ABSTRACT
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks an actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure is often encountered due to inherent or acquired resistance to chemotherapy. Previous studies implicated PI3K/Akt/mTOR signaling pathway in cancer stem cells (CSCs) enrichment and hence chemoresistance. The present study aimed at investigating the potential effect of piperine (PIP), an amide alkaloid isolated from Piper nigrum, on enhancing the sensitivity of TNBC cells to doxorubicin (DOX) in vitro on MDA-MB-231 cell line and in vivo in an animal model of Ehrlich ascites carcinoma solid tumor. Results showed a synergistic interaction between DOX and PIP on MDA-MB-231 cells. In addition, the combination elicited enhanced suppression of PI3K/Akt/mTOR signaling that paralleled an upregulation in this pathway's negative regulator, PTEN, along with a curtailment in the levels of the CSCs surrogate marker, aldehyde dehydrogenase-1 (ALDH-1). Meanwhile, in vivo investigations demonstrated the potential of the combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities. Notably, the combination failed to change cleaved poly-ADP ribose polymerase levels suggesting a pro-necrotic rather than pro-apoptotic mechanism. Overall, these findings suggest a potential role of PIP in decreasing the resistance to DOX in vitro and in vivo, likely by interfering with the PI3K/Akt/mTOR pathway and CSCs.
Subject(s)
Alkaloids , Benzodioxoles , Doxorubicin , Neoplastic Stem Cells , Phosphatidylinositol 3-Kinases , Piperidines , Polyunsaturated Alkamides , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Triple Negative Breast Neoplasms , Doxorubicin/pharmacology , Polyunsaturated Alkamides/pharmacology , Piperidines/pharmacology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Humans , Alkaloids/pharmacology , Benzodioxoles/pharmacology , Animals , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/drug effects , Female , Cell Line, Tumor , TOR Serine-Threonine Kinases/metabolism , Drug Synergism , Mice , Drug Resistance, Neoplasm/drug effects , Apoptosis/drug effectsABSTRACT
Silybum marianum, known as milk thistle (MT), is traditionally used to manage liver diseases. This study aimed to investigate the role of MT extract topical application as a potential treatment for imiquimod (IMQ)-induced psoriatic lesions in mice with particular emphasis on phosphoinositol-3 Kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and Kelch-like ECH-associated protein 1 (KEAP1)/ nuclear factor erythroid-2-related factor (NRF2)/ nuclear factor-kappa B (NF-κB) molecular cascades involvement. To address this aim, forty male Swiss albino mice were subdivided into four groups (n = 10 mice/group): control, IMQ model, standard group where mice were treated topically with IMQ, then the anti-psoriatic mometasone cream, and MT extract-treated group where mice were treated topically with IMQ followed by MT extract. In most measured parameters, MT extract, rich in silymarin, exhibited potent anti-psoriatic activity comparable to the standard cortisone treatment. MT extract mitigated dorsal skin erythema, scaling, and epidermal thickening, reflected by lowering the Psoriasis Area Severity Index (PASI) score. Moreover, it alleviated IMQ-induced splenomegaly. Mechanistically, the PI3K/AKT/mTOR pathway was the main functional pathway behind such improvements, where it was significantly inhibited by MT extract application. This led to NRF2 activation via KEAP1 downregulation with subsequent anti-inflammatory effect proven by reducing NF-κB, interleukin (IL)-23, and IL-17A and antioxidant ability proven by boosting the antioxidant glutathione and heme oxygenase-1. Such improvements were confirmed by alleviating the histopathological alteration. Thus, MT extract could be a promising therapeutic agent for psoriasis treatment by inhibiting PI3K/AKT/mTOR cascade, along with NRF2 signaling activation.
Subject(s)
Kelch-Like ECH-Associated Protein 1 , NF-E2-Related Factor 2 , NF-kappa B , Oxidative Stress , Phosphatidylinositol 3-Kinases , Plant Extracts , Proto-Oncogene Proteins c-akt , Psoriasis , Signal Transduction , Silybum marianum , TOR Serine-Threonine Kinases , Animals , Male , NF-E2-Related Factor 2/metabolism , TOR Serine-Threonine Kinases/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Mice , Oxidative Stress/drug effects , NF-kappa B/metabolism , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Psoriasis/drug therapy , Psoriasis/immunology , Psoriasis/chemically induced , Plant Extracts/therapeutic use , Plant Extracts/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Silybum marianum/chemistry , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Humans , Imiquimod , Disease Models, Animal , Skin/drug effects , Skin/pathology , Skin/metabolismABSTRACT
BACKGROUND: Alzheimer's disease is a neurodegenerative age-related disease that primarily affects the elderly population leading to progressive memory impairments and neural deficits. It is counted as a major cause of geriatric dependency and disability. The pathogenesis of Alzheimer's disease incidence is complex and involves various hypotheses, including the cholinergic hypothesis, deposition of ß-amyloid plaques, neuroinflammation, oxidative stress, and apoptosis. Conventional treatments such as donepezil aim to delay the symptoms but do not affect the progression of the disease and may cause serious side effects like hepatoxicity. The use of natural candidates for Alzheimer's disease treatment has drawn the attention of many researchers as it offers a multitargeted approach. METHODS: This current study investigates the metabolic profiles of total defatted methanolic extract of Vitex pubescens bark and its polar fractions, viz. ethyl acetate and n-butanol, using ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry(UPLC-ESI-QTOF/MS/MS) technique as well as evaluate the antioxidant using free radical scavenging assays, viz. DPPH and ABTS assays and in-vitro acetylcholinesterase inhibitory activities using Ellman's microplate assay. RESULTS: Metabolic profiling revealed a total of 71, 43, and 55 metabolites tentatively identified in the defatted methanolic extract, ethyl acetate, and n-butanol fractions, respectively. Phenolic acids were the most abundant class, viz. benzoic acids, and acyl quinic acid derivatives followed by flavonoids exemplified mainly by luteolin-C-glycosides and apigenin-C-glycosides. Quantification of the total phenolic and flavonoid contents in the total defatted methanolic extract confirmed its enrichment with phenolics and flavonoids equivalent to 138.61 ± 9.39 µg gallic acid/mg extract and 119.63 ± 4.62 µg rutin/mg extract, respectively. Moreover, the total defatted methanolic extract exhibited promising antioxidant activity confirmed through DPPH and ABTS assays with a 50% inhibitory concentration (IC50) value equivalent to 52.79 ± 2.16 µg/mL and 10.02 ± µg/mL, respectively. The inhibitory activity of acetylcholine esterase (AchE) was assessed using in-vitro Ellman's colorimetric assay, the total defatted methanolic extract, ethyl acetate, and n-butanol fractions exhibited IC50 values of 52.9, 15.1 and 108.8 µg/mL that they proved the significant inhibition of AchE activity. CONCLUSION: The results obtained herein unraveled the potential use of the total methanolic extract of Vitex pubescens bark and its polar fractions as natural candidates for controlling Alzheimer's disease progression.
Subject(s)
Antioxidants , Cholinesterase Inhibitors , Plant Bark , Plant Extracts , Tandem Mass Spectrometry , Vitex , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antioxidants/pharmacology , Cholinesterase Inhibitors/pharmacology , Plant Bark/chemistry , Tandem Mass Spectrometry/methods , Vitex/chemistry , Chromatography, High Pressure Liquid , Spectrometry, Mass, Electrospray Ionization , HumansABSTRACT
BACKGROUND: Natural propolis has been used since decades owing to its broad-spectrum activities. Burn injuries are a global health problem with negative impacts on communities. Bacterial infections usually accompany burns, which demand implementation of antibiotics. Antibiotics abuse led to emergence of microbial drug resistance resulting in poor treatment outcomes. In such instances, the promising alternative would be natural antimicrobials such as propolis. OBJECTIVE: Full chemical profiling of propolis and evaluation of in vitro antibacterial, antioxidant and anti-inflammatory activities as well as in vivo burn healing properties. METHODS: Chemical profiling of propolis was performed using Liquid chromatography (UHPLC/MS-PDA and HPLC-PDA). In vitro assessment was done using Disc Diffusion susceptibility test against Staphylococcus aureus and infected burn wound mice model was used for in vivo assessment. In vitro antioxidant properties of propolis were assessed using DPPH, ABTS and FRAP techniques. The anti-inflammatory effect of propolis was assessed against lipopolysaccharide/interferon-gamma mediated inflammation. RESULTS: UHPLC/MS-PDA results revealed identification of 71 phytochemicals, mainly flavonoids. Upon flavonoids quantification (HPLC-PDA), Pinocembrin, chrysin and galangin recorded high content 21.58±0.84, 22.73±0.68 and 14.26±0.70 mg/g hydroalcoholic propolis extract, respectively. Propolis showed concentration dependent antibacterial activity in vitro and in vivo burn healing via wound diameter reduction and histopathological analysis without signs of skin irritation in rabbits nor sensitization in guinea pigs. Propolis showed promising antioxidant IC50 values 46.52±1.25 and 11.74±0.26 µg/mL whereas FRAP result was 445.29±29.9 µM TE/mg. Anti-inflammatory experiment results showed significant increase of Toll-like receptor 4 (TLR4), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels. Nitric oxide and iNOS were markedly increased in Griess assay and western blot respectively. However, upon testing propolis against LPS/IFN-γ-mediated inflammation, TLR4, IL-6 and TNF-α expression were downregulated at transcriptional and post-transcriptional levels. CONCLUSION: Propolis proved to be a promising natural burn healing agent through its antibacterial, antioxidant and anti-inflammatory activities.
Subject(s)
Anti-Bacterial Agents , Anti-Inflammatory Agents , Antioxidants , Burns , Propolis , Staphylococcus aureus , Wound Healing , Propolis/chemistry , Propolis/pharmacology , Animals , Burns/drug therapy , Burns/pathology , Antioxidants/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Bacterial Agents/pharmacology , Mice , Wound Healing/drug effects , Staphylococcus aureus/drug effects , Male , Phytochemicals/pharmacology , Phytochemicals/chemistry , Chromatography, High Pressure Liquid , Flavonoids/pharmacology , Microbial Sensitivity TestsABSTRACT
Mikania micrantha is utilized as a therapeutic for the treatment of various human ailments including insect bites, rashes and itches of skin, chicken pox, healing of sores and wounds, colds and fever, nausea, jaundice, rheumatism, and respiratory ailments. This study aimed at summarizing the traditional uses, phytochemical profile, and biological activities of M. micrantha based on obtainable information screened from different databases. An up-to-date search was performed on M. micrantha in PubMed, Science Direct, clinicaltrials.gov, and Google Scholar databases with specific keywords. No language restrictions were imposed. Published articles, theses, seminar/conference papers, abstracts, and books on ethnobotany, phytochemistry and pharmacological evidence were considered. Based on the inclusion criteria, this study includes 53 published records from the above-mentioned databases. The results suggest that fresh leaves and whole plant are frequently used in folk medicine. The plant contains more than 150 different phytochemicals under the following groups: essential oils, phenolics and flavonoids, terpenes, terpene lactones, glycosides, and sulfated flavonoids. It contains carbohydrates and micronutrients including vitamins and major and trace minerals. M. micrantha possesses antioxidant, anti-inflammatory, anti-microbial, anti-dermatophytic, anti-protozoal, anthelmintic, cytotoxic, anxiolytic, anti-diabetic, lipid-lowering and antidiabetic, spasmolytic, memory-enhancing, wound-healing, anti-aging, and thrombolytic activities. No clinical studies have been reported to date. M. micrantha might be one of the potential sources of phytotherapeutic compounds against diverse ailments in humans. Studies are required to confirm its safety profile in experimental animals prior to initiating clinical trials. Moreover, adequate investigation is also crucial to clarify exact mechanism of action for each biological effect.
Subject(s)
Mikania , Plants, Medicinal , Animals , Humans , Phytotherapy , Ethnopharmacology , Ethnobotany , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Flavonoids , Plant Extracts/chemistryABSTRACT
Obesity is one of the major metabolic syndrome risk factors upon which altered metabolic pathways follow. This study aimed to discern altered metabolic pathways associated with obesity and to pinpoint metabolite biomarkers in serum of obese rats fed on high fructose diet using metabolomics. Further, the effect of standardized green versus black caffeinated aqueous extracts (tea and coffee) in controlling obesity and its comorbidities through monitoring relevant serum biomarkers viz. Leptin, adiponectin, spexin, malondialdehyde, total antioxidant capacity. Liver tissue oxidative stress (catalase, super oxide dismutase and glutathione) and inflammation (IL-1ß and IL-6) markers were assessed for green coffee and its mixture with green tea. Results revealed improvement of all parameters upon treatments with more prominence for those treated with green caffeinated extract (coffee and tea) especially in mixture. Upon comparing with obese rat group, the green mixture of coffee and tea exhibited anti-hyperlipidemic action through lowering serum triglycerides by 35.0% and elevating high density lipoprotein by 71.0%. Black tea was likewise effective in lowering serum cholesterol and low density lipoprotein by 28.0 and 50.6%, respectively. GC-MS- based metabolomics of rat serum led to the identification of 34 metabolites with obese rat serum enriched in fatty acids (oleamide).
Subject(s)
Antioxidants , Coffee , Rats , Male , Animals , Antioxidants/pharmacology , Plant Extracts/pharmacology , Obesity/metabolism , Tea/adverse effects , Anti-Inflammatory Agents/therapeutic use , Metabolomics , BiomarkersABSTRACT
Urginea maritima L. (squill) species is widely spread at the Mediterranean region as two main varieties, i.e., white squill (WS) and red squill (RS), that are recognized for several health potentials. The major secondary metabolite classes of the squill are cardiac glycosides, mainly, bufadienolides, flavonoids, and anthocyanins. Herein, a multiplex MS and NMR metabolomics approach targeting secondary and aroma compounds in WS and RS was employed for varieties classification. Solid-phase micro extraction-gas chromatography/mass spectroscopy (SPME-GC/MS), ultra-high-performance liquid chromatography/mass spectrometry (UPLC/MS), as well as nuclear magnetic resonance (NMR) provided fingerprinting and structural confirmation of the major metabolites for both types of the squill. For comparison of the different platforms' classification potential, multivariate data analysis was employed. While Bufadienolides, viz. "hydroxy-scilliglaucosidin-O-rhamnoside, desacetylscillirosidin-O-rhamnoside and bufotalidin-O-hexoside" as well as oxylipids, were enriched in WS, flavonoids, i.e., dihydro-kaempferol-O-hexoside and its aglycon, taxifolin derivative, were predominant in RS. A cytotoxicity screening against three cancer cell lines, including breast adenocarcinoma (MCF-7), lung (A-549), and ovarian (SKOV-3) cell lines was conducted. Results revealed that WS was more effective on A-549 and SKOV-3 cell lines (WS IC50 0.11 and 0.4 µg/mL, respectively) owing to its abundance of bufadienolides, while RS recorded IC50 (MCF7 cell line) 0.17 µg/mL since is is rich inflavonoids.
ABSTRACT
Tuberculosis is a highly infectious ailment worldwide. The emergence of multi-drug resistance and serious adverse effects of anti-TB drugs have led to the continuous search of natural candidates. This study aimed to analyse the chemical profile of Vitex pinnata (VP) bark lipophilic extract using GC-MS also evaluating its anti-TB and cytotoxic activities. GC-MS revealed a total of 81 compounds which representing 86% identified compounds. In vitro anti-TB of VP lipophilic extract was evaluated using the Microplate Alamar Blue Assay which exhibited MIC value of 62.5 µg/mL. In vitro cytotoxicity was evaluated using Water Soluble formazan assay recording IC50 > 100 and 200 µg/mL using Vero and A-549 cell lines, respectively. In silico docking study was performed on the major identified compounds, n-nonane showed the most favourable binding affinity (ΔG) equals to -33.34 Kcal/mol. The results obtained herein unravelled the potential use of VP n-hexane extract as a natural anti-TB.
ABSTRACT
The purpose of this study was to demonstrate the antimicrobial effects of natural essential oils (EO) and determine their preservative action. Eight natural essential oils were tested against Staphylococcus aureus, Escherichia coli, and Candida albicans representing gram positive, gram negative, and fungi, respectively. The plant materials were used in this study viz. Thymus vulgaris-thyme (TV), Mentha virdis (MV), Mentha longifolia (ML), Rosmarinus officinalis-rosemary (RO), Lavandula dentata-lavender (LD), Origanum majorana-oregano (OM), which belong to the Lamiaceae family. The other two plants were Cymbopogon citratus-lemon grass (family Poaceae) (CC), and Eucalyptus globulus (family Myrtaceae) (EG). Employing the disc diffusion susceptibility test, minimum inhibitory and minimum bactericidal concentrations were estimated for each oil, followed by the addition of oils to pasteurized apple juice after microbial induction. The results revealed that thyme oil showed the maximum zone of inhibition against all tested microbes enriched with monoterpenes class viz. eucalyptol (24.3%), thymol (17.4%), and γ-terpinene (15.2%). All other tested oils exhibited a concentration-dependent inhibition of growth and their MIC ranged from 0.1 to 100 µL/mL. The recorded minimum bactericidal concentration values were apparently double the minimum inhibitory concentration. The EO of Mentha virdis followed by Mentha longifolia showed maximum antimicrobial activity against the tested organisms in pasteurized apple juice. A gas chromatography-mass spectroscopy (GC-MS) analysis of lemon grass, thyme, and Mentha virdis essential oils showed their enrichment with monoterpenes class recording 97.10, 97.04, and 97.61%, respectively.
ABSTRACT
The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.
Subject(s)
Alkaloids , Chemical and Drug Induced Liver Injury , Piper , Silymarin , Rats , Animals , Acetaminophen/toxicity , Rats, Sprague-Dawley , Cytochrome P-450 CYP2E1 , Gas Chromatography-Mass Spectrometry , Chemical and Drug Induced Liver Injury/pathology , Methanol/pharmacology , Plant Bark , Plant Extracts/therapeutic use , Liver , Alkaloids/pharmacology , Silymarin/pharmacology , Bilirubin , Lipids/pharmacology , Fatty Acids , Serum Albumin , Esters/pharmacologyABSTRACT
Diospyros species (DS), "Ebenaceae," were known for their therapeutic uses in folk medicine since days of yore. Thereafter, scientific evidence related their health benefits to a myriad of chemical classes, for instance, naphthoquinones, flavonoids, tannins, coumarins, norbergenin derivatives, sterols, secoiridoids, sesquiterpenes, diterpenoids, triterpenoids, volatile organic compounds (VOCs), and carotenoids. The available literature showed that more than 200 compounds were isolated and identified via spectroscopic techniques. Many pharmacological activities of DS have been previously described, such as antioxidant, neuroprotective, antibacterial, antiviral, antiprotozoal, antifungal, antiinflammatory, analgesic, antipyretic and cosmeceutical, investigated, and confirmed through versatile in vitro and in vivo assays. Previous studies proved that genus Diospyros is a rich reservoir of valuable bioactive compounds. However, further comparative studies among its different species are recommended for more precise natural source-based drug discovery and clinical application. Accordingly, this review is to recall the chemical abundance and diversity among different members of genus Diospyros and their ethnopharmacological and pharmacological uses. PRACTICAL APPLICATIONS: Practically, providing sufficient background on both secondary metabolites divergence and pharmacological properties of genus Diospyros has many fruitful aspects. As demonstrated below, extracts and many isolated compounds have significant curative properties, which can lead to the discovery of pharmaceutically relevant alternative substitutes to conventional medicine. Consequently, molecular docking on various receptors can be applied. On the grounds, Naoxinqing tablets, a standardized herbal product containing D. kaki leaves extract, have been patented and recorded in Chinese Pharmacopeia as an approved Traditional Chinese Medicine (TCM) for the treatment of cerebro- and cardiovascular diseases, although the underlying mechanism remains under advisement. Moreover, the antimicrobial applications of DS are of considerable concern; since the widespread use of antibiotics resulted in different forms of bacterial resistance, hence, limiting and compromising effective treatment. In addition, as a result of contemporary rampant memory disorders, neuroprotective activities of different extracts of DS became of great emphasis.
Subject(s)
Diospyros , Phytotherapy , Molecular Docking Simulation , Phytochemicals/chemistry , Plant Extracts/chemistryABSTRACT
Acylated flavonoids are widely distributed natural metabolites in medicinal plants and foods with several health attributes. A large diversity of chemical structures of acylated flavonoids with interesting biological effects was reported from several plant species. Of these, 123 compounds with potential antimicrobial, antiparasitic, anti-inflammatory, anti-nociceptive, analgesic, and anti-complementary effects were selected from several databases including SCI-Finder, Scopus, Google Scholar, Science Direct, PubMed, and others. Some selected reported biologically active flavonoids were docked in the active binding sites of some natural enzymes, namely acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, aldose reductase, and HIV integrase, in an attempt to underline the key interactions that might be responsible for their biological activities.
Subject(s)
Butyrylcholinesterase , Flavonoids , Acetylcholinesterase , Flavonoids/chemistry , Flavonoids/pharmacology , Molecular Docking Simulation , Plant Extracts/chemistry , alpha-Glucosidases/metabolismABSTRACT
GC-MS profiling and metabolomics study of anise and star anise oils obtained by hydrodistillation, n-hexane, and microwave-assisted extraction methods were conducted herein. Trans-anethole was the major phenylpropanoid in both oils. Principal component and hierarchical cluster analyses revealed a clear separation of different extraction methods. Microwave-assisted star anise oil (MSA) revealed the highest anethole content (93.78%). MSA oil showed antioxidant activity using DPPH and ABTS assays, this was verified via an in-silico docking study of its major compounds on human tyrosinase and NAD(P)H oxidase. Trans-anethole displayed the best fitting scores (-8.9 and -10.1 Kcal/mole, respectively). MSA oil showed promising cytotoxic activity on different cell lines, mainly the cervical (HeLa) cell lines. Cell cycle inhibition at the G0-G1 phase was observed with an early apoptotic effect of the oil on HeLa cells. Trans-anethole achieved the best docking scores (-7.9, -9.3 and -9.9 Kcal/mole) for in-silico study on EGFR, CDK2 and CDK4 enzymes engaged in cancer, respectively.
Subject(s)
Antioxidants , Oils, Volatile , Allylbenzene Derivatives , Anisoles , Antioxidants/pharmacology , Gas Chromatography-Mass Spectrometry , HeLa Cells , Humans , Oils, Volatile/chemistryABSTRACT
This study aims to identify the major phytochemical constituents in Aquilaria malaccensis (Thymelaeaceae) ethanolic leaf extract (ALEX-M) and elucidate their ability to suppress nitric oxide (NO) production from a murine macrophage-like cell line (RAW 264.7) stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Dichloromethane (DCM) and ethyl acetate (EtOAc) fractions of ALEX-M were subjected to column chromatography. Eight known compounds were isolated for the first time from this species. Compounds were identified using spectroscopic techniques (IR, UV, HRESIMS, and 1D and 2D NMR). Anti-inflammatory activity of both extract and isolated compounds were investigated in vitro. The fractions offered the isolation of epifriedelanol (1), 5-hydroxy-7,4'-dimethoxyflavone (2), luteolin-7,3',4'-trimethyl ether (3), luteolin-7,4'-dimethyl ether (4), acacetin (5), aquilarinenside E (6), iriflophenone-2-O-α-l-rhamnopyranoside (7), and iriflophenone-3-C-ß-glucoside (8). The findings suggest the pharmacological potential of the crude extract (ALEX-M) and its isolates as natural anti-inflammatory agents, capable of suppressing NO production in RAW 264.7 cells stimulated by LPS/IFN-γ.
ABSTRACT
PURPOSE: To design and optimize trans-cinnamic acid-loaded PLGA nanoparticles (CIN-PLGA-NPs) and assess its inhibitory effect on epithelial-mesenchymal transition (EMT) in triple-negative breast cancer. METHODS: The quality by design approach was used to correlate the formulation parameters (PLGA amount and Poloxamer188 concentration) and critical quality attributes (entrapment efficiency percent, particle size and zeta potential). Design of CIN-PLGA-NPs formulations was done based on central composite response surface design and formulated by nanoprecipitation method. In addition, the optimized CIN-PLGA-NPs formulation was further evaluated for morphology using transmission electron microscopy and in vitro dissolution test. The cytotoxicity of CIN-PLGA-NPs optimized formula in comparison to the free trans-cinnamic acid (CIN-Free) was investigated in vitro using MDA-MB-231, triple-negative breast cancer cells, followed by scratch wound assay for evaluating the impact on the migratory potential of MDA-MB-231 cells. In vivo antitumor activity was evaluated using Ehrlich ascites carcinoma solid tumor animal model where tumor volumes were measured at different time points and necrotic/apoptotic indices were estimated in tumor sections. EMT markers, E- and N-cadherin, were assessed in solid tumors as well. RESULTS: The optimized formulation showed entrapment efficiency of 76.98%, particle size of 186.3 nm with a smooth spherical surface and zeta potential of -28.47 mV indicating its stability. Furthermore, CIN-PLGA-NPs optimized formula released 60.8±1.89% of the total CIN-Free within 24 hours compared to 29±1.25% of the raw CIN-Free indicating improved dissolution rate. The optimized formula showed superior cytotoxicity on MDA-MB-231 cells compared to its free counterpart as well as increased wound closure percentage along with reduced tumor size in mice and increased necrotic and apoptotic indices. Tumor levels of E-cadherin and N-cadherin were indicative of EMT inhibition. CONCLUSION: Our findings proved the capability of PLGA nanoparticles in loading trans-cinnamic acid in addition to enhancing its antitumor efficacy in triple-negative breast cancer possibly via inhibiting EMT.
Subject(s)
Breast Neoplasms , Nanoparticles , Animals , Breast Neoplasms/drug therapy , Cinnamates , Drug Carriers , Epithelial-Mesenchymal Transition , Female , Humans , Mice , Particle SizeABSTRACT
Medicinal plant extracts are increasingly considered a major source of innovative medications and healthcare products. This study focused on preparing a polyphenol enriched water extract of Egyptian celery "Apium graveolens L., Apiaceae" aerial parts (TAE) in an endeavor to accentuate its antioxidant capacity as well as its antimicrobial activity. (TAE) of celery was partitioned against different organic solvents to yield dichloromethane (DCM), ethyl acetate (EAC), and butanol (BUOH) fractions. (TAE) and the organic fractions thereof besides the remaining mother liquor (ML) were all screened for their antioxidant capacity using various protocols viz. monitoring the reducing amplitudes for ferric ions (FRAP), and radical scavenging potentials of oxygen (ORAC), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and metal chelation assays. The examination procedure revealed both (TAE) extract and (DCM) fraction, to pertain the highest antioxidant potentials, where the IC50 of the (TAE) using ABTS and metal chelation assays were ca. 34.52 ± 3.25 and 246.6 ± 5.78 µg/mL, respectively. The (DCM) fraction recorded effective results using the FRAP, ORAC, and DPPH assays ca. 233.47 ± 15.14 and 1076 ± 25.73 µM Trolox equivalents/mg sample and an IC50 474.4 ± 19.8 µg/mL, respectively. Additionally, both (TAE) and (DCM) fraction exerted antimicrobial activities recording inhibition zones (mm) (13.4 ± 1.5) and (12.0 ± 1.0) against Staphylococcus aureus and (11.0 ± 1.2) and (10.0 ± 1.3) against Escherichia coli, respectively, with no anti-fungal activity. Minimum inhibitory concentration (MIC) of (TAE) and (DCM) fraction were 1250 and 2500 µg/mL, respectively. UPLC/ESI/TOF-MS unveiled the chemical profile of both (TAE) and (DCM) fraction to encompass a myriad of active polyphenolic constituents including phenylpropanoids, coumarins, apigenin, luteolin, and chrysoeriol conjugates.
Subject(s)
Apium/metabolism , Plant Components, Aerial/chemistry , Plant Extracts/pharmacology , Antioxidants/pharmacology , Apiaceae , Apium/enzymology , Apium/physiology , Chromatography, High Pressure Liquid/methods , Egypt , Flavonoids/analysis , Microbial Sensitivity Tests , Phenols/analysis , Picrates/chemistry , Plants, Medicinal/drug effects , Polyphenols/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Sulfonic Acids/analysisABSTRACT
Benincasa hispida (Thunb.) Cogn. (Cucurbitaceae) is an annual climbing plant, native to Asia with multiple therapeutic uses in traditional medicine. This updated review is aimed at discussing the ethnopharmacological, phytochemical, pharmacological properties, and molecular mechanisms highlighted in preclinical experimental studies and toxicological safety to evaluate the therapeutic potential of this genus. The literature from PubMed, Google Scholar, Elsevier, Springer, Science Direct, and database was analyzed using the basic keyword "Benincasa hispida." Other searching strategies, including online resources, books, and journals, were used. The taxonomy of the plant has been made by consulting "The Plant List". The results showed that B. hispida has been used in traditional medicine to treat neurological diseases, kidney disease, fever, and cough accompanied by thick mucus and to fight intestinal worms. The main bioactive compounds contained in Benincasa hispida have cytotoxic, anti-inflammatory, and anticancer properties. Further safety and efficacy investigations are needed to confirm these beneficial therapeutic effects and also future human clinical studies.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Cucurbitaceae/chemistry , Dietary Supplements/analysis , Medicine, Traditional/methods , Phytochemicals/pharmacology , Animals , HumansABSTRACT
Background: Essential oils represent a major class of natural products which are known for their antimicrobial activity. This study aimed to determine the composition of four Piper essential oils by gas chromatography mass spectrometry, attenuated total reflection infrared, and chemometric analysis. Results: Monoterpene was the most predominant class in Piper nigrum and white pepper (87.6 and 80%, respectively) with the dominance of α-pinene, ß-pinene, 3-carene, limonene, and ß-caryophyllene. Sesquiterpenes represented 50, 19.6, and 12.3% of the essential oils of Piper longum, white pepper, and P. nigrum, respectively. Unlike other species, Piper cubeba oil was found to be rich in aromatics (59%), with eugenol (10.7%) and methyl eugenol (47.4%) representing the major components along with ß-myrcene (21.2%) and 1,8-cineole (6.4%). Only P. longum essential oil comprised about 18.2% of alkanes and 13.6% of alkenes. Application of chemometric analysis utilizing GC/MS and ATR-IR data displayed the same segregation pattern where both principal component analysis and hierarchal cluster analysis revealed that white pepper was most closely related to P. nigrum while being completely discriminated from other Piper species. The Piper oils showed promising inhibitory effects on Helicobacter pylori. P. longum oil recorded the most efficient anti-Helicobacter activity [minimum inhibitory concentration (MIC) value of 1.95 µg/ml, which is the same as the MIC of clarithromycin], followed by the oil of white pepper (MIC = 3.90 µg/ml), while P. cubeba and P. nigrum produced the lowest activity (MIC value of 7.81 µg/ml). Conclusion: Piper essential oils can be used as nutritional supplements or therapeutic drugs to protect against H. pylori infection.
ABSTRACT
Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.
Subject(s)
Aromatase Inhibitors/pharmacology , Breast Neoplasms/pathology , Citrus/chemistry , Estrogen Receptor Modulators/pharmacology , Plant Extracts/pharmacology , Animals , Aromatase/metabolism , Breast Neoplasms/enzymology , Female , Humans , Mice , Xenograft Model Antitumor AssaysABSTRACT
Several corona viral infections have created serious threats in the last couple of decades claiming the death of thousands of human beings. Recently, corona viral epidemic raised the issue of developing effective antiviral agents at the earliest to prevent further losses. Natural products have always played a crucial role in drug development process against various diseases, which resulted in screening of such agents to combat emergent mutants of corona virus. This review focuses on those natural compounds that showed promising results against corona viruses. Although inhibition of viral replication is often considered as a general mechanism for antiviral activity of most of the natural products, studies have shown that some natural products can interact with key viral proteins that are associated with virulence. In this context, some of the natural products have antiviral activity in the nanomolar concentration (e.g., lycorine, homoharringtonine, silvestrol, ouabain, tylophorine, and 7-methoxycryptopleurine) and could be leads for further drug development on their own or as a template for drug design. In addition, a good number of natural products with anti-corona virus activity are the major constituents of some common dietary supplements, which can be exploited to improve the immunity of the general population in certain epidemics.