Galangin Suppresses Pro-Inflammatory Gene Expression in Polyinosinic-Polycytidylic Acid-Stimulated Microglial Cells

( Min-ji Choi ),( Jin-sun Park ),( Jung-eun Park ),( Han Su Kim ),( Hee-sun Kim ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.6

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-κB activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. To investigate whether PPAR-γ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-γ antagonist before treatment of galangin. We found that PPAR-γ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-κB, and PPAR-γ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

Galangin Suppresses Pro-Inflammatory Gene Expression in Polyinosinic-Polycytidylic Acid-Stimulated Microglial Cells

Choi, Min-Ji,Park, Jin-Sun,Park, Jung-Eun,Kim, Han Su,Kim, Hee-Sun The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.6

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-${\kappa}B$ activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, known to play an anti-inflammatory role. To investigate whether PPAR-${\gamma}$ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-${\gamma}$ antagonist before treatment of galangin. We found that PPAR-${\gamma}$ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-${\alpha}$ and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-${\kappa}B$, and PPAR-${\gamma}$ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

Galangin Suppresses Pro-Inflammatory Gene Expression in Polyinosinic-Polycytidylic Acid-Stimulated Microglial Cells

최민지,박진선,박정은,김한수,김희선 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.6

Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-κB activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. To investigate whether PPAR-γ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-γ antagonist before treatment of galangin. We found that PPAR-γ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-κB, and PPAR-γ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.

The natural flavonoid galangin inhibits osteoclastic bone destruction and osteoclastogenesis by suppressing NF-κB in collagen-induced arthritis and bone marrow-derived macrophages

Huh, J.E.,Jung, I.T.,Choi, J.,Baek, Y.H.,Lee, J.D.,Park, D.S.,Choi, D.Y. North-Holland ; Elsevier Science Ltd 2013 european journal of pharmacology Vol.698 No.1

We investigated the effect of galangin, a natural flavonoid, on osteoclastic bone destruction in collagen-induced arthritis and examined the molecular mechanisms by which galangin affects osteoclastogenesis in bone marrow derived macrophages. In mice with collagen-induced arthritis, administration of galangin significantly reduced the arthritis clinical score, edema and severity of disease without toxicity. Interestingly, galangin treatment during a later stage of collagen-induced arthritis, using mice with a higher clinical arthritis score, still significantly slowed the progression of the disease. Extensive cartilage and bone erosive changes as well as synovial inflammation, synovial hyperplasia and pannus formation were dramatically inhibited in arthritic mice treated with galangin. Furthermore, galangin-treated arthritic mice showed a significant reduction in the concentrations of IL-1β, TNF-α and IL-17 . We found that galangin inhibited osteoclastogenic factors and osteoclast formation in bone marrow-derived macrophages and osteoblast co-cultured cells, and increased osteoprotegerin (OPG) levels in osteoblasts. Galangin and NF-κB siRNA suppressed RANKL-induced phosphorylation of the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not AKT and extracellular signal-regulated kinase ½ (ERK½). Also, the JNK inhibitor SP600125 and p38 inhibitor SB203580 reduced RANKL-induced expressions of phospho-c-Jun, c-fos and NFATc1 genes during osteoclast development. In addition, galangin suppressed RANKL-induced phosphorylation of NF-κB, phospho-IκBα, inflammatory cytokines and osteoclast formation in bone marrow-derived macrophages. Our data suggest that galangin prevented osteoclastic bone destruction and osteoclastogenesis in osteoclast precursors as well as in collagen-induced arthritis mice without toxicity via attenuation of RANKL-induced activation of JNK, p38 and NF-κB pathways.

Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated microglia: Critical role of PPAR-γ signaling pathway

Choi, M.J.,Lee, E.J.,Park, J.S.,Kim, S.N.,Park, E.M.,Kim, H.S. Pergamon Press 2017 Biochemical pharmacology Vol.144 No.-

Since microglia-associated neuroinflammation plays a pivotal role in the progression of neurodegenerative diseases, controlling microglial activation has been suggested as a potential therapeutic strategy. Here, we investigated the anti-inflammatory effects of galangin (3,5,7-trihydroxyflavone) in microglia and analyzed the underlying molecular mechanisms. Galangin inhibited the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines and enhanced the expression of anti-inflammatory interleukin (IL)-10 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Galangin also suppressed microglial activation and the expression of pro-inflammatory markers in LPS-injected mouse brains. The results of mechanistic studies have shown that galangin inhibited LPS-induced phosphorylation of p38 mitogen activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor (NF)-κB activity. On the contrary, galangin increased the activity of transcription factors, such as nuclear factor-E2-related factor 2 (Nrf2), cAMP response element-binding protein (CREB), and peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. In addition, galangin showed antioxidant effects by suppressing the expression of NADPH oxidase subunits p47<SUP>phox</SUP> and gp91<SUP>phox</SUP>, and by enhancing hemeoxygenase-1. We then investigated whether PPAR-γ was involved in the anti-inflammatory function of galangin. Pretreatment with a PPAR-γ antagonist or siRNA significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α, nitric oxide (NO), and IL-6 in LPS-stimulated microglia. Moreover, the PPAR-γ antagonist reversed the effects of galangin on NF-κB, Nrf2, and CREB. Altogether, our data suggest that PPAR-γ plays a key role in mediating the anti-inflammatory effects of galangin by modulating the NF-κB and Nrf2/CREB signaling pathways.

Galangin enhances TGF-β1-mediated growth inhibition by suppressing phosphorylation of threonine 179 residue in Smad3 linker region

Kwak, Mi-Kyung,Yang, Kyung-Min,Park, Jinah,Lee, Siyoung,Park, Yuna,Hong, Eunji,Sun, Eun Jin,An, Haein,Park, Sujin,Pang, Kyoungwha,Lee, Jihee,Kang, Jin Muk,Kim, Pyunggang,Ooshima, Akira,Kim, Seong-Jin Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>Smad3 linker phosphorylation is a candidate target for several kinases that play important roles in cancer cell initiation, proliferation and progression. Also, Smad3 is an essential intracellular mediator of TGF-β1-induced transcriptional responses during carcinogenesis. Therefore, it is highly advantageous to identify and develop inhibitors targeting Smad3 linker phosphorylation for the treatment of cancers. Galangin (3,5,7-trihydroxyflavone) has been known to be an active flavonoid showing a cytotoxic effect on several cancer cells. However, the mechanism of action of galangin in various cancers remains unclear, and there has been no report concerning regulation of Smad3 phosphorylation by galangin. In the present study, we show that galangin significantly induced apoptosis and inhibited cell proliferation in the presence of TGF-β1 in both human prostate and pancreatic cancer cell lines. Particularly, galangin effectively inhibits phosphorylation of the Thr-179 site at Smad3 linker region through suppression of CDK4 phosphorylation. Thus, galangin can be a promising candidate as a selective inhibitor to suppress phosphorylation of Smad3 linker region.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Galangin significantly induced apoptosis in the presence of TGF-β1. </LI> <LI> Galangin inhibits phosphorylation of the Thr-179 site at the Smad3 linker region. </LI> <LI> Galangin suppresses CDK4-mediated Smad3 linker phosphorylation. </LI> </UL> </P>

플라보노이드 갤랑인의 항산화 작용에 대한 분광학적 연구

박형련,박철호 한국피부과학연구원 2017 아시안뷰티화장품학술지 Vol.15 No.4

Purpose: The properties of the flavonoid galangin were investigated via ultravioletvisible (UV-Vis) spectroscopy to obtain further insights into its anti-oxidant behavior. Methods: A UV–Vis spectrophotometer was employed to obtain the absorption spectra of galangin. To clarify the oxidation process of galangin, its spectroscopic behavior was examined not only in different media, such as aerated and deaerated water, but also at different pH values of solution. Results: After the addition of galangin to water, the UV–Vis absorption spectra of the solution changed over time. In addition, the UV–Vis absorption spectra of galangin changed not only in an aerated neutral solution but also in a deaerated basic galangin solution, indicating the occurrence of oxidation. With an increase in the pH values of the solution, the oxidation rate of galangin increased. Spectral changes were not observed for the deaerated acidic solution. Conclusion: The UV–Vis spectroscopy results indicated that galangin is more stable in an acidic aqueous solution than in a basic solution. The reactive oxygen species (ROS) can react with both galangin as well as normal skin cells in a human body as a result of competition. The acidic form of flavonoid is acceptable when flavonoid compounds are used as skin-care products. 목적: 본 연구에서는 항산화 기능을 갖는다고 알려진 플라보노이드 갤랑인의 항산화 특성을 분광학적 방법을 이용하여 고찰해 보고자 한다. 방법: 산성과 염기성 수용액에서의 갤랑인 분자의 흡수스펙트럼을 자외선 분광광도계를 이용하여 측정하였다. 결과: 갤랑인의 흡수스펙트럼 형태는 수용액 중에 존재하고 있는 산소나 이온화된 갤랑인 음이온의 생성에 의해 크게 변화하였는데, 이는 갤랑인이 퀴논 계열로 산화되기 때문이라는 것을 알 수 있었다. 이러한 갤랑인의 산화반응은 용액의 pH에 의존하는데, pH가 증가하여 갤랑인 음이온의 농도가 진해지면 갤랑인이 산화되는 정도는 훨씬 빨라졌다. 반면에 산소가 제거된 산성 수용액 상태에서는 산성도의 세기나 보관시간에 관계없이 흡수피크의 형태가 일정하게 유지되어 산화제가 없는 경우 산화반응이 거의 진행되지 않고 비교적 안정하게 존재할 수 있음을 확인하였다. 결론: 갤랑인과 같은 플라보노이드 화합물을 피부미용제로 이용하는 경우에는 산성 상태에서 보관하고 제조하였을 경우에 훨씬 더 안정한 상태로 존재할 수 있어 더 나은 항산화제의 역할을 할 것으로 판단된다.

사염화탄소에 의해 유발된 간독성에 대한 galangin의 보호효과

정배동(Bae Dong Jung),김천호(Cheon Ho Kim),김정한(Jung Han Kim),허문영(Moon Young Heo) 대한약학회 1996 약학회지 Vol.40 No.3

In order to evaluate the protective effects of galangin on CCl4-induced hepatotoxicity, GOT, GPT and malondialdehyde(MDA) values were measured in ICR mice. Galangin,a flavonoid compound, was administered orally for six days and immediately CCl4 was injected intraperitoneally after the last dose of galangin. Mice were sacrificed at 24h after the administration of CCl4. In the multiple pre-treatments for 6 consecutive days, galangin showed more potent protective effects than silymarin as reference active compound in serum GOT, GPT and MDA values in the liver at all doses tested. Antioxidative activity was determined by measuring the amounts of MDA formed from ethyl linoleate by H2O2 in vitro. Galangin showed higher inhibition than silymarin. These results demonstrate a possible hepato-protective role of galangin against CCl4-induced hepatotoxicity in vivo and H2O2-induced lipid peroxidation in vitro. Therefore, galangin may be capable of protecting hepatotoxicity.

Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes

( Susara Ruwan Kumara Madduma Hewage ),( Mei Jing Piao ),( Kyoung Ah Kang ),( Yea Seong Ryu ),( Pattage Madushan Dilhara Jayatissa Fernando ),( Min Chang Oh ),( Jeong Eon Park ),( Kristina Shilnikova 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.4

Previously, we demonstrated that galangin (3,5,7-trihydroxyflavone) protects human keratinocytes against ultraviolet B (UVB)-induced oxidative damage. In this study, we investigated the effect of galangin on induction of antioxidant enzymes involved in synthesis of reduced glutathione (GSH), and investigated the associated upstream signaling cascades. By activating nuclear factor-erythroid 2-related factor (Nrf2), galangin treatment significantly increased expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS). This activation of Nrf2 depended on extracellular signal-regulated kinases (ERKs) and protein kinase B (AKT) signaling. Inhibition of GSH in galangin-treated cells attenuated the protective effect of galangin against the deleterious effects of UVB. Our results reveal that galangin protects human keratinocytes by activating ERK/AKTNrf2, leading to elevated expression of GSH-synthesizing enzymes.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation

Kaiwen Lin,Datian Fu,Zhongtao Wang,Xueer Zhang,Canyang Zhu 대한통증학회 2024 The Korean Journal of Pain Vol.37 No.2

Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalininduced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX- 2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenantriggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF- κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.