Atriplex portulacoides L. derived phytochemicals mitigate acetic acid induced colitis in rats via orchestrating Nrf2/Keap1 signalling and LncRNAs gene expression
APME dose-dependently and significantly reduced the pro-inflammatory cytokine TNF-α, mitigated malondialdehyde levels, and restored total antioxidant capacity in colonic tissue compared to the untreated ulcerative group, demonstrating substantial improvements in colonic architecture and cellular integrity.
Abstract
This study is the first to elucidate the mechanistic actions of Atriplex portulacoides L. methanolic extract (APME) as a natural treatment of acetic acid-induced ulcerative colitis on rat model. Phytochemical metabolic profiling of APME was determined through the determination of total phenolic and flavonoid contents, alongside negative mode LC–ESI–MS/MS analysis. Furthermore, chromatographic and spectroscopic investigations were employed to fractionate and structurally characterize the metabolites present within APME fractions. The therapeutic potential of APME in UC was evaluated by integrating histological and immunohistochemical analyses. Quantification of oxidative stress, inflammation-related, and lncRNAs (FENDRR and Neat1) gene expression was established. APME was evaluated for its total phenolic content and total flavonoid content. LC–ESI–MS/MS analysis in negative ionization mode identified 35 bioactive metabolites within APME. Stigmasterol (1) and 20-Hydroxyecdysone (2) were isolated by column chromatography from the n-hexane and ethyl acetate fractions, respectively, and characterized using spectroscopic analysis. APME dose-dependently and significantly (p < 0.05) reduced the pro-inflammatory cytokine TNF-α, mitigated malondialdehyde levels, and restored total antioxidant capacity in colonic tissue compared to the untreated ulcerative group. APME`s treatments markedly upregulated the mRNA expression levels of Nrf2 and HO-1, while concurrently suppressing NF-κB mRNA expression. Also, it showed a regulatory effect on FENDRR and Neat1. Histological, immunohistochemical, and morphometric assessments further supported these findings, demonstrating substantial improvements in colonic architecture and cellular integrity. Notably, APME represents a potential antioxidant and anti-inflammatory therapeutic candidate for UC. It modulates FENDRR and Neat1, revealing promising targets for IBD therapy.
Hyperuricemia has become a global metabolic disease, and its progression is closely associated with renal dysfunction and inflammatory injury. Given the limitations of current interventions, it is urgent to discover safe and effective bioactive components from edible natural products. Suaeda maritima subsp. salsa (L.) Soó (JP) is a traditional edible halophyte rich in flavonoids, phenolic acids, and alkaloids. It is considered a plant with health-promoting potential. In this study, we investigated the uric acid-lowering and renoprotective effects of its ethyl acetate extract (JP-EA) and elucidated the underlying mechanisms using network pharmacology, molecular docking, and experimental validation. The results showed that JP-EA significantly reduced serum uric acid levels, improved renal function, and alleviated renal inflammation and fibrosis in hyperuricemic mice. Mechanistically, JP-EA inhibited xanthine oxidase (XOD) activity, downregulated urate reabsorption transporters (URAT1 and GLUT9), upregulated excretion transporters (ABCG2 and OAT1), and suppressed the MAPK/NF-κB/NLRP3 inflammatory pathway, as demonstrated by Western blot and immunofluorescence analyses. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified five key bioactive components, including diosmetin, luteolin, and quercetin, as the major constituents responsible for the observed activities. In conclusion, JP-EA mitigates hyperuricemia and renal inflammatory injury by regulating the MAPK/NF-κB/NLRP3 pathway, supporting its potential application as a functional food ingredient.
Xuan-Jin Li, Shu-Tao Sun, Ying-Ying Chen et al.· Food Quality and Safety· 0 citations
Gul-BuOH affords dose-dependent protection against Cd-induced liver injury by modulating oxidative stress, inflammation, metal detoxification, and metabolic pathways, supporting the traditional use of G. ulmifolia and its potential as a multi-target hepatoprotective agent.
O. A. Elsabagh, Abdelbaset M. Elgamal, Heba A. Hassan et al.· PLoS ONE· 0 citations
Introduction Hyperuricemia (HUA) is a major risk factor for gout and renal injury, underscoring the need for safe and effective natural dietary interventions. This study investigated the chemical composition and antihyperuricemic effects of dealcoholized Zhuyeqing liquor extract (ZLE) using both cellular and animal models. Methods The nutritional composition and phytochemical profile of ZLE were characterized by quantitative analysis and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). The antihyperuricemic activity of ZLE was evaluated in adenosine-induced HepG2 cells and in a hypoxanthine/potassium oxonate-induced mouse model of HUA by assessing uric acid (UA) metabolism, hepatorenal function, urate transporter expression, and renal inflammatory signaling. Results Quantitative analysis showed that ZLE is rich in polysaccharides, terpenes, and flavonoids. UPLC–MS/MS identified 389 phytochemical constituents, predominantly iridoid glycosides, organic acids, and flavonoids. In adenosine-induced HepG2 cells, ZLE significantly reduced UA production and xanthine oxidase (XOD) activity. In HUA mice, ZLE dose-dependently decreased serum UA levels, improved renal and hepatic function by reducing serum creatinine, blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase levels, and inhibited hepatic XOD activity. Furthermore, ZLE restored renal urate homeostasis through coordinated regulation of key urate transporters and alleviated HUA-induced renal inflammation and histopathological injury by suppressing the lipopolysaccharide-mediated NLRP3/Caspase-1 signaling pathway. Discussion These findings demonstrate that ZLE exerts antihyperuricemic and renoprotective effects through coordinated modulation of uric acid production, renal urate transport, and inflammatory signaling. The results support the potential application of ZLE as a functional food ingredient for dietary management of HUA and provide a scientific basis for translating traditional dietary resources into modern nutritional interventions.
Bing Xu, Xiao-Xia Li, Rong Liu et al.· Frontiers in Nutrition· 0 citations
Pajanelia longifolia (Willd.) is a traditionally used medicinal plant with limited scientific evidence regarding its phytochemical composition and pharmacological properties. This study aimed to characterize the phytochemical constituents of P. longifolia leaves and to evaluate their antioxidant, hypoglycemic, antidiarrheal, and analgesic potentials using the DPPH radical‐scavenging assay, oral glucose tolerance test, castor oil‐induced diarrhea, tail immersion, and acetic acid‐induced writhing models, respectively. Methanolic leaf extract was subjected to GC–MS/MS analysis for phytochemical profiling. Molecular docking, drug‐likeness, pharmacokinetic, and toxicity analyses were performed to explore potential interactions between identified phytochemicals and target proteins. GC–MS/MS analysis identified 76 phytochemical constituents, including γ‐sitosterol, squalene, loliolide, and various fatty acid derivatives. Among the tested fractions, the chloroform fraction demonstrated the maximum hypoglycemic and antidiarrheal activities. In contrast, the n‐hexane and ethyl acetate fractions showed notable central and peripheral analgesic effects, respectively. The aqueous fraction exhibited the strongest antioxidant activity. Molecular docking revealed favorable interactions of several identified compounds, particularly γ‐sitosterol and phthalazine derivatives, with human pancreatic α‐amylase, M1 muscarinic acetylcholine receptor, μ‐opioid receptor, and cyclooxygenase‐2. Drug‐likeness, ADMET, and QSAR analyses further supported the pharmacological relevance of selected compounds. The combined findings suggest that the plant is a promising source of bioactive molecules.
Md Rasul Karim, Md Alfaz Hossain, M. Shamim et al.· Chemistry and Biodiversity· 0 citations
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, affecting 37–52% of the population and potentially progressing to cirrhosis and hepatocellular carcinoma. Effective treatments remain limited, making nutraceuticals such as flavonoids promising therapeutic alternatives. Opuntia ficus-indica (L.) (OFI) has demonstrated beneficial effects against MAFLD, although its active compounds remain unclear. In this study, the complexity of the OFI sample was addressed through fractionation by sequential exhaustive extraction (SEE), resulting in six fractions enriched with different compound families, and metabolic markers related to steatosis were evaluated. Butanol (BT), ethanol (ET), and water (WA) extracts reduced lipid accumulation by 18–21%. BT and WA fractions also improved glucose uptake and decreased ketone body and reactive oxygen species production. UPLC-MS analysis showed that the WA extract was rich in piscidic acid and exhibited the highest antioxidant activity, whereas the BT displayed the strongest antisteatotic effect. Glycosylated flavonoids, representing 78% of the BT, were the predominant compounds. Isorhamnetin-glucosyl-rhamnosyl-rhamnoside and isorhamnetin-glucosyl-pentoside were inversely associated with triglyceride release, oxidative stress, and ketone body production. These findings identify isorhamnetin derivatives as key bioactive compounds underlying OFI’s beneficial effects against hepatic steatosis.
Jorge Alberto Uribe-Echeverría, Marilena Antunes-Ricardo· Foods· 0 citations
Endophytic fungi represent a valuable source of bioactive compounds with diverse pharmacological properties. In this study, we explored the antioxidant potential of secondary metabolites produced by Neopestalotiopsis clavispora (N.clavispora), an endophytic fungus isolated from Oroxylum indicum Kurz stem bark. N.clavispora extract was subjected to UPLC-MS analysis to profile its bioactive components, and its antioxidant capacity was assessed using the DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging assay. For in vivo evaluation, Swiss albino mice were administered with 100 mg/kg bodyweight dose of extract for five consecutive days, followed by exposure to 2 Gy of gamma radiation at a dose rate of 3.58 Gy/min. Subsequent measurements of superoxide dismutase (SOD) activity in liver homogenate were conducted to assess antioxidant enzyme response. The data obtained from UPLC-MS, showed, cimicifoetiside B (identified by UNIFI database matching; 44% relative abundance) as the predominant metabolite. N. clavispora extract showed moderate DPPH scavenging (IC₅₀ 82.86 μg/mL vs ascorbic acid 19.01 μg/mL). Molecular docking using cimicifoetiside B against the antioxidant enzyme Superoxide dismutase (SOD), revealing a docking score of −4.96 kcal/mol with 1 hydrogen bond. Molecular dynamics simulations confirmed the interaction with a binding energy of –12.36 ± 02.32 kcal/mol. Binding affinities and molecular interaction profiles indicated possible association with SOD. In vivo, N.clavispora extract at 100 mg/kg body weight/day yielded SOD activity of 1.98 ± 0.38 vs. radiation group 0.78 ± 0.13. These results suggest N.clavispora may have antioxidant related activity under the conditions tested, supporting further in vitro and in vivo studies.
Sushma Swaroopa, Amshumala Bhoothakallu Lolajaksha, T. Gnanasekaran et al.· PLoS ONE· 0 citations
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