PMID: 

J Cell Physiol. 2019 Feb 11. Epub 2019 Feb 11. PMID: 30741414

Abstract Title: 

Galangin ameliorates cardiac remodeling via the MEK1/2-ERK1/2 and PI3K-AKT pathways.

Abstract: 

Cardiac remodeling is associated with inflammation and apoptosis. Galangin, as a natural flavonol, has the potent function of regulating inflammation and apoptosis, which are factors related to cardiac remodeling. Beginning 3 days after aortic banding (AB) or Sham surgery, mice were treated with galangin for 4 weeks. Cardiac remodeling was assessed according to echocardiographic parameters, histological analyses, and hypertrophy and fibrosis markers. Our results showed that galangin administration attenuated cardiac hypertrophy, dysfunction, and fibrosis response in AB mice and angiotensin II-treated H9c2 cells. The inhibitory action of galangin in cardiac remodeling was mediated by MEK1/2-extracellular-regulated protein kinases 1/2 (ERK1/2)-GATA4 and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-glycogen synthase kinase 3β (GSK3β) activation. Furthermore, we found that galangin inhibited inflammatory response and apoptosis. Our findings suggest that galangin protects against cardiac remodeling through decreasing inflammatory responses and apoptosis, which are associated with inhibition of the MEK1/2-ERK1/2-GATA4 and PI3K-AKT-GSK3β signals.

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PMID: 

Biomed Res Int. 2019 ;2019:3018357. Epub 2019 May 26. PMID: 31240210

Abstract Title: 

Galangin Suppresses Renal Inflammation via the Inhibition of NF-B, PI3K/AKT and NLRP3 in Uric Acid Treated NRK-52E Tubular Epithelial Cells.

Abstract: 

Renal inflammation can result in renal injury. Uric acid (UA) is the final product of purine metabolism in humans and because of the lack of urate oxidase, UA may accumulate in tissues, including kidney, causing inflammation. Galangin was isolated from a traditional Chinese medicine plant and possesses several beneficial effects, working as an anti-oxidant, anti-mutagenic, anti-tumor, anti-inflammatory, anti-microbial, and anti-viral agent. Therefore, this study aimed at investigating the molecular mechanism of galangin in the attenuation of UA induced renal inflammation in normal rat kidney epithelial cells NRK-52E. Our findings suggested that galangin treatment efficiently protected NRK-52E cells against UA induced renal inflammation by decreasing tumor necrosis factor (TNF)-, interleukin (IL)-1, IL-18, prostaglandin E2 (PGE2), and nitric oxide (NO) release, and it inhibited nitric oxide synthase (iNOS), prostaglandin endoperoxide synthase 2 (PTGS2), TNF-, IL-1, and IL-18 mRNA expression. In addition, galangin was not exerting any cytotoxicity at the concentrations that were effective against inflammation as assessed by CCK8 assay. Moreover, western blotting showed that galangin treatment effectively inhibited nuclear factor-kappa B (NF-B), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) signaling pathway activation. Taken together, these findings suggested that galangin plays a pivotal role in renal inflammation by suppressing inflammatory responses, which might be closely associated with the inhibition of NLRP3 inflammasome, NF-B and PI3K/AKT signaling pathway activation.

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PMID: 

J Cancer. 2019 ;10(19):4499-4508. Epub 2019 Jul 25. PMID: 31528214

Abstract Title: 

Galangin inhibits epithelial-mesenchymal transition and angiogenesis by downregulating CD44 in glioma.

Abstract: 

Galangin (3,5,7‑trihydroxyflavone), a natural flavonoid present in plants, has been reported to possess anticancer properties in various types of cancers comprising glioma. The underlying mechanism, however, has not been fully elucidated. CD44, a hall marker in glioma, has been reported to be associated with epithelial-mesenchymal transition (EMT) and angiogenesis, which play important roles in glioma progression. In this study, we aimed to investigate whether galangin can inhibit EMT, angiogenesis and CD44 expression in glioma. We observed that galangin inhibited the proliferation, migration, invasion andangiogenesis of glioma cells in a dose-dependent manner, suppressed the expression of CD44 and inhibited angiogenesis of glioma cells through downregulating vascular endothelial growth factor (VEGF) in HUVECs. In addition, the overexpression of CD44 in U87 and U251 cells partly abolished the effects of galangin on glioma cells. Moreover, galangin suppressed tumor growth in an intracranial glioma mouse model. These results indicate that galangin is a potential novel drug for glioblastoma treatment due to its ability to suppress of CD44, EMT and angiogenesis.

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PMID: 

Front Oncol. 2019 ;9:942. Epub 2019 Sep 27. PMID: 31612107

Abstract Title: 

The Natural Flavonoid Galangin Elicits Apoptosis, Pyroptosis, and Autophagy in Glioblastoma.

Abstract: 

Galangin (GG), a flavonoid, elicits a potent antitumor activity in diverse cancers. Here, we evaluated the efficacy of GG in the treatment of human glioblastoma multiforme (GBM) and investigated the molecular basis for its inhibitory effects in the disease. GG inhibited viability and proliferation of GBM cells (U251, U87MG, and A172) in a dose-dependent manner (IC= 221.8, 262.5, 273.9μM, respectively;

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PMID: 

Environ Toxicol. 2020 Feb ;35(2):115-123. Epub 2019 Sep 30. PMID: 31566298

Abstract Title: 

Protective effects of galangin against HO-induced aging via the IGF-1 signaling pathway in human dermal fibroblasts.

Abstract: 

Galangin, a natural flavonol, has anti-inflammatory and antioxidative potential. However, the cytoprotective effects of galangin against oxidative-induced aging in human fibroblasts have not been well studied. IGF-1 signaling pathway is associated with the control of aging and longevity in human. The goal of this study was to investigate the effects of galangin on human skin fibroblast HS68 cells under HOexposure to induce aging. In this study, we demonstrate that galangin could decrease the levels of pro-inflammatory proteins and enhanced collagen formation through promoting the IGF-1R pathway. Furthermore, aging markers such as senescence-associatedβ-galactosidase p53, p21, and p16were upregulated under HOexposure and galangin could reverse its effects. Taken together, these data indicated that anti-inflammatory and antiaging activities of galangin may be mediated through the IGF-1R signaling pathway. These findings may provide the evidence for galangin to develop as an antiwrinkle product on human skin.

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PMID: 

Nutrients. 2020 Jan 29 ;12(2). Epub 2020 Jan 29. PMID: 32013062

Abstract Title: 

Galangin Protects against Symptoms of Dextran Sodium Sulfate-induced Acute Colitis by Activating Autophagy and Modulating the Gut Microbiota.

Abstract: 

Galangin is a natural flavonoid that has been reported to provide substantial health benefits. Nevertheless, little is known about the potential effects of galangin against inflammatory bowel diseases. Here, an in vivo study was performed to investigate the preventive effects of galangin against dextran sulphate sodium (DSS)-induced acute murine colitis, which mimics the symptoms of human ulcerative colitis (UC). Pre-treatment with galangin (15 mg/kg,) resulted in a significant decreased in the macroscopic signs of DSS-induced colitic symptoms, including a decreased disease activity index, prevention of the colon length shortening, and alleviation of the pathological changes occurring in the colon. Colonic pro-inflammatory mediators, including tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6, as well as myeloperoxidase activities were decreased following galangin pre-treatment when compared with the DSS control group. Moreover, galangin pre-treatment significantly increased the expressions of autophagy-related proteins and promoted the formation of autophagosome in the colon. Galangin pre-treatment increased the diversity of the gut microbiota, and this was accompanied by increased levels of short-chain fatty acids. These observed changes could involve the modulating effects conferred by galangin in relation to some specific bacteria populations, including the recovery ofspp., and increasedspp. Overall, these results support the use of galangin in the prevention of UC.

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PMID: 

Mol Med Rep. 2018 Jan ;17(1):667-673. Epub 2017 Oct 27. PMID: 29115634

Abstract Title: 

Galangin increases ERK1/2 phosphorylation to decrease ADAM9 expression and prevents invasion in A172 glioma cells.

Abstract: 

Galangin (3,5,7‑trihydroxyflavone), is a natural flavonoid present in plants. Galangin is reported to exhibit anti‑cancer properties against various cancer types. The aim of the present study was to display the effects of galangin on glioma and its mechanism of action in A172 human glioma cancer cells. The results clearly indicated that treatment of galangin inhibited A172 cell migration and invasion under non‑toxic doses. A human proteinase array assay was conducted to elucidate the potential effects of galangin, and the obtained results demonstrated that treatment of galangin inhibited ADAM9 proteinexpression and mRNA expression, that are known to contribute to cancer progression. Sustained extracellular signal‑regulated kinase (Erk)1/2 activation was also monitored, which contributed to ADAM9 protein expression and mRNA inhibition as investigated using western blotting analysis and reversetranscription‑quantitative polymerase chain reaction experiment. Erk1/2 inhibition by inhibitor or small interfering (si)Erk transfection markedly terminated galangin‑inhibited A172 migration and invasion via an Erk1/2 activation mechanism. Collective results suggested that galangin may act as an effective chemotherapeutic agent for glioma cancer depending on its ability to bring about ADAM9 and Erk1/2 activation.

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PMID: 

Biomed Pharmacother. 2018 Jan ;97:851-863. Epub 2017 Nov 7. PMID: 29136761

Abstract Title: 

Galangin inhibits the cell progression and induces cell apoptosis through activating PTEN and Caspase-3 pathways in retinoblastoma.

Abstract: 

Retinoblastoma is reported as a rare cancer that occurs during childhood. Although several treatments are available for retinoblastoma, there is a need for alternative new treatment modalities for retinoblastoma with better safety and efficacy profile. Galangin (3,5,7-trihydroxyflavone), is a flavonoid compound, which is found in high concentration in lesser galangal. Galangin has been reported to have various bioactivities, including anti-inflammation, anti-oxidative stress and anti-cancer through various pathways. The objective of our study was to explore the effects of galangin on the suppression of retinoblastoma in vitro and in vivo. Using MTT analysis, transwell-chamber migration analysis, colony-forming analysis, wound healing analysis, immunofluorescent assay of KI-67, we found that galangin exhibited a suppressive effect on human retinoblastoma cell proliferation and migration. Moreover, PTEN, a tumor-suppressor, was increased by galangin in cancer cells and in tumor tissues isolated from retinoblastoma xenograft models. Additionally, galangin reduced protein kinase B (Akt) phosphorylation, which was associated with PTEN up-regulation. Galangin-reduced Akt activation and cell proliferation was abolished by PTEN knockdown, which might be associated with the over-expression of phosphatidylinositol-3,4,5-triphosphate (PIP3)/diphosphate product (PIP2). Furthermore, flow cytometry, Hoechst 33258 staining and western blot assays indicated that galangin could induce apoptosis through promoting Caspase-3 pathway, which was, at least partly, dependent on PTEN expression. Our data illustrated that galangin treatment suppressed the growth of retinoblastoma tumor in vivo by anti-proliferative and apoptogenic mechanisms. Thus, galangin might be a safe and promising non-chemotherapeutic drug, which could be useful as an adjuvant against retinoblastoma.

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PMID: 

Int J Mol Sci. 2017 Dec 21 ;19(1). Epub 2017 Dec 21. PMID: 29267220

Abstract Title: 

Galangin Reduces the Loss of Dopaminergic Neurons in an LPS-Evoked Model of Parkinson's Disease in Rats.

Abstract: 

Parkinson's disease (PD) is caused by the loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN). Neuroinflammation, which is marked by microglial activation, plays a very important role in the pathogenesis of PD. Pro-inflammatory mediators produced by activated microglia could damage DA neurons. Hence, the inhibition of microglial activation may provide a new approach for treating PD. Galangin has been shown to inhibit inflammation in a variety of diseases, but not PD. In this study, we aimed to investigate the anti-inflammatory effect of galangin and the underlying mechanisms in Lipopolysaccharide (LPS) induced PD models. We first examined the protective effect of galangin in the LPS-induced PD rat model. Specifically, we investigated the effects on motor dysfunction, microglial activation, and the loss of DA neurons. Then, galangin was used to detect the impact on the inflammatory responses and inflammatory signaling pathways in LPS-induced BV-2 cells. The in vivo results showed that galangin dose-dependently attenuates the activation of microglia, the loss of DA neurons, and motor dysfunction. In vitro, galangin markedly inhibited LPS-induced expression of tumor necrosis factorα (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase 2 (COX-2), and induced nitric oxide synthase (iNOS) via associating with the phosphorylation of c-JUN N-terminal Kinase (JNK), p38, protein kinase B (AKT), and nuclear factor κB (NF-κB) p65. Collectively, the results indicated that galangin has a role in protecting DA neurons by inhibiting microglial activation.

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PMID: 

Anticancer Res. 2018 03 ;38(3):1377-1389. PMID: 29491062

Abstract Title: 

Galangin Induces p53-independent S-phase Arrest and Apoptosis in Human Nasopharyngeal Carcinoma Cells Through Inhibiting PI3K-AKT Signaling Pathway.

Abstract: 

BACKGROUND/AIM: Anti-cancer activity of 3,5,7-trihydroxyflavone (galangin) has been documented in a variety of cancer types; however, its effect on human nasopharyngeal carcinoma (NPC) cells remains undetermined.MATERIALS AND METHODS: Human NPC cell lines were treated with galangin. Apoptosis was analyzed by assessing nuclear condensation, cleavage of pro-caspase-3 and poly ADP-ribose polymerase (PARP), and DNA fragmentation. Short hairpin RNA-mediated silencing of p53 was used for characterizing the role of p53 in the anti-cancer activity of galangin. Phosphatidylinositol 3-kinase (PI3K) inhibitor, protein kinase B (AKT) inhibitor, and ectopic expression of wild type p85α or p85α mutant lacking p110α-binding ability were utilized to confirm the involvement of PI3K/AKT inactivation in galangin-induced apoptosis.RESULTS: Galangin induces apoptosis and S-phase arrest by attenuating the PI3K/AKT signaling pathway. Silencing of p53 did not block the anti-cancer activity of galangin on NPC cells.CONCLUSION: Galangin effects on apoptosis and S-phase arrest in NPC cells are mediated via interfering with the PI3K-AKT signaling pathway in a p53-independent manner.

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