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Hydrophobic bioactive compounds like astaxanthin (AST) exhibit poor water solubility and low bioavailability. Liposomes, which serve as nanocarriers, are known for their excellent biocompatibility and minimal immunogenicity. Traditionally, liposomes have been primarily constructed using phospholipids and cholesterol. However, the intake of cholesterol may pose a risk to human health. Phytosterol ester was reported to reduce level of cholesterol and improve properties of liposomes. In this study, phytosterol oleate was used to prepare liposomes instead of cholesterol to deliver AST (AST-P-Lip). The size range of AST-P-Lip was 100-220 nm, and the morphology was complete and uniform. In vitro studies showed that AST-P-Lip significantly enhanced the antioxidant activity and oral bioavailability of AST. During simulated digestion, AST-P-Lip protected AST from damage by gastric and intestinal digestive fluid. Additionally, AST-P-Lip had a good storage stability and safety. These results provide references for the preparation of novel liposomes and the delivery of bioactive compounds.
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Non-viral nanoparticles (NPs) have seen heightened interest as a delivery method for a variety of clinically relevant nucleic acid cargoes in recent years. While much of the focus has been on lipid NPs, non-lipid NPs, including polymeric NPs, have the possibility of improved efficacy, safety, and targeting, especially to non-liver organs following systemic administration. A safe and effective systemic approach for intracellular delivery to the lungs could overcome limitations to intratracheal/intranasal delivery of NPs and improve clinical benefit for a range of diseases including cystic fibrosis. Here, engineered biodegradable poly (beta-amino ester) (PBAE) NPs are shown to facilitate efficient delivery of mRNA to primary human airway epithelial cells from both healthy donors and individuals with cystic fibrosis. Optimized NP formulations made with differentially endcapped PBAEs and systemically administered in vivo lead to high expression of mRNA within the lungs in BALB/c and C57 B/L mice without requiring a complex targeting ligand. High levels of mRNA-based gene editing were achieved in an Ai9 mouse model across bronchial, epithelial, and endothelial cell populations. No toxicity was observed either acutely or over time, including after multiple systemic administrations of the NPs. The non-lipid biodegradable PBAE NPs demonstrate high levels of transfection in both primary human airway epithelial cells and in vivo editing of lung cell types that are targets for numerous life-limiting diseases particularly single gene disorders such as cystic fibrosis and surfactant deficiencies.
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Endowing biodegradable plastics with easy recyclability can reduce competition with food resources and further enhance their environmental friendliness. In this work, 4-carboxyphenylboronic acid was grafted onto the side chains of hydroxyethyl cellulose and compounded with inexpensive cornstarch. Upon the introduction of tannic acid, stable and reversible borate ester bond rapidly formed, yielding composite biodegradable plastic films with outstanding mechanical properties and facile recyclability. The formation of a dynamic cross-linked network mitigates the aggregation of gelatinized starch molecules, enhancing the flexibility and durability of the crosslinked film. Testing revealed that while maintaining high tensile strength, the elongation at break of the crosslinked film increased by 952.86â¯%. The static water contact angle was improved from 32.74° to 78.82°, with a change of <5° within 1â¯min, demonstrating enhanced water resistance. Excellent antioxidant and thermal stability were also characterized, the crosslinked film can be easily dissolved by heating in water at pHâ¯=â¯6.5 and reshaped in water at pHâ¯=â¯7.2. After five times of regeneration, the tensile strength loss was as low as 5.68â¯%. This eco-friendly and efficient recycling process is promising during green chemistry.
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Background: Cerebral ischaemia-reperfusion injury (CIRI) could worsen the inflammatory response and oxidative stress in brain tissue. According to previous studies, ferulic acid methyl ester (FAME), as the extract with the strongest comprehensive activity in the traditional Chinese medicine Huang Hua oil dot herb, has significant anti-oxidative stress and neuroprotective functions, and can effectively alleviate CIRI, but its mechanism of action is still unclear. Methods: Firstly, the pharmacological effects of FAME were investigated by in vitro oxidative stress and inflammatory experiments. Secondly, evaluate the therapeutic effects of FAME in the treatment of CIRI by brain histopathological staining and cerebral infarct area by replicating the in vivo MACO model. Thirdly, RNA-Seq and network pharmacology were utilized to predict the possible targets and mechanisms of FAME for CIRI at the molecular level. Finally, the expression of key target proteins, as well as the key regulatory relationships were verified by molecular docking visualization, Western Blotting and immunohistochemistry. Results: The results of in vitro experiments concluded that FAME could significantly reduce the content of TNF-α, IL-1ß and ROS, inhibiting COX-2 and iNOS protein expression in cells(p<0.01). FAME was demonstrated to have anti-oxidative stress and anti-inflammatory effects. The results of in vivo experiments showed that after the administration of FAME, the area of cerebral infarction in rats with CIRI was reduced, the content of Bcl-2 and VEGF was increased(p<0.05). Network pharmacology and RNA-Seq showed that the alleviation of CIRI by FAME may be through PI3K-AKT and HIF-1 signaling pathway. Enhanced expression of HIF-1α, VEGF, p-PI3K, p-AKT proteins in the brain tissues of rats in the FAME group was verified by molecular docking and Western Blotting. Conclusion: FAME possesses significant anti-inflammatory and anti-oxidative stress activities and alleviates CIRI through the PI3K/HIF-1α/VEGF signaling pathway.
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The utilization of high-performance ester materials in addressing soil erosion and conserving water remains a crucial area of research in soil remediation. Currently, however, the mechanism underlying the role of these materials in vegetation restoration remains unclear, hampering the accurate determination of the optimal ratio of high-performance ester composite materials for soil enhancement. To address this issue, this study examines the mechanism of how high-performance ester composite materials affect the germination and growth of plant seeds through soilless cultivation experiments. The results revealed that the high-performance ester composite materials significantly enhanced seed germination ability and fostered plant seedling growth. Notably, the promotional effects of the ester adhesive and water-retaining materials within the high-performance ester composite varied. Specifically, the adhesive material significantly spurred radicle development, while the water-retaining material significantly accelerated germ growth. Varying concentrations of adhesive materials exerted distinct effects on plant growth. In particular, a small amount of adhesive materials enhanced seed germination, whereas excessive amounts exhibited inhibitory effects. Consequently, the optimal adhesive materials dosage conducive to plant growth and the optimal weight ratio of adhesive to water-retaining materials were ascertained. Additionally, the underlying mechanism of high-performance ester composite materials influence plant growth was elucidated. Overall, this research offers a theoretical foundation for the optimal ratio adjustment of high-performance ester composite materials to optimize soil improvement efforts.
Subject(s)
Esters , Germination , Seeds , Soil , Germination/drug effects , Soil/chemistry , Esters/chemistry , Seeds/growth & development , Seeds/drug effects , Seedlings/growth & development , Seedlings/drug effects , Plant Development/drug effects , Water/chemistry , Adhesives/chemistryABSTRACT
As the derivative of konjac glucomannan (KGM), carboxymethyl konjac glucomannan (CMK) has attracted increasing attention in the polysaccharide hydrogel fields with the aim of improving the performance related to drug delivery and release. In this study, we prepared a CMK-based hydrogel with dual characteristic crosslinks, and unlocked new applications of this type of hydrogel in soft sensor fields. CMK and poly (vinyl alcohol) were used as substrates, and physical crosslinks were constructed via the freeze-thawing treatments and covalent crosslinks were built via the boronic ester bonding. As-prepared hydrogel possessed significantly improved mechanical performance because the boronic ester bonding, on the one hand, well associated the two kinds of polymer chains, and on the other hand, played the role of 'sacrificial crosslinks'. Furthermore, the occurrence of dynamic boronic ester bonding gave the hydrogel strain- and temperature-sensitive ionic conductivity, and therefore, the hydrogels could be used to identify human motions and as-resulted environmental temperature alterations, and worked well in various scenarios. This work activates new application of CMK in the multimodal sensing field, and also proposes an intriguing way of building multiple crosslinks in the KGM derivative-based hydrogels.
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Polymorphisms in the cholesteryl ester transfer protein (CETP) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular health. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene with AHRR in 607 people from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-min step test and was estimated as the difference between resting and post-exercise heart rate, i.e., delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels, next to conventional risk factors, were applied in the statistical analyses. Among the examined five SNPs, two showed a significant association with lower ΔHR (rs1532624-Cdominant: B = -8.41, p < 0.001; rs708272-Gdominant: B = -8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-Cdominant: OR = 0.44, p = 0.004; rs708272-Gdominant: OR = 0.43, p = 0.003). Among the ten haplotypes, two showed significant association with lower ΔHR (H3-CAGCA: B = -6.81, p = 0.003; H9-CGGCG: B = -14.64, p = 0.015) and lower risk of adverse AHRR (H3-CAGCA: OR = 0.58, p = 0.040; H9-CGGCG: OR = 0.05, p = 0.009) compared to the reference haplotype (H1-AGACG). Our study is the first to report a significant association between CETP gene polymorphisms and AHRR. It also confirms that the association of the CETP gene with cardiovascular risk is mediated by changes in heart rate in response to physical activity, in addition to its effect on lipid profile.
Subject(s)
Cholesterol Ester Transfer Proteins , Exercise , Haplotypes , Heart Rate , Polymorphism, Single Nucleotide , Humans , Cholesterol Ester Transfer Proteins/genetics , Male , Female , Heart Rate/genetics , Middle Aged , Adult , Cholesterol, HDL/blood , Aged , HungaryABSTRACT
Glycosaminoglycans (GAGs), including hyaluronic acid (HA), chondroitin sulfate (CS)/dermatan sulfate (DS), heparan sulfate (HS)/heparin (HP), and keratan sulfate (KS), play pivotal roles in living organisms. Generally, GAGs are analyzed after enzymatic digestion into unsaturated or saturated disaccharides. Due to high structural similarity between disaccharides, however, separation during analysis is challenging. Additionally, little is known about the structures of GAGs and their functional relationships. Elucidating the function of GAGs requires highly sensitive quantitative analytical methods. We developed a method for the simultaneous analysis of 18 types of disaccharides derived from HA (1 type), CS/DS (7 types), HS/HP (8 types), and KS (2 types) potentially detectable in analyses of human urine. The simple method involves HPLC separation with fluorescence detection following derivatization of GAG-derived disaccharides using 4-aminobenzoic acid ethyl ester (ABEE) as a pre-labeling agent and 2-picoline borane as a reductant. The ABEE derivatization reaction can be performed under aqueous conditions, and excess derivatization reagents can be easily, rapidly, and safely removed. This method enables highly sensitive simultaneous analysis of the 18 abovementioned types of GAG-derived disaccharides using HPLC with fluorescence detection in small amounts of urine (1 mL) in a single run. The versatile method described here could be applied to the analysis of GAGs in other biological samples.
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The development of photoresponsive shape memory materials based on the photothermal conversion properties of lignin and the low activation energy of the dynamic covalent borate bond is of great importance. In this paper, a kind of lignin-based vitrimer polymer (LBP) containing dynamic boronic ester bonds was prepared by a "sulfhydryl-epoxy" click reaction and etherification reaction. The results show that the rigid segment EP-EL (lignin-based epoxy resin) and BDB (2,2'-(1,4-phenylene)-bis-[4-mercapto-1,3,2-dioxaneborane]) with benzene ring structure can impart tensile strength (20.8 MPa) to the LBP, while the flexible segment PEG imparts good elongation at break (15 %). The dynamic binding and dissociation exchange mechanism of the boronic ester bonds enables LBP to exhibit thermal remodelling properties (up to 36.2 %) and water-assisted self-healing properties at room temperature (up to 49.0 %). In addition, LBP exhibits excellent thermal and light-responsive shape memory properties due to its own photothermal conversion performance (photothermal conversion efficiency up to 18.2 %) and the dynamic boronic ester bond thermal activation bond exchange mechanism. The insulating properties of LBP make it suitable for use in high temperature protection circuit devices and light-responsive circuit devices. This study provides new insights into the design and application of Vitrimer and photoresponsive shape memory polymers, and also offers a new avenue for high-value utilization of lignin.
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Substrate specificity in non-aqueous esterification catalyzed by commercial lipases activated by hydration-aggregation pretreatment was investigated. Four microbial lipases from Rhizopus japonicus, Burkholderia cepacia, Rhizomucor miehei, and Candida antarctica (fraction B) were used to study the effect of the carbon chain length of saturated fatty acid substrates on the esterification activity with methanol in n-hexane. Hydration-aggregation pretreatment had an activation effect on all lipases used, and different chain length dependencies of esterification activity for lipases from different origins were demonstrated. The effects of various acidic substrates with different degrees of unsaturation, aromatic rings, and alcohol substrates with different carbon chain lengths on esterification activity were examined using R. japonicus lipase, which demonstrated the most remarkable activity enhancement after hydration-aggregation pretreatment. Furthermore, in the esterification of myristic acid with methanol catalyzed by the hydrated-aggregated R. japonicus lipase, maximum reaction rate (5.43 × 10-5 mmol/(mg-biocat min)) and Michaelis constants for each substrate (48.5â¯mM for myristic acid, 24.7â¯mM for methanol) were determined by kinetic analysis based on the two-substrate Michaelis-Menten model.
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Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor. Previous research has demonstrated similar pharmacokinetic (PK) responses to single doses of obicetrapib between Japanese and White males, but the PK responses have not been established in Chinese individuals. The purpose of this randomized, parallel, open-label trial was to characterize the PK and pharmacodynamic (PD; CETP activity and plasma lipids) responses and safety of single doses (5, 10, or 25 mg; N = 36) and multiple doses (10 mg for 14 days; N = 12) of obicetrapib in healthy Chinese individuals. The maximum concentration and area under the drug concentration-time curve of obicetrapib from 0 h to infinity increased with dose after all single doses of obicetrapib. After 7 consecutive days of dosing, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol reached their minimum and maximum changes of 42% reduction and 108% increase, respectively. Primary PK and PD parameters after single- and multiple-dose administration of obicetrapib were similar to those in healthy white participants in previous studies. One participant in the 5 mg dose group experienced a treatment-emergent adverse event of decreased white blood cell and neutrophil counts, which resolved without intervention. In conclusion, these findings support the inclusion of Chinese individuals in the ongoing phase 3 clinical development program of obicetrapib.
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Aroma is an important indicator of fruit flavor, but mechanisms of aroma formation in strawberries (Fragaria spp.) during natural ripening are still not clear. In this study, aroma compounds in strawberry cultivars were analyzed using gas chromatography-mass spectrometry (GC-MS). Richly creamy strawberry cultivars in particular expressed high levels of vanillin acetate and coumarin (up-regulated by 12.6- and 9.8-fold, respectively), while the aroma-free cultivars were dominated by differential changes in terpenes and alcohols. Further research using liquid chromatography-mass spectrometry (LC-MS) and RNA-Seq indicated that the activation of the phenylpropanoid biosynthesis and alpha-linolenic acid metabolic pathways constituted the key to formation of aroma compounds in creamy strawberry cultivars. The results of this study not only provide a well-defined database to detect aroma compounds in different strawberry cultivars but also explore the underlying mechanisms of creamy aroma formation in strawberries.
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Stimuli activatable systems have the potential to deliver drugs to targeted areas by releasing therapeutic agents in response to diseased specific microenvironments such as the acidic environment commonly found in diseased tissues. This review article focuses on gossypol, a bioactive compound with inherent toxicity due to its formyl groups. It highlights the potential of imine-linked gossypol-based prodrugs and nanoparticle formulations for targeted delivery and controlled release. The unique presence of polyphenolic cores on gossypol can be utilized to prepare nanoparticles. This review offers valuable insights into designing safer and more effective drug delivery systems by elucidating the masking effect and stimuli-responsive release mechanisms. Numerous examples demonstrate the conversion of formyl groups to imines, creating prodrugs that mask reactive functionalities and offer pH-responsive release. This insight can guide the design of combination therapeutics, where a second drug with an amine terminal group can form imine-linked prodrugs. Additionally, the second part discusses the use of polyphenolic moieties to create stable nanoparticles from infinite polymeric networks. Through a comprehensive examination of gossypol's properties and applications, this review emphasizes the broader implications of such a masking strategy for optimizing the therapeutic benefits of many similar bioactive compounds while minimizing adverse effects.
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Propolis is a natural resinous substance made by bees through mixing various plant sources. Propolis has been widely recognized as a functional food due to its diverse range of beneficial bioactivities. However, the therapeutic effects of consuming propolis against atopic dermatitis (AD) remain largely unknown. The current study aimed to investigate the potential efficacy of propolis against AD and explore the active compound as well as the direct molecular target. In HaCaT keratinocytes, propolis inhibited TNF-α-induced interleukin (IL)-6 and IL-8 secretion. It also led to a reduction in chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage-derived chemokine (MDC), while restoring the levels of barrier proteins, filaggrin and involucrin. Propolis exhibited similar effects in AD-like human skin, leading to the suppression of AD markers and the restoration of barrier proteins. In DNCB-induced mice, oral administration of propolis attenuated AD symptoms, improved barrier function, and reduced scratching frequency and transepidermal water loss (TEWL). In addition, propolis reversed the mRNA levels of AD-related markers in mouse dorsal skin. These effects were attributed to caffeic acid phenethyl ester (CAPE), the active compound identified by comparing major components of propolis. Mechanistic studies revealed that CAPE as well as propolis could directly and selectively target MKK4. Collectively, these findings demonstrate that propolis may be used as a functional food agent for the treatment of AD.
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BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown. METHODS: A total of 24 patients with T2DM and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period. RESULTS: During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P<0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (P<0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs. CONCLUSIONS: In patients with T2DM and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2DM and HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.
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OBJECTIVES: Ketone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to assess the tolerability and safety of KE ingestion in a cohort of older adults. DESIGN: Randomized, placebo-controlled, double-blinded, parallel-arm trial (NCT05585762). SETTING: General community, Northern California, USA. PARTICIPANTS: Community-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n = 30; M = 15, F = 15; age = 76 y, range 65-90 y) were randomized and n = 23 (M = 14, F = 9) completed the protocol. INTERVENTION: Participants were randomly allocated to consume either KE (25 g bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil daily for 12 weeks. MEASUREMENTS: Tolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events. RESULTS: There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n = 2 (14.3% [90% CI = 2.6-38.5]); PLA n = 1 (7.1% [90% CI = 0.4-29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2 and 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group. CONCLUSIONS: This KE was safe and well-tolerated in this study of healthy older adults. These results provide an initial foundation for use of KEs in clinical research with older adults.
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This study sought to analyze the oxidative products [acid value (AV), free fatty acids (FFA), conjugated dienoic acid (CDA), p-anisidine value (p-AV), antioxidant-prooxidant balance (APB) value] and toxic compounds [3-monochloropropane diol (3-MCPD), glycidyl ester (GE)] in edible oils after deep-frying. The deep-frying edible oils evaluated herein included soybean oil (S), palm oil (P), canola oil (C), grape seed oil (G), and a 1:1 blend (SC, SG, PC, PG, and CG). As frying time increased, the level of AV in PC, total FFA contents in CG, and p-AV in CG significantly increased up to 200%, 45.5%, and 410.5%, respectively (p < 0.05). The levels of 3-MCPD, and GE were 0.81-6.28 µg/mL and 0.14-2.84 µg/mL, respectively. The levels of 3-MCPD, GE, CDA, and APB changed significantly as frying time increased. Analysis of the correlation between oxidation products and toxic compounds indicated that the contents of 3-MCPD and palmitic acid were positively correlated. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01494-9.
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Inferior fast-charging and low-temperature performances remain a hurdle for lithium-ion batteries. Overcoming this hurdle is extremely challenging primarily due to the low conductivity of commercial ethylene carbonate (EC)-based electrolytes and the formation of undesirable solid electrolyte interphases with poor Li+-ion diffusion kinetics. Here, a series of EC-free fast-charging electrolytes (FCEs) by incorporating a fluorinated ester, methyl trifluoroacetate (MTFA), as a special cosolvent into a practically viable LiPF6-dimethyl carbonate-fluoroethylene carbonate system, is reported. With a solvent-dominated solvation structure, MTFA facilitates the formation of thin, yet robust, interphases on both the cathode and anode. Commercial 1 Ah graphite|LiNi0.8Mn0.1Co0.1O2 pouch cells filled with the FCE exhibit ≈80% capacity retention over 3000 cycles at 3 C and 4 C (15 min) charging rates in the full range of 0-100% state-of-charge. Moreover, even at a low operating temperature of -20 °C, the 1 Ah cell retains a high capacity of 0.65 Ah at a 2 C discharge rate and displays virtually no capacity fade on cycling at a C/5 rate. The work highlights the power of electrolyte design in achieving extra-fast-charging and low-temperature performances.
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Introduction: Despite the high phenolic content of Annona muricata, little is known about its anti-hypertensive and antihyperlipidemic properties. This study evaluated the anti-hypertensive and antihyperlipidemic potential of A. muricata leaf extracts. Materials and methods: Forty-two male Wistar rats were divided into seven groups of six animals each. N-nitro-L-arginine methyl ester (L-NAME) was used to induce hypertension and hyperlipidemia. Results: Phytochemical screening of Annona muricata leaf extracts (AMLE) revealed the presence of saponins, alkaloids, flavonoids, tannins, coumarins, steroids, terpenoids, and phenols. Comparing the methanol extract with the ethyl acetate fraction, quantification revealed that the methanol extract contained more phenolics, flavonoids, and alkaloids. The AMLE rats significantly reduced triglycerides, total cholesterol, LDL, VLDL, atherogenic index, coronary risk index, and blood pressure. The significant decrease in GSH, catalase, SOD, GST, and oxidative stress markers (MDA, nitrites, and MPO) was reversed by AMLE in a dose-dependent manner. Also, the elevated serum levels of TNF-α and IL-1ß in the hypertensive rats were attenuated in the treatment groups. Discussion: This study suggests the potential ameliorative effects of Annona muricata leaf extracts against L-NAME-induced hypertension in rats. Notably, the study showed the antioxidant and anti-inflammatory properties of A. muricata leaf extracts, which is seen in its ability to attenuate oxidative stress and inflammatory cytokines in L-NAME-induced hypertensive rats. A. muricata extracts also decreased atherogenic risk and improved lipid profiles.