Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1β, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds—adenosine and N6-(2-hydroxyethyl) adenosine (HEA)—inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.
The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CC MeOH ) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20-500 mg/kg of CC MeOH significantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CC MeOH (100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CC MeOH may be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CC MeOH also decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CC MeOH in vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.
Pogostemon cablin (PC) is a herbal medicine traditionally applied to treat not only common cold, nausea and diarrhea but also headache and fever. The aim of this study was to investigate the analgesic and anti-inflammatory properties of standardized PC methanol extract (PCMeOH) in vivo. Investigations were performed in mice with two analgesic models. One was acetic acid-induced writhing response and the other formalin-induced paw licking. The anti-inflammatory effect was tested by λ-carrageenan (Carr)-induced mice paw edema. These analgesic experimental results indicated that PCMeOH (1.0 g/kg) decreased the acetic acid-induced writhing responses and PCMeOH (0.5 and 1.0 g/kg) decreased the licking time in the second phase of the formalin test. Moreover, Carr-induced paw edema inflammation was significantly reduced in a dose-dependent manner when PCMeOH (0.5 and 1.0 g/kg) was administered 3 and 4 h after the Carr injection. Mechanistic studies showed that PCMeOH decreased the levels of malondialdehyde in the edema paw by increasing the activities of anti-oxidant enzymes, such as superoxide dismutase, glutathione peroxidase and glutathione reductase, in the liver and decreasing the cyclooxygenase 2 and tumor necrosis factor-α activities in the edema paw. This study has demonstrated the analgesic and anti-inflammatory effects of PCMeOH, thus verifying its popular use in traditional medicine.
Scopoletin exists in nature as an anti-oxidant, hepatoprotective, and anti-inflammatory activities reagent. In this study, we have investigated the analgesic effects of the scopoletin using the models of acetic acid-induced writhing response and the formalin test, the anti-inflammatory effects of scopoletin using model of λ-carrageenan (Carr)-induced paw edema. The treatment of ICR mice with scopoletin inhibited the numbers of writhing response and the formalin-induced pain in the late phase. This study demonstrated that the administration of scopoletin resulted in the reduction of Carr-induced mice edema, and it increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) after Carr injection. We also demonstrated scopoletin significantly attenuated the malondialdehyde (MDA) level in the edema paw after Carr injection. Scopoletin decreased the NO, tumor necrosis factor (TNF-α) and prostaglandin E2 (PGE2) levels on serum after Carr injection. Scopoletin decreased Carr-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the edema paw. These anti-inflammatory mechanisms of scopoletin might be related to the decrease in the level of MDA via increasing the activities of SOD, CAT, and GPx in the edema paw. Also, scopoletin could affect the production of NO, TNF-α, and PGE2, and therefore affect the anti-inflammatory effects.
In this study, we evaluated the synergistic effect of ginger and nifedipine on anti-platelet aggregation in normal human volunteers and hypertensive patients. The results showed that the percentage of platelet aggregation induced by collagen, ADP and epinephrine in hypertensive patients was larger than that in normal volunteers. Either aspirin or ginger could potentiate the anti-platelet aggregation effect of nifedipine in normal volunteer and hypertensive patients. These results suggested that ginger and nifedipine possessed synergistic effect on anti-platelet aggregation. A combination of 1 g ginger with 10 mg nifedipine per day could be valuable for cardiovascular and cerebrovascular complication due to platelet aggregation.
Inflammation is related to several chronic diseases, including cancer and atherosclerosis. Taxillus sutchuenensis (Lecomte) Danser is a special folk medicinal plant in Taiwan. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antiproliferative activities of the aqueous-thanol extract from T. sutchuenensis (AETS) and its fractions. TEAC, DPPH radicals, total phenolic compounds, total flavonoid content, inhibition of NO production in LPS-induced RAW264.7 cells, and inhibition of cancer cell proliferation were tested. Among all fractions, the ethyl-acetate (EA) fraction showed the highest TEAC and DPPH radical scavenging activities. The EA fraction also had the highest polyphenol and flavonoid content. The EA fractions also decreased LPS-induced NO production and the expression of iNOS and COX-2 in RAW264.7 cells. The antiproliferative activities of the aqueous/ethanol extract and fractions were studied in vitro using A549 cells, and the results were consistent with their antioxidant capacities. EA fractions had the highest antiproliferative activity with an IC(50) of 454.38 ± 1.48 μg/ml. Quercetin also had antioxidant, anti-inflammatory, and antiproliferative activities. Quercetin might be an important bioactive compound in T. sutchuenensis. The experimental data indicated that T. sutchuenensis is a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds.
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