Multiple organs injury and myocardial energy metabolism disorders induced by isoproterenol.

The study sought to assess the detrimental effects of isoproterenol (ISO) on major organs and investigate the potential reversibility of these adverse reactions in mice. Male mice were divided into normal control, 0.2 mg/kg.d and 3.0 mg/kg.d ISO groups, and were subcutaneously administered of the respective doses for 14 consecutive days. Subsequently, a recovery period experiment was conducted, replicating the aforementioned procedure, followed by an additional 2-week recovery period for the mice. Following 14 consecutive days of administration, mice treated with ISO exhibited notable cardiac damage manifested by abnormal ECG patterns, dysregulated energy metabolism, elevated cardiac hypertrophy, and increased heart pathological score. Additionally, the administration of ISO resulted in liver and kidney damage, as evidenced by increased pathological score, serum albumin level, and urea level. Lung damage was also observed, indicated by an increase in lung pathological score. Furthermore, the administration of ISO at a dosage of 3.0 mg/kg.d resulted in a decrease in liver mass index, serum iron content, and an increase in lung mass index. After a 2-week recovery period, mice treated with ISO showed abnormalities in ECG patterns and dysregulated myocardial energy metabolism, accompanied by a decrease in serum iron content. Histopathological examinations revealed continued pathological changes in the heart and lung, as well as significant hemosiderin deposition in the spleen. Furthermore, the group treated with ISO at a dosage of 3.0 mg/kg.d showed an increase in serum AST and TP levels. In summary, the study demonstrates that both 0.2 mg/kg.d and 3.0 mg/kg.d doses of ISO can induce damage to the heart, liver, lung, kidney, and spleen, with the higher dose causing more severe injuries. After a 2-week withdrawal period, the liver, kidney, and thymus injuries caused by 0.2 mg/kg ISO shows signs of recovery, while damage to the heart, lung, and spleen persists. The thymus injury mostly recovers, with minimal kidney pathology, but significant damage to the heart, liver, and lung remains even after the withdrawal period for the 3.0 mg/kg ISO dose.

Anti-inflammatory effects of Eucommia ulmoides Oliv. male flower extract on lipopolysaccharide-induced inflammation.

BACKGROUND: Eucommia ulmoides Oliv. is a medicinal plant native to China, with its bark (Eucommiae Cortex) traditionally being used for medicinal purposes. Previous research has shown that Eucommia male flowers can exert anti-inflammatory, analgesic, antibacterial, and other pharmacological effects, including immune regulation. This study explored the anti-inflammatory effects of the 70% ethanol extract of male flowers (EF) of E. ulmoides in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-administered mice. METHODS: Cytotoxicity of EF for RAW 264.7 cells was investigated using Cell Counting Kit-8. The production of proinflammatory mediators, nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 was determined using enzyme-linked immunosorbent assays. IL-17, IL-23, and IL-10 mRNA levels were determined using quantitative real-time polymerase chain reaction. Activation of the nuclear factor (NF)-κB pathway in RAW 264.7 cells was investigated via Western blotting. In vivo anti-inflammatory effects of EF were studied in an LPS-induced acute inflammation mouse model by analyzing lung tissue histopathology, serum TNF-α and IL-6 levels, and myeloperoxidase (MPO) activity in lung tissue. RESULTS: EF showed no significant cytotoxicity at concentrations from 10 to 60 µg/mL (cell viability > 80%) in the CCK-8 cell viability assay. EF inhibited the RAW 264.7 cell proliferation (EF 60 µg/mL, 120 µg/mL, and 250 µg/mL vs. negative control: 87.31 ±â€Š2.39% vs. 100.00 ±â€Š2.50%, P = 0.001; 79.01 ±â€Š2.56 vs. 100.00 ±â€Š2.50%, P < 0.001; and 64.83 ±â€Š2.50 vs. 100.00 ±â€Š2.50%, P < 0.001), suppressed NO (EF 20 µg/mL and 30 µg/mL vs. LPS only, 288.81 ±â€Š38.01 vs. 447.68 ±â€Š19.07 µmol/L, P = 0.004; and 158.80 ±â€Š45.14 vs. 447.68 ±â€Š19.07 µmol/L, P < 0.001), TNF-α (LPS+EF vs. LPS only, 210.20 ±â€Š13.85 vs. 577.70 ±â€Š5.35 pg/mL, P < 0.001), IL-1ß (LPS+EF vs. LPS only, 193.30 ±â€Š10.80 vs. 411.03 ±â€Š42.28 pg/mL, P < 0.001), and IL-6 (LPS+EF vs. LPS only, 149.67 ±â€Š11.60 vs. 524.80 ±â€Š6.24 pg/mL, P < 0.001) secretion, and downregulated the mRNA expression of IL-17 (LPS+EF vs. LPS only, 0.23 ±â€Š0.02 vs. 0.43 ±â€Š0.12, P < 0.001), IL-23 (LPS+EF vs. LPS only, 0.29 ±â€Š0.01 vs. 0.42 ±â€Š0.06, P=0.002), and IL-10 (LPS+EF vs. LPS only, 0.30 ±â€Š0.01 vs. 0.47 ±â€Š0.01, P=0.008) in LPS-stimulated RAW 264.7 cells. EF inhibited the LPS-induced NF-κB p65 (LPS+EF 20 µg/mL and 30 µg/mL vs. LPS only: 0.78 ±â€Š0.06 vs. 1.17 ±â€Š0.08, P < 0.001; and 0.90 ±â€Š0.06 vs. 1.17 ±â€Š0.08, P =0.002) and inhibitor of kappa B (IκBα) phosphorylation (LPS+EF 20 µg/mL and 30 µg/mL vs. LPS only: 0.25 ±â€Š0.01 vs. 0.63 ±â€Š0.03, P < 0.001; and 0.31 ±â€Š0.01 vs. 0.63 ±â€Š0.03, P < 0.001), LPS+EF 30 µg/mL inhibited IκB kinase (IKKα/ß) phosphorylation (LPS+EF 30 µg/mL vs. LPS only, 1.12 ±â€Š0.14 vs. 1.71 ±â€Š0.25, P = 0.002) in RAW 264.7 cells. Furthermore, EF 10 mg/kg and EF 20 mg/kg inhibited lung tissue inflammation in vivo and suppressed the serum TNF-α (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 199.99 ±â€Š186.49 vs. 527.90 ±â€Š263.93 pg/mL, P=0.001; and 260.56 ±â€Š175.83 vs. 527.90 ±â€Š263.93 pg/mL, P = 0.005), and IL-6 (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 41.26 ±â€Š30.42 vs. 79.45 ±â€Š14.16 pg/ ml, P = 0.011; and 42.01 ±â€Š26.26 vs. 79.45 ±â€Š14.16 pg/mL, P = 0.012) levels and MPO (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 3.19 ±â€Š1.78 vs. 5.39 ±â€Š1.51 U/g, P = 0.004; and 3.32 ±â€Š1.57 vs. 5.39 ±â€Š1.51 U/g, P = 0.006) activity in lung tissue. CONCLUSIONS: EF could effectively inhibit the expression of inflammatory factors and overactivation of neutrophils. Further investigation is needed to evaluate its potential for anti-inflammation therapy.

Comparative Studies of Different Extracts from Eucommia ulmoides Oliv. against Rheumatoid Arthritis in CIA Rats.

To compare efficacy of different extracts from Eucommia ulmoides Oliv. with both immune inflammation and joint destruction in collagen induced arthritis (CIA) rat model. Rats were divided into normal group (Nor), control group (CIA), TG group (treated with tripterygium glycoside), E70 group (treated with 70% ethanol extract from Eucommia ulmoides Oliv.), EA group (treated with ethyl acetate fraction from E70), and EN group (treated with n-butyl alcohol fraction from E70). All extracts from Eucommia ulmoides Oliv. could significantly inhibit ankle swelling, pathological manifestations, and cytokine levels in serum and spleen, by using foot volume measurement, H&E staining, ELISA, and RT-QPCR methods, respectively. All extracts could significantly inhibit rough joint surface and marginal osteophytes, improve RANKL/OPG ratio, and decrease MMP-9 expression, by using micro-CT and immunohistochemical staining. The activation of IKK/NF-κB signaling pathway was also inhibited by all extracts. In addition, ethyl acetate fraction from E70 presented better effect on RANKL/OPG system. This study identified effective extracts from Eucommia ulmoides Oliv. relieving immune inflammation and maintaining structural integrity of joints in CIA rats.

[Effect of oxymatrine on pathological change in brain tissue of newborn mice infected by cytomegalovirus].

OBJECTIVE: To study the effect of oxymatrine on pathological change in brain tissue of newborn mice infected by cytomegalovirus (CMV). METHODS: CMV of TCID50 was inoculated into the brain of the newborn mice, and the morphological change in the brain tissue infected by CMV was observed with light microscope and transmission electron microscope. RESULTS: In the model control group, the results showed that there were some inflammatory cellular infiltration and focal necrosis in the brain tissue of newborn mice infected by CMV. The ultrastructure change in the brain tissue showed that the nuclear membrane of cerebral neurons sunk, the chromatin deformed and fused into masses, the cytoplasm vacuolated, the endoplasmic reticulum disarranged and the Nissl's body was blurred or disappeared. After being treated with oxymatrine (50 mg/kg, ip) for 15 days, those pathological changes of the brain tissue in the newborn mice could be significantly improved. CONCLUSION: Oxymatrine has an obvious inhibition on CMV in vivo.