Objective: To evaluate the anti-shigellosis activity of the hydroethanol extract of Diospyros gilletii (D. gilletii) stem bark in Shigella flexneri (S. flexneri)-induced diarrheal mice.
Methods: The hydroethanolic extract was obtained by maceration of D. gilletii stem bark in 70% hydroethanol (waterethanol; 30:70, v/v) solution. Then, mice pretreated with cyclophosphamide for immunosuppression were administered orally with an inoculum containing S. flexneri, and subsequently treated with 100, 200, and 400 mg/kg of the hydroethanol extracts for 10 days. The bacterial colonies were enumerated and hematological and biochemical parameters were determined. Serum pro-inflammatory mediators including IL-1β, IL-18, and TNF-α, and nitric oxide levels were quantified by ELISA. Histological analyses of the kidney, liver, and colon were also conducted.
Results: Treatment with 200 and 400 mg/kg of the hydroethanolic extracts markedly inhibited the growth of S. flexneri. Moreover, treatment with D. gilletii extract downregulated the levels of IL-1β, IL-18, and TNF-α, and restored hematological and biochemical parameters as well as histological architecture of the colon, liver, and kidneys. Additionally, the oral administration of 2000 mg/kg D. gilletii extract did not induce any sign of toxicity, with a median lethal dose greater than 2000 mg/kg.
Conclusions: D. gilletii extract demonstrates the anti-shigellosis effects in S. flexneri-induced diarrheal mice, supporting the traditional use of this plant in treating diarrhea.
Objective: To investigate the effect of synbiotic mulberry on kidney injury in a dextran sodium sulfate (DSS)-induced colitis model.
Methods: Male Wistar rats were given drinking water containing 4% DSS for 7 days. Subsequently, the rats were treated by oral gavage with synbiotic mulberry at 250, 500, and 1000 mg/kg, sulfasalazine at 100 mg/kg, or synbiotic at 1000 mg/kg for an additional 7 days while receiving 0.4% DSS in drinking water. The severity of colitis was evaluated based on the disease activity index score. On day 14, plasma was collected, and the kidneys were harvested to evaluate kidney injury parameters and histological changes. In addition, the expression of genes associated with kidney injury was determined by quantitative RT-PCR.
Results: Treatment with all doses of synbiotic mulberry significantly lowered the disease activity index score, accompanied by reductions in kidney histopathological changes, malondialdehyde concentration, and plasma cystatin C levels. Kidney fibrosis was also ameliorated by 500 and 1000 mg/kg of synbiotic mulberry. Treatment with 250 and 500 mg/kg of synbiotic mulberry downregulated IL-18 mRNA expression, while KIM-1 mRNA expression was reduced and plasma lipopolysaccharide-binding protein level was restored by 1000 mg/kg of synbiotic mulberry.
Conclusions: Synbiotic mulberry ameliorates kidney injury in rats with DSS-induced colitis. It may be further explored as a treatment of kidney injury under colitis conditions.
Objective: To investigate the synergistic effects of auranofm and schisandrin A (SA) on cell proliferation inhibition and apoptosis induction in human hepatocellular carcinoma Hep3B cells.
Methods: Cell viability was assessed using MTT to determine the synergistic effects of auranofin and SA. Three-dimensional (3D) culture models were used to evaluate the effects on spheroid structure and size. Apoptosis was analyzed by flow cytometry for sub-G1 populations, annexin V staining, and Western blotting for apoptotic markers. Reactive oxygen species (ROS) production was measured using DCF-DA staining.
Results: Our results showed that combined treatment with auranofin and SA led to a significant reduction in cell viability compared with either compound alone, with isobologram analysis confirming their synergistic interactions. Under 3D culture conditions, auranofin and SA disrupted the compact structure of spheroids, leading to a loosened and disorganized morphology at the periphery, which appeared as an increase in spheroid size. Moreover, the induction of apoptosis by auranofin and SA was evidenced by elevated sub-G1 phase populations, increased annexin V-positive cells, and upregulation of apoptotic markers such as cleaved poly (ADP-ribose) polymerase 1 and cleaved caspase-3. Notably, auranofin combined with SA markedly enhanced ROS production, which was mitigated by the ROS scavenger N-acetylcysteine. Additionally, the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was downregulated in response to auranofin and SA treatment, and further apoptotic effects were observed following PI3K inhibition with LY294002.
Conclusions: Auranofin combined with SA promotes apoptosis of hepatocellular carcinoma via ROS generation and inhibition of the PBK/Akt pathway.
Objective: To assess the effects of turmeric extract and its compounds on oxidative stress, inflammation, and apoptosis in acetaminophen-induced liver injury.
Methods: HepG2 cells were administered with acetaminophen (40 mM) to induce hepatotoxicity, followed by treatment with turmeric extract and its isolated compounds including curcumin, demethoxycurcumin, bis-demethoxycurcumin and ar-turmerone at 5, 25, and 125 μg/mL. IL-1β, IL-6, and IL-10 levels were quantified with ELISA kits. Further, qRT-PCR was used to analyze the mRNA expression of JNK, Casp-9, and Casp-3. Meanwhile, the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.
Results: Acetaminophen administration caused an increase in the levels of lactate dehydrogenase, nitric oxide, IL-1β, IL-6, and the mRNA expression of JNK, Casp-9, and Casp-3 in HepG2 cells while reducing IL-10 levels. Treatment with turmeric extract, curcumin, demethoxycurcumin, bis-demethoxycurcumin, and ar-turmerone lowered IL-1β, IL-6, nitric oxide, and lactate dehydrogenase levels, downregulated the mRNA expression of JNK, Casp-9, and Casp-3, and increased IL-10 levels.
Conclusions: Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.