Sepsis is a clinical condition causing tissue damage as a result of infection and an exaggerated immune response. Sepsis causes 11 million deaths annually, a third of which are associated with acute lung injury (ALI). Rapid and effective treatment is crucial to improve survival rates. Punica granatum (pomegranate) is rich in polyphenols and demonstrates strong antioxidant activity, while amifostine acts as a free radical scavenger. This study aimed to investigate the antioxidant and anti-inflammatory effects of P. granatum peel extract (PGPE) and amifostine in sepsis-related ALI. Experimental groups included Control, CLP (cecal ligation and puncture-induced sepsis), Amf (200 mg/kg amifostine, intraperitoneally), and PGPE250, and PGPE500 (250 and 500 mg/kg PGPE via oral gavage, respectively). Thiobarbituric acid reactive substances (TBARS), total thiol (TT), tumor necrosis factor-alpha (TNF-α) levels, and metalloproteinases 2 and 9 (MMP-2 and MMP-9) were assessed in the lung tissue. Biochemical analysis demonstrated that TBARS and TNF-α levels significantly decreased in both the PGPE and amifostine treatment groups compared to the CLP group, while TT levels showed notable improvement. Histopathological evaluation revealed reduced MMP-2 and MMP-9 immunopositivity in the PGPE250 and PGPE500 groups. These findings highlight the lung-protective properties of PGPE, underscoring its potential as a therapeutic agent for sepsis-induced acute lung injury.

Sepsis is an exaggerated immune response resulting from systemic inflammation, which can damage tissues and organs. Acute kidney injury has been detected in at least one-third of patients with sepsis. Sepsis-associated acute kidney injury increases the risk of a secondary infection. Rapid diagnosis and appropriate initiation of antibiotics can significantly reduce mortality and morbidity. However, microorganisms are known to develop resistance to antibiotics. Estimations indicate that the annual casualties caused by microbial resistance will surpass cancer fatalities by 2050. The prevalence of bacterial infections and their growing antibiotic resistance has brought immediate attention to the search for novel treatments. Plant-derived supplements contain numerous bioactive components with therapeutic potential against a variety of conditions, including infections. Punica granatum peel is rich in phenolic compounds. The purpose of this study was to determine the anti-inflammatory and anti-bacterial properties of P. granatum peel extract (PGPE) on lipopolysaccharide (LPS)-induced acute kidney injury. Experimental groups were Control, LPS (10 mg/kg LPS, intraperitoneally), PGPE100, and PGPE300 (100 and 300 mg/mL PGPE via oral gavage, respectively, for 7 days). According to biochemical results, serum blood urea nitrogen (BUN), creatinine (Cr) and C-reactive protein (CRP), kidney tissue thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) levels significantly decreased in the PGPE groups compared to the LPS group. Histopathological and immunohistochemical findings revealed that toll-like receptor 4 (TLR4) level and nuclear factor kappa B (NF-κB) expression increased in the LPS group compared to the Control group. In addition, the anti-Gram-negative activity showed a dose-dependent effect on Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa with the agar well diffusion method and the minimal inhibitory concentration (MIC). The MIC value was remarkable, especially on A. baumannii. We conclude that PGPE has the potential to generate desirable anti-bacterial and anti-inflammatory effects on LPS-induced acute kidney injury in rats.

The development of antibiotic resistance has become a global health challenge, resulting in approximately 800,000 deaths per year. The rapid rise in multidrug-resistant (MDR) pathogens has prompted an urgent need for antimicrobial alternatives. Punica granatum L. peel has long been valued for its rich bioactive polyphenols with potent antimicrobial properties. In this study, P. granatum L. peel extract (PGPE) was integrated with chitosan nanoparticles (CH-PGPE) to enhance antimicrobial efficacy while minimizing potential cytotoxicity. The antimicrobial potential of PGPE and CH-PGPE was evaluated with agar well diffusion, disk diffusion, and minimum inhibitory concentration (MIC) analyses against standard ATCC and clinical MDR strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. MTT assay evaluated the biocompatibility and anti-proliferative potential of PGPE on ARPE-19 (normal retinal pigment epithelial), HeLa (human cervical cancer), and A549 (human lung carcinoma) cell lines. PGPE exhibited antibacterial activity, and CH-PGPE reduced MIC values by approximately two-fold. Both PGPE and CH-PGPE demonstrated comparable or superior inhibition compared to several conventional antibiotics, particularly against MDR strains. The MTT assay revealed that PGPE was non-cytotoxic to normal ARPE-19 cells, while exhibiting the highest antiproliferative potency against A549 cells and a moderate inhibitory response in HeLa cells. The nanoparticle-supported formulation enhanced the antimicrobial efficacy of PGPE and also exhibited selective anti-proliferative activity against cancer cells without affecting normal cells.

One-third of approximately 10 million deaths due to sepsis in a year are due to acute lung injury, and there is no effective treatment yet. Due to its high phenol content, Punica granatum L. bark extract exhibits high antioxidant activity. Amifostine is a free radical scavenger that converts into active thiol in tissues. This study aimed to investigate the antioxidative and anti-inflammatory effects of 2 different doses of PG peel extract and amifostine in sepsis-related acute lung injury. Fifty rats were randomly allocated into 5 groups. Group 1 served as the control group with no sepsis. The remaining groups 2-5 served as the cecal-ligation-puncture (CLP) groups. Group 3 was administered 200 mg/kg amifostine intraperitoneally (ip) 15 minutes before sepsis induction. Groups 4 and 5 received, respectively, 250 mg/kg and 500 mg/kg PG peel extract by oral gavage 9 days before and 30 minutes after the CLP procedure, with a total of 10 doses. MMP-2 and MMP-9 were investigated by immunohistochemical methods. MMP-2 and MMP-9 concentrations significantly increased in the sepsis group compared to the other 4 groups. This study provides evidence that Amifostine and Punica granatum pericarp benefit lung tissue in a rat model of sepsis induced by cecal-ligation puncture.

Increasing incidence of candidiasis and emergence of antifungal resistance necessitate the development of alternative antifungal strategies. In this context, the antifungal activity of the crude extract of Punica granatum L. peel (PGPE) and its chitosan nanoparticle-coated formulation (PGPE-CSNPs) was investigated against Candida albicans (ATCC 10231), Candida glabrata (ATCC 66032), Candida kefyr (ATCC 46764), Candida parapsilosis (ATCC 22019), and Candida tropicalis (ATCC 13803). Although the individual antimicrobial activities of PGPE and CSNPs have been investigated, their combined application against Candida spp. remains unexplored in the literature. The antifungal efficacy was evaluated using agar well diffusion, disk diffusion, minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) testing, and compared with fluconazole and amphotericin B. The morphological characterization of PGPE-CSNPs was performed using scanning electron microscopy (SEM), which confirmed successful encapsulation and revealed a smoother surface with uniformly distributed nanometric pore structures and reduced aggregation compared to uncoated CSNPs. PGPE-CSNPs showed greater inhibition zones than amphotericin B, except against C. albicans. The CSNPs formulation reduced the MIC from 8 µg/mL to 4 µg/mL and the MFC from 16 µg/mL to 8 µg/mL, representing a two-fold enhancement against C. albicans. No enhancement in activity was observed against C. glabrata, whereas for C. kefyr, only MFC values decreased from 8 µg/mL to 4 µg/mL. For both C. parapsilosis and C. tropicalis, MIC values reduced from 16 µg/mL to 8 µg/mL, and MFC values reduced from 32 µg/mL to 16 µg/mL for both species. PGPE-CSNPs exhibited significantly lower MIC and MFC values than the crude extract alone (p < 0.05). These findings suggest that chitosan-based nanocarriers may enhance the antifungal efficacy of plant-derived bioactive compounds, highlighting their potential as a promising alternative antifungal strategy, a combinatorial approach not previously reported in the literature.