Dietary supplementation of Acer truncatum leaf extract alleviates oxidative-stress induced impairment of ovarian function in laying hens via Nrf2-mediated antioxidant defense and VEGF-mediated angiogenesis
Aug 2026· Stress Biology· Vol 6· 0 citations· 70 references
Medicine
TL;DR
By reversing dysregulation of key genes such as VEGFA, KDR, and FN1, ATLE restored core pathways including focal adhesion and ECM–receptor interaction and coordinated processes such as extracellular matrix, angiogenesis, and response to wounding, driving a systemic remodeling of the ovarian reproductive microenvironment toward homeostasis.
Abstract
This study aimed to evaluate the potential of Acer truncatum leaf extract (ATLE) to mitigate oxidative-stress–induced impairment of reproductive function in laying hens, with a focus on mechanisms involving antioxidant defense, angiogenesis, and ovarian microenvironment homeostasis. Oxidative stress was induced by tert-butyl hydroperoxide (tBHP) injection. Hens were randomly assigned to a control group (CON), an oxidative stress group (BCON), and an oxidative stress group supplemented with 0.6% ATLE (BATLE). Egg-laying performance, ovarian morphology, reproductive hormones, oxidative stress markers, and angiogenesis indicators were evaluated and integrated with transcriptomic analysis. The results were as follows: 1) Production and Morphology: ATLE supplementation alleviated (P < 0.05) the tBHP-induced decrease in egg laying rate and elevation in feed conversion ratio (FCR). It also mitigated (P < 0.05) reductions in the number of hierarchical follicles and the ovarian stroma index while restoring (P < 0.05) serum concentrations of LH and GH, thereby re-establishing reproductive endocrine balance. 2) Antioxidant Defense: ATLE activated (P < 0.05) Nrf2 and increased (P < 0.05) transcription of downstream antioxidant genes, including SOD3, GPX3, PRDX4, GSR and CAT, thereby enhancing (P < 0.05) the SOD and CAT activities and reducing (P < 0.05) MDA concentrations within both serum and ovarian tissues. 3) Vascular Network Support: ATLE attenuated (P < 0.05) the tBHP-induced downregulation of angiogenic factors, including protein levels of VEGF, ANGPT1, and HIF-1α and mRNA expression levels of VEGFA, ANGPT1, ANGPT2, ITGA5, and MMP9. 4) Microenvironment Remodeling: Transcriptomic integration revealed that ATLE-mediated repair overlapped (> 88%) with oxidative-stress–induced damage across functional modules. By reversing dysregulation of key genes such as VEGFA, KDR, and FN1, ATLE restored core pathways including focal adhesion and ECM–receptor interaction, and coordinated processes such as extracellular matrix, angiogenesis, and response to wounding, driving a systemic remodeling of the ovarian reproductive microenvironment toward homeostasis. In summary, this study demonstrated that ATLE activated multiple signaling axes, notably Nrf2 and VEGF. As a result, ATLE enhanced antioxidant defenses against oxidative damage and promoted vascular health and microenvironmental remodeling in the ovary. Together, these effects preserved the structural integrity and function of the laying hen reproductive system. These findings supported the potential of ATLE as a natural feed additive and provided a scientific rationale for using nutritional strategies to alleviate oxidative stress and improve reproductive health in laying hens.
Oxidative stress is a major challenge in weaned piglet production because it impairs intestinal health, nutrient utilization, and growth performance; however, the effects of dietary epigallocatechin-3-gallate (EGCG) on intestinal dysfunction under oxidative stress conditions have not been fully elucidated. This study examined whether dietary EGCG supplementation could improve intestinal function in weaned pigs subjected to Diquat-induced oxidative stress. Thirty-two weaned piglets were allocated to four treatments according to a 2 × 2 factorial arrangement involving dietary EGCG supplementation (0 or 50 mg/kg) and exposure to saline or Diquat (50 mg/kg body weight). Diquat exposure impaired intestinal morphology and antioxidant status and altered the transcription of genes associated with epithelial barrier integrity and redox regulation. Dietary EGCG supplementation partially attenuated these alterations, as reflected by improvements in villus architecture, intestinal antioxidant indices, and the mRNA expression of barrier- and antioxidant-related genes. These findings indicate that dietary EGCG supplementation was associated with improved intestinal function in weaned pigs exposed to oxidative stress. These beneficial effects may be related, at least in part, to changes in redox status, inflammatory responses, epithelial barrier-related gene expression, and selected gut microbial populations. This study supports EGCG as a potential bioactive dietary factor for maintaining intestinal health under oxidative stress conditions.
Abamectin (ABM) is a macrocyclic lactone insecticide that induces oxidative stress and testicular toxicity, but its specific effects on male reproductive function remain unclear. Here, we tested whether an aqueous extract of Salvia officinalis (S. officinalis) could mitigate ABM-induced testicular injury in adult male rats, focusing on mitochondrial fusion and apoptosis. Thirty-six rats were divided into six groups: control, S. officinalis extract (100mg/kg), low-dose ABM (0.5mg/kg), high-dose ABM (1mg/kg), S. officinalis + low-dose ABM, and S. officinalis + high-dose ABM, for 70 days. Our results showed that the extract was rich in total phenolics and flavonoids. The main phenolic compounds were ferulic acid, syringic acid, caffeic acid, p-coumaric acid, and α-tocopherol, while the main flavonoids were luteolin, 2'-hydroxyflavone, apigenin, and quercetin. Rats exposed to ABM had lower sperm concentration and motility, more abnormal sperm, and markedly lower serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone in a dose-dependent manner. Furthermore, testicular malondialdehyde and nitric oxide levels increased, whereas catalase activity, glutathione levels, and the activities of superoxide dismutase and glutathione S-transferase decreased. Gene expression analysis showed reduced mitofusin-1 and mitofusin-2 and increased p53 and caspase-9 expression. Notably, co-administration of S. officinalis with ABM improved sperm quality, hormone levels, antioxidant status, gene expression, and testicular tissue structure. Our findings highlight the protective mechanisms of S. officinalis, including enhancing antioxidant defenses, promoting mitochondrial fusion, and inhibiting the intrinsic apoptotic pathway. These results suggest that the S. officinalis extract could have therapeutic potential for ABM-induced male reproductive toxicity.
Mohammed Eleyan, Mohamad Abou Auda, Mohamed Hussien et al.· Reproductive Toxicology· 0 citations
Background Oxidative stress and inflammation play key pathological mechanisms involved in the development of chronic diseases. Although tea blister blight reduces commercial tea quality, pathogen-induced stress may enhance the accumulation of bioactive phenolics and flavonoids, making infected leaves a potential resource for the food-medicine homology framework. This study aimed to evaluate the protective effects of a tea blister blight aqueous extract (TBB) against copper sulfate (CuSO4)-induced oxidative and inflammatory stress in zebrafish (Danio rerio) embryos. Methods Zebrafish embryos were exposed to 3 μM CuSO4 and co-treated with TBB at concentrations of 0.3–0.9 mg/mL. Developmental toxicity was evaluated based on survival, hatching, and morphological outcomes. Oxidative stress was assessed by measuring malondialdehyde (MDA) levels and antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT). The expression of genes related to antioxidant defense, inflammation, and apoptosis was also analyzed. Results TBB treatment significantly increased embryo survival by 12.74–15.81% and the hatching rate by 46.12–51.38% than the CuSO4-exposed group. TBB also reduced CuSO4-induced developmental toxicity by increasing body length by 15.38–16.35% and improving the sinus venosus–bulbus arteriosus distance by 10.40–14.80%. In addition, TBB significantly mitigated oxidative stress by reducing MDA levels by 16.74–25.61% and enhancing SOD and CAT activities by 31.29–72.35% and 69.66–92.37%, respectively. Gene expression analysis showed that TBB upregulated antioxidant-related genes (Mn-sod, CAT, and Gpx1a), suppressed proinflammatory genes (TNF-α, NF–κB, NLRP3, and IL-1β), and downregulated the pro-apoptotic gene bax, while enhancing anti-inflammatory (IL-10) and anti-apoptotic (Bcl-2) expression. Conclusion These findings demonstrate that TBB provides multilevel biological protection through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Importantly, this study provides a new perspective by demonstrating that tea leaves infected with tea blister blight disease, rather than being discarded or managed solely through fungicide application, can be valorized as a bioactive-enriched resource for applications in functional nutrition and health-promoting products.
Jiaqi Liu, Hoang Huy Nguyen, Yuqing Ma et al.· Frontiers in Nutrition· 0 citations
Maternal aging is associated with increased oxidative stress and decreased mitochondrial function, which deteriorate oocyte quality. Ginsenoside Re (GRe), an antioxidant derived from Panax ginseng, has been reported to alleviate cellular damage and extend healthy lifespan. In this study, we investigated the protective effects of GRe on in vitro-matured bovine oocytes and elucidated the underlying mechanisms. Oocyte aging-like oxidative stress conditions were induced by adding 20 mg/mL D-galactose (D-gal) to the in vitro maturation (IVM) medium; GRe treatment involved supplementing the medium with various GRe concentrations (25, 50, and 100 μg/mL). GRe treatment significantly improved maturation, with 50 μg/mL GRe showing the most pronounced effect. This recovery was accompanied by reduced accumulation of reactive oxygen species and improved mitochondrial capacity and biogenesis, mediated by SIRT1/Nrf2 signaling. Consequently, GRe improved embryonic developmental ability. These findings suggest that GRe may improve oocyte quality in the context of aging and associated oxidative stress.
Seo-Young Hyeon, C. Perera, Seung-Eun Lee et al.· International Journal of Mol...· 0 citations
Background Skeletal muscle atrophy is characterized by impaired protein synthesis, increased proteolysis, oxidative stress, and mitochondrial dysfunction. Phytoceutical interventions with antioxidant and cytoprotective properties may offer therapeutic potential in muscle-wasting conditions. Objective To assess the effects of LI12542F6 SMI, a standardized formulation of Sphaeranthus indicus (SI) flower heads and Mangifera indica (MI) bark extracts (2:1), on dexamethasone (DEX)-induced skeletal muscle atrophy and to elucidate the underlying molecular mechanisms. Design In vitro studies assessed antioxidant activity, endothelial nitrite production, protein synthesis, and the activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling (PI3K/AKT/mTOR) pathway, with or without DEX. In vivo, male Sprague Dawley rats received DEX (0.1 mg/kg body weight) and were supplemented with SMI (0, 45, or 90 mg/kg body weight) for 12 days. Outcomes included lean body mass, grip strength, muscle histology, antioxidant enzyme activity, and the expression of anabolic and catabolic protein markers. Results SMI enhanced reactive oxygen species scavenging and increased endothelial nitrite production via PI3K/AKT-mediated activation of endothelial nitric oxide synthase. In DEX-treated rats, SMI attenuated declines in lean body mass, grip strength, and muscle fiber morphology. Mechanistically, SMI improved antioxidant markers, activated PI3K/AKT/mTOR signaling and myogenic markers, and suppressed catabolic and apoptotic proteins. The hepatic or renal biochemical parameters were unaltered. Discussion These findings indicate that SMI mitigates glucocorticoid-induced muscle atrophy through coordinated modulation of oxidative stress, mitochondrial function, and anabolic signaling pathways. The activation of PI3K/AKT/mTOR signaling appears central to its effects, linking antioxidant activity with enhanced protein synthesis and the suppression of apoptotic signaling. Conclusions SMI attenuates DEX-induced skeletal muscle atrophy and improves functional and molecular markers. These findings suggest further investigation and clinical substantiation of this phytoceutical as a possible intervention for muscle-wasting conditions.
Sreenath Kundimi, T. Rao, G. Park et al.· Food & Nutrition Research· 0 citations
Objective
This study examined the potential protective role of date palm fruit extract (DPFE) and its underlying mechanisms against busulfan-induced sperm damage and infertility.
Methods
Sixty male Wistar rats were allocated to control, busulfan alone (10 mg/kg), DPFE alone (4 mg/kg), and busulfan+DPFE co-treatment groups for a period of 56 days. Semen parameters were evaluated along with DNA fragmentation, assessed using the sperm chromatin dispersion test, and protamine deficiency, detected by chromomycin A3 staining. Testicular oxidative stress was assessed by measuring malondialdehyde (MDA) levels as well as superoxide dismutase (SOD) and catalase (CAT) activities.
Results
Phytochemical analysis confirmed the high polyphenolic and flavonoid content of DPFE. Busulfan significantly induced testicular oxidative stress, as evidenced by increased MDA levels and reduced SOD and CAT activities. These alterations were accompanied by significant declines in sperm motility and viability, deterioration of sperm morphology, and marked increases in protamine deficiency and DNA fragmentation. Co-administration of DPFE significantly counteracted these adverse effects by normalizing testicular oxidative status, reflected by decreased MDA levels and restoration of SOD and CAT activities. Consequently, DPFE improved sperm motility and morphology and, importantly, reduced the proportion of sperm exhibiting high DNA fragmentation and protamine deficiency.
Conclusion
Antioxidant-rich DPFE exerts a significant protective effect against busulfan-induced testicular toxicity, with its mechanism strongly linked to attenuation of testicular oxidative injury, thereby improving conventional sperm quality and, critically, preserving sperm chromatin structure and DNA integrity.
H. Akbari· Clinical and Experimental Re...· 0 citations
