Extracts of tropical green seaweed Caulerpa lentillifera reduce hepatic lipid accumulation by modulating lipid metabolism molecules in HepG2 cells.

Seaweed has attracted attention as a bioactive source for preventing different chronic diseases, including liver injury and non-alcoholic fatty liver disease, the leading cause of liver-related mortality. Caulerpa lentillifera is characterized as tropical edible seaweed, currently being investigated for health benefits of its extracts and bioactive substances. This study examined the effects of C. lentillifera extract in ethyl acetate fraction (CLEA) on controlling lipid accumulation and lipid metabolism in HepG2 cells induced with oleic acid through the in vitro hepatic steatosis model. Gas chromatography-mass spectrometry (GC-MS) analysis indicated that CLEA contained diverse organic compounds, including hydrocarbons, amino acids, and carboxylic acids. Docked conformation of dl-2-phenyltryptophane and benzoic acid, two major bioactive CLEA components, showed high affinity binding to SIRT1 and AMPK as target molecules of lipid metabolism. CLEA reduced lipid accumulation and intracellular triglyceride levels in HepG2 cells stimulated with oleic acid. The effect of CLEA on regulating expression of lipid metabolism-related molecules was investigated by qPCR and immunoblotting. CLEA promoted expression of the SIRT1 gene in oleic acid-treated HepG2 cells. CLEA also reduced expression levels of SREBF1, FAS, and ACC genes, which might be related to activation of AMPK signaling in lipid-accumulated HepG2 cells. These findings suggest that CLEA contains bioactive compounds potentially reducing triglyceride accumulation in lipid-accumulated HepG2 hepatocytes by controlling lipid metabolism molecules.

Effects of Riceberry Rice Bran Oil Supplementation on Oxidative Stress and Cardiovascular Risk Biomarkers in Older Adults with Prehypertension.

We investigated the changes in the oxidative stress and cardiovascular disease risk biomarkers, including the activity of the cardiac autonomic nervous system, in older adults with prehypertension following Riceberry rice bran oil supplementation. A total of 35 women aged 60 to 76 years with prehypertension were randomly allocated to two groups, one of which was supplemented with rice bran oil (n=18) and the other with Riceberry rice bran oil (n=17) at 1,000 mg daily for 8 weeks. Prior to and after the supplementation, oxidative stress and cardiovascular risk biomarkers (primary outcomes), heart rate variability, and blood pressure (secondary outcomes) were investigated. Results showed that plasma malondialdehyde, blood glutathione disulfide, and tumor necrosis factor-alpha levels were significantly decreased, and the ratio of reduced glutathione to glutathione disulfide significantly increased in both groups after supplementation (all P<0.05). No significant differences were observed between groups. Heart rate variability and blood pressure did not statistically significantly change subsequent to supplementation in either group and did not differ between groups. In conclusion, Riceberry rice bran oil supplementation for 8 weeks alleviates oxidative stress and inflammation in older adults with prehypertension to a similar extent as rice bran oil supplementation.

Upregulation of Pro-inflammatory Cytokine Expression Following Chronic Paracetamol Treatment in Astrocyte.

The present study aimed to investigate the effect of APAP treatment on the expression of pro-inflammatory cytokines in the astrocytes. The mouse astrocyte cells (C8-D1A) were treated with APAP at the concentration of 100 µM for 24 h, 16 and 28 days. The expressions of pro-inflammatory cytokines and NF-kB were determined using western blot analysis. Furthermore, the expression and localization of phosphorylation of NF-kB were detected by immunohistochemical and immunofluorescent analysis. The ultrastructure of C8-D1A cells was as well monitored. The results revealed that acute APAP treatment (24 h) had no effect on the expression of pro-inflammatory cytokines and pNF-kB. This treatment did not alter the ultrastructure of C8-D1A cells when compared with those in the control cells. However, the results obtained from the study on chronic APAP-treated cells (16 and 28 days) showed the different effect of APAP treatment. The results obtained from western blot analysis showed the increment of pro-inflammatory cytokine (IL-1ß and TNF-α) expressions and the activation of NF-kB signaling pathway. Nuclear translocation of pNF-kB and alteration of several cell structures were well observed in the C8-D1A cells with chronic APAP treatment. The results obtained from this study suggest that chronic APAP treatment can induce an upregulation of pro-inflammatory cytokines (IL-1ß and TNFα) in astrocytes. This alteration implies the involvement of the activation of NF-kB signaling pathway.

Up-regulation of calcitonin gene-related peptide in trigeminal ganglion following chronic exposure to paracetamol in a CSD migraine animal model.

Previously, our group has demonstrated that chronic paracetamol (APAP) treatment induces alterations to the trigeminovascular nociceptive system in the cortical spreading depression (CSD) migraine animal model. The calcitonin gene related peptide (CGRP) is a key neuropeptide involved in the activation of the trigeminovascular nociceptive system. Therefore, this study examined the expression levels of CGRP in the trigeminal ganglion (TG) after chronic APAP exposure (0, 15, and 30 days) using a CSD model. Rats were divided into control, CSD only, APAP only and APAP treatment with CSD groups. A single injection (i.p.) of APAP (200 mg/kg body weight) was given to the 0-day APAP-treated groups, while the other APAP-treated groups received daily injections for 15 and 30 days. CSD was induced by the topical application of KCl to the parietal cortex. The protein expression of CGRP in the TG was evaluated by immunohistochemistry, and the CGRP mRNA level was investigated by real-time quantitative reverse transcription polymerase chain reaction. The results revealed that the induction of CSD significantly increased the level of CGRP protein but had no effect on CGRP mRNA level. Pretreatment with APAP 1 hour before CSD activation significantly reduced CGRP expression induced by CSD. In contrast, chronic treatment with APAP (15 and 30 days) significantly enhanced CGRP expression in both protein and mRNA levels when compared with the control groups. In combination with CSD, the expression of CGRP further increased in the animal with 30 day treatment. These findings indicate that chronic treatment with APAP induces an increase of CGRP expression in the TG. This alteration may be associated with the increased trigeminovascular nociception observed in our previous studies.

Chronic paracetamol treatment increases alterations in cerebral vessels in cortical spreading depression model.

Recently, a number of non-beneficial effects of chronic treatment with paracetamol (APAP) have been reported in several systems, including circulatory system. In this study, the effects of acute (1 hour) and chronic (30 days) APAP treatments on cerebral microvessels in a cortical spreading depression (CSD) migraine animal model were investigated. Rats were divided into control, CSD only, and APAP treatment with or without CSD groups. A single dose (200 mg/kg body weight) or once-daily APAP treatment over 30 days was intraperitoneally injected into the acute and chronic APAP treated groups, respectively. CSD was induced by topical application of potassium chloride on the parietal cortex. Ultrastructural alterations and the expressions of cell adhesion molecules (ICAM-1 and VCAM-1) of the cerebral microvessels were monitored in all experimental groups. The results demonstrated that the induction of CSD caused ultrastructural alterations of the cerebral endothelial cells, as indicated by increases in microvillous and pinocytic formations and swelling of the astrocytic foot plates. The expression of ICAM-1 was significantly elevated in the CSD groups as compared with the control groups. Pretreatment with APAP 1 hour prior to CSD activation attenuated the alterations induced by CSD. However, chronic APAP treatment resulted in an enhancement of the ultrastructural alterations and the expressions of cell adhesion molecules in the cerebral microvessels that were induced by CSD. Interestingly, the rats that received chronic APAP treatment alone exhibited higher degrees of ultrastructural alterations and ICAM-1 expression than those in the control group. Based on these results, we suggest that short-term treatment with APAP has no effect on cerebral microvessels and that chronic APAP treatment can alter cerebral microvasculature, especially when combined with CSD activation.

Hibiscus sabdariffa Linnaeus aqueous extracts attenuate the progression of renal injury in 5/6 nephrectomy rats.

Hibiscus sabdariffa Linn. (HS) is a tropical wild plant with antioxidant, antibacterial, antihypertensive, and lipid-lowering properties. In several animal models, HS aqueous extracts reduced the severity of the multi-organ injuries such as hypertension and diabetic nephropathy. One of the multiorgan injuries is chronic kidney disease (CKD), which results from the loss of nephron function. HS was used in a 5/6 nephrectomy (5/6 Nx) rat model to determine if it could attenuate the progression of CKD. HS (250 mg/kg/day) or placebo was orally administered to 5/6 Nx male Sprague-Dawley rats. The Nx+HS group had fewer renal injuries as measured by blood urea nitrogen, serum creatinine, creatinine clearance, and renal pathology when compared with the Nx group. In order to determine which property of HS, either vasodilatory and/or antioxidant, was important in attenuating the progression of CKD, systolic blood pressure (SBP) and serum levels of malondialdehyde (MDA) were assessed. In the Nx+HS group, the SBP and the serum levels of MDA were significantly lower at Week 7. In conclusion, through either antihypertensive and/or antioxidant properties, HS was able to attenuate the progression of renal injury after 5/6 Nx. Hence, HS should be considered as one of the new, promising drugs that can be used to attenuate the progression of CKD.