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1.
Life (Basel) ; 14(4)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38672810

ABSTRACT

The authors were not aware of errors made in one small subsection (Section 6.17. Antidiarrheal Effect, including the data in the table of effects) of this paper [...].

2.
J Cancer ; 15(3): 577-589, 2024.
Article in English | MEDLINE | ID: mdl-38213720

ABSTRACT

Cancer is rapidly becoming the leading cause of death globally. This study aimed to identify edible foods with cytotoxic and/or antioxidant activities that can prevent cancer when consumed in a regular diet. Sixty-eight edible foods were purchased from the local market, and the materials were extracted with 80% methanol. The cytotoxic activity of the extracts was evaluated using MTT on HeLa, H2228, HEK293, and H3122 cell lines. To study apoptosis, triple fluorescence labeling with DAPI, Annexin V, and propidium iodide was used. The phenolic content, antioxidant capacity, and free radical scavenging capabilities were studied using conventional spectrophotometric techniques. Among the edible foods, carrot, pointed gourd, wax gourd, ficus, apple, lemon, cumin seed, and white peppercorn showed moderate cytotoxicity in HeLa cells. The growth of HeLa cells was significantly inhibited dose-dependently by tomato, banana, Indian spinach, guava, lemon peel, and coriander (IC50, 24.54, 17.89, 13.18, 9.33, 1.23, and 2.96 µg/mL, respectively). Tomato, Indian spinach, lemon peel, and coriander exerted significant dose-dependent inhibition of H2228, HEK293, and H3122 cell proliferation. The tomato, Indian spinach, lemon peel, and coriander extracts induced HeLa cell apoptosis. White peppercorn, amaranth, apple, wax gourd, cumin seed, taro, and lemon peel contained significant amounts of polyphenols and showed high antioxidant activity. White peppercorn, apple, coriander, lemon peel, and ficus significantly scavenged DPPH free radicals (IC50 values of 10.23, 12.02, 13.49, 13.8, and 14.0 µg/mL, respectively). The overall results suggest that the daily intake of these antioxidant-rich cytotoxic foods can prevent or reduce the risk of cancer.

3.
Heliyon ; 10(1): e23400, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38170014

ABSTRACT

Natural products have been important parts of traditional medicine since ancient times, with various promising health effects. Leea aequata (L. aequata), a natural product, has been widely used for treating several diseases due to its promising pharmacological activities. Therefore, the present study aimed to explore the phytochemical profiling and molecular docking of the antioxidant-rich part of L. aequata leaves and its antiproliferative activity. L. aequata leaves were extracted with methanol, followed by fractionation with the respective solvents to obtain the petroleum ether, chloroform, ethyl acetate, and aqueous fractions. The antioxidant activity was evaluated by spectrophotometric methods. The cytotoxic and antiproliferative activities were detected using MTT colorimetric and confocal microscopy methods, respectively. Phytochemical compositions were analyzed using gas chromatography‒mass spectrometry analysis. Computer aided (molecular docking SwissADME, AdmetSAR and pass prediction) analyses were undertaken to sort out the best-fit phytochemicals present in the plant responsible for antioxidant and anticancer effects. Among the fractions, the ethyl acetate fraction was the most abundant polyphenol-rich fraction and showed the highest antioxidant, reducing power, and free radical scavenging activities. Compared to untreated MCF-7 cells, ethyl acetate fraction-treated MCF-7 cells showed an increase in apoptotic characteristics, such as membrane blebbing, chromatin condensation, and nuclear fragmentation, causing apoptosis and decreased proliferation of HeLa and MCF-7 cells. Furthermore, gas chromatography mass spectrometry data revealed that the ethyl acetate fraction contained 16 compounds, including methyl esters of long-chain fatty acids, which are the major chemical constituents. Moreover, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to have antioxidant and cytotoxic activity, as confirmed by computer-aided models. A strong correlation was observed between the antioxidant and polyphenolic contents and the anticancer activity. In conclusion, we explored the possibility that L. aequata could be a promising source of antioxidants and anticancer agents with a high phytochemical profile.

4.
Int J Cardiol Heart Vasc ; 49: 101303, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38076346

ABSTRACT

Background: Spontaneous coronary artery dissection (SCAD) is a relatively rare condition affecting predominantly young adults, with a prevalence of female sex. The best management of SCAD is still unclear and not adequately evidence-based both in the acute phase but especially over the long-term. We therefore aimed to evaluate the impact of medical therapy usually adopted for coronary artery disease on long-term outcome in SCAD patients. Methods: We performed a meta-regression analysis including all the studies evaluating the long-term outcome of patients affected by SCAD. We used long-term mortality, recurrent SCAD, admission for angina and major adverse cardio-vascular events (MACE) as dependent variables and the rates of discharge drug rates (beta-blockers, statins, renin-angiotensin-aldosterone system inhibitors, aspirin, dual antiplatelet therapy (DAPT)) as independent variables. Results: Fourteen observational studies were included with a long-term follow-up of 3.5 ± 1.7 years. No statistically significant correlations between drug therapy (beta-blockers, statins, calcium channel blockers, nitrates, renin-angiotensin-aldosterone inhibitors) and mortality, MACE, admission for angina, and SCAD recurrence were found. Higher aspirin use rates were significantly correlated with lower admission rates for angina (p < 0.05); DAPT, however, showed a borderline correlation with higher rates of SCAD recurrence (p = 0.068). Conclusions: In a meta-regression analysis including observational studies aspirin use rates correlated with lower long-term rates of admission for angina, while a borderline correlation between DAPT and rates of SCAD recurrence was found. Other drugs usually used for the treatment of coronary artery disease do not seem to impact long-term outcome of SCAD patients.

5.
Biomed Pharmacother ; 168: 115788, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37913731

ABSTRACT

Parkinson's Disease (PD), a neurodegenerative disorder, is characterized by the degeneration of progressive dopaminergic (DA) neurons in the substantia nigra region of the human midbrain. Although just what causes PD remains a mystery, it is known that oxidative stress (OS) as well as mitochondrial dysfunction, neuro-inflammation, and insufficient neurotrophic support play a role in the disease's pathophysiology. Phytochemicals are a diverse small molecule group derived from plants that can be classified into numerous classes on the basis of their biological activities and chemical structure. Of these groups of phytochemicals, the most abundant, which has well-established anti-Parkinson's effects, are polyphenols. Flavonoids, including naringin and naringenin, genistein, kaempferol, anthocyanins, epigallocatechin-3-gallate, and baicalein are plant-based biologically active polyphenols, which have been shown to exhibit therapeutic potential when used as treatment for a variety of pathological illnesses, such as neurodegenerative diseases (NDs) and PD. Recently, it was reported that flavonoids have beneficial effects on PD, such as the protection of DA neurons, improvement of motor and cognitive abilities, regulation of signaling pathways, and modulation of OS and neuro-inflammation. In addition, by changing the composition of bacteria in gut microbiota, flavonoids reduce pathogenic strains and promote the growth of beneficial strains. In this context, the current paper will provide a literature review on the neurological roles that flavonoids play, as one of the most abundant phytochemical families, in PD.


Subject(s)
Gastrointestinal Microbiome , Parkinson Disease , Humans , Flavonoids/pharmacology , Flavonoids/therapeutic use , Flavonoids/metabolism , Parkinson Disease/metabolism , Anthocyanins/pharmacology , Polyphenols/pharmacology , Polyphenols/therapeutic use , Polyphenols/metabolism , Inflammation/metabolism , Dopaminergic Neurons
6.
Cell Death Dis ; 14(8): 544, 2023 08 23.
Article in English | MEDLINE | ID: mdl-37612317

ABSTRACT

Statins are the most prescribed lipid-lowering agents worldwide. Their use is generally safe, although muscular toxicity occurs in about 1 in 10.000 patients. In this study, we explored the role of the endocannabinoid system (ECS) during muscle toxicity induced by simvastatin. In murine C2C12 myoblasts exposed to simvastatin, levels of the endocannabinoids AEA and 2-AG as well the expression of specific miRNAs (in particular miR-152) targeting the endocannabinoid CB1 gene were increased in a time-dependent manner. Rimonabant, a selective CB1 antagonist, exacerbated simvastatin-induced toxicity in myoblasts, while only a weak opposite effect was observed with ACEA and GAT211, selective orthosteric and allosteric agonists of CB1 receptor, respectively. In antagomiR152-transfected myoblasts, simvastatin toxicity was in part prevented together with the functional rescue of CB1. Further analyses revealed that simvastatin in C2C12 cells also suppresses PKC and ERK signaling pathways, which are instead activated downstream of CB1 receptor stimulation, thus adding more insight into the mechanism causing CB1 functional inactivation. Importantly, simvastatin induced similar alterations in skeletal muscles of C57BL/6 J mice and primary human myoblasts. In sum, we identified the dysregulated expression of the endocannabinoid CB1 receptor as well as the impairment of its downstream signaling pathways as a novel pathological mechanism involved in statin-induced myopathy.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , MicroRNAs , Humans , Animals , Mice , Mice, Inbred C57BL , Simvastatin/pharmacology , Endocannabinoids , Receptor, Cannabinoid, CB1/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Muscle, Skeletal
7.
Int J Mol Sci ; 24(13)2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37446131

ABSTRACT

Astragalus membranaceus (Fisch.) Bunge root is used as herbal medicine for its immunomodulating activities in Chinese medicine. Recently, beneficial properties of A. membranaceus on allergic diseases have been proposed. Here we investigated the role of a commercial extract of A. membranaceus, standardized to 16% polysaccharides, in regulating the immune-inflammatory response in vitro and in vivo and its therapeutic application in asthma. A. membranaceus extract inhibited prostaglandin E2 and leukotriene C4 production in stimulated J774 and peritoneal macrophages, respectively. The extract also reduced interlukin-1ß, tumor necrosis factor-α, and nitrite production, affecting inducible nitric oxide synthase expression. In vivo experiments confirmed the anti-inflammatory properties of A. membranaceus, as evident by a reduction in zymosan-induced peritoneal cellular infiltration and pro-inflammatory mediator production. The efficacy of A. membranaceus extract in modulating the immune response was confirmed in a model of allergic airway inflammation. Extracts improve lung function by inhibiting airway hyperresponsiveness, airway remodeling, and fibrosis. Its anti-asthmatic effects were further sustained by inhibition of the sensitization process, as indicated by a reduction of ovalbumin-induced IgE levels and the mounting of a Th2 immune response. In conclusion, our data demonstrate the anti-inflammatory properties of the commercial extract of A. membranaceus and its beneficial effects on asthma feature development.


Subject(s)
Anti-Asthmatic Agents , Asthma , Animals , Mice , Astragalus propinquus , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Asthma/chemically induced , Asthma/drug therapy , Asthma/prevention & control , Anti-Asthmatic Agents/pharmacology , Anti-Asthmatic Agents/therapeutic use , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Immunoglobulin E , Ovalbumin/toxicity , Mice, Inbred BALB C
8.
Fitoterapia ; 169: 105624, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37500017

ABSTRACT

Cordia oncocalyx Allemão is an endemic economically underexploited plant from Brazilian semi-arid region. Herein, we carried out a well-defined bibliographic review about the pharmacological activities of oncocalyxones from C. oncocalyx and mechanisms responsible for the biomedical properties. MeSH terms were used in the scientific databases for a narrative exploration. Technological development and bioproducts were also examined. Cordia oncocalyx is a deciduous tree of sexual reproduction rich in terpenoid quinones. Among them, oncocalyxone A, a 1,4-benzoquinone, the main compound from heartwood ethanol extracts, revealed anti-inflammatory and anti-edematogenic actions induced by carrageenan and dextran and antinociceptive potential in mice provoked by acetic acid and formalin. Oncocalyxone A inhibits platelet aggregation via activation of the soluble guanylate cyclase enzyme and blocks glycation processes. In addition to the antimicrobial effects against protozoa, fungi and bacteria and relaxation of smooth muscles, oncocalyxone A reduces mean blood pressure and glycemia in diabetic rats, decreases glomerular filtration parameters and tubular transport of electrolytes, and presents in vitro antimitotic and cytotoxic action upon different types of cancers, including resistant lung carcinoma lines. It has low oral acute toxicity (LD50 > 2000 mg/kg) and activates cellular apoptosis through the production of free radicals and interactions with DNA. However, no patents were found, which also emphasizes that Brazil, as the cradle of the main articles on C. oncocalyx, is wasting time and money. Moreover, slight systemic deleterious effects in mammals stimulate the use of oncocalyxone A and related compounds as lead constituents of safer drugs against chronic diseases.


Subject(s)
Cordia , Diabetes Mellitus, Experimental , Rats , Mice , Animals , Cordia/chemistry , Molecular Structure , Plant Extracts/pharmacology , Plant Extracts/chemistry , Chronic Disease , Mammals
9.
Phytother Res ; 37(10): 4375-4397, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37434291

ABSTRACT

Cancer is the most common cause of death worldwide, following cardiovascular diseases. Cancer is a multifactorial disease and many reasons such as physical, chemical, biological, and lifestyle-related factors. Nutrition, which is one of the various factors that play a role in the prevention, development, and treatment of many types of cancer, affects the immune system, which is characterized by disproportionate pro-inflammatory signaling in cancer. Studies investigating the molecular mechanisms of this effect have shown that foods rich in bioactive compounds, such as green tea, olive oil, turmeric, and soybean play a significant role in positively changing the expression of miRNAs involved in the regulation of genes associated with oncogenic/tumor-suppressing pathways. In addition to these foods, some diet models may change the expression of specific cancer-related miRNAs in different ways. While Mediterranean diet has been associated with anticancer effects, a high-fat diet, and a methyl-restricted diet are considered to have negative effects. This review aims to discuss the effects of specific foods called "immune foods," diet models, and bioactive components on cancer by changing the expression of miRNAs in the prevention and treatment of cancer.

10.
Toxins (Basel) ; 15(6)2023 05 24.
Article in English | MEDLINE | ID: mdl-37368657

ABSTRACT

Plants evolve to synthesize various natural metabolites to protect themselves against threats, such as insects, predators, microorganisms, and environmental conditions (such as temperature, pH, humidity, salt, and drought). Plant-derived toxic proteins are often secondary metabolites generated by plants. These proteins, including ribosome-inactivating proteins, lectins, protease inhibitors, α-amylase inhibitors, canatoxin-like proteins and ureases, arcelins, antimicrobial peptides, and pore-forming toxins, are found in different plant parts, such as the roots, tubers, stems, fruits, buds, and foliage. Several investigations have been conducted to explore the potential applications of these plant proteins by analyzing their toxic effects and modes of action. In biomedical applications, such as crop protection, drug development, cancer therapy, and genetic engineering, toxic plant proteins have been utilized as potentially useful instruments due to their biological activities. However, these noxious metabolites can be detrimental to human health and cause problems when consumed in high amounts. This review focuses on different plant toxic proteins, their biological activities, and their mechanisms of action. Furthermore, possible usage and removal strategies for these proteins are discussed.


Subject(s)
Plant Proteins , Plants, Toxic , Animals , Humans , Insecta , Lectins/pharmacology , Plant Proteins/genetics , Protease Inhibitors/pharmacology
11.
Probiotics Antimicrob Proteins ; 15(4): 1014-1031, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37222849

ABSTRACT

It is well-known that probiotics have key roles in the crosstalk between the gut and brain in terms of nutrition and health. However, when investigating their role in nutrition and health, it can be important to discriminate probiotics used as foods, food supplements, or drugs. For clarification of this terminology, the Food and Drug Administration (FDA) has established a new "live biotherapeutic products" (LBP) category, expressing pharmaceutical expectations and to reduce confusion in the literature. Growing evidence advises that the community of microorganisms found in the gut microbiota is associated with psychological conditions. Hence, it is thought that LBPs may positively affect depression, anxiety, bipolar disorder, and schizophrenia by reducing inflammation, improving gut microbiota, and balancing gut neurometabolites. This review focuses on the specific position of probiotics as LBPs in psychological conditions. Condition-specific potential pathways and mechanisms of LBPs and the prominent strains are discussed in the light of novel studies for future research, dietetic and pharmaceutical applications.


Subject(s)
Dietetics , Gastrointestinal Microbiome , Probiotics , Brain-Gut Axis , Probiotics/therapeutic use , Dietary Supplements
12.
Heliyon ; 9(4): e15016, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37089286

ABSTRACT

The current study sought to determine the anxiolytic, antidepressant, and anti-inflammatory properties of distilled water-soluble extract of beehive (WSE-BH). Gas chromatography-mass spectrometry (GC-MS) studies were used to characterize the chemical compositions obtained from beehives extracted in water and methanol (also fractions). The GC-MS analysis identified 19 compounds in WSE-BH, including high total phenol and flavonoid contents, compared with the methanol extract (21 compounds), ethyl acetate fraction (9 compounds), and CCl4 fraction (27 compounds). The oral administration of WSE-BH (50 and 150 mg/kg) showed significant anxiolytic activities assessed by time spent in (30.80% and 39.47%, respectively) and entry into (47.49% and 55.93%, respectively) the open arms of the elevated plus-maze (EPM). Only the 150 mg/kg dose resulted in a significant effect on the number of head-dipping events in the hole-board test (HBT) (40.2 ± 2.33; p < 0.01) vs. diazepam (64.33 ± 3.16; p < 0.001). Both the 50 and 150 mg/kg doses resulted in significant (p < 0.001) decreases in immobility in the forced swim test (FST) and tail suspensions test (TST), corresponding to the effect of fluoxetine. WSE-BH inhibited histamine-induced paw edema significantly beginning at 60 min, with the 150 mg/kg dose having the highest effect at 180 min. The current findings suggested that WSE-BH had anxiolytic, antidepressant, and anti-inflammatory properties.

13.
J Transl Med ; 21(1): 240, 2023 04 02.
Article in English | MEDLINE | ID: mdl-37009872

ABSTRACT

Type 2 diabetes mellitus (T2DM), one of the main types of Noncommunicable diseases (NCDs), is a systemic inflammatory disease characterized by dysfunctional pancreatic ß-cells and/or peripheral insulin resistance, resulting in impaired glucose and lipid metabolism. Genetic, metabolic, multiple lifestyle, and sociodemographic factors are known as related to high T2DM risk. Dietary lipids and lipid metabolism are significant metabolic modulators in T2DM and T2DM-related complications. Besides, accumulated evidence suggests that altered gut microbiota which plays an important role in the metabolic health of the host contributes significantly to T2DM involving impaired or improved glucose and lipid metabolism. At this point, dietary lipids may affect host physiology and health via interaction with the gut microbiota. Besides, increasing evidence in the literature suggests that lipidomics as novel parameters detected with holistic analytical techniques have important roles in the pathogenesis and progression of T2DM, through various mechanisms of action including gut-brain axis modulation. A better understanding of the roles of some nutrients and lipidomics in T2DM through gut microbiota interactions will help develop new strategies for the prevention and treatment of T2DM. However, this issue has not yet been entirely discussed in the literature. The present review provides up-to-date knowledge on the roles of dietary lipids and lipidomics in gut-brain axis in T2DM and some nutritional strategies in T2DM considering lipids- lipidomics and gut microbiota interactions are given.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/metabolism , Brain-Gut Axis , Lipidomics , Glucose , Dietary Fats
14.
Plants (Basel) ; 12(6)2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36986906

ABSTRACT

Java plum is widely recognized as a plant with valuable medicinal properties, originating from Indonesia and India and distributed globally in the tropic and sub-tropic regions of the world. The plant is rich in alkaloids, flavonoids, phenyl propanoids, terpenes, tannins, and lipids. The phytoconstituents of the plant seeds possess various vital pharmacological activities and clinical effects including their antidiabetic potential. The bioactive phytoconstituents of Java plum seeds include jambosine, gallic acid, quercetin, ß-sitosterol, ferulic acid, guaiacol, resorcinol, p-coumaric acid, corilagin, ellagic acid, catechin, epicatechin, tannic acid, 4,6 hexahydroxydiphenoyl glucose, 3,6-hexahydroxy diphenoylglucose, 1-galloylglucose, and 3-galloylglucose. Considering all the potential beneficial effects of the major bioactive compounds present in the Jamun seeds, in the current investigation, the specific clinical effects and the mechanism of action for the major bioactive compounds along with the extraction procedures are discussed.

16.
Front Pharmacol ; 14: 1130562, 2023.
Article in English | MEDLINE | ID: mdl-36762108

ABSTRACT

Gastrointestinal cancer represents one of the most diagnosed types of cancer. Cancer is a genetic and multifactorial disease, influenced by the host and environmental factors. It has been stated that 20% of cancer is caused by microorganisms such as Helicobacter pylori, hepatitis B and C virus, and human papillomavirus. In addition to these well-known microorganisms associated with cancer, it has been shown differences in the composition of the microbiota between healthy individuals and cancer patients. Some studies have suggested the existence of the selected microorganisms and their metabolites that can promote or inhibit tumorigenesis via some mechanisms. Recent findings have shown that gut microbiome and their metabolites can act as cancer promotors or inhibitors. It has been shown that gastrointestinal cancer can be caused by a dysregulation of the expression of non-coding RNA (ncRNA) through the gut microbiome. This review will summarize the latest reports regarding the relationship among gut microbiome, ncRNAs, and gastrointestinal cancer. The potential applications of diagnosing and cancer treatments will be discussed.

17.
EMBO Mol Med ; 15(3): e16225, 2023 03 08.
Article in English | MEDLINE | ID: mdl-36594243

ABSTRACT

Nothing is known about the potential implication of gut microbiota in skeletal muscle disorders. Here, we provide evidence that fecal microbiota composition along with circulating levels of short-chain fatty acids (SCFAs) and related metabolites are altered in the mdx mouse model of Duchenne muscular dystrophy (DMD) compared with healthy controls. Supplementation with sodium butyrate (NaB) in mdx mice rescued muscle strength and autophagy, and prevented inflammation associated with excessive endocannabinoid signaling at CB1 receptors to the same extent as deflazacort (DFZ), the standard palliative care for DMD. In LPS-stimulated C2C12 myoblasts, NaB reduces inflammation, promotes autophagy, and prevents dysregulation of microRNAs targeting the endocannabinoid CB1 receptor gene, in a manner depending on the activation of GPR109A and PPARγ receptors. In sum, we propose a novel disease-modifying approach in DMD that may have benefits also in other muscular dystrophies.


Subject(s)
Muscular Dystrophy, Duchenne , Animals , Mice , Autophagy , Dysbiosis , Endocannabinoids/metabolism , Inflammation/metabolism , Mice, Inbred mdx , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/genetics , Intestines
18.
Clin Exp Pediatr ; 66(8): 320-331, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36397260

ABSTRACT

Phenylketonuria (PKU), an autosomal recessive inherited metabolic disorder, is caused by a mutation in the phenylalanine hydroxylase (PAH) gene on the 12th chromosome. Defective PAH activity ultimately leads to increased phenylalanine (Phe) blood concentrations (hyperphenylalaninemia) that harm the brain. The primary purpose of PKU treatment is to maintain the blood Phe level to prevent certain undesired effects. Hence, lifelong medical nutrition therapy is recommended for these patients. The usefulness of natural protein sources may be limited, as they are based on individual Phe tolerance, and a patient's daily protein requirements are supported by Phe-free amino acid mixtures. A few PKU treatment centers recently started using supplemental casein glycomacropeptide, pegvaliase, or large neutral amino acids, and some patients are treated by responding to tetrahydrobiopterin, which works as a pharmaceutical chaperone (prescribed as sapropterin dihydrochloride). This review discusses the efficacy and safety considerations of basic medical nutrition approaches and newgeneration protein substitutes that are used to treat PKU.

19.
Br J Pharmacol ; 180(2): 235-251, 2023 01.
Article in English | MEDLINE | ID: mdl-36168728

ABSTRACT

BACKGROUND AND PURPOSE: Transient receptor potential melastatin type-8 (TRPM8) is a cold-sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC). EXPERIMENTAL APPROACH: TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8-/- mice in models of sporadic and colitis-associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC. KEY RESULTS: TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt-Frizzled signalling hyperactivation and adenomatous polyposis coli down-regulation. In sporadic and colitis-associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/ß-catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of ß-catenin and its target oncogenes such as C-Myc and Cyclin D1. CONCLUSION AND IMPLICATIONS: Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.


Subject(s)
Colorectal Neoplasms , TRPM Cation Channels , Wnt Signaling Pathway , Animals , Humans , Mice , beta Catenin/metabolism , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism , Prognosis , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism , Wnt Signaling Pathway/genetics
20.
Molecules ; 27(23)2022 Nov 26.
Article in English | MEDLINE | ID: mdl-36500342

ABSTRACT

Centaurea pichleri subsp. pichleri, Conyza canadensis, and Jasminum fruticans are traditionally used plants grown in Turkey. Methanol extracts were obtained from these plants and pharmacological activity studies and phytochemical analyses were carried out. To evaluate the phytochemical composition, spectrophotometric and chromatographic techniques were used. The extracts were evaluated for antioxidant activity by DPPH●, ABTS●+ radical scavenging, and FRAP assays. The cytotoxic effects of the extracts were investigated on DU145 prostate cancer and A549 lung cancer cell lines. The anti-inflammatory effects of extracts were investigated on the NO amount, TNF-α, IFN-γ, and PGE 2 levels in lipopolysaccharide-stimulated Raw 264.7 cells. The richest extract in terms of phenolic compounds (98.19 ± 1.64 mgGAE/gextract) and total flavonoids (21.85 ± 0.64 mgCA/gextract) was identified as C. pichleri subsp. pichleri methanol extract. According to antioxidant activity determinations, the C. pichleri subsp. pichleri extract was found to be the most active extract. Finally, the C. pichleri subsp. pichleri methanol extract was revealed to be the most effective inhibitor of viability in the cytotoxic activity investigation, and the extract with the best anti-inflammatory action. The findings point to C. pichleri subsp. pichleri as a promising source of bioactive compounds in the transition from natural sources to industrial uses, such as new medications, cosmeceuticals, and nutraceuticals.


Subject(s)
Centaurea , Conyza , Erigeron , Oleaceae , Plants, Medicinal , Antioxidants/chemistry , Centaurea/chemistry , Plants, Medicinal/chemistry , Methanol , Plant Extracts/pharmacology , Plant Extracts/chemistry , Phytochemicals/pharmacology , Anti-Inflammatory Agents/pharmacology
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