Findings indicate that black mulberry fruit extract partially mitigates VPA-induced hepatocellular injury, primarily by enhancing glutathione-dependent antioxidant defenses.
Abstract
Valproic acid (VPA) is widely used to treat neurological and psychiatric disorders but may cause hepatotoxicity partly through oxidative stress and impaired cellular metabolism. This study investigated whether black mulberry (Morus nigra L.) fruit extract attenuates VPA-induced injury in rat FaO hepatoma cells. Cells were exposed to VPA acutely (500 μg/mL for 28 hours) or chronically (120 μg/mL for 4 weeks). Mulberry extract (0.1 mg/mL) was added 3 hours before acute VPA exposure and maintained throughout co-treatment or administered during the final 24 hours of chronic exposure. Cell viability, hydrogen peroxide production, antioxidant enzyme activities, hepatocellular injury markers, glucose concentration, and extracellular 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging capacity were assessed. Compared with VPA alone, mulberry extract significantly increased glutathione peroxidase (GPx) activity under both acute and chronic conditions. During chronic VPA exposure, it also increased glutathione S-transferase (GST) activity and extracellular ABTS radical-scavenging capacity, improved cell viability, and reduced extracellular alanine aminotransferase (ALT) activity. During acute exposure, mulberry significantly reduced extracellular aspartate aminotransferase (AST) activity, whereas the improvement in cell viability was not statistically significant. Hydrogen peroxide production did not differ among acute treatment groups, and mulberry did not restore superoxide dismutase or catalase activity. These findings indicate that black mulberry fruit extract partially mitigates VPA-induced hepatocellular injury, primarily by enhancing glutathione-dependent antioxidant defenses. Further dose-response and in vivo studies are required to confirm its hepatoprotective potential.
OBJECTIVE
Resorcinol bis(diphenyl phosphate) (RDP) is a widely used organophosphate flame retardant, yet data on its reproductive toxicity are limited. This study evaluated the gonadotoxic effects of RDP and the protective potential of ethanolic Citrus sinensis peel extract (EECS) in male Wistar rats.
METHODS
Twenty-eight rats were randomized into four oral treatment groups: control, RDP (500 mg/kg), EECS (600 mg/kg), and RDP+EECS, administered for 14 days.
RESULTS
RDP exposure significantly impaired sperm quality and reduced circulating testosterone levels. Testicular dysfunction was accompanied by qualitative histoarchitectural distortion, oxidative stress, inflammatory responses, and apoptosis. Co-administration of EECS ameliorated these effects, improving sperm parameters and antioxidant status and reducing inflammatory and apoptotic markers.
CONCLUSION
RDP induces testicular dysfunction through oxidative-inflammatory and mitochondrial pathways, whereas EECS exerts protective effects via antioxidant and anti-inflammatory mechanisms. These findings suggest that EECS may be a promising agent against RDP-induced reproductive toxicity.
T. Olatunji, A. Odetayo, H. Abdulrahim et al.· JBRA Assisted Reproduction· 0 citations
Diethylnitrosamine (DEN) induces oxidative stress, lipid peroxidation, and hepatocellular damage, highlighting the need to identify effective hepatoprotective agents. Although Carica papaya, Azadirachta indica, and Allium sativum possess recognized antioxidant and anti-inflammatory potential, evidence regarding their combined hepatoprotective effects remains limited. This study compared the effects of their individual and combined extracts against DEN-induced liver injury in male albino Wistar rats. Rats weighing 150–200 g were allocated to six groups (n = 6): normal control, DEN-only, papaya extract, neem extract, garlic extract, and combined-extract groups. DEN was administered intraperitoneally at 100 mg/kg once weekly for eight weeks. Ethanolic plant extracts prepared through Soxhlet extraction were administered orally at doses ranging from 100 to 400 mg/kg daily. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, malondialdehyde, and glutathione concentrations were assessed using standard biochemical assays, while liver tissues were evaluated histologically following hematoxylin and eosin staining. Data were analyzed using analysis of variance followed by Tukey’s post hoc test, with statistical significance established at p < 0.05. DEN exposure significantly increased liver enzymes, bilirubin, and malondialdehyde while reducing glutathione, confirming substantial hepatic injury. The individual extracts provided moderate protection, as demonstrated by partial normalization of biochemical markers and improved histological features. Hepatoprotection increased with dosage, with the strongest effects observed at 300–400 mg/kg. The combined extract produced the greatest protective effect, with biochemical indices approaching normal control values, improved antioxidant status, and restoration of hepatic architecture. These findings indicate that combining papaya, neem, and garlic extracts may provide greater hepatoprotection than administering the individual extracts against DEN-induced liver injury. The study supports further mechanistic and preclinical evaluation of this polyherbal formulation before its potential therapeutic application in liver-disease management.
Egeonu Us, Umaru Ij, Izam Ed et al.· African Journal of Clinical...· 0 citations
Over 25% of people worldwide have liver illnesses, which kill nearly 2 million. This study assessed the hepatoprotective potential of Baccaurea motleyana fruit acetone extract (BMF‐AE) against CCl4‐induced liver injury. GC–MS phytochemical profiling identified nine metabolites, with linoleic acid ethyl ester, quercetin, and gallic acid as predominant bioactives known for hepatoprotective activity. The antioxidant activity of BMF‐AE was significant in DPPH and ABTS assays, with IC50 values of 112.55 and 127 µg/mL, respectively. In vivo hepatoprotective efficacy was assessed in five groups (n = 5) that received oral BMF‐AE (200 or 400 mg/kg) for 14 days. Positive control was 100 mg/kg silymarin. The CCl4‐induced increase in serum ALT, AST, ALP, and bilirubin was dramatically reduced, while BMF‐AE restored albumin levels (p < 0.05). Treatment reduced hepatic TBARS and restored glutathione and catalase activity, reducing oxidative stress. Histopathological investigation demonstrated maintained liver architecture in treated rats. Molecular docking analysis revealed that quercetin and linoleic acid ethyl ester bind strongly to targets of oxidative stress and inflammation, including xanthine oxidoreductase, interleukin‐6, tumor necrosis factor‐α, and PARP‐1, suggesting potential hepatoprotective effects. BMF‐AE may be a promising natural therapy for oxidative stress‐mediated liver injury, according to this study, due to its antioxidant phytoconstituents.
Mahmudul Hasan, Safayat Hossen Momen, Momena Akter et al.· Chemistry and Biodiversity· 0 citations
Despite the traditional application of Sophora moorcroftiana seeds (SMS) in Tibetan medicine for heat-clearing, damp-drying, anti-inflammatory and detoxifying properties, the anti-inflammatory mechanisms of SMS remain insufficiently understood and warrant systematic investigation. This study evaluated the protective effects of an ethanolic SMS extract against lipopolysaccharide (LPS)-induced oxidative stress and inflammation in RAW 264.7 macrophages, with emphasis on the p62/Keap1/Nrf2 signaling pathway. In vitro, the extract exhibited significant DPPH, ABTS and ·OH radical scavenging activities, as well as ferric-reducing antioxidant power, in a clear concentration dependent manner. An inflammatory model was established by stimulating RAW 264.7 cells with LPS, followed by treatment with graded concentrations of the ethanolic SMS extract. The extract significantly reduced LPS-induced nitric oxide production and decreased the secretion of TNF-α, IL-6 and IL-1β, while suppressing iNOS and COX-2 expression at both mRNA and protein levels. In parallel, the extract alleviated oxidative stress, as evidenced by reduced intracellular reactive oxygen species (ROS) and MDA levels, increased antioxidant defenses including SOD, GSH and CAT, and decreased LDH release. At the protein-expression level, SMS treatment was accompanied by differential changes in p62, Keap1, total Nrf2 and HO-1 expression, suggesting that its effects may involve regulatory processes associated with cellular stress and antioxidant defense. Collectively, the ethanolic extract of SMS attenuated LPS-induced inflammatory and oxidative stress responses in RAW 264.7 macrophages. These effects may be associated with the suppression of inflammatory mediator production, reduction in the cellular oxidative stress burden and modulation of proteins involved in cellular stress responses and antioxidant defense.
Nianshou Zhao, Hongya Li, Peng Ji et al.· Antioxidants· 0 citations