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Bioinformation 2023It is of interest to develop potent and safer anti-inflammatory drugs from plants, as medicinal plants and herbs attained great attention in the medical world due to...
It is of interest to develop potent and safer anti-inflammatory drugs from plants, as medicinal plants and herbs attained great attention in the medical world due to their multifunctional activities. This article studied the anti-inflammatory effects of lauric acid (LA), thiocolchicoside (TC) and thiocolchicoside-lauric acid (TC-LA) formulation. The anti-inflammatory effects of these compounds were determined by following the methods of inhibition of protein denaturation and proteinase inhibition activity. This was assessed at different concentrations to determine the 50% inhibition concentration (IC50) of the compounds. The result indicated that the activity of LA, TC, TC-LA formulation, and reference drug increased with the increase in the concentration from 10-50 µg/ml, thus proving the activity of LA, TC, and TC-LA formulation against inflammation was in a dose-dependent manner. The percentage of inhibition of protein denaturation was 59.56%, 66.94%, 86.62%, and 60.34% for LA, TC, the combination of TC-LA and standard drug, and the IC50 values were found to be 44.78 µg/mL, 37.65 µg/mL, 27.15 µg/mL and 43.42 µg/mL, respectively. The percentage of proteinase inhibition activity of LA, TC, and a combination of TC-LA and the standard drug was 66.65%, 77.49%, 94.07%, and 69.83%, and IC50 of LA, TC, a combination of TC-LA and standard drug were35.5 µg/mL, 32.12 µg/mL, 24.35 µg/mL and 37.80 µg/mL, respectively. We found out that lauric acid, thiocolchicoside, and thiocolchicoside-lauric acid formulation exhibited significant anti-inflammatory activity.
PubMed: 38046516
DOI: 10.6026/973206300191075 -
RSC Advances Jul 2023The modification of natural products is one of the key areas of synthetic organic chemistry for obtaining valuable chemical building blocks that have medicinal...
The modification of natural products is one of the key areas of synthetic organic chemistry for obtaining valuable chemical building blocks that have medicinal significance. In this study, lauric acid-based hydrazones, namely ()-'-(2-nitrobenzylidene)dodecanehydrazide (NBDH), ()-'-(naphthalen-1-ylmethylene)dodecanehydrazide (NMDH), and ()-'-(4-fluorobenzylidene)dodecanehydrazide (FBDH), were synthesized and characterized using spectroscopic techniques. The newly synthesized lauric acid-based hydrazones were screened for their anticancer and antioxidant potential. The antioxidants showed their activity by inhibiting the oxidative chain reactions that produce reactive oxygen species. The antioxidant activity showed that NBDH exhibited the maximum DPPH inhibitory activity when compared with that of NMDH and FBDH, whereas the anticancer activity showed that FBDH exhibited maximum percent viability when compared to that of NBDH and NMDH. The reactivity and biological needs of the synthesized compounds NBDH, NMDH, and FBDH were met by performing geometrical, FT-IR vibrational, UV-visible, global reactivity parameters (GRP), MEP, FMO, NBO, ELF, LOL, and nonlinear optical (NLO) analysis at the DFT/B3LYP/6-311+G(d,p) level. NBO analysis confirmed the existence of extended conjugation and intramolecular charge transfer among NBDH, NMDH, and FBDH, which have the lowest gap in π → π*, which are in line with the FMO results where successful charge transfer occurred from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO). GRP analysis confirmed the potential of NBDH, NMDH, and FBDH for biological, electronic, and NLO applications. It is clear from the comparative analysis of the urea molecule that NBDH, NMDH, and FBDH all comprise fine NLO properties.
PubMed: 37476049
DOI: 10.1039/d3ra02433d -
Polymers Dec 2023Both guided bone and guided tissue regeneration are techniques that require the use of barrier membranes. Contamination and infection of the surgical area is one of the... (Review)
Review
Both guided bone and guided tissue regeneration are techniques that require the use of barrier membranes. Contamination and infection of the surgical area is one of the most feared complications. Some current lines of research focus on functionalizing these membranes with different antimicrobial agents. The objective of this study was to carry out a review of the use and antibacterial properties of regeneration membranes doped with antimicrobials such as zinc, silver, chlorhexidine, and lauric acid. The protocol was based on PRISMA recommendations, addressing the PICO question: "Do membranes doped with non-antibiotic antimicrobials have antibacterial activity that can reduce or improve infection compared to membranes not impregnated with said antimicrobial?" Methodological quality was evaluated using the RoBDEMAT tool. A total of 329 articles were found, of which 25 met the eligibility criteria and were included in this review. Most studies agree that zinc inhibits bacterial growth as it decreases colony-forming units, depending on the concentration used and the bacterial species studied. Silver compounds also decreased the secretion of proinflammatory cytokines and presented less bacterial adhesion to the membrane. Some concentrations of chlorhexidine that possess antimicrobial activity have shown high toxicity. Finally, lauric acid shows inhibition of bacterial growth measured by the disk diffusion test, the inhibition zone being larger with higher concentrations. Antimicrobial agents such as zinc, silver, chlorhexidine, and lauric acid have effective antibacterial activity and can be used to dope regenerative membranes in order to reduce the risk of bacterial colonization.
PubMed: 38201760
DOI: 10.3390/polym16010095 -
Molecules (Basel, Switzerland) Nov 2023Camphene, C12-C18 fatty acids, and titanium sulfate were used as raw materials to study the synthesis of long-chain fatty acid isobornyl esters. Products were analyzed...
Camphene, C12-C18 fatty acids, and titanium sulfate were used as raw materials to study the synthesis of long-chain fatty acid isobornyl esters. Products were analyzed quantitatively by gas chromatography (GC), characterized by nuclear magnetic resonance spectroscopy (hydrogen and carbon), and evaluated using toxicity tests. The optimum reaction conditions were as follows: n(lauric acid):n(camphene) = 2.5:1, m(titanium sulfate):m(camphene) = 0.25:1, reaction temperature of 80 °C, and reaction time of 25 h. Under these conditions, the content of isobornyl laurate in the product was 74.49%, and the content of purified product was 95.02%. The reaction kinetics for isobornyl laurate showed an apparent first-order reaction in the first 9 h with an activation energy of 31.01 kJ/mol. The reaction conditions of myristic acid, palmitic acid, and stearic acid were similar to those of lauric acid, but the reaction time had to be increased as the molecular weight of the fatty acid increased. Toxicity tests for four types of long-chain fatty acid isobornyl esters showed that the samples had low toxicity.
PubMed: 38005232
DOI: 10.3390/molecules28227510 -
Nature Communications Jun 2023GPR84 is an orphan class A G protein-coupled receptor (GPCR) that is predominantly expressed in immune cells and plays important roles in inflammation, fibrosis, and...
GPR84 is an orphan class A G protein-coupled receptor (GPCR) that is predominantly expressed in immune cells and plays important roles in inflammation, fibrosis, and metabolism. Here, we present cryo-electron microscopy (cryo-EM) structures of Gα protein-coupled human GPR84 bound to a synthetic lipid-mimetic ligand, LY237, or a putative endogenous ligand, a medium-chain fatty acid (MCFA) 3-hydroxy lauric acid (3-OH-C12). Analysis of these two ligand-bound structures reveals a unique hydrophobic nonane tail -contacting patch, which forms a blocking wall to select MCFA-like agonists with the correct length. We also identify the structural features in GPR84 that coordinate the polar ends of LY237 and 3-OH-C12, including the interactions with the positively charged side chain of R172 and the downward movement of the extracellular loop 2 (ECL2). Together with molecular dynamics simulations and functional data, our structures reveal that ECL2 not only contributes to direct ligand binding, but also plays a pivotal role in ligand entry from the extracellular milieu. These insights into the structure and function of GPR84 could improve our understanding of ligand recognition, receptor activation, and Gα-coupling of GPR84. Our structures could also facilitate rational drug discovery against inflammation and metabolic disorders targeting GPR84.
Topics: Humans; Ligands; Cryoelectron Microscopy; Receptors, G-Protein-Coupled; Fatty Acids; Inflammation
PubMed: 37277332
DOI: 10.1038/s41467-023-38985-6 -
Animals : An Open Access Journal From... Apr 2024(1) Background: This study determined whether adding butyric acid and lauric acid glycerides in nursing pigs' feed would improve growth performance, proteinogram,...
(1) Background: This study determined whether adding butyric acid and lauric acid glycerides in nursing pigs' feed would improve growth performance, proteinogram, biochemical parameters, and antioxidant status. (2) Methods: Ninety male pigs were divided into five groups with six repetitions per group: NC, negative control (no additive); TRI-BUT, addition of tributyrin in the basal ration; MDT-BUT, addition of mono-, di-, and triglycerides of butyric acid in the basal feed; MDT-LAU, the addition of mono-, di-, and triglycerides of lauric acid in the basal feed; and PC, positive control (addition of gentamicin in the basal feed). (3) Results: PC, TRI-BUT, and MDT-LAU resulted in a high average daily WG from days 1 to 39 ( < 0.01). MDT-LAU, MDT-BUT, and PC resulted in a greater feed:gain from days 1 to 39 than the NC ( = 0.03). Great concentrations of the gamma globulin fraction in all groups were observed than in the NC ( = 0.01). Ceruloplasmin, haptoglobin, and C-reactive protein concentrations were lower in all groups than in the NC ( < 0.05). Higher serum glutathione S-transferase activity was observed in the TRI-BUT and MDT-BUT than in the PC ( = 0.04). (4) Conclusions: The addition of butyric acid and lauric acid glycerides in the diet of pigs in the nursery phase can replace growth promoters since the products improve the growth performance, reduce acute-phase proteins, and increase gamma globulin concentrations.
PubMed: 38672322
DOI: 10.3390/ani14081174 -
The EMBO Journal Feb 2024Metabolic syndrome combines major risk factors for cardiovascular disease, making deeper insight into its pathogenesis important. We here explore the mechanistic basis...
Metabolic syndrome combines major risk factors for cardiovascular disease, making deeper insight into its pathogenesis important. We here explore the mechanistic basis of metabolic syndrome by recruiting an essential patient cohort and performing extensive gene expression profiling. The mitochondrial fatty acid metabolism enzyme acyl-CoA synthetase medium-chain family member 3 (ACSM3) was identified to be significantly lower expressed in the peripheral blood of metabolic syndrome patients. In line, hepatic ACSM3 expression was decreased in mice with metabolic syndrome. Furthermore, Acsm3 knockout mice showed glucose and lipid metabolic abnormalities, and hepatic accumulation of the ACSM3 fatty acid substrate lauric acid. Acsm3 depletion markedly decreased mitochondrial function and stimulated signaling via the p38 MAPK pathway cascade. Consistently, Acsm3 knockout mouse exhibited abnormal mitochondrial morphology, decreased ATP contents, and enhanced ROS levels in their livers. Mechanistically, Acsm3 deficiency, and lauric acid accumulation activated nuclear receptor Hnf4α-p38 MAPK signaling. In line, the p38 inhibitor Adezmapimod effectively rescued the Acsm3 depletion phenotype. Together, these findings show that disease-associated loss of ACSM3 facilitates mitochondrial dysfunction via a lauric acid-HNF4a-p38 MAPK axis, suggesting a novel therapeutic vulnerability in systemic metabolic dysfunction.
Topics: Humans; Mice; Animals; Metabolic Syndrome; p38 Mitogen-Activated Protein Kinases; Liver; Fatty Acids; Coenzyme A Ligases; Lauric Acids
PubMed: 38191811
DOI: 10.1038/s44318-023-00020-1 -
Journal of Neuroinflammation Nov 2023Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation...
BACKGROUND
Lipid metabolism has a crucial role in neural repair in neurodegenerative diseases. We recently revealed that lipogenesis-mediated interleukin-33 (IL-33) upregulation lead to blood-brain barrier (BBB) repair after ischemic stroke. However, manipulating the key enzyme fatty acid synthase (FASN) to enhance lipogenesis was very challenging. Glyceryl triacetate (GTA) was used as a donor of acetate and precursor of acetyl coenzyme A, the key substrate for de novo lipogenesis catalyzed by FASN. Therefore, we hypothesized that GTA would promote lipogenesis the peri-infarct after ischemic stroke and contribute to the BBB repair through IL-33.
METHODS
Middle cerebral artery occlusion (MCAO) was performed on C57BL mice and GTA was gavage administrated (4 g/kg) on day 2 and 4 after MCAO. Lipogenesis was evaluated by assessment of the protein level of FASN, lipid droplets, and fatty acid products through liquid chromatography-mass spectrometry in the peri-infarct area on day 3 after MCAO, respectively. BBB permeability was determined by extravasation of Evans blue, IgG and dextran, and levels of tight junction proteins in the peri-infarct area on day 7 after MCAO, respectively. Infarct size and neurological defects were assessed on day 7 after MCAO. Brain atrophy on day 30 and long-term sensorimotor abilities after MCAO were analyzed as well. The inhibitor of FASN, C75 and the virus-delivered FASN shRNA were used to evaluate the role of FASN-driven lipogenesis in GTA-improved BBB repair. Finally, the therapeutic potential of recombinant IL-33 on BBB repair and neurological recovery was evaluated.
RESULTS
We found that treatment with GTA increased the lipogenesis as evidenced by lipid droplets level and lauric acid content, but not the FASN protein level. Treatment with GTA increased the IL-33 level in the peri-infarct area and decreased the BBB permeability after MCAO. However, infarct size and neurological defect score were unchanged on day 7 after MCAO, while the long-term recovery of sensorimotor function and brain atrophy were improved by GTA. Inhibition of lipogenesis using C75 or FASN shRNA reversed the beneficial effect of GTA. Finally, exogenous IL-33 improved BBB repair and long-term functional recovery after stroke.
CONCLUSION
Collectively, we concluded that treatment with GTA improved the BBB repair and functional recovery after ischemic stroke, probably by the enhancement of lipogenesis and IL-33 expression.
Topics: Mice; Animals; Ischemic Stroke; Blood-Brain Barrier; Interleukin-33; Lipogenesis; Mice, Inbred C57BL; Stroke; Infarction, Middle Cerebral Artery; RNA, Small Interfering; Atrophy; Brain Ischemia
PubMed: 37968698
DOI: 10.1186/s12974-023-02942-3 -
Cureus Sep 2023The present study explored the anti-inflammatory, antimicrobial, antioxidant, and cytotoxic effects of a combination of chitosan thiocolchicoside and lauric acid (CTLA)...
AIM
The present study explored the anti-inflammatory, antimicrobial, antioxidant, and cytotoxic effects of a combination of chitosan thiocolchicoside and lauric acid (CTLA) nanogel. Materials and methods: A nanogel formulation of thiocolchicoside and lauric acid was developed and tested for potential applications. The antimicrobial activity was assessed using the well diffusion method, while the antioxidant activity was evaluated using the 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radical scavenging assay and hydrogen peroxide (HO) antioxidant assay methods. The anti-inflammatory activity was determined through the egg albumin denaturation method, the bovine serum albumin denaturation method, and the membrane stabilization assay. A brine shrimp lethality assay was used to study the cytotoxic effect of the nanogel.
RESULTS
We identified significant positive outcomes for the CTLA nanogel. The results showed a percentage of inhibition of 81% at 50μg/mL, which showed the nanogel's significant anti-inflammatory activity by inhibiting bovine serum albumin denaturation. The anti-inflammatory properties of the nanogel were comparable to the standard diclofenac sodium at all tested concentrations. The egg albumin denaturation assay results revealed a percentage inhibition of 76% at 50 μg/mL. In the membrane stabilization assay, a percentage inhibition of 86% was obtained at a concentration of 50 μg/mL against 89% for the standard drug. The nanogel exhibited a zone of inhibition of 20 mm against and 22 mm with a dilution of 100 µg/mL of CTLA nanogel against . The antioxidant activity was studied by using the DPPH method, 50 μg/ml has an 89% inhibition, which was similar to the standard. The inhibitory activity of CTLA nanogel at 50 μg/ml was 81.6% in the hydroxyl free radical scavenging assay, which was comparable to the standard drug. At 5 μg/mL concentration of CTLA nanogel, approximately 90% of the nauplii remained alive after 48 hours.
CONCLUSION
The CTLA nanogel showed excellent anti-inflammatory and antioxidant properties suggesting its potential for managing inflammatory conditions and oxidative stress-related disorders.
PubMed: 37900405
DOI: 10.7759/cureus.46003 -
Heliyon Nov 2023Ethanol (EtOH) is most widely used in alcoholic beverages to prepare alcohol. As EtOH is mainly metabolised in the liver, the excessive consumption of EtOH forms a...
Ethanol (EtOH) is most widely used in alcoholic beverages to prepare alcohol. As EtOH is mainly metabolised in the liver, the excessive consumption of EtOH forms a primary toxic metabolic product called acetaldehyde, as the gradual increase in acetaldehyde leads to liver injury, as reported. Lauric acid (LA) is rich in antioxidant, antifungal, antibacterial, anticancer, and antiviral properties. LA is an edible component highly present in coconut oil. However, no report on LA protective effects against the EtOH-instigated hepatotoxicity exists. Therefore, the experiment is carried out to investigate the potency effects of LA on EtOH-instigated hepatotoxicity in thirty male albino rats. Rats were divided into five groups (n-6): control DMSO alone, EtOH -intoxicated, EtOH + LA 180 mg/kg, EtOH + LA 360 mg/kg, and LA alone were administered orally using oral gavage. The study measured body weight every weekend in all rat groups. The rats were sacrificed and assessed for serum markers (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase), antioxidant activity (superoxide dismutase, reduced glutathione, glutathione peroxidase), lipid peroxidation (malondialdehyde), histopathological, cytokine levels (TNF-α, IL-1β and IL-6), protein expression (caspase 3 and caspase 8 and Bcl-2 and HNF4α) were evaluated after the 56-days study period. The impact of EtOH intoxication reduces the rat's body weight by 90 g, upregulates the liver enzyme markers, depletes the antioxidant levels, produces malondialdehyde, changes the histoarchitecture (periportal inflammation and hepatocyte damage), downregulates the Bcl-2 expressions and HNF4α, and elevates the expression of cytokines and apoptotic markers. LA alleviated EtOH-induced liver toxicity by significant (p < 0.05) modulation of biochemical levels, caspase-8/3 signalling, reducing pro-inflammatory cytokines, and restoring the normal histoarchitecture, upregulating the Bcl-2 and HNF4α Expressions. In conclusion, LA treatment can protect the liver against EtOH-induced hepatotoxicity, evidenced by alleviating Oxidative stress, lipid peroxidation, inflammation, apoptosis, and upregulation of HNF4α.
PubMed: 37908709
DOI: 10.1016/j.heliyon.2023.e21267