Health outcomes associated with phytosterols: An umbrella review of systematic reviews and meta-analyses of randomized controlled trials.

BACKGROUND: Phytosterols (PS), as a kind of plant active ingredients, have many benefits to human health. However, there is currently no comprehensive overview of the clinical evidence and an assessment of the evidence quality. PURPOSE: We conducted an umbrella review, which incorporated verification spanning a number of meta-analyses and systematic reviews to clarify the link that existed between PS consuming and health outcomes. METHODS: The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research and ultimately included 23 articles involving 79 results. Methodological quality and the validity of evidence received designation in the included meta-analyses leveraging the Assessment of Multiple Systematic Reviews (AMSTAR-2) and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS: The consumption of PS makes a contribution to the alleviation of metabolic conditions such as hypercholesterolemia, diabetes, obesity, and hypertension. Its most essential function is to decrease cholesterol absorption, leading to dramatically reductions in total cholesterol and low density lipoprotein cholesterol. Furthermore, utilizing PS products can have a favorable impact on managing apolipoprotein levels along with decreasing the probability of obtaining atherosclerotic cardiovascular disease. CONCLUSION: This umbrella review summarized a range of beneficial functions of PS to humans, highlighting the promising potential for the development of PS into functional foods.

Hawthorn fruit extract protect against MC-LR-induced hepatotoxicity by attenuating oxidative stress and apoptosis.

Microcystins (MCs) is a class of cyclic heptapeptide compounds with biological activity. There is no effective treatment for liver injury caused by MCs. Hawthorn is a medicinal and edible plant traditional Chinese medicine with hypolipidemic, reducing inflammation and oxidative stress in the liver. This study discussed the protective effect of hawthorn fruit extract (HFE) on liver damage caused by MC-LR and the underlying molecular mechanism. After MC-LR exposure, pathological changes were observed and hepatic activity of ALT, AST and ALP were increased obviously, but they were remarkably restored with HFE administration. In addition, MC-LR could significantly reduce SOD activity and increase MDA content. Importantly, MC-LR treatment resulted in mitochondrial membrane potential decreased, and Cytochrome C release, eventually leading to cell apoptosis rate increase. HFE pretreatment could significantly alleviate the above abnormal phenomena. To examine the mechanism of protection, the expression of critical molecules in the mitochondrial apoptosis pathway was examined. The levels of Bcl-2 was inhibited, and the levels of Bax, Caspase-9, Cleaved Caspase-9, and Cleaved caspase-3 were upregulated after MC-LR treatment. HFE reduced MC-LR-induced apoptosis via reversing the expression of key proteins and genes in the mitochondrial apoptotic pathway. Hence, HFE could alleviate MC-LR induced hepatotoxicity by reducing oxidative stress and apoptosis.

Effects of sea buckthorn (Hippophae rhamnoides L.) on factors related to metabolic syndrome: A systematic review and meta-analysis of randomized controlled trial.

The purpose of this meta-analysis is to explore whether the supplement of sea buckthorn affects the factors related to metabolic syndrome. The related RCTs from five databases were systematically searched and comprehensively random effects model was used to calculate SMD and 95% CI. The Cochrane deviation risk tool was used to evaluate the deviation risk. Fifteen studies were involved in the meta-analysis. First, sea buckthorn supplementation reduced triglycerides [-0.722 (-1.129, -0.316); p < .001], total cholesterol [-0.345 (-0.639, -0.051); p = .021], low density lipoprotein cholesterol [-0.396 (-0.755, -0.037); p = .031], and increased high density lipoprotein cholesterol [0.370 (0.056, 0.684); p = .021] in overall subjects. Second, subgroup analysis showed that sea buckthorn supplementation reduced lipids only in people with abnormal lipid metabolism. Third, sea buckthorn had no effect on blood sugar, blood pressure, and BMI of the overall subjects. Sea buckthorn may affect the lipid metabolism in circulation, but it cannot affect blood glucose, blood pressure, and BMI. These indicators are closely associated with metabolic syndrome. This study may contribute to the development and utilization of sea buckthorn, and may provide a new and safer way for the prevention and treatment of metabolic syndrome. The limitation of this study is high heterogeneity, even if subgroup analysis is used. However, more clinical studies are needed to determine the real effect of sea buckthorn on metabolic syndrome.

Chronic vitamin D3 supplementation alleviates cognition impairment via inhibition of oxidative stress regulated by PI3K/AKT/Nrf2 in APP/PS1 transgenic mice.

Oxidative stress plays essential role in the pathogenesis of Alzheimer's disease, and vitamin D3 (VD3) is a nutrient with neuroprotective and antioxidant activities. The present study aimed to confirm the neuroprotective effect and the ameliorative effect of cortical oxidative stress of VD3 in APP/PS1 transgenic mice. APP/PS1 mice were treated with VD3 for 20 weeks. After treatment, Morris Water Maze test was used to evaluate cognitive level. Western blotting was used to determine APP, p-tau, tau and PI3K/AKT/Nrf2 pathway-related protein expression levels. Immunohistochemical staining was performed to determine the levels of ß amyloid peptide (Aß) deposition. Enzyme linked immunosorbent assay was used to determine the 25(OH)D3 levels and oxidative stress status. Our results showed that treatment with VD3 ameliorated behavioral deficits of APP/PS1 mice. In addition, the administration of VD3 significantly increased the cortical 25(OH)D3 levels, while reducing the levels of cortical Aß deposition and decreasing the expression levels of cortical APP, tau and p-tau in APP/PS1 mice. Moreover, VD3 protected the cortex against oxidative stress by enhancing the levels of superoxide dismutase, glutathione and total antioxidant capacity, and downregulating the malondialdehyde levels. Furthermore, VD3 clearly activated the PI3K/AKT/Nrf2 pathway, thereby elevating the expression levels of HO1 and NQO1. We concluded that VD3 improved cognitive function and cortical Alzheimer-like pathology of APP/PS1 mice, which may be related to the inhibition of oxidative stress via activation the PI3K/AKT/Nrf2 pathway.

The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis.

Natural bioactive compounds abundantly presented in foods and medicinal plants have recently received a remarkable attention because of their various biological activities and minimal toxicity. In recent years, many natural compounds appear to offer significant effects in the regulation of ferroptosis. Ferroptosis is the forefront of international scientific research which has been exponential growth since the term was coined. This type of regulated cell death is driven by iron-dependent phospholipid peroxidation. Recent studies have shown that numerous organ injuries and pathophysiological processes of many diseases are driven by ferroptosis, such as cancer, arteriosclerosis, neurodegenerative disease, diabetes, ischemia-reperfusion injury and acute renal failure. It is reported that the initiation and inhibition of ferroptosis plays a pivotal role in lipid peroxidation, organ damage, neurodegeneration and cancer growth and progression. Recently, many natural phytochemicals extracted from edible plants have been demonstrated to be novel ferroptosis regulators and have the potential to treat ferroptosis-related diseases. This review provides an updated overview on the role of natural bioactive compounds and the potential signaling pathways in the regulation of ferroptosis.

Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress.

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions.

A polysaccharide from Ganoderma atrum inhibits tumor growth by induction of apoptosis and activation of immune response in CT26-bearing mice.

Ganoderma atrum is one species of edible and pharmaceutical mushroom with various biological activities. Recently, a novel polysaccharide, PSG-1, was purified from G. atrum. The antitumor activity and its mechanism of action were studied. In vitro, PSG-1 has little effect on inhibiting proliferation of CT26 tumor cells. However, the tumor size was significantly decreased in PSG-1-treated mice. The results showed that PSG-1 induced apoptosis in CT26 cells. Moreover, the intracellular cyclic AMP (cAMP) level and protein kinase A (PKA) activity were markedly increased in PSG-1-treated mice. In contrast, the contents of cyclic GMP and DAG and the PKC activity were decreased. Similarly, the expression of PKA protein was upregulated, while PKC protein expression in PSG-1-treated group was lowered. Additionally, PSG-1 increased the immune organ index and serum biochemistry parameter. In general, PSG-1 enhances the antitumor immune response, induces apoptosis in CT26-bearing mice, and could be a safe and effective adjuvant for tumor therapy or functional food.

Polysaccharide from Ganoderma atrum evokes antitumor activity via Toll-like receptor 4-mediated NF-κB and mitogen-activated protein kinase signaling pathways.

Ganoderma atrum has been used as a traditional Chinese medicine for centuries. In this study, the antitumor activity of a novel G. atrum polysaccharide (PSG-1) was investigated in vitro and in vivo using S180 tumor-bearing mice. The results showed that PSG-1 significantly inhibited the proliferation of S180 via the activation of macrophages in a dose-dependent manner. PSG-1-primed macrophages exhibited a higher tumoricidal activity than untreated macrophages. Administration of PSG-1 significantly inhibited the growth of transplantable sarcoma S180-bearing mice and increased macrophage phagocytosis and the levels of cytokines and nitride oxide. Expression of Toll-like receptor (TLR) 4 in the membrane was markedly increased in PSG-1-treated groups, suggesting that it may be a possible receptor for PSG-1. PSG-1 also promoted the translocation of the p65 subunit of NF-κB from cytosol to nucleus and the degradation of IκBα. Moreover, the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2, and c-Jun N-terminal kinase in macrophages was improved by PSG-1 in a dose-dependent manner. Therefore, it is suggested that PSG-1 may elicit its antitumor effect by improving immune system functions through TLR4-mediated NF-κB and MAPK signaling pathways.