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

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-1ß, 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-1ß, 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.

Near-infrared-responsive GE11-CuS@Gal nanoparticles as an intelligent drug release system for targeting therapy against oral squamous cell carcinoma.

Galangin (Gal) is a natural plant flavonoid. More and more evidence shows that Gal can achieve anti-tumor effects by regulating various mechanisms. However, its poor water solubility, low bioavailability, and insufficient lesion targeting limit its clinical application. To overcome these shortcomings, we designed and developed a mesoporous nanosystem (GE11-CuS) that actively located the target area and photo-controlled drug release, which promoted the rapid accumulation of drugs in tumor tissues under NIR irradiation, thus achieving positive effects against cancer. In this study, we explored the application of the Gal-loaded nanometer system (GE11-CuS@Gal) in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. The results exhibited that GE11-CuS@Gal had excellent targeting ability and could accumulate efficiently in tumor cells (HSC-3). Meanwhile, the temperature of GE11-CuS@Gal increasing rapidly under NIR illumination damaged the integrity of the carrier and allowed Gal molecules to escape from the pores of the nanoparticles. When the accumulation of Gal in the nidus reached a certain level, the intracellular ROS level could be significantly increased and the antioxidative stress pathway mediated by Nrf2/OH-1 was effectively blocked, to inhibit the growth and migration of tumors. In conclusion, the GE11-CuS improved the antitumor activity of Gal in the body, which laid a foundation for the treatment of OSCC with traditional Chinese medicine ingredients.

Evaluation and molecular docking study of two flavonoids from Oroxylum indicum (L.) Kurz and their semi-synthetic derivatives as histone deacetylase inhibitors.

Chrysin (5,7-dihydroxyflavone, 6) and galangin 3-methyl ether (5,7-dihydroxy-3-methoxy flavone, 7) were obtained from the leaves of Oroxylum indicum (L.) Kurz in 4% and 6% yields, respectively. Both compounds could act as pan-histone deacetylase (HDAC) inhibitors. Structural modification of these lead compounds provided thirty-eight derivatives which were further tested as HDAC inhibitors. Compounds 6b, 6c, and 6q were the most potent derivatives with the IC50 values of 97.29 ± 0.63 µM, 91.71 ± 0.27 µM, and 96.87 ± 0.45 µM, respectively. Molecular docking study indicated the selectivity of these three compounds toward HDAC8 and the test against HDAC8 showed IC50 values in the same micromolar range. All three compounds were further evaluated for the anti-proliferative activity against HeLa and A549 cell lines. Compound 6q exhibited the best activity against HeLa cell line with the IC50 value of 13.91 ± 0.34 µM. Moreover, 6q was able to increase the acetylation level of histone H3. These promising HDAC inhibitors deserve investigation as chemotherapeutic agents for treating cancer.

Galangin attenuates doxorubicin-induced cardiotoxicity via activating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling pathway to suppress oxidative stress and inflammation.

Doxorubicin (DOX) has aroused contradiction between its potent anti-tumor capacity and severe cardiotoxicity. Galangin (Gal) possesses antioxidant, anti-inflammatory, and antiapoptotic activities. We aimed to explore the role and underlying mechanisms of Gal on DOX-induced cardiotoxicity. Mice were intraperitoneally injected with DOX (3 mg/kg, every 2 days for 2 weeks) to generate cardiotoxicity model and Gal (15 mg/kg, 2 weeks) was co-administered via gavage daily. Nuclear factor erythroid 2-related factor 2 (Nrf2) specific inhibitor, ML385, was employed to explore the underlying mechanisms. Compared to DOX-insulted mice, Gal effectively improved cardiac dysfunction and ameliorated myocardial damage. DOX-induced increase of reactive oxygen species, malondialdehyde, and NADPH oxidase activity and downregulation of superoxide dismutase (SOD) activity were blunted by Gal. Gal also markedly blocked increase of IL-1ß, IL-6, and TNF-α in DOX-insulted heart. Mechanistically, Gal reversed DOX-induced downregulation of Nrf2, HO-1, and promoted nuclear translocation of Nrf2. ML385 markedly blunted the cardioprotective effects of Gal, as well as inhibitive effects on oxidative stress and inflammation. Gal ameliorates DOX-induced cardiotoxicity by suppressing oxidative stress and inflammation via activating Nrf2/HO-1 signaling pathway. Gal may serve as a promising cardioprotective agent for DOX-induced cardiotoxicity.

Pharmacological activities and therapeutic potential of galangin, a promising natural flavone, in age-related diseases.

BACKGROUND: The extension of average life expectancy and the aggravation of population aging have become the inevitable trend of human development. In an aging society, various problems related to medical care for the elderly have become increasingly prominent. However, most of the age-related diseases have the characteristics of multiple diseases at the same time, prone to complications, and atypical clinical manifestations, which bring great difficulties to its treatment. Galangin (3,5,7-trihydroxyflavone) is a natural active compound extracted from the root of Alpinia officinarum Hance (Zingiberaceae). Recently, many studies have shown that galangin has potential advantages in the treatment of neurodegenerative diseases and cardiovascular and cerebrovascular diseases, which are common in the elderly. In addition, it also showed that galangin had prospective activities in the treatment of tumor, diabetes, liver injury, asthma and arthritis. PURPOSE: This review aims to systematically summarize and discuss the effects and the underlying mechanism of galangin in the treatment of age-related diseases. METHODS: We searched PubMed, SciFinder, Web of Science and CNKI literature database resources, combined with the keywords "galangin", "neurodegenerative disease", "tumor", "diabetes", "pharmacological activity", "drug combination", "pharmacokinetics", "drug delivery system" and "safety", and comprehensively reviewed the pharmacological activities and mechanism of galangin in treating age-related diseases. RESULTS: According to the previous studies on galangin, the anti-neurodegenerative activity, cardiovascular and cerebrovascular protective activity, anti-tumor activity, anti-diabetes activity, anti-arthritis activity, hepatoprotective activity and antiasthmatic activity of galangin were discussed, and the related mechanisms were classified and summarized in detail. In addition, the drug combination, pharmacokinetics, drug delivery system and safety of galangin were furtherly discussed. CONCLUSIONS: This review will provide reference for galangin in the treatment of age-related diseases. Meanwhile, further experimental research and long-term clinical trials are needed to determine the therapeutic safety and efficacy of galangin.

Galangin: A food-derived flavonoid with therapeutic potential against a wide spectrum of diseases.

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.

Galangin inhibits programmed cell death-ligand 1 expression by suppressing STAT3 and MYC and enhances T cell tumor-killing activity.

BACKGROUND: The flavonoid galangin (3,5,7-trihydroxyflavone) is derived from the root of Alpinia officinarum Hance, an edible and medicinal herb. Galangin has many biological activities, such as anti-inflammatory, anti-microbial, anti-viral, anti-obesogenic, and anti-oxidant effects. However, the anti-tumor mechanism of galangin remains unclear. PURPOSE: To elucidate the anti-tumor mechanisms of galangin in vitro and in vivo. METHODS: MTT, western blotting, immunoprecipitation, RT-PCR, and immunofluorescence assays were used to assess the mechanism of galangin inhibiting PD-L1 expression. The effect of galangin on T cell activity was analyzed in Hep3B/T cell co-cultures. Colony formation, EdU, migration, and invasion assays were performed to explore the effect of galangin on cancer progression and metastasis. Anti-tumor effects of galangin were investigated in a xenograft model. RESULTS: Galangin inhibited PD-L1 expression dose-dependently, which plays a major role in tumor progression. Moreover, galangin blocked STAT3 activation through the JAK1/JAK2/Src signaling pathway and Myc activation through the Ras/RAF/MEK/ERK signaling pathway. Galangin reduced PD-L1 expression by suppressing STAT3 and Myc cooperatively. Galangin increased the killing effect of T cells on tumor cells in Hep3B/T cell co-cultures. Moreover, galangin inhibited tumor cell proliferation, migration, and invasion through PD-L1. In vivo experiments showed that galangin suppressed tumor growth. CONCLUSION: Galangin enhances T-cell activity and inhibits tumor cell proliferation, migration, and invasion through PD-L1. The current study emphasizes the anti-tumor properties of galangin, offering new insights into the development of tumor therapeutics targeting PD-L1.

The molecular mechanisms underlying anti-inflammatory effects of galangin in different diseases.

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.

In Silico Target Identification of Galangin, as an Herbal Flavonoid against Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a heterogenous group of malignancies in the bile duct, which proliferates aggressively. CCA is highly prevalent in Northeastern Thailand wherein it is associated with liver fluke infection, or Opisthorchis viverrini (OV). Most patients are diagnosed in advanced stages, when the cancer has metastasized or severely progressed, thereby limiting treatment options. Several studies investigate the effect of traditional Thai medicinal plants that may be potential therapeutic options in combating CCA. Galangin is one such herbal flavonoid that has medicinal properties and exhibits anti-tumor properties in various cancers. In this study, we investigate the role of Galangin in inhibiting cell proliferation, invasion, and migration in OV-infected CCA cell lines. We discovered that Galangin reduced cell viability and colony formation by inducing apoptosis in CCA cell lines in a dose-dependent manner. Further, Galangin also effectively inhibited invasion and migration in OV-infected CCA cells by reduction of MMP2 and MMP9 enzymatic activity. Additionally, using proteomics, we identified proteins affected post-treatment with Galangin. Enrichment analysis revealed that several kinase pathways were affected by Galangin, and the signature corroborated with that of small molecule kinase inhibitors. Hence, we identified putative targets of Galangin using an in silico approach which highlighted c-Met as candidate target. Galangin effectively inhibited c-Met phosphorylation and subsequent signaling in in vitro CCA cells. In addition, Galangin was able to inhibit HGF, a mediator of c-Met signaling, by suppressing HGF-stimulated invasion, as well as migration and MMP9 activity. This shows that Galangin can be a useful anti-metastatic therapeutic strategy in a subtype of CCA patients.

[Galangin alleviates learning and memory impairments in APP/PS1 double- transgenic mice by regulating Akt/MEF2D/Beclin-1 signaling pathway].

The study aimed to investigate the effects of galangin on learning and memory impairments and Akt/MEF2 D/Beclin-1 signaling pathway in APP/PS1 double-transgenic mice. The mice in this experiment were divided into the normal group, model group, low-(25 mg·kg~(-1)), medium-(50 mg·kg~(-1)), and high-dose(100 mg·kg~(-1)) galangin groups, donepezil(3 mg·kg~(-1)) group, Akt inhibitor(25 mg·kg~(-1)) group, and autophagy inhibitor(30 mg·kg~(-1)) group, with ten in each group, and administered with the corresponding drugs for 30 successive days. On the 24 th day of medication, the water maze and dark avoidance tests were performed. The levels of p-tau, ß-amyloid peptide 1-42(Aß_(42)), acetylcholinesterase(AChE), ß-site amyloid precursor protein cleaving enzyme 1(BACE1), and amyloid precursor protein(APP) in hippocampus were detected by ELISA, the Beclin-1 mRNA expression by RT-PCR, the expression of Aß_(42) and glial fibrillary acidic protein(GFAP) by immunohistochemistry, and the expression of myocyte enhancer factor 2 D(MEF2 D) by immunofluorescence assay. The pathological changes in hippocampus were observed after HE staining, and the expression of Akt, MEF2 D, and Beclin-1 in hippocampus were assayed by Western blot. These results showed that compared with the normal group, the model group exhibited prolonged swimming time, increased number of errors and electric shocks, up-regulated p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened incubation period, decreased p-Akt and MEF2 D, and obvious hippocampal injury. Compared with the model group, donepezil and galangin shortened the swimming time, reduced the number of errors and electric shocks, down-regulated the expression of p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, prolonged the incubation period, up-regulated p-Akt and MEF2 D, and improved the pathological changes in hippocampus. Compared with the autophagy inhibitor group, galangin prolonged the swimming time, elevated the number of errors and electric shocks, enhanced the expression of p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened the incubation period, and diminished the expression of p-Akt and MEF2 D. In conclusion, galangin improves the learning and memory impairments and hippocampal neuron injury of APP/PS1 mice, which may be related to its regulation of Akt/MEF2 D/Beclin-1 signaling pathway.

Evaluation of toxicological safety and quality control of Luobufukebiri pill.

ETHNOPHARMACOLOGICAL RELEVANCE: The Luobufukebiri pill is one of the characteristic medicines of Uygur nationality in Xinjiang. It has the effect of warming and tonifying the brain and kidney, benefiting the heart and filling the essential functions, mainly used to treat impotence, depression, spermatorrhea, premature ejaculation, bodily weakness, emaciation, and neurasthenia. AIM OF THE STUDY: This study evaluated the toxicology and developed a quality control protocol of Luobufukebiri pill to ensure its safety and effectiveness in clinical applications. MATERIALS AND METHODS: Acute toxicity in mice was studied by the maximum-dose method, and the toxic reactions in mice were observed within two weeks. In the study of Sub-chronic toxicity, SD rats were randomized into four groups: three drug groups which were treated with 8.00, 2.67, and 0.80 g/kg of Luobufukebiri pill, respectively, and one control group which was treated with the same volume of distilled water. Subsequently, at 30 days of medication and 30 days of drug withdrawal, the hematologic indexes, biochemical indexes, organ coefficient, and pathological sections of main organs were detected, respectively. According to the prescription, the contents of 8 active components in the pill were quantified simultaneously. The chromatographic conditions were as follows: Stepwise gradient elution was carried out using 0.1% formic acid (solvent A) and acetonitrile (solvent B), 0-8 min, 80% → 60% B; 8-25 min, 60% → 25%B. The flow rate was 1.0 mL/min, the column was maintained at 25 °C, and the injected sample volume was 10 µL. RESULTS: The acute toxicity experiment documented a large dose of Luobufukebiri pill had no significant effect on organ and body weight and did not cause apparent damage to parenchymal organs. At Sub-chronic toxicity, the behavior of rats was as normal as the control group. There were some differences in hematologic indexes, serum biochemical indexes, and organ coefficient tests between the drug and control groups, but they had no toxic significance. No obvious pathological changes were observed in the pathological sections of major organs. In conclusion, this study demonstrated that the clinical dose of Luobufukebiri pill was far less than its toxic dose, and it had reliable safety. The contents of eight index components of Luobufukebiri pill were measured. All calibration curves exhibited good linearity with correlation coefficients better than 0.9997. The relative standard deviations of precision, reproducibility, stability, and recovery were less than 2.0%, demonstrating the stability and reliability of the method. CONCLUSIONS: This study further confirmed the safety of Luobufukebiri pill in clinical practice. A rapid, accurate, and convenient RP-HPLC-PDA detection method has been developed for the simultaneous detection of eight active compounds in the pharmaceutical samples of Luobufukebiri pill. This study provided a reference for the safety and enhancement of the quality standards of Luobufukebiri pill.

The Antimicrobial Properties of Poplar and Aspen-Poplar Propolises and Their Active Components against Selected Microorganisms, including Helicobacter pylori.

There is a noticeable interest in alternative therapies where the outcome is the eradication of the Gram-negative bacterium, Helicobacter pylori (H. pylori), for the purpose of treating many stomach diseases (chronic gastritis and peptic ulcers) and preventing stomach cancer. It is especially urgent because the mentioned pathogen infects over 50% of the world's population. Recent studies have shown the potential of natural products, such as medicinal plant and bee products, on the inhibition of H. pylori growth. Propolis is such a bee product, with known antimicrobial activities. The main scope of the study is the determination of the antimicrobial activity of ethanolic extracts from 11 propolis samples (mostly from Poland, Ukraine, Kazakhstan, and Greece) against H. pylori, as well as selected bacterial and yeast species. The most effective against H. pylori was the propolis from Ukraine, with an MIC = 0.02 mg/mL while the rest of samples (except one) had an MIC = 0.03 mg/mL. Moreover, significant antimicrobial activity against Gram+ bacteria (with an MIC of 0.02-2.50 mg/mL) and three yeasts (with an MIC of 0.04-0.63 mg/mL) was also observed. A phytochemical analysis (polyphenolic profile) of the propolis samples, by ultra-high-performance liquid chromatography-diode array detector-mass spectrometry (UPLC-DAD-MS), was performed. An evaluation of the impact of the propolis components on antimicrobial activity, consisting of statistical analyses (principal component analysis (PCA) and hierarchical fuzzy clustering), was then performed. It was observed that the chemical composition characteristics of the poplar propolis correlated with higher antibacterial activity, while that of the poplar and aspen propolis correlated with weaker antibacterial activity. To summarize the activity in vitro, all tested propolis samples indicate that they can be regarded as useful and potent factors in antimicrobial therapies, especially against H. pylori.

Identification of galangin as the bioactive compound from Alpinia calcarata (Haw.) Roscoe rhizomes to inhibit IRAK-1/ MAPK/ NF-κB p65 and JAK-1 signaling in LPS stimulated RAW 264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia calcarata (Haw.) Roscoe rhizomes are used to treat diabetes, rheumatism, gastrointestinal problems, inflammatory diseases, cough and respiratory problems in traditional practices. The primary objective of the study is to identify and isolate anti-inflammatory bioactive compounds from A.calcarata rhizomes and to assess its molecular mechanism. MATERIALS AND METHODS: The bioassay-guided fractionation of methanolic extract of A. calcarata rhizomes yielded chloroform fraction as the effective fraction and galangin as the bioactive compound identified by NMR studies. The anti-inflammatory action of galangin was evaluated by determining NO and cytokine production in LPS stimulated RAW264.7 cells. Further, its mechanism was studied on the expression levels of mRNA and protein targets by qPCR and Western blot analysis. RESULTS: Based on the MTT assay, the concentration of 3.1-25 µM of galangin was selected for further studies. Galangin reduced the levels of NO and proinflammatory cytokines (TNF-α, IL-1ß and IL-6) production in LPS induced RAW 264.7 cells in a dose-dependent manner. In addition, the qPCR analysis revealed a reduction in the mRNA expression levels of COX-2, IRAK 1 and JAK 1 in galangin treated LPS stimulated RAW 264.7 cells in a dose-dependent manner. Western blot analysis implicated that galangin has markedly reduced the protein expression levels of cell signaling regulators (JAK-1, IRAK-1, MyD88, MAPK (p38 and ERK) and NF-κB p65). CONCLUSION: From the results, it is evident that the inhibition of these cell signaling regulators has contributed to the anti-inflammatory effects of galangin. To our knowledge, we are the first to report IRAK-1 and JAK-1 as therapeutic targets of galangin for its anti-inflammatory effect.

Quantification of Flavonoids in Alpinia officinarum Hance. via HPLC and Evaluation of its Cytotoxicity on Human Prostate Carcinoma (LNCaP) and Breast Carcinoma (MCF-7) Cells.

BACKGROUND: Various plant species have been shown to be effective in the prevention or adjuvant therapy of cancer. Alpinia officinarum and its main phytochemicals have also been the subject of several studies for their anticancer properties. OBJECTIVE: The objective of this study is to analyze the extracts of A. officinarum to quantify flavonoids and to evaluate the growth inhibitory effects of the extracts on MCF-7 and LNCaP cells. METHODS: A. officinarum aqueous and hydroalcoholic extracts were analyzed by using High-Performance Liquid Chromatography (HPLC) for the quantification of three flavonoid compounds. Then, MCF-7, LNCaP, and fibroblast cells were treated with several concentrations (25, 50, 100, 200, and 400 µg/mL) of extracts (24, 48 and 72h). Cell viability was assessed using an MTT assay. Flow cytometry was conducted to evaluate apoptosis. RESULTS: Galangin and kaempferol (3.85 and 1.57 mg/g dry extract) were quantified, respectively, in hydroalcoholic and aqueous extracts using a validated method. The hydroalcoholic extract significantly decreased the viability of MCF-7 (IC50: 43.45µg/mL for 48h) and LNCaP cells (IC50: 168 µg/mL for 48h). The aqueous extract reduced cancer cell viability by more than 50% only at 200 and 400 µg/mL (72 h). Treatment of primary fibroblasts with both extracts showed no significant decrease in cell viability (25-100 µg/mL; 24 and 48h). The hydroalcoholic extract induced a significant increase in apoptotic cells in both MCF-7 and LNCaP cells. CONCLUSION: Obtained results demonstrated the cytotoxicity of A. officinarum through apoptosis induction in two cancer cell lines. Further investigations are required to determine the underlying apoptotic cell death mechanisms induced by A. officinarum in cancerous cells.

Extracts from European Propolises as Potent Tyrosinase Inhibitors.

Tyrosinase is a key enzyme in the melanogenesis pathway. Melanin, the product of this process, is the main pigment of the human skin and a major protection factor against harmful ultraviolet radiation (UVR). Increased melanin synthesis due to tyrosinase hyperactivity can cause hyperpigmentation disorders, which in consequence causes freckles, age spots, melasma, or postinflammatory hyperpigmentation. Tyrosinase overproduction and hyperactivity are triggered by the ageing processes and skin inflammation as a result of oxidative stress. Therefore, the control of tyrosinase activity is the main goal of the prevention and treatment of pigmentation disorders. Natural products, especially propolis, according to their phytochemical profile abundant in polyphenols, is a very rich resource of new potential tyrosinase inhibitors. Therefore, this study focused on the assessment of the tyrosinase inhibitory potential of six extracts obtained from the European propolis samples of various origins. The results showed the potent inhibitory activity of all tested propolis extracts towards commercially available mushroom tyrosinase. The four most active propolis extracts showed inhibitory activity in the range of 86.66-93.25%. Apart from the evaluation of the tyrosinase inhibition, the performed research included UHPLC-DAD-MS/MS (ultra high performance liquid chromatography coupled with diode array detection and tandem mass spectrometry) phytochemical profiling as well as antioxidant activity assessment using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2"-azino-bis(3-ethylbenzothiazoline-6-sulfuric acid (ABTS) radical scavenging tests. Moreover, statistical analysis was used to correlate the tyrosinase inhibitory and antioxidant activities of propolis extracts with their phytochemical composition. To summarise, the results of our research showed that tested propolis extracts could be used for skin cosmeceutical and medical applications.

Galangin attenuates IL-1ß-induced catabolism in mouse chondrocytes and ameliorates murine osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is one of the most common chronic diseases, which is characterized by cartilage degeneration, subchondral osteosclerosis, and synovitis. Accumulating evidence has shown that galangin, a flavonoid derived from medicinal herbs, exhibits numerous pharmacological activities in various diseases. This study aimed to investigate the effects of galangin on interleukin (IL)-1ß-induced inflammation in mouse chondrocytes and explore the underlying mechanisms. METHODS: In this study, we investigated the protective effects of galangin on IL-1ß-induced inflammatory response in vitro using the CCK-8 assay, RT-qPCR, western blotting, and immunofluorescence staining. In addition, the therapeutic effects of galangin on the anterior cruciate ligament transection (ACLT) mouse model were also explored in vivo. Results: Galangin treatment suppressed the expression of IL-1ß-induced inflammatory cytokines, such as nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-6. Furthermore, galangin attenuated hypertrophic conversion and the extracellular matrix degradation via inhibiting the expression of catabolic enzymes. Mechanistically, galangin inhibited the activation of the JNK and ERK MAPK pathways and nuclear factor kappa-B (NF-κB) signaling pathway. In addition, galangin treatment ameliorated cartilage degeneration in an OA model in vivo. Conclusion: Galangin suppressed the IL-ß-induced inflammatory response in vitro and ameliorated cartilage degeneration in vivo via inhibiting the NF-κB pathway and JNK and ERK pathways, suggesting its potential as an effective candidate for the treatment of OA.

[Galangin enhances autophagy by inhibiting NF-κB pathway in gastric cancer MGC-803 cells].

This study aimed to explore the effects of galangin on energy metabolism and autophagy in gastric cancer MGC803 cells and the underlying mechanism. Cell counting kit-8(CCK-8) was used to detect the effects of galangin at different concentrations on via-bility of MGC803 cells after 48 h intervention. Western blot was carried out to measure the effects of galangin on expression of proteins related to autophagy, nuclear factor-κB(NF-κB) pathway and energy metabolism, followed by the determination of its effects on mRNA expression of energy metabolism-related proteins by Real-time quantitative PCR(qPCR). The impact of galangin on autophagy was explored using AutophagyGreen dye reagent, with autophagosomes and lysosomes observed under the transmission electron microscope(TEM). Nude mice transplanted with gastric cancer MGC803 cells via subcutaneous injection were randomly divided into the following three groups: control(0.5% sodium carboxymethyl cellulose, once a day), 5-fluorouracil(5-FU, 50 mg·kg~(-1), twice a week), and galangin(120 mg·kg~(-1), once a day) groups. The body weight and tumor volume were measured once every three days with a vernier caliper at the same time point by the same person. After 21-d treatment, the tumor tissue was isolated and weighed for the calculation of the tumor-suppressing rate. The comparison with the control group revealed that galangin inhibited the viability of MGC803 cells, up-regulated the protein expression of microtuble-associated protein 1 light chain 3 B(LC3 B) Ⅱ, inhibited the phosphorylation of NF-κB pathway-related proteins, and promoted the formation of autophagosomes in MGC803 cells. However, it did not obviously affect the expression of energy metabolism-related proteins. Furthermore, galangin at 120 mg·kg~(-1) significantly reduced the tumor weight and volume in mice, enhanced LC3 BⅡ protein expression, and inhibited the phosphorylation of NF-κB pathway-related proteins. All these have suggested that galangin inhibited the growth of gastric cancer MGC803 cells both in vivo and in vitro, possibly by inhibiting the NF-κB pathway and enhancing autophagy.

A comprehensive review on chemotherapeutic potential of galangin.

Galangin, a non-toxic phytochemical is known to possess several therapeutic applications. Mounting evidences have demonstrated that galangin a naturally available flavonoid exerts anticancer effects via several mechanisms. The phytocompound induces apoptosis and renders antiangiogenic property. Additionally, galangin has demonstrated significate results in combating various cancer types when administered in combination with other phytocompounds or with gold nanoparticles (GNPs). The present article is a critical review of galangin for its treatment on different types of cancer and its usability as an alternative cancer therapeutics.

Metabolic products of European-type propolis. Synthesis and analysis of glucuronides and sulfates.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a bee-derived product used since antiquity for its general health-giving properties and is especially noted for its anti-bacterial activity. In more recent times, propolis has been employed against more specific targets such as antiproliferative effects vs cancer cells, wound healing and type-2 diabetes. AIM OF THE STUDY: European (poplar)-type propolis from New Zealand contains a number of hydroxy cinnamic acid esters and a set of aglycone flavonoid compounds, mainly chrysin, galangin, pinocembrin and pinobanksin. Propolis is usually taken orally and propolis metabolites quickly appear in the plasma of the ingested. In this work we aimed to identify the major flavonoid plasma metabolites by direct analysis of the plasma. MATERIALS AND METHODS: After consumption of a large dose of propolis in a single sitting, blood samples were taken and analysed using LCMS/MS. The major flavonoid metabolites identified were also synthesised using chemical (sulfates) or enzymatic methods (glucuronides). RESULTS: Both the sulfate and glucuronide conjugates of the four major propolis flavonoids are readily detected in human plasma after propolis ingestion. Preparation of the sulfates and glucuronides of the four major flavonoids allowed the relative proportions of the various metabolites to be determined. Although the sulfates are seen as large peaks in the LCMS/MS, the glucuronides are the dominant conjugate species. CONCLUSIONS: This study shows most of the flavonoids in the plasma are present as 7-O-glucuronides with only galangin showing some di-glucuronidation (3,7-O-diglucuronide). No evidence was found for hydroxy cinnamic acid type metabolites in the plasma samples.

Flavonoids and hERG channels: Friends or foes?

The cardiac action potential is regulated by several ion channels. Drugs capable to block these channels, in particular the human ether-à-go-go-related gene (hERG) channel, also known as KV11.1 channel, may lead to a potentially lethal ventricular tachyarrhythmia called "Torsades de Pointes". Thus, evaluation of the hERG channel off-target activity of novel chemical entities is nowadays required to safeguard patients as well as to avoid attrition in drug development. Flavonoids, a large class of natural compounds abundantly present in food, beverages, herbal medicines, and dietary food supplements, generally escape this assessment, though consumed in consistent amounts. Continuously growing evidence indicates that these compounds may interact with the hERG channel and block it. The present review, by examining numerous studies, summarizes the state-of-the-art in this field, describing the most significant examples of direct and indirect inhibition of the hERG channel current operated by flavonoids. A description of the molecular interactions between a few of these natural molecules and the Rattus norvegicus channel protein, achieved by an in silico approach, is also presented.