Urantide decreases hepatic steatosis in rats with experimental atherosclerosis via the MAPK/Erk/JNK pathway

Luu

Natural Product Communications

et al. 2022

Hypertension is a significant public health issue that is increasing in prevalence and can have dangerous complications. This atherosclerotic disease occurs due to lifestyle choices, such as being sedentary, eating fast foods, and a lack of physical exercise. Atherosclerosis has gradually become the leading cause of death worldwide. Currently, the trend of using natural products to supplement and replace synthetic drugs is being considered in many places. This study evaluated the antihypertensive and anti-atherosclerosis effects of Nano NO plus capsules on hypertensive and atherosclerotic rat models. The results showed that Nano NO plus given to rats at doses of 420 mg/kg and 840 mg/kg lowered systolic, diastolic, and average blood pressure (BP) without affecting heart rate. Nano NO plus capsules also increased nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH), and decreased malondialdehyde (MDA) in the rats’ plasma. All of these effects were comparable to those of Losartan at 25 mg/kg. Furthermore, doses of 420 mg/kg and 840 mg/kg reduced blood lipid test indexes, including triglyceride (TG) levels, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and atherogenic index (AI). At the same time, Nano NO plus capsules increased the levels of high-density lipoprotein-cholesterol (HDL-C) in the blood and protected against atherosclerotic lesions of the abdominal aorta in the studied rats. These results indicate that Nano NO plus is a potential product to treat hypertension and atherosclerotic.

Section: Discussionmentioning

confidence: 70%

In Vivo Effect of Nano NO Plus Capsules on Hypertensive and Atherosclerotic rat Models

Luu

Natural Product Communications

et al. 2022

Evidence-Based Complementary and Alternative Medicine

“…The liver is an important organ regulating the homeostasis of lipid metabolism. In patients with atherosclerosis, the excessive increase of lipid levels, which exceeds the metabolic capacity of the liver, will damage the structure and function of the liver, resulting in hepatic steatosis [ 35 ]. Growing evidence has shown that hepatic steatosis is not only an indicator of atherosclerosis but also an early regulator to promote the development of atherosclerosis [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Polydatin and Polygonatum sibiricum Polysaccharides in Combating Atherosclerosis via Suppressing TLR4-Mediated NF-κB Activation in ApoE-Deficient Mice

Zhao

Zhu

et al. 2022

Objective. Atherosclerosis is a chronic inflammatory disease, which is closely related to hyperlipidemia, inflammatory responses, and oxidative stress. As natural products, polydatin (PD) and Polygonatum sibiricum polysaccharides (PSP) have remarkable pharmacological effects in anti-inflammatory, antioxidant stress, and lipid regulation. In this study, we sought to investigate whether the combination of polydatin and P. sibiricum polysaccharides play an anti-atherosclerotic role in alleviating inflammatory responses by inhibiting the toll-like receptor4 (TLR4)/myeloid differentiation factor88(MyD88)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods. Thirty-two ApoE-/- mice were fed with a high-fat diet (HFD) starting at the age of 8 weeks. Mice were randomly divided into four groups; (1) model group, (2) PD (100 mg/kg) + PSP (50 mg/kg) group, (3) TAK-242 (3 mg/kg) (TLR4 inhibitor) group, (4) PD (100 mg/kg) + PSP (50 mg/kg) + TAK-242 (3 mg/kg) group. Eight age-matched wild-type C57BL/6J mice fed an ordinary diet were used as a control group. Blood lipid levels were measured with an automatic biochemical analyzer. The lipid accumulation and histopathological changes in the aorta and liver were observed by Oil Red O and hematoxylin and eosin (H&E) staining, respectively. ELISA was performed to measure the serum levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Western blot analysis was performed to analyze the expression of key proteins in the TLR4/MyD88/NF-κB signaling pathway. Results. Compared with the model group, the combination of PD and PSP significantly inhibit serum lipids (low-density lipoprotein cholesterol, total cholesterol, and triglyceride) and cell adhesion molecules (VCAM-1, ICAM-1). Oil Red O staining indicated that the combination of PD and PSP decrease lipid accumulation in the aorta and liver. Moreover, H&E staining suggested that the combination of PD and PSP alleviate aortic intimal hyperplasia, inflammatory cell infiltration, and hepatic steatosis. Finally, the combination of PD and PSP inhibit the expression of TLR4, MyD88, and the phosphorylation level of NF-κB p65 protein in the aorta. Conclusions. Polydatin synergizes with P. sibiricum polysaccharides in preventing the development of atherosclerosis in ApoE–/– mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Cell Biochemistry & Function

“…Both the body weight and liver weight of each rat from each group were evaluated. The hepatic index was calculated by the formula: Liver index = liver weight/body weight × 100% 14 …”

Section: Methodsmentioning

confidence: 99%

The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis

Atef,

Abou Hashish,

Hafez

et al. 2023

Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon‐like peptide 1 receptor (GLP‐1R) agonist that act as a novel antidiabetic drug with broad‐spectrum anti‐inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA‐induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid‐treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT‐PCR technique. Hepatic NF‐κB and TNF‐α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA‐hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA‐induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.