam, D., Choi, D. Y., Park, D. S., Lee, S. H., & Lee, J. D. (2014). Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway. Journal of Natural Products, 77(11), 2423–2431. https://doi.org/10.1021/np500417d
- Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., Yamaguchi, M., Namiki, S., Nakayama, R., Tabata, M., Ogata, H., Kubota, N., Takamoto, I., Hayashi, Y. K., Yamauchi, N., Waki, H., Fukayama, M., Nishino, I., Tokuyama, K., … Kadowaki, T. (2010). Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature, 464(7293), 1313–1319. https://doi.org/10.1038/nature08991
- Jeong, Y. H., Park, J. S., Kim, D. H., Kang, J. L., & Kim, H. S. (2017). Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation. Pharmacological Research, 119, 431–442. https://doi.org/10.1016/j.phrs.2017.02.027
- Jha, S., Brickey, W. J., & Ting, J. P. (2017). Inflammasomes in myeloid cells: Warriors within. Microbiology Spectrum, 5(1), 305–324. https://doi.org/10.1128/microbiolspec.MCHD-0049-2016
- Jung, S. W., Kim, S. M., Kim, Y. G., Lee, S. H., & Moon, J. Y. (2020). Uric acid and inflammation in kidney disease. American Journal of Physiology. Renal Physiology, 318(6), F1327–f1340. https://doi.org/10.1152/ajprenal.00272.2019
- Kalantar, M., Kalantari, H., Goudarzi, M., Khorsandi, L., Bakhit, S., & Kalantar, H. (2019). Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats. Pharmacological Reports, 71(4), 746–752. https://doi.org/10.1016/j.pharep.2019.04.004
- Kamel, E. O., Gad-Elrab, W. M., Ahmed, M. A., Mohammedsaleh, Z. M., Hassanein, E. H. M., & Ali, F. E. M. (2023). Candesartan protects against cadmium-induced hepatorenal syndrome by affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1-7 signals. Biological Trace Element Research, 201(4), 1846–1863. https://doi.org/10.1007/s12011-022-03286-4
- Kaminska, B. (2005). MAPK signalling pathways as molecular targets for anti-inflammatory therapy—from molecular mechanisms to therapeutic benefits. Biochimica et Biophysica Acta, 1754(1–2), 253–262. https://doi.org/10.1016/j.bbapap.2005.08.017
- Kanneganti, T. D., Body-Malapel, M., Amer, A., Park, J. H., Whitfield, J., Franchi, L., Taraporewala, Z. F., Miller, D., Patton, J. T., Inohara, N., & Núñez, G. (2006). Critical role for cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. The Journal of Biological Chemistry, 281(48), 36560–36568. https://doi.org/10.1074/jbc.M607594200
- Kaur, J. (2014). A comprehensive review on metabolic syndrome. Cardiology Research and Practice, 2014, 943162. https://doi.org/10.1155/2014/943162
- Kawano, S., Kubota, T., Monden, Y., Tsutsumi, T., Inoue, T., Kawamura, N., Tsutsui, H., & Sunagawa, K. (2006). Blockade of NF-kappaB improves cardiac function and survival after myocardial infarction. American Journal of Physiology Heart and Circulatory Physiology, 291(3), H1337–H1344. https://doi.org/10.1152/ajpheart.01175.2005
- Khalaf, M. M., Hassanein, E. H. M., Shalkami, A. S., Hemeida, R. A. M., & Mohamed, W. R. (2022). Diallyl disulfide attenuates methotrexate-induced hepatic oxidative injury, inflammation and apoptosis and enhances its anti-tumor activity. Current Molecular Pharmacology, 15(1), 213–226. https://doi.org/10.2174/1874467214666210525153111
- Kim, M. E., Park, P. R., Na, J. Y., Jung, I., Cho, J. H., & Lee, J. S. (2019). Anti-neuroinflammatory effects of galangin in LPS-stimulated BV-2 microglia through regulation of IL-1β production and the NF-κB signaling pathways. Molecular and Cellular Biochemistry, 451(1–2), 145–153. https://doi.org/10.1007/s11010-018-3401-1
- King, C. S., & Nathan, S. D. (2017). Idiopathic pulmonary fibrosis: Effects and optimal management of comorbidities. The Lancet Respiratory Medicine, 5(1), 72–84. https://doi.org/10.1016/s2213-2600(16)30222-3
- Koenders, M. I., & van den Berg, W. B. (2015). Novel therapeutic targets in rheumatoid arthritis. Trends in Pharmacological Sciences, 36(4), 189–195. https://doi.org/10.1016/j.tips.2015.02.001
- Kong, N., Lan, Q., Su, W., Chen, M., Wang, J., Yang, Z., Park, R., Dagliyan, G., Conti, P. S., Brand, D., Liu, Z., Stohl, W., Zou, H., & Zheng, S. G. (2012). Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells. Annals of the Rheumatic Diseases, 71(9), 1567–1572. https://doi.org/10.1136/annrheumdis-2011-201052
- Kumar, S., & Pandey, A. K. (2013). Chemistry and biological activities of flavonoids: An overview. Scientific World Journal, 2013, 162750. https://doi.org/10.1155/2013/162750
- Kummer, J. A., Broekhuizen, R., Everett, H., Agostini, L., Kuijk, L., Martinon, F., Bruggen, R. V., & Tschopp, J. (2007). Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. The Journal of Histochemistry and Cytochemistry, 55(5), 443–452. https://doi.org/10.1369/jhc.6A7101.2006
- Kuna, L., Jakab, J., Smolic, R., Raguz-Lucic, N., Vcev, A., & Smolic, M. (2019). Peptic ulcer disease: A brief review of conventional therapy and herbal treatment options. Journal of Clinical Medicine, 8(2), 179. https://doi.org/10.3390/jcm8020179
- Lambrecht, B. N., & Hammad, H. (2015). The immunology of asthma. Nature Immunology, 16(1), 45–56. https://doi.org/10.1038/ni.3049
- Laveti, D., Kumar, M., Hemalatha, R., Sistla, R., Naidu, V. G., Talla, V., Verma, V., Kaur, N., & Nagpal, R. (2013). Anti-inflammatory treatments for chronic diseases: A review. Inflammation & Allergy Drug Targets, 12(5), 349–361. https://doi.org/10.2174/18715281113129990053
- Lawrence, M. C., Jivan, A., Shao, C., Duan, L., Goad, D., Zaganjor, E., Osborne, J., McGlynn, K., Stippec, S., Earnest, S., Chen, W., & Cobb, M. H. (2008). The roles of MAPKs in disease. Cell Research, 18(4), 436–442. https://doi.org/10.1038/cr.2008.37
- Lee, A. S., Ellman, M. B., Yan, D., Kroin, J. S., Cole, B. J., van Wijnen, A. J., & Im, H. J. (2013). A current review of molecular mechanisms regarding osteoarthritis and pain. Gene, 527(2), 440–447. https://doi.org/10.1016/j.gene.2013.05.069
- Lee, H. N., Shin, S. A., Choo, G. S., Kim, H. J., Park, Y. S., Kim, B. S., Kim, S. K., Cho, S. D., Nam, J. S., Choi, C. S., Che, J. H., Park, B. K., & Jung, J. Y. (2018). Anti-inflammatory effect of quercetin and galangin in LPS stimulated RAW264.7 macrophages and DNCB-induced atopic dermatitis animal models. International Journal of Molecular Medicine, 41(2), 888–898. https://doi.org/10.3892/ijmm.2017.3296
- Lee, S., Lee, H. J., Kim, S. C., & Joo, J. K. (2020). Association between nutrients and metabolic syndrome in middle-aged Korean women. Archives of Endocrinology and Metabolism, 64(3), 298–305. https://doi.org/10.20945/2359-3997000000252
- Lee, Y. Y., Lee, E. J., Park, J. S., Jang, S. E., Kim, D. H., & Kim, H. S. (2016). Anti-inflammatory and antioxidant mechanism of tangeretin in activated microglia. Journal of Neuroimmune Pharmacology, 11(2), 294–305. https://doi.org/10.1007/s11481-016-9657-x
- Levy, D. E., & Darnell, J. E., Jr. (2002). Stats: Transcriptional control and biological impact. Nature Reviews Molecular Cell Biology, 3(9), 651–662. https://doi.org/10.1038/nrm909
- Li, Q., & Verma, I. M. (2002). NF-kappaB regulation in the immune system. Nature Reviews Immunology, 2(10), 725–734. https://doi.org/10.1038/nri910
- Li, X., Jiang, J., Yang, Z., Jin, S., Lu, X., & Qian, Y. (2021). Galangin suppresses RANKL-induced osteoclastogenesis via inhibiting MAPK and NF-κB signalling pathways. Journal of Cellular and Molecular Medicine, 25(11), 4988–5000. https://doi.org/10.1111/jcmm.16430
- Liang, X., Wang, P., Yang, C., Huang, F., Wu, H., Shi, H., & Wu, X. (2021). Galangin inhibits gastric cancer growth through enhancing STAT3 mediated ROS production. Frontiers in Pharmacology, 12, 646628. https://doi.org/10.3389/fphar.2021.646628
- Lin, Q., Zhang, Y., Hong, W., Miao, H., Dai, J., & Sun, Y. (2022). Galangin ameliorates osteoarthritis progression by attenuating extracellular matrix degradation in chondrocytes via the activation of PRELP expression. European Journal of Pharmacology, 936, 175347. https://doi.org/10.1016/j.ejphar.2022.175347
- Liu, C., Chu, D., Kalantar-Zadeh, K., George, J., Young, H. A., & Liu, G. (2021). Cytokines: From clinical significance to quantification. Advanced Science, 8(15), e2004433. https://doi.org/10.1002/advs.202004433
- Liu, T., Zhang, L., Joo, D., & Sun, S. C. (2017). NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy, 2, 17023. https://doi.org/10.1038/sigtrans.2017.23
- Liu, Y. N., Zha, W. J., Ma, Y., Chen, F. F., Zhu, W., Ge, A., Zeng, X. N., & Huang, M. (2015). Galangin attenuates airway remodelling by inhibiting TGF-β1-mediated ROS generation and MAPK/Akt phosphorylation in asthma. Scientific Reports, 5, 11758. https://doi.org/10.1038/srep11758
- Lu, H., Yao, H., Zou, R., Chen, X., & Xu, H. (2019). Galangin suppresses renal inflammation via the inhibition of NF-κB, PI3K/AKT and NLRP3 in uric acid treated NRK-52E tubular epithelial cells. BioMed Research International, 2019, 3018357. https://doi.org/10.1155/2019/3018357
- Lu, Y. C., Yeh, W. C., & Ohashi, P. S. (2008). LPS/TLR4 signal transduction pathway. Cytokine, 42(2), 145–151. https://doi.org/10.1016/j.cyto.2008.01.006
- Luo, H., Gu, R., Ouyang, H., Wang, L., Shi, S., Ji, Y., Bao, B., Liao, G., & Xu, B. (2021). Cadmium exposure induces osteoporosis through cellular senescence, associated with activation of NF-κB pathway and mitochondrial dysfunction. Environmental Pollution, 290, 118043. https://doi.org/10.1016/j.envpol.2021.118043
- Luo, Y., Wu, W., Gu, J., Zhang, X., Dang, J., Wang, J., Zheng, Y., Huang, F., Yuan, J., Xue, Y., Fu, Q., Kandalam, U., Colello, J., & Zheng, S. G. (2019). Human gingival tissue-derived MSC suppress osteoclastogenesis and bone erosion via CD39-adenosine signal pathway in autoimmune arthritis. eBioMedicine, 43, 620–631. https://doi.org/10.1016/j.ebiom.2019.04.058
- Ma, R., Yuan, F., Wang, S., Liu, Y., Fan, T., & Wang, F. (2018). Calycosin alleviates cerulein-induced acute pancreatitis by inhibiting the inflammatory response and oxidative stress via the p38 MAPK and NF-κB signal pathways in mice. Biomedicine & Pharmacotherapy, 105, 599–605. https://doi.org/10.1016/j.biopha.2018.05.080
- Ma, Z. G., Zhang, X., Yuan, Y. P., Jin, Y. G., Li, N., Kong, C. Y., Song, P., & Tang, Q. Z. (2018). A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice. Clinical Science, 132(6), 685–699. https://doi.org/10.1042/cs20180160
- Mahmoud, A. M., Germoush, M. O., Alotaibi, M. F., & Hussein, O. E. (2017). Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity. Biomedicine & Pharmacotherapy, 86, 297–306. https://doi.org/10.1016/j.biopha.2016.12.047
- Mahmoud, N. A., Hassanein, E. H. M., Bakhite, E. A., Shaltout, E. S., & Sayed, A. M. (2023). Apocynin and its chitosan nanoparticles attenuated cisplatin-induced multiorgan failure: Synthesis, characterization, and biological evaluation. Life Sciences, 314, 121313. https://doi.org/10.1016/j.lfs.2022.121313
- Majithia, V., & Geraci, S. A. (2007). Rheumatoid arthritis: Diagnosis and management. The American Journal of Medicine, 120(11), 936–939. https://doi.org/10.1016/j.amjmed.2007.04.005
- Manohar, S., & Leung, N. (2018). Cisplatin nephrotoxicity: A review of the literature. Journal of Nephrology, 31(1), 15–25. https://doi.org/10.1007/s40620-017-0392-z
- Martinon, F., Burns, K., & Tschopp, J. (2002). The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Molecular Cell, 10(2), 417–426. https://doi.org/10.1016/s1097-2765(02)00599-3
- Matricon, J., Barnich, N., & Ardid, D. (2010). Immunopathogenesis of inflammatory bowel disease. Self Nonself, 1(4), 299–309. https://doi.org/10.4161/self.1.4.13560
- Matthay, M. A., Ware, L. B., & Zimmerman, G. A. (2012). The acute respiratory distress syndrome. The Journal of Clinical Investigation, 122(8), 2731–2740. https://doi.org/10.1172/jci60331
- Matthay, M. A., & Zemans, R. L. (2011). The acute respiratory distress syndrome: Pathogenesis and treatment. Annual Review of Pathology, 6, 147–163. https://doi.org/10.1146/annurev-pathol-011110-130158
- McInnes, I. B., & Schett, G. (2011). The pathogenesis of rheumatoid arthritis. The New England Journal of Medicine, 365(23), 2205–2219. https://doi.org/10.1056/NEJMra1004965
- Murtaza, G., Virk, H. U. H., Khalid, M., Lavie, C. J., Ventura, H., Mukherjee, D., Ramu, V., Bhogal, S., Kumar, G., Shanmugasundaram, M., & Paul, T. K. (2019). Diabetic cardiomyopathy—A comprehensive updated review. Progress in Cardiovascular Diseases, 62(4), 315–326. https://doi.org/10.1016/j.pcad.2019.03.003
- Neumann, H., Kotter, M. R., & Franklin, R. J. (2009). Debris clearance by microglia: An essential link between degeneration and regeneration. Brain, 132(Pt 2), 288–295. https://doi.org/10.1093/brain/awn109
- Neurath, M. F., & Leppkes, M. (2019). Resolution of ulcerative colitis. Seminars in Immunopathology, 41(6), 747–756. https://doi.org/10.1007/s00281-019-00751-6
- Otake, Y., & Walle, T. (2002). Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9. Drug Metabolism and Disposition, 30(2), 103–105. https://doi.org/10.1124/dmd.30.2.103
- Park, S. Y., Jin, M. L., Wang, Z., Park, G., & Choi, Y. W. (2016). 2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glucoside exerts anti-inflammatory effects on lipopolysaccharide-stimulated microglia by inhibiting NF-κB and activating AMPK/Nrf2 pathways. Food and Chemical Toxicology, 97, 159–167. https://doi.org/10.1016/j.fct.2016.09.010
- Patel, D., Patel, K., Gadewar, M., & Tahilyani, V. (2012). Pharmacological and bioanalytical aspects of galangin-a concise report. Asian Pacific Journal of Tropical Biomedicine, 2(1), S449–S455.
- Peng, W., & Novak, N. (2015). Pathogenesis of atopic dermatitis. Clinical and Experimental Allergy, 45(3), 566–574. https://doi.org/10.1111/cea.12495
- Prasatthong, P., Meephat, S., Rattanakanokchai, S., Khamseekaew, J., Bunbupha, S., Prachaney, P., Maneesai, P., & Pakdeechote, P. (2021). Galangin resolves cardiometabolic disorders through modulation of AdipoR1, COX-2, and NF-κB expression in rats fed a high-fat diet. Antioxidants, 10(5), 769. https://doi.org/10.3390/antiox10050769
- Radu, A. F., & Bungau, S. G. (2021). Management of rheumatoid arthritis: An overview. Cell, 10(11), 2857. https://doi.org/10.3390/cells10112857
- Ram, P. T., & Iyengar, R. (2001). G protein coupled receptor signaling through the Src and Stat3 pathway: Role in proliferation and transformation. Oncogene, 20(13), 1601–1606. https://doi.org/10.1038/sj.onc.1204186
- Ramadan, S. A., Kamel, E. M., Ewais, M. A., Khowailed, A. A., Hassanein, E. H. M., & Mahmoud, A. M. (2023). Flavonoids of Haloxylon salicornicum (Rimth) prevent cisplatin-induced acute kidney injury by modulating oxidative stress, inflammation, Nrf2, and SIRT1. Environmental Science and Pollution Research International, 30(7), 49197–49214. https://doi.org/10.1007/s11356-023-25694-2
10.1007/s11356-023-25694-2 Google Scholar
- Rangarajan, P., Karthikeyan, A., & Dheen, S. T. (2016). Role of dietary phenols in mitigating microglia-mediated neuroinflammation. Neuromolecular Medicine, 18(3), 453–464. https://doi.org/10.1007/s12017-016-8430-x
- Richeldi, L., Collard, H. R., & Jones, M. G. (2017). Idiopathic pulmonary fibrosis. Lancet, 389(10082), 1941–1952. https://doi.org/10.1016/s0140-6736(17)30866-8
- Ritchie, R. H., & Abel, E. D. (2020). Basic mechanisms of diabetic heart disease. Circulation Research, 126(11), 1501–1525. https://doi.org/10.1161/circresaha.120.315913
- Robbins, D. J., Zhen, E., Owaki, H., Vanderbilt, C. A., Ebert, D., Geppert, T. D., & Cobb, M. H. (1993). Regulation and properties of extracellular signal-regulated protein kinases 1 and 2 in vitro. The Journal of Biological Chemistry, 268(7), 5097–5106.
- Roux, P. P., & Blenis, J. (2004). ERK and p38 MAPK-activated protein kinases: A family of protein kinases with diverse biological functions. Microbiology and Molecular Biology Reviews, 68(2), 320–344. https://doi.org/10.1128/mmbr.68.2.320-344.2004
- Roy, A. J., Maut, C., Gogoi, H. K., Ahmed, S. I., & Kashyap, A. (2022). A review on herbal drugs used in the treatment of peptic ulcer. Current Drug Discovery Technologies, 20(3), e121222211869. https://doi.org/10.2174/1570163820666221212142221
10.2174/1570163820666221212142221 Google Scholar
- Salama, S. A., Abd-Allah, G. M., Gad, H. S., & Kabel, A. M. (2022). Galangin attenuates cadmium-evoked nephrotoxicity: Targeting nucleotide-binding domain-like receptor pyrin domain containing 3 inflammasome, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa B signaling. Journal of Biochemical and Molecular Toxicology, 36(7), e23059. https://doi.org/10.1002/jbt.23059
- Salama, S. A., & Elshafey, M. M. (2021). Galangin mitigates iron overload-triggered liver injury: Up-regulation of PPARgamma and Nrf2 signaling, and abrogation of the inflammatory responses. Life Sciences, 283, 119856. https://doi.org/10.1016/j.lfs.2021.119856
- Sami, D. H., Soliman, A. S., Khowailed, A. A., Hassanein, E. H. M., Kamel, E. M., & Mahmoud, A. M. (2022). 7-hydroxycoumarin modulates Nrf2/HO-1 and microRNA-34a/SIRT1 signaling and prevents cisplatin-induced oxidative stress, inflammation, and kidney injury in rats. Life Sciences, 310, 121104. https://doi.org/10.1016/j.lfs.2022.121104
- Samsu, N. (2021). Diabetic nephropathy: Challenges in pathogenesis, diagnosis, and treatment. BioMed Research International, 2021, 1497449. https://doi.org/10.1155/2021/1497449
- Sangaraju, R., Alavala, S., Nalban, N., Jerald, M. K., & Sistla, R. (2021). Galangin ameliorates imiquimod-induced psoriasis-like skin inflammation in BALB/c mice via down regulating NF-κB and activation of Nrf2 signaling pathways. International Immunopharmacology, 96, 107754. https://doi.org/10.1016/j.intimp.2021.107754
- Sangaraju, R., Nalban, N., Alavala, S., Rajendran, V., Jerald, M. K., & Sistla, R. (2019). Protective effect of galangin against dextran sulfate sodium (DSS)-induced ulcerative colitis in Balb/c mice. Inflammation Research, 68(8), 691–704. https://doi.org/10.1007/s00011-019-01252-w
- Sansone, P., & Bromberg, J. (2012). Targeting the interleukin-6/Jak/stat pathway in human malignancies. Journal of Clinical Oncology, 30(9), 1005–1014. https://doi.org/10.1200/jco.2010.31.8907
- Scanlon, P. H., Aldington, S. J., & Stratton, I. M. (2013). Epidemiological issues in diabetic retinopathy. Middle East African Journal of Ophthalmology, 20(4), 293–300. https://doi.org/10.4103/0974-9233.120007
- Schietroma, M., Pessia, B., Carlei, F., Mariani, P., Sista, F., & Amicucci, G. (2016). Intestinal permeability and systemic endotoxemia in patients with acute pancreatitis. Annali Italiani di Chirurgia, 87, 138–144.
- Schieven, G. L. (2005). The biology of p38 kinase: A central role in inflammation. Current Topics in Medicinal Chemistry, 5(10), 921–928. https://doi.org/10.2174/1568026054985902
- Schindler, C., Levy, D. E., & Decker, T. (2007). JAK-STAT signaling: From interferons to cytokines. The Journal of Biological Chemistry, 282(28), 20059–20063. https://doi.org/10.1074/jbc.R700016200
- Serra, D., Rufino, A. T., Mendes, A. F., Almeida, L. M., & Dinis, T. C. (2014). Resveratrol modulates cytokine-induced Jak/STAT activation more efficiently than 5-aminosalicylic acid: An in vitro approach. PLoS One, 9(10), e109048. https://doi.org/10.1371/journal.pone.0109048
- Shariati, S., Kalantar, H., Pashmforoosh, M., Mansouri, E., & Khodayar, M. J. (2019). Epicatechin protective effects on bleomycin-induced pulmonary oxidative stress and fibrosis in mice. Biomedicine & Pharmacotherapy, 114, 108776. https://doi.org/10.1016/j.biopha.2019.108776
- Shibata, R., Sato, K., Pimentel, D. R., Takemura, Y., Kihara, S., Ohashi, K., Funahashi, T., Ouchi, N., & Walsh, K. (2005). Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nature Medicine, 11(10), 1096–1103. https://doi.org/10.1038/nm1295
- Shu, Y. S., Tao, W., Miao, Q. B., Lu, S. C., & Zhu, Y. B. (2014). Galangin dampens mice lipopolysaccharide-induced acute lung injury. Inflammation, 37(5), 1661–1668. https://doi.org/10.1007/s10753-014-9894-1
- Singh, D., Saini, A., Singh, R., & Agrawal, R. (2022). Galangin, as a potential anticancer agent. Revista Brasileira de Farmacognosia, 32(3), 331–343.
- Skurk, T., Alberti-Huber, C., Herder, C., & Hauner, H. (2007). Relationship between adipocyte size and adipokine expression and secretion. The Journal of Clinical Endocrinology and Metabolism, 92(3), 1023–1033. https://doi.org/10.1210/jc.2006-1055
- Sly, P. D., Boner, A. L., Björksten, B., Bush, A., Custovic, A., Eigenmann, P. A., Gern, J. E., Gerritsen, J., Hamelmann, E., Helms, P. J., Lemanske, R. F., Martinez, F., Pedersen, S., Renz, H., Sampson, H., von Mutius, E., Wahn, U., & Holt, P. G. (2008). Early identification of atopy in the prediction of persistent asthma in children. Lancet, 372(9643), 1100–1106. https://doi.org/10.1016/s0140-6736(08)61451-8
- Sohn, S. J., Huh, I. H., Au, W. W., & Heo, M. Y. (1998). Antigenotoxicity of galangin against N-methyl-N-nitrosourea. Mutation Research, 402(1–2), 231–236. https://doi.org/10.1016/s0027-5107(97)00302-3
- Song, Q., Zhao, Y., Yang, Y., Han, X., & Duan, J. (2021). Astragaloside IV protects against retinal iron overload toxicity through iron regulation and the inhibition of MAPKs and NF-κB activation. Toxicology and Applied Pharmacology, 410, 115361. https://doi.org/10.1016/j.taap.2020.115361
- Song, Y. D., Liu, Y. Y., Li, D. J., Yang, S. J., Wang, Q. F., Liu, Y. N., Li, M.-K., Mei, C.-P., Cui, H.-N., Chen, S.-Y., & Zhu, C. J. (2021). Galangin ameliorates severe acute pancreatitis in mice by activating the nuclear factor E2-related factor 2/heme oxygenase 1 pathway. Biomedicine & Pharmacotherapy, 144, 112293. https://doi.org/10.1016/j.biopha.2021.112293
- Su, W., Fan, H., Chen, M., Wang, J., Brand, D., He, X., He, X., Quesniaux, V., Ryffel, B., Zhu, L., Liang, D., & Zheng, S. G. (2012). Induced CD4+ forkhead box protein-positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1. The Journal of Allergy and Clinical Immunology, 130(2), 444–452.e447. https://doi.org/10.1016/j.jaci.2012.05.011
- Sun, S. C. (2011). Non-canonical NF-κB signaling pathway. Cell Research, 21(1), 71–85. https://doi.org/10.1038/cr.2010.177
- Sutterwala, F. S., Ogura, Y., Szczepanik, M., Lara-Tejero, M., Lichtenberger, G. S., Grant, E. P., Bertin, J., Coyle, A. J., Galán, J. E., Askenase, P. W., & Flavell, R. A. (2006). Critical role for NALP3/CIAS1/cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity, 24(3), 317–327. https://doi.org/10.1016/j.immuni.2006.02.004
- Tan, X., Wen, X., & Liu, Y. (2008). Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-kappaB signaling. Journal of the American Society of Nephrology, 19(9), 1741–1752. https://doi.org/10.1681/asn.2007060666
- Thangaiyan, R., Arjunan, S., Govindasamy, K., Khan, H. A., Alhomida, A. S., & Prasad, N. R. (2020). Galangin attenuates isoproterenol-induced inflammation and fibrosis in the cardiac tissue of albino Wistar rats. Frontiers in Pharmacology, 11, 585163. https://doi.org/10.3389/fphar.2020.585163
- Thomas, P. G., Dash, P., Aldridge, J. R., Jr., Ellebedy, A. H., Reynolds, C., Funk, A. J., Martin, W. J., Lamkanfi, M., Webby, R. J., Boyd, K. L., Doherty, P. C., & Kanneganti, T. D. (2009). The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity, 30(4), 566–575. https://doi.org/10.1016/j.immuni.2009.02.006
- Ting, D. S., Cheung, G. C., & Wong, T. Y. (2016). Diabetic retinopathy: Global prevalence, major risk factors, screening practices and public health challenges: A review. Clinical & Experimental Ophthalmology, 44(4), 260–277. https://doi.org/10.1111/ceo.12696
- Tomar, A., Vasisth, S., Khan, S. I., Malik, S., Nag, T. C., Arya, D. S., & Bhatia, J. (2017). Galangin ameliorates cisplatin induced nephrotoxicity in vivo by modulation of oxidative stress, apoptosis and inflammation through interplay of MAPK signaling cascade. Phytomedicine, 34, 154–161. https://doi.org/10.1016/j.phymed.2017.05.007
- Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334
- Villarreal-Molina, M. T., & Antuna-Puente, B. (2012). Adiponectin: Anti-inflammatory and cardioprotective effects. Biochimie, 94(10), 2143–2149. https://doi.org/10.1016/j.biochi.2012.06.030
- Vina, E. R., & Kwoh, C. K. (2018). Epidemiology of osteoarthritis: Literature update. Current Opinion in Rheumatology, 30(2), 160–167. https://doi.org/10.1097/bor.0000000000000479
- Wang, H. B., Huang, S. H., Xu, M., Yang, J., Yang, J., Liu, M. X., Wan, C. X., Liao, H. H., Fan, D., & Tang, Q. Z. (2019). Galangin ameliorates cardiac remodeling via the MEK1/2-ERK1/2 and PI3K-AKT pathways. Journal of Cellular Physiology, 234(9), 15654–15667. https://doi.org/10.1002/jcp.28216
- Wang, L., Liu, H., He, Q., Gan, C., Li, Y., Zhang, Q., Yao, Y., He, F., Ye, T., & Yin, W. (2020). Galangin ameliorated pulmonary fibrosis in vivo and in vitro by regulating epithelial-mesenchymal transition. Bioorganic & Medicinal Chemistry, 28(19), 115663. https://doi.org/10.1016/j.bmc.2020.115663
- Wang, S., & Colonna, M. (2019). Microglia in Alzheimer's disease: A target for immunotherapy. Journal of Leukocyte Biology, 106(1), 219–227. https://doi.org/10.1002/jlb.Mr0818-319r
- Wang, Y., Tu, Q., Yan, W., Xiao, D., Zeng, Z., Ouyang, Y., Huang, L., Cai, J., Zeng, X., Chen, Y. J., & Liu, A. (2015). CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway. Biochemical and Biophysical Research Communications, 456(1), 373–379. https://doi.org/10.1016/j.bbrc.2014.11.090
- Wen, S. Y., Chen, J. Y., Weng, Y. S., Aneja, R., Chen, C. J., Huang, C. Y., & Kuo, W. W. (2017). Galangin suppresses H2O2-induced aging in human dermal fibroblasts. Environmental Toxicology, 32(12), 2419–2427. https://doi.org/10.1002/tox.22455
- Wick, G., Backovic, A., Rabensteiner, E., Plank, N., Schwentner, C., & Sgonc, R. (2010). The immunology of fibrosis: Innate and adaptive responses. Trends in Immunology, 31(3), 110–119. https://doi.org/10.1016/j.it.2009.12.001
- Widmann, C., Gibson, S., Jarpe, M. B., & Johnson, G. L. (1999). Mitogen-activated protein kinase: Conservation of a three-kinase module from yeast to human. Physiological Reviews, 79(1), 143–180. https://doi.org/10.1152/physrev.1999.79.1.143
- Willis, B. C., Liebler, J. M., Luby-Phelps, K., Nicholson, A. G., Crandall, E. D., du Bois, R. M., & Borok, Z. (2005). Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: Potential role in idiopathic pulmonary fibrosis. The American Journal of Pathology, 166(5), 1321–1332. https://doi.org/10.1016/s0002-9440(10)62351-6
- Xia, B., Di, C., Zhang, J., Hu, S., Jin, H., & Tong, P. (2014). Osteoarthritis pathogenesis: A review of molecular mechanisms. Calcified Tissue International, 95(6), 495–505. https://doi.org/10.1007/s00223-014-9917-9
- Xin, P., Xu, X., Deng, C., Liu, S., Wang, Y., Zhou, X., Ma, H., Wei, D., & Sun, S. (2020). The role of JAK/STAT signaling pathway and its inhibitors in diseases. International Immunopharmacology, 80, 106210. https://doi.org/10.1016/j.intimp.2020.106210
- Xu, Y. X., Wang, B., & Zhao, X. H. (2017). In vitro effects and the related molecular mechanism of galangin and quercetin on human gastric cancer cell line (SGC-7901). Pakistan Journal of Pharmaceutical Sciences, 30(4), 1279–1287.
- Yeh, J., Whited, L., Saliba, R. M., Rondon, G., Banchs, J., Shpall, E., Champlin, R., & Popat, U. (2021). Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era. Blood Advances, 5(24), 5599–5607. https://doi.org/10.1182/bloodadvances.2021004846
- Yu, H., Lin, L., Zhang, Z., Zhang, H., & Hu, H. (2020). Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduction and Targeted Therapy, 5(1), 209. https://doi.org/10.1038/s41392-020-00312-6
- Yu, S., Gong, L. S., Li, N. F., Pan, Y. F., & Zhang, L. (2018). Galangin (GG) combined with cisplatin (DDP) to suppress human lung cancer by inhibition of STAT3-regulated NF-κB and Bcl-2/Bax signaling pathways. Biomedicine & Pharmacotherapy, 97, 213–224. https://doi.org/10.1016/j.biopha.2017.10.059
- Zha, W. J., Qian, Y., Shen, Y., Du, Q., Chen, F. F., Wu, Z. Z., Li, X., & Huang, M. (2013). Galangin abrogates ovalbumin-induced airway inflammation via negative regulation of NF-kappaB. Evidence-Based Complementary and Alternative Medicine, 2013, 767689. https://doi.org/10.1155/2013/767689
- Zhan, C., Shi, M., Wu, R., He, H., Liu, X., & Shen, B. (2019). MIRKB: A myocardial infarction risk knowledge base. Database: The Journal of Biological Databases and Curation, 2019, 1–9. https://doi.org/10.1093/database/baz125
- Zhang, C. (2014). Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control. Protein & Cell, 5(10), 750–760. https://doi.org/10.1007/s13238-014-0083-7
- Zhang, C., Luo, C. L., Shang, G. S., Jiang, D. X., & Song, Q. (2021). Galangin enhances anticancer efficacy of 5-fluorouracil in esophageal cancer cells and xenografts through NLR family pyrin domain containing 3 (NLRP3) downregulation. Medical Science Monitor, 27, e931630. https://doi.org/10.12659/msm.931630
- Zhang, J., Liu, H., Song, C., Zhang, J., Wang, Y., Lv, C., & Song, X. (2018). Astilbin ameliorates pulmonary fibrosis via blockade of Hedgehog signaling pathway. Pulmonary Pharmacology & Therapeutics, 50, 19–27. https://doi.org/10.1016/j.pupt.2018.03.006
- Zhang, Q., Lenardo, M. J., & Baltimore, D. (2017). 30 Years of NF-κB: A blossoming of relevance to human pathobiology. Cell, 168(1–2), 37–57. https://doi.org/10.1016/j.cell.2016.12.012
- Zhang, T., Mei, X., Ouyang, H., Lu, B., Yu, Z., Wang, Z., & Ji, L. (2019). Natural flavonoid galangin alleviates microglia-trigged blood-retinal barrier dysfunction during the development of diabetic retinopathy. The Journal of Nutritional Biochemistry, 65, 1–14. https://doi.org/10.1016/j.jnutbio.2018.11.006
- Zhang, W., Tang, B., Huang, Q., & Hua, Z. (2013). Galangin inhibits tumor growth and metastasis of B16F10 melanoma. Journal of Cellular Biochemistry, 114(1), 152–161. https://doi.org/10.1002/jcb.24312
- Zhang, Y. Z., & Li, Y. Y. (2014). Inflammatory bowel disease: Pathogenesis. World Journal of Gastroenterology, 20(1), 91–99. https://doi.org/10.3748/wjg.v20.i1.91
- Zhou, Y., Fang, L., Jiang, L., Wen, P., Cao, H., He, W., Dai, C., & Yang, J. (2012). Uric acid induces renal inflammation via activating tubular NF-κB signaling pathway. PLoS One, 7(6), e39738. https://doi.org/10.1371/journal.pone.0039738
- Zou, Q. Y., Wu, H. F., Tang, Y. L., & Chen, D. Z. (2016). A new labdane diterpene from the rhizomes of Alpinia officinarum. Natural Product Research, 30(1), 1–6. https://doi.org/10.1080/14786419.2015.1012717
- Zou, W. W., & Xu, S. P. (2018). Galangin inhibits the cell progression and induces cell apoptosis through activating PTEN and Caspase-3 pathways in retinoblastoma. Biomedicine & Pharmacotherapy, 97, 851–863. https://doi.org/10.1016/j.biopha.2017.09.144
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