Aug 2026· PLoS ONE· Vol 21, pp. e0355464· 0 citations· 97 references
Medicine
TL;DR
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.
Abstract
Background Guazuma ulmifolia is traditionally used for liver disorders, but its protective mechanisms against heavy metal toxicity are poorly defined. This study evaluated the phytochemical profile and hepatoprotective mechanisms of G. ulmifolia butanol extract (Gul-BuOH) against cadmium-induced liver injury. Methods and findings Gul-BuOH was chemically profiled by UPLC-PDA-ESI–qTOF-MS/MS. Cadmium hepatotoxicity was induced in rats, followed by Gul-BuOH treatment (100 and 200 mg/kg). Liver injury, oxidative stress, inflammation, gene expression (Let-7a, HOTAIR), histopathology, HO-1/Sirt-1 immunoreactivity, and serum metabolomic changes were assessed. Chemical profiling led to the annotation of 42 compounds, including mainly flavonoids and phenolic acids, highlighting the rich phytochemical composition of G. ulmifolia. CdCl2 exposure increased hepatic Cd accumulation and elevated ALT, AST, and ALP, reduced TAC, and increased NO and MDA. Gul-BuOH significantly reduced hepatic Cd levels by 2.6- and 3.2-fold, restored TAC by 38.3% and 83.2%, and decreased NO (56.3% and 63.4%) and MDA (45.4% and 54.6%) at 100 and 200 mg/kg, respectively. Inflammatory markers NF-κB-p and TNF-α were markedly suppressed, while miRNA Let-7a was upregulated and lncRNA HOTAIR was downregulated. Histological and immunohistochemical analyses revealed near-complete restoration of hepatic architecture and normalization of HO-1 and Sirt-1 expression at the high dose. Serum metabolomics’ OPLS-DA model performance indicators demonstrated strong reliability, with an R2Y (explained variance) of 0.991 and a Q2 (predictive variance) of 0.988). The model identified 36 significantly altered metabolites that were largely normalized by Gul-BuOH, implicating linoleic acid metabolism, amino acid biosynthesis, and ascorbate-related pathways. Conclusion 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.
U. lactuca showed promising effects against sub-chronic liver injury, primarily due to its rich nutritional profile, and its incorporation into the Pakistani diet may reduce disease and economic burden while supporting functional food and nutraceutical industries.
Noohela Khan, W. Ahmed, Muhammad Asif Ali et al.· Foods· 0 citations
Methamphetamine (METH) abuse is linked to significant hepatic injury, driven by oxidative stress, inflammatory pathway activation, autophagic dysregulation, and apoptosis induction. This study explored the hepatoprotective and anti‐inflammatory potential of the brown seaweed
Hormophysa cuneiformis
extract against METH‐induced liver damage in adult male Wistar rats.
Extracts prepared using methanol, ethanol, hexane, and water were screened for antioxidant activity. The methanolic extract, selected for further investigation, was characterized by phytochemical analysis and GC–MS profiling. Molecular docking was performed to evaluate the interactions of the identified bioactive compounds with TNF‐α and LC3B‐II. The cytotoxicity and selectivity of the methanolic extract were assessed using HepG‐2 hepatocellular carcinoma and WI‐38 normal cells. Its hepatoprotective effects were further evaluated in vivo in METH‐treated adult male Wistar rats using biochemical, Western blot, immunohistochemical, and histopathological analyses.
The methanolic extract showed the greatest antioxidant activity, achieving 57.16% ± 1.96% DPPH radical scavenging and 54.71% ± 0.84% ferric‐reducing antioxidant power. Although these values were lower than those of ascorbic acid (97.23 ± 0.48%), the methanolic extract exhibited higher antioxidant potential than the other extracts. Secondary metabolites, including alkaloids, saponins, tannins, and total phenolic compounds, were detected in notable amounts. GC‐MS analysis identified oleic acid, palmitic acid, linoleic acid, and arachidonic acid as the major constituents. The extract exhibited dose-dependent cytotoxicity against HepG–2 cells, with an IC50 of 77.14 ± 1.63 µg mL
−1
, while showing lower toxicity toward WI-38 cells (CC50 = 141.99 ± 3.54 µg mL
−1
), indicating selective antiproliferative activity and a favorable safety margin. In vivo, METH administration significantly elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels. Oral co-treatment with the
H. cuneiformis
methanolic extract (15 mg kg
−1
) significantly attenuated METH-induced hepatocellular injury, lowering serum ALT from 89.33 to 54.33 U L
−1
, AST from 294.33 to 57.33 U L
−1
, and ALP from 264.67 to 189.00 U L
−1
. Western blot analysis showed that METH markedly increased LC3B-II and Beclin-1 expression, whereas co-administration of the extract significantly reduced both proteins. Immunohistochemical analysis also demonstrated increased caspase-3- and NF-κB-positive cells in the METH-treated group, which were significantly reduced following H. cuneiformis treatment.
Collectively, these findings suggest that
H. cuneiformis
exerts hepatoprotective effects against METH-induced liver injury through antioxidant, anti-inflammatory, anti-apoptotic, and autophagy-modulating mechanisms.
Mayada E. Elhusseiny, Rabab El-kelany, Rania A. El-Shenody et al.· Frontiers in Pharmacology· 0 citations
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.
M. Hassan, Marwa M. Mona, Marwa M. Abd-Elsalam et al.· InflammoPharmacology· 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
Excessive use of acetaminophen (APAP) significantly contributes to drug-induced liver injury (DILI). Auricularia heimuer polysaccharides have significant hepatoprotective potential, however their mode of action in mitigating DILI is not yet elucidated. This study isolated and purified a novel polysaccharide, Ahp-1, from the fruiting bodies of A. heimuer, with a molecular weight of 270.161 kDa. Structural analysis revealed that the principal glycosidic linkages in Ahp-1 are 6-Gal, 6-Glc, t-Fuc, and 2,6-Gal, which form dimers by cross-linking of polysaccharide chains. Animal studies indicated that Ahp-1 reduces oxidative stress, elevates the relative abundance of beneficial bacteria within the gut microbiota, regulates microbial balance, and promotes the synthesis of favorable metabolites like Trigonelline. Moreover, following fecal microbiota transplantation (FMT), Ahp-FMT augments tight junction proteins and short-chain fatty acids (SCFAs), thus restoring the intestinal barrier. This subsequently stimulates the AMPK/GSK3β and Nrf2/HO-1 signaling pathways to mitigate DILI. These results provide novel opportunities for using A. heimuer polysaccharides as functional foods or hepatoprotective agents.
Ying-Di Dai, De-Tian Li, Si-Jia Ma et al.· Food Science and Human Welln...· 0 citations
PO confers hepatoprotection via the gut–liver axis, which is associated with changes in ceramide metabolism and ferroptosis-related markers, which is associated with changes in ceramide metabolism and ferroptosis-related markers.
Huanghui Qin, Runxiao Chen, Ying Shi et al.· Frontiers in Pharmacology· 0 citations
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