Multidrug-resistant (MDR) Escherichia coli (E. coli) is a major global health threat, causing increased morbidity, mortality, and healthcare burden. It is a common cause of community- and hospital-acquired infections, with a strong ability to acquire and disseminate resistance genes via horizontal gene transfer and mutations. This review provides an overview of MDR E. coli, focusing on resistance mechanisms, diagnostic approaches, and control strategies. Key resistance mechanisms include production of extended-spectrum β-lactamases (ESBLs), carbapenemases, efflux pump overexpression, target site alterations, and reduced membrane permeability. Quorum sensing and biofilm formation further enhance bacterial survival and resistance. Diagnostic methods range from conventional antimicrobial susceptibility testing to advanced molecular and genomic techniques such as PCR and whole-genome sequencing. Emerging tools, including Fourier transform infrared spectroscopy, surface-enhanced Raman spectroscopy, MALDI-TOF MS, automated systems, and biosensors, offer rapid and accurate detection. Control strategies involve antimicrobial stewardship programs, alternative therapies such as natural compounds and QS inhibitors, and strict infection prevention measures. Addressing MDR E. coli requires a multidisciplinary approach integrating timely diagnosis, effective treatment, and robust infection control policies. A comprehensive literature search was conducted across major databases, and selected studies were qualitatively analyzed to summarize current knowledge and highlight emerging trends. Understanding these aspects is essential for limiting the spread of MDR E. coli and improving clinical outcomes globally.
Objective: To determine the qualitative and quantitative phytochemical components in the aqueous leaf extract of Trigonella foenum-graecum L. (AqE-TFG) and evaluate its therapeutic potential against high-fat diet-associated dyslipidemia in high-fat diet-induced obese rats. Methods: A total of 24 healthy adult male albino rats were randomly divided into 4 groups ( n =6): Group 1 (normal control), Group 2 (untreated dyslipidemic control), Group 3 and 4 (low and high dose treatments of AqE-TFG 250 mg/kg and 500 mg/kg). Blood samples were collected for the estimation of lipid profile, oxidative markers, biochemical parameters, and histopathology of adipose tissue. Gene expression analysis was performed using qRT PCR. Results: AqE-TFG showed antioxidant activity (IC 50 = 4.82 μg/mL). HPLC analysis showed the presence of sinapic acid, p -coumaric acid, gallic acid, salicylic acid, kaempferol, ferulic acid, chlorogenic acid, quercetin, and HB acid. AqE-TFG remarkably inhibited body weight gain and restored the lipid profile. Furthermore, AqE-TFG elevated superoxide dismutase and catalase levels. Besides, AqE- TFG significantly downregulated mRNA expression levels of dual oxidase-related genes ( Duox, Duoxa-1, Duox2 ) and downstream MAPK/JNK signaling cascade genes ( MAPK8, Traf4, Traf6 ). Adipose tissue histology showed well-organized, intact adipocytes in treatment groups. Conclusions: AqE-TFG has both preventive and therapeutic effects against high-fat diet-induced dyslipidemia. AqE-TFG could enhance antioxidant defense and restore histopathological lesions via MAPK/JNK signaling pathway.
Objective: To investigate the antiviral potential of Sonchus arvensis L. extracts against dengue virus (DENV)-1 and DENV-2 in vitro , and elucidate its underlying antiviral mechanisms. Methods: The cytotoxicity of the ethanol, ethyl acetate, and n -hexane extracts of Sonchus arvensis L. was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, followed by post-treatment antiviral assays. Multiple treatment regimens were conducted to assess antiviral effects at different stages of the DENV replication cycle. qRT-PCR analysis was performed to evaluate the effects of the ethanol extract on genes associated with host innate immune and inflammatory responses. Results: The CC 50 values of the ethanol, ethyl acetate, and n -hexane extracts were 391.5 μg/mL, 104.9 μg/mL, and 409.2 μg/mL, respectively. The ethanol and ethyl acetate extracts reduced DENV- 1 and DENV-2 titers by >90% at 30-50 μg/mL, while the n -hexane extract showed comparable activity against DENV-2. The ethanol extract at 30 μg/mL demonstrated potent multi-stage antiviral activity, including direct virucidal, prophylactic, anti-adsorption, and anti-internalization effects. qRT-PCR analysis revealed no significant change in IFN-β expression but marked suppression of NF-κB , TNF-α , and IL-6 expression. Conclusions: Sonchus arvensis L. ethanol extracts demonstrate potent multi-stage antiviral activity against DENV in vitro , highlighting its ability to inhibit viral entry, reduce viral replication, and attenuate excessive inflammatory responses.
Objective: To evaluate the cardioprotective effects of resveratrol and curcumin, individually and in combination, against doxorubicin- induced cardiac toxicity and explore the underlying mechanisms via network pharmacology. Methods: In silico target prediction, enrichment analyses, and Cytoscape network modeling were performed to investigate shared molecular targets and pathways among resveratrol, curcumin and doxorubicin. Male Wistar rats ( n =6/group) received oral treatments of vehicle, nebivolol (5 mg/kg), resveratrol (20 mg/kg), curcumin (100 mg/kg), resveratrol plus curcumin for 28 d, with cardiotoxicity induced via doxorubicin (2.5 mg/kg, i.p .) on days 7 and 14. Cardioprotection was evaluated using electrocardiographic, hemodynamic, biochemical, RT-PCR, and histopathological assays. Results: Network analysis revealed four common targets (NFE2L2/ Nrf2, TNF, CYP3A4, and MAPT) with significant protein-protein interaction enrichment ( P =0.019 6), implicating modulation of redox balance, inflammation, and xenobiotic metabolism. Concomitant therapy with resveratrol and curcumin significantly mitigated doxorubicin-induced cardiac injury by suppressing relative heart weight, reducing myocardial infarction area, reversing electrocardiographic and conduction abnormalities, attenuating dyslipidemia, and lowering serum CK-MB, LDH, and troponin I leakage ( P < 0.05). Furthermore, combination treatment was more effective in restoring cardiac antioxidants, decreasing lipid peroxidation, downregulating mRNA expressions of TNF-α and NF-κB , upregulating Nrf2 mRNA expression, and improving myocardial architecture compared with individual monotherapies. Conclusions: Concomitant therapy with resveratrol and curcumin confers robust cardioprotection against doxorubicin-induced cardiotoxicity in rats, likely via coordinated activation of Nrf2- mediated antioxidant defenses and suppression of TNF-α/NF- κB-driven inflammation, supporting their potential for future investigation as adjunct therapies during anthracycline treatment.
Hantaviruses are rodent-borne zoonotic pathogens responsible for two major clinical syndromes: Hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome/cardiopulmonary syndrome. Although significant progress has been achieved in hantavirus research over recent decades, major challenges remain in surveillance, diagnostics, therapeutics, and vaccine development. This review comprehensively synthesizes current evidence on hantavirus virology, taxonomy, reservoir ecology, transmission dynamics, global epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention, and One Health surveillance strategies. Particular emphasis is placed on the immunopathological mechanisms underlying endothelial dysfunction and vascular hyperpermeability, the hallmark features of severe disease. The review further explores how climate variability, land-use change, biodiversity loss, and rodent population dynamics shape spillover risk and geographic expansion. Current diagnostic approaches, including serology, RT-PCR, and next-generation sequencing, are critically evaluated alongside emerging point-of-care technologies. Therapeutic limitations are highlighted, particularly the absence of universally effective antivirals and globally approved vaccines. Key research gaps identified include inadequate surveillance in South Asia and Africa, insufficient understanding of Andes virus human-to-human transmission, limited validation of rapid diagnostics, and unresolved mechanisms of immune- mediated pathology. Adopting a One Health perspective, this review proposes priority research and public health directions to strengthen global preparedness, improve outbreak prediction, and accelerate development of effective diagnostics, therapeutics, and vaccines against hantavirus disease.
Classical swine fever remains a major threat to global pig production systems, despite decades of sustained control endeavours. Its causative agent classical swine fever virus (CSFV) employs a highly coordinated set of immune evasion mechanisms to weaken host antiviral defences and permit extensive viral replication. A central focus of this strategy is the antigen-presentation machinery, where CSFV disrupts both major histocompatibility complex class (MHC)-I and MHC-II pathways in macrophages and dendritic cells, which are its primary immune cell reservoirs. By suppressing interferon signaling, dysregulating NF-kB activation, and impairing the maturation of antigen-presenting cells, CSFV compromises peptide processing, co-stimulatory signaling, and T-cell priming. These defects propagate through the adaptive immune system, leading to delayed cytotoxic responses, inadequate CD4 + T-cell help, and impaired humoral immunity. CSFV simultaneously reshapes macrophage polarization, drives profound dendritic cell dysfunction, induces lymphoid apoptosis, and modulates γδ T-cell activity in a manner that correlates with viral virulence. In addition, viral remodeling of intracellular organelles further limits antigen presentation and exacerbates immunopathology. Together, these interconnected mechanisms create a permissive cellular environment that facilitates viral persistence and amplifies disease severity. Understanding how CSFV manipulates antigen-presentation pathways provides crucial insights for the design of next-generation vaccines and therapeutic strategies capable of restoring robust antiviral immunity.
Objective: To investigate the inhibitory effects of Ishige okamurae extract (IOE) against osteoclastogenesis in vitro and in vivo. Methods: The effects of IOE on osteoclast differentiation were examined in receptor activator of nuclear factor-KB ligand (RANKL)-stimulated bone marrow macrophages. Cell viability was examined using an MTT assay, while osteoclast formation and differentiation were determined by tartrate-resistant acid phosphatase (TRAP) staining kit. Protein expression levels of osteoclast-related factors, transcriptional factors, and signaling molecules involved in osteoclastogenesis were analyzed by Western blotting. The effect of IOE was examined in the ovariectomy (OVX) mouse model following oral administration, and osteoclast-related parameters were analyzed using 3D X-ray microscopy. Results: IOE significantly reduced RANKL-induced osteoclast formation and differentiation without causing cytotoxic effects on bone marrow macrophages. It suppressed the formation of TRAP-positive multinuclear osteoclasts and downregulated the expression of osteoclast- related factors, such as TRAP (ACP5), matrix metalloproteinase-9, calcitonin receptor, and cathepsin K. Furthermore, IOE significantly inhibited the expression of key transcriptional factors, such as nuclear factor of activated T cells, cytoplasmic 1, and c-Fos. Mechanistically, IOE attenuated the activation of upstream extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-KB (NF-kB) cascades. In OVX mice, administration of IOE significantly improved bone microstructural parameters such as trabecular thickness, number, volume, and separation. Conclusions: The present findings demonstrate that IOE inhibits osteoclastogenesis via blockage of ERK, JNK, and NF-kB signaling pathways in vitro. Furthermore, IOE administration reduces bone loss in OVX mice. These results show that IOE has the potential to be a functional food for the prevention of osteoporosis.
Objective: To explore whether gomisin D, a lignan derived from Schisandra chinensis, protects against podocyte injury in diabetic kidney disease and to elucidate its underlying mechanisms. Methods: Network pharmacology was employed to analyze the potential interactions between gomisin D and podocyte injury- related targets in diabetic nephropathy. A high glucose-induced injury model of mouse podocyte MPC5 cells was established, and the effect of gomisin D on podocyte injury was subsequently evaluated by measurement of reactive oxygen species levels and biochemical markers and Western blotting. Molecular docking and further molecular biology assays were conducted to explore the interaction between gomisin D and the target protein. Results: Gomisin D inhibited high glucose-induced oxidative stress, improved cell viability, and preserved the expression of podocin and synaptopodin. Network pharmacology identified glycogen synthase kinase-3β (GSK3β) as a key target. Molecular docking predicted a potential interaction between gomisin D and GSK3β, which was further validated by drug affinity responsive target stability and cellular thermal shift assay, confirming direct binding in live cells. Mechanistically, gomisin D enhanced the phosphorylation of GSK3β at Ser9, promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and upregulated levels of downstream antioxidant proteins heme oxygenase-1 and NAD(P) H quinone oxidoreductase 1. Furthermore, forced expression of the constitutively active GSK3β mutant S9A decreased GSK3β (Ser9) phosphorylation and reversed gomisin D-induced upregulation of these antioxidant markers. Conclusions: Gomisin D mitigates high glucose-induced podocyte injury in vitro by inhibiting oxidative stress via activation of the GSK3β(Ser9)/Nrf2/ARE signaling pathway.
Objective:To evaluate the effect of isorhamnetin on diabetic kidney disease and elucidate its underlying mechanisms.Methods:A high glucose-stimulated mouse podocyte (MPC-5) model was employed to evaluate the effects of isorhamnetin on podocyte injury, secretion of inflammatory cytokines, NLRP3 inflammasome activation, pyroptosis, mitochondrial function, cytosolic release of mtDNA, and activation of the cGAS-STING signaling pathway. Nigericin (an NLRP3 activator) and siRNA were used in combination to clarify the regulatory relationships between these pathways. Furthermore, a mouse model of diabetic kidney disease was established and treated with isorhamnetin via intragastric administration. Blood glucose and renal function parameters were measured, renal histopathological changes were examined, and alterations in podocyte marker proteins, inflammasome activation, pyroptosis, mitochondrial damage, and the cGAS-STING pathway in kidney tissues were analyzed.Results:Isorhamnetin alleviated high glucose-induced abnormalities in podocyte marker proteins and cellular injury. It also inhibited NLRP3 inflammasome activation, thereby attenuating pyroptosis. Furthermore, isorhamnetin stabilized mitochondrial membrane potential, decreased mitochondrial ROS production, suppressed excessive opening of the mitochondrial permeability transition pore, alleviated mitochondrial damage, and reduced cytosolic mtDNA release, which in turn suppressed activation of the cGAS-STING pathway. Knockdown of STING inhibited high glucose-induced NLRP3-dependent pyroptosis. Consistently, isorhamnetin improved renal function in mice with diabetic kidney disease, attenuated glomerulosclerosis and fibrosis, and markedly suppressed mitochondrial damage, mtDNA leakage, cGAS-STING activation, and NLRP3-mediated pyroptosis and inflammatory responses in renal tissues.Conclusions:Isorhamnetin treatment attenuates diabetic kidney disease by improving mitochondrial homeostasis and inhibiting the cGAS-STING/NLRP3 inflammasome pathway.
Objective:To investigate the modulatory effects of a Morus alba leaf extract(FBCC-EP1619)on melanogenesis using enzymatic,cellular,and zebrafish models. Methods:Phytochemical profiling was conducted using UPLC-QTOF-MS/MS in negative ion mode.Mushroom tyrosinase inhibition was assessed in vitro.Cytotoxicity and melanin content were measured in B16F10 melanoma cells under basal and α-melanocyte-stimulating hormone(α-MSH)-stimulated conditions.An in vivo pigmentation model was established using α-MSH-treated zebrafish larvae,and pigmentation was quantified.Expression of melanogenesis-related genes(mitfa and tyr)was analyzed by RT-qPCR. Results:FBCC-EP1619 contained diverse phenolic and lipid-derived metabolites.The extract significantly inhibited mushroom tyrosinase activity in a concentration-dependent manner.In B16F10 cells,it did not induce cytotoxicity but increased melanin production.In contrast,in α-MSH-stimulated zebrafish larvae,FBCC-EP1619 attenuated hyperpigmentation and significantly downregulated mitfa and tyr expression,indicating system-and stimulus-dependent regulation. Conclusions:FBCC-EP1619 differentially modulates melanogenesis depending on the biological system,enhancing basal melanin production in vitro while suppressing α-MSH-induced pigmentation in vivo.These findings provide pharmacological support for the ethnopharmacological relevance of Morus alba leaves and warrant further investigation into the underlying molecular mechanisms.
Objective: To investigate whether the ethyl acetate fraction of Cyperus amuricus (C. amuricus) induces autophagy-mediated apoptosis in hepatocellular carcinoma cells via the AMPK and PI3K/Akt/mTOR signaling pathways. Methods: In vitro experiments were conducted using HepG2 and Huh7 hepatocellular carcinoma cell lines. The ethyl acetate fraction of C. amuricus was profiled by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and quantitative high-performance liquid chromatography with diode-array detection. In HepG2 cells, cytotoxicity (MTT assay), apoptosis (Annexin V/PI staining, sub-G1 analysis, and Western blot for cleaved caspase-3, Bax/Bcl-2, and cytochrome c), autophagy (acridine orange staining, LC3-II/LC3-I ratio, Beclin-1, Atg5-Atg12, Atg7, DAPK3, and autophagic flux assays with bafilomycin A1), and signaling pathways (p-AMPK and total AMPKα, and PI3K/Akt/mTOR/p70S6K by Western blot) were assessed at 100, 150 and 200 μg/mL for 3-24 h. The role of autophagy in apoptosis was further evaluated using the autophagy inhibitors 3-methyladenine and bafilomycin A1. Cytotoxicity, apoptosis, and autophagy were also assessed in Huh7 cells at 100-200 μg/mL for 24 h. Results: The ethyl acetate fraction of C. amuricus significantly reduced viability dose-dependently with an IC50 of 150 μg/mL (HepG2) and 165 μg/mL (Huh7), activated intrinsic apoptosis, and induced time-dependent autophagy with confirmed flux (P < 0.05). The fraction markedly enhanced AMPK phosphorylation while suppressing the PI3K/Akt/mTOR/p70S6K signaling (P < 0.05). Cotreatment with 3-methyladenine reduced apoptosis from 30.9% to 26.0% and decreased the levels of p-AMPKα, p-mTOR, Atg7, and Beclin-1, and increased LC3-H/LC3-I ratio (P < 0.05), while bafilomycin A1 co-treatment reduced apoptosis to 24.3% in HepG2 cells and confirmed autophagic flux as a pro-apoptotic mechanism, collectively establishing a functional role of autophagy in C. amuricus fraction-induced cell death. Conclusions: The ethyl acetate fraction of C. amuricus induces autophagy-mediated apoptosis via AMPK activation and PI3K/Akt/mTOR inhibition. Therefore, it holds great potential as a phytotherapeutic candidate for hepatocellular carcinoma, which requires further in vivo validation.
Objective:To investigate the anticancer effects of a novel benzofuran-isatin conjugate[N'-(5-methoxy-2-oxoindolin-3-ylidene)-3-methylbenzofuran-2-carbohydrazide(conjugate 5d)]against human colorectal adenocarcinoma(CRC)HT29 and metastatic SW620 colorectal cancer cells. Methods:The cytotoxic properties of conjugate 5d were evaluated using the MTT assay.Its anti-oncogenic effects were assessed by real-time monitoring of cell proliferation,migration,and invasion,and by performing a clonogenic assay.Flow cytometry was also used to assess the apoptotic status and cell cycle.Apoptosis,cell cycle,and epithelial-mesenchymal transition-related protein and gene expression levels were also measured. Results:Conjugate 5d exhibited cytotoxic effects on both CRC cells and enhanced the cytotoxic efficacy of 5-fluorouracil,irinotecan,and oxaliplatin.Conjugate 5d also induced apoptosis by modulation of anti-apoptotic(i.e.,Bcl-xl)and pro-apoptotic(i.e.,Bax,p53,cytochrome c)proteins,and MMP loss.Docking studies predicted molecular interactions of conjugate 5d with anti-apoptotic Bcl-2,revealing conjugate 5d as a potential Bcl-2 inhibitor.Regarding the oncogenic process,conjugate 5d inhibited CRC cell proliferation,migration,invasion,and colony formation,upregulated E-cadherin expression,and downregulated N-cadherin expression. Conclusions:Conjugate 5d shows significant anticancer effects against HT29 and SW620 cells by exerting pro-apoptotic and anti-metastatic activities.It also enhances the cytotoxic efficacy of conventional chemotherapeutic drugs in CRC cell lines.However,in vivo studies should be conducted to further confirm its efficacy.
Objective:To determine whether soybean oil can ameliorate 4-octylphenol-induced alterations in female hormones,minerals,ovarian antioxidants,and inflammatory cytokines in female rats. Methods:Thirty-six female rats were divided into six groups:control,soybean oil(1 mL/rat),soybean oil(2 mL/rat),4-octylphenol,4-octylphenol plus soybean oil(1 mL/rat),and 4-octylphenol plus soybean oil(2 mL/rat).Levels of female hormones,serum minerals,ovarian antioxidants,and inflammatory markers were assessed.Ovarian Na+/K+-ATPase activity and nuclear factor kappa B were also detected. Results:Soybean oil restored female hormones,serum minerals,Na+/K+-ATPase activity,and ovarian antioxidants,while lowering ovarian inflammatory markers and nuclear factor kappa B levels in 4-octylphenol-exposed female rats.Moreover,soybean oil upregulated p53 expression while downregulating Bcl-2 expression. Conclusions:Soybean oil treatment improves female hormones,minerals,ovarian oxidative stress and inflammation in 4-octylphenol-exposed rats.
Exploring natural products as therapeutic alternatives to synthetic drugs has garnered increasing research interest due to their reduced side effects and lower toxicity.Bioactive compounds derived from natural products exhibit a diverse range of pharmacological effects that help reduce cardiovascular risk,primarily by modulating key metabolic pathways.These natural compounds have demonstrated efficacy in mitigating cardiovascular risk factors such as hypertension,hyperglycemia,hyperlipidemia,obesity,and liver injury by modulating metabolism within the biological systems.Mechanistically,natural products exert their effects through coordinated regulation of systemic energy homeostasis,lipidomic and phospholipid balance,amino acid metabolism,mitochondrial bioenergetics,and gut microbiota-derived metabolites.Such modulation results in measurable changes in metabolite profiles across various biological samples,including blood,urine,feces,and tissues.Among the various mechanistic pathways involved in cardiovascular regulation,the metabolic pathway offers a more dynamic and integrative perspective of disease progression and therapeutic response,enabling identification of key metabolites and biomarkers that reflect systemic physiological changes.Furthermore,metabolomics-based approaches provide powerful tools to uncover subtle biochemical alterations that may precede overt pathological changes,making it a valuable focus in natural product therapeutics in cardiovascular research.This review focuses on current evidence on metabolite alterations associated with cardiovascular risk factors and illustrates how natural products reprogram metabolic networks to mitigate disease,providing a systems-level framework for understanding their cardioprotective effects.
Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization, phenol-sulfuric acid assay, and gel permeation chromatography. HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides; conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization, while tight junction protein expression was analyzed in HT-29 cells. Furthermore, a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression. Body weight, disease activity index, colon length, histopathology, and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide, primarily composed of galacturonic acid and various neutral sugars, with a narrow molecular weight distribution and high purity. Pectic polysaccharides significantly enhanced THP-1 macrophage viability, promoted M1 to M2 polarization, and upregulated the expression of epithelial tight junction proteins. In addition, pectic polysaccharide treatment attenuated body weight loss, lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis. It also reduced JAK2/STAT3 phosphorylation and NOS2 expression, and increased the expression of tight junction proteins (ZO-1, occludin, and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers, inhibiting the JAK2/ STAT3-NOS2 signaling, and enhancing epithelial barrier-related protein expression. These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.
Objective: To evaluate the hepatoprotective effects of skate-derived bioactives—collagen peptides (CPs) and chondroitin—against ethanol (EtOH)-induced liver injury and to elucidate their underlying mechanisms. Methods: The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models. Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers (NRF2 and GCLC). EtOH metabolism was examined by measuring alchohol-metabolizing enzymes (alcohol dehydrogenase and aldehyde dehydrogenase) and cytochrome P450 enzymes. Furthermore, lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers (SREBP-1 and FAS). Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase, and performing histological analysis. Results: In hepatocytes and zebrafish, both CPs and chondroitin reduced oxidative stress, downregulated cytochrome P450 enzymes and lipogenic markers, and enhanced antioxidant defenses, with chondroitin showing the strongest hepatoprotection. In EtOH-fed mice, chondroitin significantly improved liver enzyme profiles, reduced hepatic lipid accumulation and inflammation, and restored antioxidant and metabolic homeostasis. Conclusions: Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress, EtOH metabolism, and lipid regulation. These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage. KEYWORDS: Alcohol-associated liver disease; Chondroitin; Collagen peptides; Liver injury; Oxidative stress; Lipid metabolism
Objective: To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging. Methods: Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks. Forelimb grip strength, hanging performance, and locomotor activity were assessed. Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis, contractile-marker features, senescence- and DNA damage-associated markers, inflammatory signaling, and mitochondrial proteins. Oxidative status was assessed by determining antioxidant capacity, lipid peroxidation, and oxidative DNA damage. Transcriptomic profiling was also performed, and selected targets were validated by quantitative RT-PCR and immunostaining. In addition, differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract; senescence-associated β-galactosidase, DNA damage signaling, and cell viability were measured. Results: Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion. It also reduced collagen deposition, preserved contractile-marker immunoreactivity, attenuated senescence- and inflammation-associated signals, and increased mitochondrial protein immunoreactivity. Oxidative DNA damage was notably reduced by nacre extract. Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression, which were supported by tissue-level validation. In C2C12 myotubes, nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability. Conclusions: Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress, inflammation, mitochondrial features, and cellular senescence.
Plantago major L.,commonly known as plantain,waybread,or dooryard plantain,is a versatile medicinal plant with multiple therapeutic applications.Traditionally,various parts of the plant have been formulated into syrups,drops,ointments,vaginal suppositories,gargles,and roasted preparations to treat diverse ailments,such as liver disorders,earaches,epilepsy,asthma,stomachaches,diarrhea,constipation,polymenorrhea,and uterine disorders.The plant contains clinically valuable bioactive compounds,including polysaccharides,flavonoids,lipids,iridoid glycosides,caffeic acid derivatives,terpenoids,alkaloids,and organic acids.These bioactive constituents are the primary contributors to the plant's broad spectrum of biological activities,including antioxidant,anti-inflammatory,antibacterial,antidiarrheal,hepatoprotective,antiviral,antiphage,antinociceptive,antiulcerogenic,antigenotoxic,and immunomodulatory effects of the plant.This review comprehensively summarizes the phytochemical composition,traditional medicinal applications,and biological properties of this multifunctional medicinal plant.
Objective: To investigate the protective effects of gypenoside XVII (GP-17) against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy. Methods: Sprague-Dawley rats were randomly divided into four groups: control, cisplatin, cisplatin + GP-17, and GP-17 alone. Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury, while GP-17 was given orally at 40 mg/kg/ day for 7 d. The levels of serum creatinine and blood urea nitrogen, superoxide dismutase activity, and malondialdehyde content were measured. Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury. Moreover, the expression of mitophagy-related proteins, including PINK1, Parkin, LC3, and p62, and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays. Furthermore, human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17, with or without PINK1 siRNA transfection. Cell viability, apoptosis, reactive oxygen species levels, mitochondrial membrane potential, and the protein expression associated with the PINK1/Parkin pathway were measured. Results: In rats with cisplatin-induced acute kidney injury, GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen, attenuated tubular damage and mitochondrial ultrastructural injury, and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content. GP-17 further upregulated the protein levels of PINK1, Parkin, and LC3-II / I ratio while promoting p62 degradation, indicating enhanced mitophagic flux. In HK-2 cells, GP-17 (20 μM) co-treatment markedly attenuated cisplatin-induced cytotoxicity, apoptosis, reactive oxygen species overproduction, and mitochondrial depolarization. However, all these protective effects of GP-17 were completely abolished upon PINK1 knockdown. Conclusions: GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy, which facilitates the clearance of damaged mitochondria, alleviates oxidative stress, and inhibits renal cell apoptosis. These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.
Objective:To investigate the efficacy and underlying mechanisms of standardized Salvia miltiorrhiza extract(SMEX)in alleviating menopausal symptoms using MCF-7 cells and an ovary-intact menopause mouse model resulting from hypothalamic-pituitary-ovarian axis aging. Methods:Estrogen receptor(ER)-related molecular responses were first assessed in MCF-7 cells treated with SMEX.In vivo efficacy was then evaluated in 52-week-old female mice orally administered SMEX(50 or 100 mg/kg/day)or 17β-estradiol(E2)for 12 weeks.ER expression and downstream AKT/ERK signaling pathways in uterine tissues were determined.In addition,histological analysis of reproductive organs,assessment of serum lipid and hormone levels,neurotransmitter measurements,and behavioral tests were performed. Results:SMEX upregulated ERα and ERβ expression and suppressed pS2 mRNA in MCF-7 cells,indicating selective ER modulation.In SMEX-treated mice,uterine ER expression and activation of the AKT and ERK pathways were significantly increased,leading to partial restoration of epithelial thickness and stratification in the oviduct and vagina.SMEX also significantly reduced serum low-density lipoprotein cholesterol levels and reversed menopausal alterations in the follicle-stimulating hormone/luteinizing hormone ratio.Additionally,it elevated serotonin and norepinephrine levels in the pituitary,thereby alleviating depression-like behavior. Conclusions:SMEX modulates ER signaling and improves neurohormonal balance,effectively alleviating menopausal symptoms in both in vitro and in vivo models.This highlights its potential as a safe,natural alternative to hormone replacement therapy and as a promising functional ingredient in therapeutic natural products.
