PMID: 

J Cell Biochem. 2013 Jan ;114(1):152-61. PMID: 22887049

Abstract Title: 

Galangin inhibits tumor growth and metastasis of B16F10 melanoma.

Abstract: 

Galangin, an active flavonoid extracted from the root of the Alpinia officinarum Hance, showed a cytotoxic effect on several cancer cell lines in vitro. However, there is no information available concerning its antimetastatic effect. Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, is involved in many aspects of cellular processes such as proliferation, adhesion, and invasion. Studies have shown that FAK is a promising target for therapeutic intervention in melanoma. In the present study, proliferation of B16F10 cells was suppressed when exposed to various doses of galangin. Inhibition on proliferation by galangin was also detected by clonogenic survival assay. The capabilities of cell adhesion, cell spreading, and cell motility were impaired by galangin, reinforced by F-actin rearrangement. Molecular data showed that both FAK mRNA level and protein level were reduced dose-dependently. Additionally, galangin reduced phosphorylation of FAK (Tyr397) protein. Transient transfection reporter assays showed that galangin suppressed the transcription of FAK gene, indicating FAK expression is a candidate target of galangin. The antimetastatic function of galangin is further supported by the fact that it could inhibit the formation of tumor colonies in the lung tissue on C57BL/6J mouse lung metastatic model using B16F10 melanoma cells. Immunochemical analyses showed that galangin decreased FAK expression in vivo. These data add to our new understanding that galangin can inhibit B16F10 melanoma metastasis both in vivo and in vitro, and that FAK is a valid therapeutic target against melanoma.

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PMID: 

Eur J Pharmacol. 2013 Jan 5 ;698(1-3):57-66. Epub 2012 Sep 14. PMID: 22985747

Abstract Title: 

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

Abstract: 

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 phosphorylationof the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). 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.

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PMID: 

Cytotechnology. 2013 May ;65(3):447-55. Epub 2012 Sep 22. PMID: 23001390

Abstract Title: 

Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and sustained activation of p38 MAPK.

Abstract: 

Galangin, an active flavonoid present at high concentration in Alpinia officinarum Hance and propolis, shows cytotoxicity towards several cancer cell lines, including melanoma. However, the specific cellular targets of galangin-induced cytotoxicity in melanoma are still unknown. Here, we investigated the effects of galangin in B16F10 melanoma cells and explored the possible molecular mechanisms. Galangin significantly decreased cell viability of B16F10 cells, and also induced cell apoptosis shown by Hoechst 33342 staining and Annexin V-PI double staining flow cytometric assay. Furthermore, upon galangin treatment, disruption of mitochondrial membrane potential was observed by JC-1 staining. Western blotting analysis indicated that galangin activated apoptosis signaling cascades by cleavage of procaspase-9, procaspase-3 and PARP in B16F10 cells. Moreover, galangin significantly induced activation of phosphor-p38 MAPK in a time and dose dependent manner. SB203580, an inhibitor of p38, partially attenuated galangin-induced apoptosis in B16F10 cells. Taken together, this work suggests that galangin has the potential to be a promising agent for melanoma treatment and may be further evaluated as a chemotherapeutic agent.

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PMID: 

Pharm Biol. 2013 May ;51(5):607-13. Epub 2013 Jan 31. PMID: 23363068

Abstract Title: 

Anti-obesity effects of galangin, a pancreatic lipase inhibitor in cafeteria diet fed female rats.

Abstract: 

CONTEXT: Alpinia galanga Willd (Zingiberaceae) (AG) is a rhizomatous herb widely cultivated in shady regions of Malaysia, India, Indochina and Indonesia. It is used in southern India as a domestic remedy for the treatment of rheumatoid arthritis, cough, asthma, obesity, diabetes, etc. It was reported to have anti-obesity, hypoglycemic, hypolipidemic and antioxidant properties.OBJECTIVE: A flavonol glycoside, galangin, was isolated from AG rhizomes. Based on its in vitro pancreatic lipase inhibitory effect, the study was further aimed to clarify whether galangin prevented obesity induced in female rats by feeding cafeteria diet (CD) for 6 weeks.MATERIALS AND METHODS: The in vitro pancreatic lipase inhibitory effect of galangin was determined by measuring the release of oleic acid from triolein. For in vivo experiments, female albino rats were fed CD with or without 50 mg/kg galangin for 6 weeks. Body weight and food intake was measured at weekly intervals. On day 42, serum lipids levels were estimated and then the weight of liver and parametrial adipose tissue (PAT) was determined. The liver lipid peroxidation and triglyceride (TG) content was also estimated.RESULTS: The IC50 value of galangin for pancreatic lipase was 48.20 mg/mL. Galangin produced inhibition of increased body weight, energy intake and PAT weight induced by CD. In addition, galangin produced a significant decrease in serum lipids, liver weight, lipid peroxidation and accumulation of hepatic TGs.CONCLUSION: Galangin present in AG rhizomes produces anti-obesity effects in CD-fed rats; this may be mediated through its pancreatic lipase inhibitory, hypolipidemic and antioxidant activities.

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PMID: 

Food Chem Toxicol. 2013 Jul ;57:209-16. Epub 2013 Mar 25. PMID: 23535185

Abstract Title: 

Galangin attenuates mast cell-mediated allergic inflammation.

Abstract: 

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models. Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8. The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue. The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug. Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines. In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent.

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PMID: 

Environ Toxicol Pharmacol. 2013 Sep ;36(2):288-295. Epub 2013 Apr 19. PMID: 23686009

Abstract Title: 

Antifibrotic activity of galangin, a novel function evaluated in animal liver fibrosis model.

Abstract: 

This study aimed to investigate the effects of galangin on liver fibrosis in rats induced by subcutaneous injection of carbon tetrachloride (CCl4). The administration of CCl4 to rats for 12 weeks caused significant increase of hyaluronic acid, laminin, alanine transaminase, aspartate transaminase and decrease of total protein, albumin in serum, while the influences could be reversed by galangin. Galangin markedly reduced hepatic malondialdehyde, hydroxyproline concentration, increased activities of liver superoxide dismutase, glutathione peroxidase compared with CCl4-treated rats. Histological results indicated that galangin alleviated liver damage. In addition, treatment with galangin significantly down-regulated expressions ofα-smooth muscle actin and transforming growth factor β1. These results suggest galangin can inhibit liver fibrosis induced by CCl4 in rats, which was probably associated with its effect on removing oxygen free radicals, decreasing lipid peroxidation, as well as inhibiting hepatic stellate cells activation and proliferation.

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PMID: 

Exp Biol Med (Maywood). 2013 Sep ;238(9):1047-54. Epub 2013 Aug 7. PMID: 23925650

Abstract Title: 

Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway.

Abstract: 

Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.

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PMID: 

Eur J Pharmacol. 2013 Oct 15 ;718(1-3):235-44. Epub 2013 Sep 9. PMID: 24028940

Abstract Title: 

Galangin inhibits proliferation of HepG2 cells by activating AMPK via increasing the AMP/TAN ratio in a LKB1-independent manner.

Abstract: 

Galangin, a flavonol derived from Alpinia officinarum Hance and used as food additives in southern China, induces apoptosis and autophagy to suppress the proliferation of HepG2 cells. In this study, we demonstrated that galangin induced autophagy by increasing the ratio of AMP/TAN in HepG2 cells. It stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and LKB1, but inhibited the phosphorylation of AKT and mTOR. Inhibition of AMPK activation suppressed the dephosphorylation of mTOR to block galangin-induced autophagy. AMPK activation by galangin appeared to be independent of the LKB1 signaling pathway because the down-regulation of LKB1 by its siRNA failed to affect galangin-induced autophagy. Collectively, the findings demonstrated a novel mechanism of how galangin induces autophagy via activating AMPK in a LKB1- independent manner. The induction of autophagy can thus reflect the anti-proliferation effect of galangin in HCC cells.

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PMID: 

Food Chem Toxicol. 2013 Dec ;62:810-6. Epub 2013 Oct 22. PMID: 24161691

Abstract Title: 

Galangin inhibits proliferation of hepatocellular carcinoma cells by inducing endoplasmic reticulum stress.

Abstract: 

Prolonged endoplasmic reticulum (ER) stress may activate apoptotic pathways in cancer cells. It is suggested that ER stress has the potential of enhancing tumor death in cancer therapy. Galangin, a flavonol derived from Alpinia officinarum Hance, has been shown to suppress the proliferation of hepatocellular carcinoma cells (HCC). The aim of this study was to determine whether galangin was able to induce ER stress in HepG2, Hep3B and PLC/PRF/5 cells. The proliferation of HCC was tested by MTT method. Intracellular Ca(2+) levels were measured with Fluo3-AM.The proteins levels of GRP94, GRP78 and CHOP were detected by Western blot. To further understand the anti-HCC mechanism of galangin, mitogen-activated protein kinases (MAPKs) were detected. The results showed that galangin treatment induced ER stress was evidenced by increased protein levels of GRP94, GRP78 and CHOP, as well as increased free cytosolic Ca(2+) concentration. ER stress inhibitor 4-PBA and CHOP siRNA blocked significantly galangin-induced ER in all three cell lines. Further experiments showed that MAPKs involved in ER stress induced by galangin. In summary, galangin is identified as a stimulator of ER stress to suppress the proliferation of HCC, and may be used as a potential anti-cancer agent.

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PMID: 

Arch Pharm Res. 2018 Mar ;41(3):265-275. Epub 2014 Feb 5. PMID: 24497035

Abstract Title: 

Galangin, a dietary flavonol inhibits tumor initiation during experimental pulmonary tumorigenesis by modulating xenobiotic enzymes and antioxidant status.

Abstract: 

The aim of present study was to elucidate anti-initiating efficacy of galangin against benzo(a)pyrene (B(a)P)-induced lung carcinogenesis in male Swiss albino mice. Therefore, the activities of xenobiotic metabolic enzymes such as phase I and II were examined in lung as well as liver tissues (to compare the effects between target and non-target organs). Besides, the activities/levels of tissue marker enzymes, antioxidants, lipid peroxidation (LPO), cytochrome P450 1A1 (CYP1A1) expressions and histological observation of lungs were also analyzed. B(a)P (50 mg/kg body weight) was administered to male Swiss albino mice (20-25 g) to experimentally induce lung cancer. B(a)P-induced animals showed increased activity of phase I (Cytochrome P450, Cytochrome b5, NADPH Cytochrome P450 redcutase and NADH Cytochrome b5 reductase) drug metabolic enzymes, LPO levels, tissue marker enzymes and decreased activity of phase II metabolic enzymes (glutathione-S-transferase, DT-diaphorase and UDP-glucuronyl transferase) as well as antioxidant levels. Histological examination of lungs revealed severe alveolar and bronchiolar damages in B(a)P-induced mice. Immunohistochemical and western blot analysis of CYP1A1 increased significantly in lung tissues of B(a)P-induced animals. Treatment with galangin (20 mg/kg body weight) efficiently counteracted all the above anomalies and restored cellular homeostasis. Our results demonstrate that galangin can modify xenobiotic enzymes in murine model of pulmonary tumorigenesis.

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