Strategy for sodium-salt substitution: On the relationship between hypertension and dietary intake of cations.

Chronic diseases, especially cardiovascular diseases (CVD), have become one of the main causes affecting human health. Hypertension is a prominent representative of CVD. The formation and development of hypertension is closely related to people's daily diet. A large number of studies have shown that excessive intake of salt (NaCl) could increase the risk of hypertension. In recent years, more and more investigations have focused on other cations that may be contained in edible salt, exploring whether they have an effect on hypertension and the underlying mechanism. This article focuses on the relationship between four metal elements (potassium, calcium, magnesium, and zinc) and hypertension, by discussing the main metabolic pathway, the impact of diet intake on blood pressure, and especially the regulation mechanisms on blood pressure in detail. At the same time, some opinions and suggestions are put forward, combined with the current hot topics "salt reduction" and "salt substitution".

Alginate-Chitosan Coated Nanoliposomes as Effective Delivery Systems for Bamboo Leaf Flavonoids: Characterization, In Vitro Release, Skin Permeation and Anti-Senescence Activity.

The use of bamboo leaf flavonoids (BLF) as functional food and cosmetic ingredients is limited by low bioavailability and difficulty in being absorbed by the intestine or skin. The aim of this study was to prepare BLF-loaded alginate-chitosan coated nanoliposomes (AL-CH-BLF-Lip) to overcome these challenges. The nanocarriers were characterized by dynamic light scattering, high performance liquid chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. The biological activity was analyzed by in vitro antioxidant activity, transdermal absorption, cytotoxicity and AAPH induced HaCaT cell senescence model. The results showed that the size of nanocarriers ranged from 152.13 to 228.90 nm and had a low polydispersity index (0.25−0.36). Chitosan (CH) and alginate (AL) were successfully coated on BLF-loaded nanoliposomes (BLF-Lip), the encapsulation efficiency of BLF-Lip, BLF-loaded chitosan coated nanoliposomes (CH-BLF-Lip) and AL-CH-BLF-Lip were 71.31%, 78.77% and 82.74%, respectively. In addition, BLF-Lip, CH-BLF-Lip and AL-CH-BLF-Lip showed better in vitro release and free radical scavenging ability compared with naked BLF. In particular, the skin permeability of BLF-Lip, CH-BLF-Lip, and AL-CH-BLF-Lip increased 2.1, 2.4 and 2.9 times after 24 h, respectively. Furthermore, the use of nanoliposomes could significantly improve the anti-senescence activity of BLF (p < 0.01). Conclusively, alginate-chitosan coated nanoliposomes are promising delivery systems for BLF that can be used in functional foods and cosmetics.

4,4'-Dimethoxychalcone protects the skin from AAPH-induced senescence and UVB-induced photoaging by activating autophagy.

Aging can lead to the occurrence of many degenerative diseases, and the most intuitive consequences are mainly manifested on the skin, which is affected by both endogenous and exogenous aging factors and can be used as an ideal model organ for studying aging. 4,4'-Dimethoxychalcone (DMC), a natural flavonoid compound from Angelica sinensis, has been proven to prolong the lifespan of multiple species. However, it is not clear whether it has the effect of delaying skin aging. This study aimed to establish a skin senescent cell model induced by oxidative stress, and further, to analyze the inhibitory effect of DMC on cellular senescence, and explore its molecular mechanisms. We found that treatment of HaCaT cells with 1 mM 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) for 48 h showed significant senescent characteristics, which could be effectively alleviated by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC). DMC significantly inhibited AAPH-induced senescence, and further mechanism studies showed that the activation of autophagy which depended on the phosphorylation of ULK1 at Ser555 was necessary for DMC to alleviate senescence of HaCaT cells. In addition, the mitogen-activated protein kinase (MAPK) signal pathway was also involved in the regulation of autophagy induced by DMC. These results were also validated in UVB-induced photoaging mice. In conclusion, we successfully establish a skin senescent cell model and prove that DMC can be used as a potential therapeutic agent to intervene in skin aging.

Bamboo Leaf Flavonoids Suppress Oxidative Stress-Induced Senescence of HaCaT Cells and UVB-Induced Photoaging of Mice through p38 MAPK and Autophagy Signaling.

With the global escalation of the aging process, the research on aging mechanisms and anti-aging strategies has become a hot spot. As the most external organ of the human body, skin can be used as an ideal organ for the study of endogenous and exogenous aging. Bamboo leaf flavonoids (BLF) possess a variety of biological effects such as antioxidant, anti-bacterial, anti-inflammatory, lipid-lowering, anti-radiation, and anti-aging. However, it is still unclear whether they can delay skin aging. This study aimed to analyze the inhibitory effect of BLF on skin aging and explore their molecular mechanisms. We found that 10-40 µg/mL BLF significantly inhibited the senescence of HaCaT cells induced by AAPH, which might be related to their antioxidant and anti-inflammatory abilities. Further mechanism studies showed that mitogen-activated protein kinase (MAPK), especially the p38 MAPK pathway, was the key to BLF to alleviate the senescence of HaCaT cells. In addition, autophagy was also involved in the anti-senescence effect of BLF. The results were also verified in UVB-induced photoaging mice. Therefore, BLF can be used as a potential therapeutic agent to intervene skin aging in vitro and in vivo.

7,8-Dihydroxyflavone modulates bone formation and resorption and ameliorates ovariectomy-induced osteoporosis.

Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-Dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/ß-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3ß (p-GSK3ß), ß-catenin, Runx2, Osterix, and osteoprotegerin (OPG) was all significantly up-regulated. Knockdown of ß-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation, and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties, and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.

Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7,8-dihydroxyflavone in female mice.

OBJECTIVE: 7,8-Dihydroxyflavone (7,8-DHF), a small molecular mimetic of brain-derived neurotrophic factor (BDNF), alleviates high-fat diet-induced obesity in female mice in a sex-specific manner by activating muscular tropomyosin-related kinase B (TrkB). However, the underlying molecular mechanism for this sex difference is unknown. Moreover, muscular estrogen receptor α (ERα) plays a critical role in metabolic diseases. Impaired ERα action is often accompanied by metabolic syndrome (MetS) in postmenopausal women. This study investigated whether muscular ERα is involved in the metabolic effects of 7,8-DHF. METHODS: For the in vivo studies, 72 female C57BL/6J mice were given a low-fat diet or high-fat diet, and both received daily intragastric administration of vehicle or 7,8-DHF for 24 weeks. The hypothalamic-pituitary-ovarian (HPO) axis function was assessed by investigating typical sex-related serum hormones and the ovarian reserve. Indicators of menopausal MetS, including lipid metabolism, insulin sensitivity, bone density, and serum inflammatory cytokines, were also evaluated. The expression levels of ERα and other relevant signaling molecules were also examined. In vitro, the molecular mechanism involved in the interplay of ERα and TrkB receptors was verified in differentiated C2C12 myotubes using several inhibitors and a lentivirus short hairpin RNA-knockdown strategy. RESULTS: Long-term oral administration of 7,8-DHF acted as a protective factor for the female HPO axis function, protecting against ovarian failure, earlier menopause, and sex hormone disorders, which was paralleled by the alleviation of MetS coupled with the production of ERα-rich, TrkB-activated, and uncoupling protein 1 (UCP1) high thermogenic skeletal muscle tissues. 7,8-DHF-stimulated transactivation of ERα at serine 118 (S118) and tyrosine 537 (Y537), which was crucial to activate the BDNF/TrkB signaling cascades. In turn, activation of BDNF/TrkB signaling was also required for the ligand-independent activation of ERα, especially at the Y537 phosphorylation site. In addition, Src family kinases played a core role in the interplay of ERα and TrkB, synergistically activating the signaling pathways related to energy metabolism. CONCLUSIONS: These findings revealed a novel role of 7,8-DHF in protecting the function of the female HPO axis and activating tissue-specific ERα, which improves our understanding of this sex difference in 7,8-DHF-mediated maintenance of metabolic homeostasis and provides new therapeutic strategies for managing MetS in women.

Lanostane Triterpenoids from the Fruiting Bodies of Fomes officinalis and Their Anti-Inflammatory Activities.

In the current study, further chemical investigation of the fruiting bodies of Fomes officinalis led to isolate seven new 24-methyl-lanostane triterpenoids, named officimalonic acids I-O (1-7). Their structures were elucidated based on the analysis of spectroscopic data (HR-MS, 1D and 2D NMR, UV, IR). Compounds 1-3 possessed an unusual C-23 spirostructure moiety, while compounds 4-7 had 23,26-lactone unit. Anti-inflammatory assay revealed that compounds 3 and 5 exhibited significant inhibitory activities against NO production in LPS-induced RAW 264.7 cells and cyclooxygenase (COX-2).

Biomarkers, oxidative stress and autophagy in skin aging.

Aging is a major cause of many degenerative diseases. The most intuitive consequence of aging is mainly manifested on the skin, resulting in cumulative changes in skin structure, function and appearance, such as increased wrinkles, laxity, elastosis, telangiectasia, and aberrant pigmentation of the skin. Unlike other organs of the human body, skin is not only inevitably affected by the intrinsic aging process, but also affected by various extrinsic environmental factors to accelerate aging, especially ultraviolet (UV) radiation. Skin aging is a highly complex and not fully understood process, and the lack of universal biomarkers for the definitive detection and evaluation of aging is also a major research challenge. Oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to lipid, protein, nucleic acid and organelle damage, thus leading to the occurrence of cellular senescence, which is one of the core mechanisms mediating skin aging. Autophagy can maintain cellular homeostasis when faced with different stress conditions and is one of the survival mechanisms of cell resistance to intrinsic and extrinsic stress. Autophagy and aging have many features in common and may be associated with skin aging mediated by different factors. Here, we summarize the changes and biomarkers of skin aging, and discuss the effects of oxidative stress and autophagy on skin aging.

High Content Analysis technology for evaluating the joint toxicity of sunset yellow and sodium sulfite in vitro.

Foods contain various additives that affect our daily lives. At present, food additive safety evaluation standards are based on the toxicity of single additives, but food additives are often used in combination and may have additive, synergistic or antagonistic actions. The current study investigated the toxicity of food additives and mechanisms of damage in HepG2 cells using High Content Analysis (HCA). We used the CCK-8 assay to determine cell viability, providing an experimental basis for determining the safety of food additives. All of the food additives tested were observed to decrease the growth of HepG2 cells in a dose-dependent manner. Sunset yellow and sodium sulfite had IC50 values of 1.06, and 0.30g/L at 24h, respectively. HCA showed that both sunset yellow and sodium sulfite had synergistic effects on cell number, membrane permeability, mitochondrial membrane potential, intracellular calcium level, oxidative stress, and high dose group DNA damage.