The involvement of interleukin-18 (IL-18) and the effects of modulating its release on the course of malaria infection were investigated using Plasmodium berghei ANKA infection in ICR mice as a model. Results demonstrated that plasma IL-18 concentrations in malarial mice were significantly elevated and positively correlated with the percentage parasitaemia development. Significant expressions of IL-18 were also observed in the brain, spleen and liver tissues. Slower development of parasitaemia was observed significantly upon inhibition and neutralization of IL-18, whereas faster development of parasitaemia was recorded when the circulating levels of IL-18 were further augmented during the infection. Inhibition and neutralization of IL-18 production also resulted in a significant decrease of plasma concentrations of pro-inflammatory cytokines (TNFα, IFNγ, IL-1α and IL-6), whereas the anti-inflammatory cytokine, IL-10, was significantly increased. Augmenting the release of IL- 18 during the infection on the other hand resulted in the opposite. Early mortality in malarial mice was also observed when the circulating levels of IL-18 were further augmented. Results proved the important role of IL-18 in immune response against malaria and suggest that IL-8 is pro-inflammatory in nature and may involve in mediating the severity of the infection through a pathway of elevating the pro-inflammatory cytokine and limiting the release of anti-inflammatory cytokine.
Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.
BACKGROUND: Renal sympathetic innervation plays an important role in the control of renal hemodynamics and may therefore contribute to the pathophysiology of many disease states affecting the kidney. Thus, the present study aimed to investigate the role of the renal sympathetic nervous system in the early deteriorations of renal hemodynamics and structure in rats with pathophysiological states of renal impairment.
METHODS: Anesthetized Sprague Dawley (SD) rats with cisplatin-induced acute renal failure (ARF) or streptozotocin (STZ)-induced diabetes mellitus (DM) were subjected to a renal hemodynamic study 7 days after cisplatin and STZ administration. During the acute study, renal nerves were electrically stimulated, and responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Post mortem kidney collection was performed for histopathological assessment.
RESULTS: In innervated ARF or DM rats, renal nerve stimulation produced significantly lower (all p<0.05, vs. innervated control) renal vasoconstrictor responses. These responses were markedly abolished when renal denervation was performed (all p<0.05); however, they appeared significantly higher compared with denervated controls (all p<0.05). Kidney injury was suppressed in denervated ARF, while, irrespective of renal denervation, renal specimens from DM rats were comparable to controls.
CONCLUSIONS: Renal sympathoexcitation is involved in the pathogenesis of the renal impairment accompanying ARF and DM, and may even precede the establishment of an observable renal injury. There is a possible enhancement in the renal sensitivity to intrarenal norepinephrine following renal denervation in ARF and DM rats.
The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.
Dioscorea oppositifolia is an important crop and functional food. D. oppositifolia tuber is often adulterated with D. persimilis, D. alata, and D. fordii tuber in the commercial market. This study proposed an integrated Fourier transform infrared spectroscopy (FT-IR) with chemometric approach to differentiate these four Dioscorea species. A total of 107 Dioscorea spp. tuber samples were collected from different locations in China. Principal Component Analysis (PCA), PCA-Class, and Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA) were utilised to classify the FT-IR spectra. In this PCA is unable to differentiate the Dioscorea spp. tuber effectively. However, PCA-Class and OPLS-DA can distinguish spp. these 4 species Dioscorea tuber with high accuracy, sensitivity, and specificity. Additionally, the RMSEE, RMSEP and RMSECV values for OPLS-DA model were low, showing that it is a good model. The combination of FT-IR with the PCA-Class and OPLS-DA is practical in discriminating Dioscorea spp. tubers.
Behavioural assessment of experimental pain is an essential method for analysing and measuring pain levels. Rodent models, which are widely used in behavioural tests, are often subject to external forces and stressful manipulations that cause variability of the parameters measured during the experiment. Therefore, these parameters may be inappropriate as indicators of pain. In this article, a stepping-force analgesimeter was designed to investigate the variations in the stepping force of rats in response to pain induction. The proposed apparatus incorporates new features, namely an infrared charge-coupled device (CCD) camera and a data acquisition system. The camera was able to capture the locomotion of the rats and synchronise the stepping force concurrently so that each step could be identified. Inter-day and intra-day precision and accuracy of each channel (there were a total of eight channels in the analgesimeter and each channel was connected to one load cell and one amplifier) were studied using different standard load weights. The validation studies for each channel also showed convincing results whereby intra-day and inter-day precision were less than 1% and accuracy was 99.36-100.36%. Consequently, an in vivo test was carried out using 16 rats (eight females and eight males). The rats were allowed to randomly walk across the sensor tunnel (the area that contained eight channels) and the stepping force and locomotion were recorded. A non-expert, but from a related research domain, was asked to differentiate the peaks of the front and hind paw, respectively. The results showed that of the total movement generated by the rats, 50.27 ± 3.90% in the case of the male rats and 62.20 ± 6.12% in that of the female rats had more than two peaks, a finding which does not substantiate the assumptions made in previous studies. This study also showed that there was a need to use the video display frame to distinguish between the front and hind paws in the case of 48.80 ± 4.01% of the male rats and 66.76 ± 5.35% of the female rats. Evidently the assumption held by current researchers regarding stepping force measurement is not realistic in terms of application, and as this study has shown, the use of a video display frame is essential for the identification of the front and hind paws through the peak signals.
Regulation of renal function and haemodynamics are under a direct control from the renal sympathetic nerves and renal denervation produces overt diuresis and natriuresis in several mammalian species. However, the inter-related series of changes in renal function and haemodynamics following acute renal denervation (ARD) is not fully understood. Thus, we aimed to investigate and relate the changes in renal function and haemodynamics following acute unilateral renal denervation in anaesthetized Sprague Dawley (SD) rats.