Acetoxychavicol Acetate Research Articles

The anti-quorum sensing and biofilm inhibitory potential of Piper betle L. leaf extract and prediction of the roles of the potent phytocompounds

The leaves of Piper betle L., known as betel leaf, have immense medicinal properties. It possesses potent antimicrobial efficacies and can be a valuable tool to combat drug-resistant microorganisms. Quorum sensing (QS) inhibition is one of the best strategies to combat drug resistance. The present study investigates the anti-quorum sensing and biofilm inhibitory potential of Piper betle L. leaf extract against two bacterial strains, Chromobacterium violaceum and Pseudomonas aeruginosa. The extract produced substantial QS-inhibition zones in a biosensor strain of C. violaceum (CV026), indicating interference with quorum-sensing signals. The Results demonstrated significant inhibition in biofilm formation and different QS-regulated virulence factors (violacein, exopolysaccharides, pyocyanin, pyoverdine, elastase) in both C. violaceum and P. aeruginosa at sub-MIC concentrations of the extract and tetracycline, an antibiotic with known anti-QS activity. The quantitative real-time PCR (qRT-PCR) revealed decreased gene expression in different QS-related genes in C. violaceum (cviI, cviR, and vioA) and P. aeruginosa (lasI, lasR, lasB, rhlI, rhlR, and rhlA) strains after treatment. Gas Chromatography-Mass Spectrometry (GC-MS) analysis identified the significant phytocompounds, mainly derivatives of chavicol and eugenol, in the extract. Of these compounds, chavicol acetate (affinity: −7.00 kcal/mol) and acetoxy chavicol acetate (affinity: −7.87 kcal/mol) showed the highest potential to bind with the CviR and LasR protein, respectively, as evident from the in-silico molecular docking experiment. The findings of this endeavour highlight the promising role of Piper betle L. as a source of natural compounds with anti-quorum sensing properties against pathogenic bacteria, opening avenues for developing novel therapeutic agents to combat bacterial infections.

Synthesis of benzhydrol analogues based on 1´-acetoxychavicol acetate (ACA), as a stable and potent antiproliferative agent on breast cancer cell lines, ADMET analysis and molecular docking study.

Synthesis of benzhydrol analogues based on 1´-acetoxychavicol acetate (ACA), as a stable and potent antiproliferative agent on breast cancer cell lines, ADMET analysis and molecular docking study.

The Effect of 1'-acetoxychavicol Acetate on A549 Human Non-small Cell Lung Cancer

Lung cancer, a global leading cause of cancer mortality, requires safer and more effective treatments. 1'-acetoxychavicol acetate (ACA) is notable for its wide-ranging therapeutic properties, spanning anticancer, anti-inflammatory, and anti-obesity effects. While its efficacy has been explored in various cell lines, its potential against lung cancer remains few reported. This research aimed to investigate the impact of ACA on cytotoxicity, anti-proliferation, and antimigration potential in A549 human non-small cell lung cell lines. The investigation utilized MTT assays to assess cell viability and determined the IC50 values of ACA at 24, 48, and 72 hours to be 50.42 µM, 33.22 µM, and 21.66 µM, respectively. These results reveal a concentration- and time-dependent reduction in cell viability following ACA treatment. In addition, anti-proliferation was performed using colony-forming assays, and ACA showed notable efficacy in significantly decreasing colony formation, highlighting its strong impact on cell proliferation and viability. In the final part, ACA had promising inhibitory effects on migration, which varied depending on the dose used in the scratch assay. In conclusion, ACA highlighted cytotoxic and anti-proliferation properties of A549 cell line, supporting its potential role in lung cancer therapy pending further investigation and development.

A comparative MS-based metabolomics study and in-vitro antidiabetic assay of galangals, turmeric and ginger aided by molecular networking and chemometrics

Ginger and turmeric and the less explored galangals, are economically important spices belonging to the Zingiberaceae family, widely used in traditional medicines and nutraceuticals. The present study provides the first comparative MS based metabolomics investigation of galangals compared to major ginger drugs and in relation to their in vitro antidiabetic effects. UPLC-MS/MS metabolomic profiles of galangals, turmeric, and ginger were analyzed using GNPS molecular networking leading to the annotation of 85 metabolites of which several are first time to be reported in galangals. Principle component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA) of UPLC-MS/MS profiles revealed the enrichment of flavonoids, styrenes and oxylipids in the extracts of both galangals, whereas gingerols, aryl- and diarylheptanoids were characteristic to ginger and turmeric, respectively. Aroma profiling using SPME–GC–MS identified 96 volatiles belonging to sesqui- and monoterpene derivatives. Multivariate data analysis of GC-MS dataset revealed calamenene, guaia-1(10),11-diene and selina-3,7(11)-diene as characteristic to ginger and turmeric aroma profiles. In contrast, greater galangal was enriched in acetoxychavicol acetate, aristolene, α-farnesene versus abundance of γ-elemene in lesser galangal. Additionally, methanolic extracts of both galangals exerted potential in vitro α-glucosidase inhibitory effect accentuating its potential antidiabetic activities.

Immunomodulatory effects and mechanisms of the extracts and secondary compounds of Zingiber and Alpinia species: a review.

Zingiber and Alpinia species (family: Zingiberaceae) are popularly used in food as spices and flavoring agents and in ethnomedicine to heal numerous diseases, including immune-related disorders. However, their ethnomedicinal uses have not been sufficiently supported by scientific investigations. Numerous studies on the modulating effects of plants and their bioactive compounds on the different steps of the immune system have been documented. This review aimed to highlight up-to-date research findings and critically analyze the modulatory effects and mechanisms of the extracts and secondary compounds of several Zingiber and Alpinia species, namely, Zingiber officinale Roscoe, Z. cassumunar Roxb., Z. zerumbet (L.) Roscoe ex Sm., Alpinia galanga Linn., A. conchigera Griff, A. katsumadai Hayata, A. oxyphylla Miq., A. officinarum Hance, A. zerumbet (Pers.) Burtt. et Smith, and A. purpurata (Viell.) K. Schum. on the immune system, particularly via the inflammation-related signaling pathways. The immunomodulating activities of the crude extracts of the plants have been reported, but the constituents contributing to the activities have mostly not been identified. Among the extracts, Z. officinale extracts were the most investigated for their in vitro, in vivo, and clinical effects on the immune system. Among the bioactive metabolites, 6-, 8-, and 10-gingerols, 6-shogaol, and zerumbone from Zingiber species and cardamomin, 1'-acetoxychavicol acetate, yakuchinone, rutin, 1,8-cineole, and lectin from Alpinia species have demonstrated strong immunomodulating effects. More experimental studies using cell and animal models of immune-related disorders are necessary to further understand the underlying mechanisms, together with elaborate preclinical pharmacokinetics, pharmacodynamics, bioavailability, and toxicity studies. Many of these extracts and secondary metabolites are potential candidates for clinical development in immunomodulating agents or functional foods to prevent and treat chronic inflammatory disorders.

VIRTUAL SCREENING OF NATURAL ALPHA-GLUCOSIDASE INHIBITOR FROM ALPINIA GALANGA BIOACTIVE COMPOUNDS AS ANTI-DIABETIC CANDIDATE

Glucose toxicity become serious risk factor of type 2 diabetes mellitus. Multiple complication can be caused of the abnormal condition of glucose level in blood. Thus, managing the plasma glucose is one of the strategy to minimize the negative effects of type 2 diabetes mellitus. In this present study, we aimed to virtually evaluate the bioactive compounds from Alpinia galanga as inhibitor agent against alpha-glucosidase, which was known as carbohydrate catabolic enzyme. The 2D structure of ligands were retrieved from PubChem database (pubchem.ncbi.nlm.nih.gov/) and were evaluated based on Lipinski rule of five for ensured the druglike-ness standard, while the sequence and 3D structure of target protein, alpha-glucosidase, was retrieved from UniProt database (https://www.uniprot.org/) and was modelled through SWISS-MODEL (swissmodel.expasy.org/). All ligands used in this study then underwent optimization prior to molecular docking and analyzing procedures. According to our prediction results, we found that galangin and 1's-1'-acetoxychavicol acetate which known as bioactive compounds found in A. galanga have significant potency as inhibitor agents against the alpha-glucosidase due to its binding affinity scores and other physicochemical properties compared to the anti-diabetic drug, mignitol. Thus, from this finding, we have recent starting point to expand the potency of these bioactive compounds, especially for inhibiting the alpha-glucosidase as the novel strategy to reduce the poor prognosis of type 2 diabetes mellitus.

Technique for order preference by similarity to ideal solution (TOPSIS): a MCDM approach for selecting suitable solvent considering biochemical profiles and in vitro antibacterial efficacy of petioles of betel leaf (Piper betle L.).

Petioles of betel leaf (BLP) are the major industrial by-products of betel leaf industries sold at throwaway prices or used as cattle feed. The present work was taken up to evaluate suitable solvent based on yield, antioxidant, and antimicrobial properties to isolate extract of BLP using the Shannon entropy-TOPSIS method. Four solvents were chosen for the extraction process: hexane, toluene + ethanol (2:1), acetone, and ethanol. The findings showed that ethanol-based BLP extract had the highest TPC value, measuring 2193.71 ± 0.17mg of gallic acid equivalence/g of dry extract, while acetone-based extracts had the highest TFC value, measuring 8.03mg of quercetin equivalent/g of dry extract. Radical scavenging activities like DPPH (IC50 = 52.44μg/mL), ABTS (IC50 = 62.41μg/mL), and FRAP (8.03mg QE/g of dry extract) were found best for acetone extract. The antibacterial study of the extracts revealed that acetone extract was more sensitive to Gram-positive and Gram-negative bacterial strains followed by ethanol, toluene + ethanol, and hexane extracts. Among five foodborne bacteria, B. subtilis showed the highest susceptibility against all extracts. GC-MS analysis showed that acetoxychavicol acetate (31.27%) (PubChem ID: 119,104), germacrene D (7.24%) (PubChem Id: 531,750), isoxylic acid (22.56%) (PubChem ID: 11,892), and cis-1,2-indandiol (43.92%) (PubChem ID: 20,758) are four major compounds among 22 components. TOPSIS analysis revealed that acetone extract had the highest relative closeness value (0.71) followed by ethanol (0.65), toluene + ethanol (0.53), and hexane (0.32). These results indicate that acetone extract of BLP can be considered an alternative to synthetic active ingredients in the future. These results indicated that TOPSIS method has computational robustness for selecting a solvent comparing yield, antioxidant, and antimicrobial activities of extract of a plant part.

(1'S)-1'-Acetoxyeugenol Acetate Enhances Glucose-Stimulated Insulin Secretion.

Alpinia galanga have been widely used as spice or traditional medicine in East Asia, commonly known as Thai ginger. In the present study, seven major phenylpropanoids, (±)-1'-hydoxychavicol acetate (1; HCA), (1'S)-1'-acetoxychavicol acetate (2; ACA), (1'S)-1'-acetoxyeugenol acetate (3; AEA), eugenyl acetate (4), trans-p-coumaraldehyde (5), trans-p-acetoxycinnamyl alcohol (6), and trans-p-coumaryl diacetate (7), were isolated from the 95% EtOH and hot water extracts of the rhizomes of A. galanga by chromatographic method. Phenylpropanoids 1-7 were evaluated for glucose-stimulated insulin secretion (GSIS) effect and α-glucosidase inhibitory activity. Phenylpropanoids 1-4 increase GSIS effect without cytotoxicity in rat INS-1 pancreatic β-cells. In addition, INS-1 cells were treated with AEA (3) to determine a plausible mechanism of β-cell function and insulin secretion through determining the activation of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1). Upon treatment with AEA (3), INS-1 cells showed an increase in these protein expressions. Meanwhile, AEA (3) exhibited α-glucosidase inhibitory activity. On the basis of the above findings, we suggest AEA (3) as a potential antidiabetic agent.

ACA-28, an anticancer compound, induces Pap1 nuclear accumulation via ROS-dependent and -independent mechanisms in fission yeast.

The nucleocytoplasmic transport of proteins is an important mechanism to control cell fate. Pap1 is a fission yeast nucleocytoplasmic shuttling transcription factor of which localization is redox regulated. The nuclear export factor Crm1/exportin negatively regulates Pap1 by exporting it from the nucleus to the cytoplasm. Here, we describe the effect of an anti-cancer compound ACA-28, an improved derivative of 1'-acetoxychavicol acetate (ACA), on the subcellular distribution of Pap1. ACA-28 induced nuclear accumulation of Pap1 more strongly than did ACA. ROS inhibitor N-acetyl-L-cysteine (NAC) partly antagonized the Pap1 nuclear accumulation induced by ACA-28. NAC almost abolished Pap1 nuclear localization upon H 2 O 2 , whereas leptomycin B (LMB)-mediated inhibition of Pap1 nuclear export was resistant to NAC. Collectively, ACA-28-mediated apoptosis in cancer cells may involve ROS-dependent and -independent mechanisms.

Stability Study of Alpinia galanga Constituents and Investigation of Their Membrane Permeability by ChemGPS-NP and the Parallel Artificial Membrane Permeability Assay.

Alpinia galanga Willd., greater galangal, has been used for thousands of years as a spice as well as in traditional medicine. Its central nervous system (CNS) stimulant activity and neuroprotective effects have been proved both in animal models and human trials. However, the compounds responsible for these effects have not been identified yet. Therefore, the main constituents (p-OH-benzaldehyde (1), trans-p-coumaryl-alcohol (2), p-coumaryl-aldehyde (4), galanganol A (5), galanganol B (6), trans-p-acetoxycinnamyl alcohol (7), 1′S-1′-acetoxychavicol acetate (ACA, 9), and 1′S-1′-acetoxyeugenol acetate (AEA, 10)) were isolated to investigate their aqueous stability and passive diffusion across the gastro-intestinal tract (GIT) membrane and the blood–brain barrier (BBB) by the parallel artificial membrane permeability assay (PAMPA). Our positive results for compounds 1, 2, 4, 7, 9, and 10 suggest good permeability, thus potential contribution to the effects of greater galangal in the CNS. The results of the PAMPA-BBB were corroborated by in silico chemography-based ChemGPS-NP framework experiments. In addition, examination of the chemical space position of galangal compounds in relation to known psychostimulants revealed that all the molecules in proximity are NET/SERT inhibitors. As ACA and AEA did not show much proximity to either compound, the importance of further investigation of their degradation products becomes more pronounced.

Inhibition of lipopolysaccharide-induced inflammatory responses by 1'-acetoxychavicol acetate.

Lipopolysaccharide on gram negative bacteria can be detected by Toll-like receptor 4 (TLR4) to elicit a series of innate immune responses, leading to inflammation to eliminate the targeted pathogen. However, dysregulation in the responses results in excessive inflammation. The 1'-acetoxychavicol acetate (ACA) is a bioactive compound originated from Alpinia species known to have anti-inflammatory and apoptosis-inducing properties. Here, we found that ACA inhibits lipopolysaccharide-induced expression and production of proinflammatory cytokines such as interleukin 6 and TNFα by macrophages. ACA suppresses the activation of NF-κB and MAP kinases in TLR4 signaling. Moreover, ACA also inhibits TLR4-mediated induction of type I interferon by suppressing IRF3 activation. In lipopolysaccharide-challenged mice, ACA treatment successfully increased the survival of mice and alleviated inflammation in the lung. Thus, ACA is a potential anti-inflammatory agent to regulate excessive inflammation.

Development and validation of a reversed-phase HPLC method for quantification of 1’-acetoxychavicol acetate content in a nanostructured lipid carrier formulation

Development and validation of a reversed-phase HPLC method for quantification of 1’-acetoxychavicol acetate content in a nanostructured lipid carrier formulation

Dietary supplementation of gingerols- and shogaols-enriched ginger root extract attenuate pain-associated behaviors while modulating gut microbiota and metabolites in rats with spinal nerve ligation

Neuroinflammation is a central factor in neuropathic pain (NP). Ginger is a promising bioactive compound in NP management due to its anti-inflammatory property. Emerging evidence suggests that gut microbiome and gut-derived metabolites play a key role in NP. We evaluated the effects of two ginger root extracts rich in gingerols (GEG) and shogaols (SEG) on pain sensitivity, anxiety-like behaviors, circulating cell-free mitochondrial DNA (ccf-mtDNA), gut microbiome composition, and fecal metabolites in rats with NP. Sixteen male rats were divided into four groups: sham, spinal nerve ligation (SNL), SNL+0.75%GEG in diet, and SNL+0.75%SEG in diet groups for 30 days. Compared to SNL group, both SNL+GEG and SNL+SEG groups showed a significant reduction in pain- and anxiety-like behaviors, and ccf-mtDNA level. Relative to the SNL group, both SNL+GEG and SNL+SEG groups increased the relative abundance of Lactococcus, Sellimonas, Blautia, Erysipelatoclostridiaceae, and Anaerovoracaceae, but decreased that of Prevotellaceae UCG-001, Rikenellaceae RC9 gut group, Mucispirillum and Desulfovibrio, Desulfovibrio, Anaerofilum, Eubacterium siraeum group, RF39, UCG-005, Lachnospiraceae NK4A136 group, Acetatifactor, Eubacterium ruminantium group, Clostridia UCG-014, and an uncultured Anaerovoracaceae. GEG and SEG had differential effects on gut-derived metabolites. Compared to SNL group, SNL+GEG group had higher level of 1′-acetoxychavicol acetate, (4E)-1,7-Bis(4-hydroxyphenyl)-4-hepten-3-one, NP-000629, 7,8-Dimethoxy-3-(2-methyl-3-buten-2-yl)-2H-chromen-2-one, 3-{[4-(2-Pyrimidinyl)piperazino]carbonyl}-2-pyrazinecarboxylic acid, 920863, and (1R,3R,7R,13S)-13-Methyl-6-methylene-4,14,16-trioxatetracyclo[11.2.1.0∼1,10∼.0∼3,7∼]hexadec-9-en-5-one, while SNL+SEG group had higher level for (±)-5-[(tert-Butylamino)-2′-hydroxypropoxy]-1_2_3_4-tetrahydro-1-naphthol and dehydroepiandrosteronesulfate. In conclusion, ginger is a promising functional food in the management of NP, and further investigations are necessary to assess the role of ginger on gut-brain axis in pain management.

Development and validation of RP-HPLC method for 1΄-Acetoxychavicol acetate (ACA) and its application in optimizing the yield of ACA during its isolation from Alpinia galanga extract as well as its quantification in nanoemulsion

An isocratic RP-HPLC was developed and validated for isolation of 1΄-Acetoxychavicol acetate (ACA) from Alpinia galanga extract (AGE). Nucleodur C18 column was used as the stationary phase and mixture of acetonitrile/0.1% formic acid in water (60/40, v/v) were used as mobile phase. The elution was carried out with a flow rate of 1 mL/min. Further, the method was validated as per ICH Q2 [R1] guidelines in terms of linearity, LOD, LOQ, recovery, precision and specificity. The validated method was utilized for two purposes i.e. optimizing the isolation of ACA from AGE and quantifying ACA's concentration and release from its nanoemulsion. To achieve high yield of ACA, Central composite design (CCD) was used to optimize sieve number and solid to solvent ratio. The retention time of standard and isolated ACA were found at 5.63 min and 5.46 min respectively. The results indicated that the validated method was linear, accurate, precise and specific. During optimization, excellent correlation was observed between practical yield (3.89 ± 0.23% w/w of dried rhizomes) and predicted yield (3.73% w/w of dried rhizomes) of ACA with p value more than 0.05. The percentage of ACA loaded in the nanoemulsion was found to be 99.12 ± 0.39. The in vitro diffusion studies showed 90.12 ± 2.21% release of ACA at the end of 24 h. It was concluded that the validated method has been successfully utilized to isolate the ACA from AGE and quantify the amount of ACA present in nanoemulsion.

Discovery of 1’-acetoxychavicol acetate (ACA) as a promising antibacterial compound from galangal (Alpinia galanga (Linn.) Willd)

Galangal (Alpinia galanga (Linn.) Willd) is a perennial aromatic rhizomatous plant with great industrial importance. In this study, four major antibacterial compounds were isolated from galangal and further identified as hydroxycinnamaldehyde, cinnamaldehyde, coumaryl alcohol, and 1′-acetoxychavicol acetate (ACA). Among them, ACA was a less investigated antibacterial compound in galangal, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) 0.313 and 0.625 mg/mL, respectively, against multidrug-resistant Staphylococcus aureus SJTUF 20758. The mechanism study found that ACA significantly influenced the bacterial morphology and damaged the bacterial cell membrane integrity. Furthermore, quantitative proteomic analysis indicated that ACA at sub-MIC, on one hand, inhibited the expression of proteins associated with cell wall and membrane synthesis, osmotic regulation, and bacterial adhesion and invasion. On the other hand, it increased the expression of proteins pertinent to oxidative stress response, respiratory chain, and ATP synthesis. Therefore, ACA might initially target cell membrane by changing the expression of key membrane proteins involved in maintaining normal cell membrane functions, leading to the damage of cell membrane integrity, and also might trigger the survival response of bacteria. In general, to the best of our knowledge, it is for the first time to clarify the antibacterial mechanism of ACA. In addition, galangal is a promising spice rich in antibacterial compounds, especially ACA, which may be used as natural preservatives in the food industry.

1'-Acetoxychavicol acetate, a potent transient receptor potential ankyrin 1 agonist derived from Thai ginger, prevents visceral fat accumulation in mice fed with a high-fat and high-sucrose diet.

1'-Acetoxychavicol acetate (ACA) is found in Thai ginger (Alpinia galanga) and is a powerful agonist of transient receptor potential ankyrin 1 (TRPA1). In a diet-induced obesity mouse model, ACA reduced fat deposition. Sympathetic nerve activation was also indicated in the ACA-fed group. This study is expected to promote the utilization of food containing TRPA1 agonists to treat obesity.

1'-Acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression.

The nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing (NLRP) 3 inflammasome is a multiprotein complex that triggers Caspase-1-mediated IL-1β production and pyroptosis, and its dysregulation is associated with the pathogenesis of inflammatory diseases. 1'-Acetoxychavicol acetate (ACA) is a natural compound in the rhizome of tropical ginger Alpinia species with anti-microbial, anti-allergic and anti-cancer properties. In this study, we found that ACA suppressed NLRP3 inflammasome activation in mouse bone marrow-derived macrophages and human THP-1 monocytes. ACA inhibited Caspase-1 activation and IL-1β production by NLRP3 agonists such as nigericin, monosodium urate (MSU) crystals, and ATP. Moreover, it suppressed oligomerization of the adapter molecule, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1-mediated cleavage of pyroptosis executor Gasdermin D. Mechanistically, ACA inhibited generation of mitochondrial reactive oxygen species (ROS) and prevented release of oxidized mitochondrial DNA, which trigger NLRP3 inflammasome activation. ACA also prevented NLRP3 inflammasome activation in vivo, as evidenced in the MSU crystal-induced peritonitis and dextran sodium sulfate-induced colitis mouse models accompanied by decreased Caspase-1 activation. Thus, ACA is a potent inhibitor of the NLRP3 inflammasome for prevention of NLRP3-associated inflammatory diseases.

Development and Evaluation of 1′-Acetoxychavicol Acetate (ACA)-Loaded Nanostructured Lipid Carriers for Prostate Cancer Therapy

1′-acetoxychavicol acetate (ACA) extracted from the rhizomes of Alpinia conchigera Griff (Zingiberaceae) has been shown to deregulate the NF-ĸB signaling pathway and induce apoptosis-mediated cell death in many cancer types. However, ACA is a hydrophobic ester, with poor solubility in an aqueous medium, limited bioavailability, and nonspecific targeting in vivo. To address these problems, ACA was encapsulated in a nanostructured lipid carrier (NLC) anchored with plerixafor octahydrochloride (AMD3100) to promote targeted delivery towards C-X-C chemokine receptor type 4 (CXCR4)-expressing prostate cancer cells. The NLC was prepared using the melt and high sheer homogenization method, and it exhibited ideal physico-chemical properties, successful encapsulation and modification, and sustained rate of drug release. Furthermore, it demonstrated time-based and improved cellular uptake, and improved cytotoxic and anti-metastatic properties on PC-3 cells in vitro. Additionally, the in vivo animal tumor model revealed significant anti-tumor efficacy and reduction in pro-tumorigenic markers in comparison to the placebo, without affecting the weight and physiological states of the nude mice. Overall, ACA-loaded NLC with AMD3100 surface modification was successfully prepared with evidence of substantial anti-cancer efficacy. These results suggest the potential use of AMD3100-modified NLCs as a targeting carrier for cytotoxic drugs towards CXCR4-expressing cancer cells.

1′-Acetoxychavicol Acetate from Alpinia galanga Represses Proliferation and Invasion, and Induces Apoptosis via HER2-signaling in Endocrine-Resistant Breast Cancer Cells

Estrogen receptor-positive breast cancer patients have a good prognosis, but 30% of these patients will experience recurrence due to the development of resistance through various signaling pathways. This study aimed to evaluate the mode of anticancer effects of 1'-acetoxychavicol acetate, which is isolated from the rhizomes of Alpinia galanga in estrogen receptor positive (MCF7) human epidermal growth factor receptor 2-overexpressed (MCF7/HER2), and endocrine-resistant breast cancer cells (MCF7/LCC2 and MCF7/LCC9). 1'-Acetoxychavicol acetate showed antiproliferation in a concentration- and time-dependent fashion and had higher potency in human epidermal growth factor receptor 2-overexpressed cell lines. This was associated with down-regulation of human epidermal growth factor receptor 2, pERK1/2, pAKT, estrogen receptor coactivator, cyclin D1, and MYC proto-oncogene while in vivo and significant reduction in the tumor mass of 1'-acetoxychavicol acetate-treated zebrafish-engrafted breast cancer groups. The anti-invasive effects of 1'-acetoxychavicol acetate were confirmed in vitro by the matrigel invasion assay and with down-regulation of C - X-C chemokine receptor type 4, urokinase plasminogen activator, vascular endothelial growth factor, and basic fibroblast growth factor 2 genes. The down-regulation of urokinase plasminogen activator and fibroblast growth factor 2 proteins was also validated by molecular docking analysis. Moreover, 1'-acetoxychavicol acetate-treated cells exhibited lower expression levels of the anti-apoptotic Bcl-2 and Mcl-1 proteins in addition to enhanced stress-activated kinases/c-Jun N-terminal kinase 1/2 and poly-ADP ribose polymerase cleavage, indicating apoptotic cell induction by 1'-acetoxychavicol acetate. Moreover, 1'-acetoxychavicol acetate had higher potency in human epidermal growth factor receptor 2-overexpressed cell lines regarding its inhibition on human epidermal growth factor receptor 2, pAKT, pERK1/2, PSer118, and PSer167-ERα proteins. Our findings suggest 1'-acetoxychavicol acetate mediates its anti-cancer effects via human epidermal growth factor receptor 2 signaling pathway.

A Novel Insecticidal Molecule Extracted from Alpinia galanga with Potential to Control the Pest Insect Spodoptera frugiperda.

Simple SummaryThe fall armyworm is an insect pest that feeds on many plants, including plants of agronomic importance, such as corn and rice. In addition, it has developed resistance to the main families of synthetic insecticides. There is, therefore, a need to find new, more environmentally friendly molecules to control this pest. We have extracted a molecule from greater galangal and tested its activity as an insecticide on the fall armyworm. This natural molecule causes larval growth inhibition and larval developmental abnormalities. To understand its action, a cell model with Sf9 cells was used. The molecule is much more toxic to insect cells than to human cells. It affects cell proliferation and induces cell death. This study demonstrates that a molecule extracted from an edible plant may have potential in the future development of botanical insecticides for the control of insect pests.Spodoptera frugiperda, a highly polyphagous insect pest from America, has recently invaded and widely spread throughout Africa and Asia. Effective and environmentally safe tools are needed for successful pest management of this invasive species. Natural molecules extracted from plants offer this possibility. Our study aimed to determine the insecticidal efficacy of a new molecule extracted from Alpinia galanga rhizome, the 1′S-1′-acetoxychavicol acetate (ACA). The toxicity of ACA was assessed by topical application on early third-instar larvae of S. frugiperda. Results showed that ACA caused significant larval growth inhibition and larval developmental abnormalities. In order to further explore the effects of this molecule, experiments have been performed at the cellular level using Sf9 model cells. ACA exhibited higher toxicity on Sf9 cells as compared to azadirachtin and was 38-fold less toxic on HepG2 cells. Inhibition of cell proliferation was observed at sublethal concentrations of ACA and was associated with cellular morphological changes and nuclear condensation. In addition, ACA induced caspase-3 activity. RT-qPCR experiments reveal that ACA induces the expression of several caspase genes. This first study on the effects of ACA on S. frugiperda larvae and cells provides evidence that ACA may have potential as a botanical insecticide for the control of S. frugiperda.