Astragaloside IV protects cardiomyocytes from hypoxic injury by regulating endoplasmic reticulum stress via eIF2α/CHOP signaling pathway.

Endoplasmic reticulum stress (ER stress) is suggested to promote cardiomyocyte apoptosis and ultimately lead to ischemic injury. Inhibition of ER stress-induced apoptosis may be a therapeutic strategy for MI injury. Astragaloside-IV (AST) from Astragalus membranaceus (Fisch) Bge, was reported to have cardioprotective properties. In this study, we investigated the protective effect of AST on cardiomyocytes against hypoxia injury by regulating ER stress and inhibiting apoptosis. H9c2 cardiomyocytes were divided into three groups, normal group, hypoxia group and AST group. Cell viability was determined by CCK-8 assay. Intracellular reactive oxygen species (ROS) production was detected by DCFH-DA (2,7- dichloro-dihydrofluorescein diacetate) florescent staining. The study showed that AST treatment could significantly increase the cell viability of H9c2 cells exposed to hypoxia. Furthermore, AST could restrain cell apoptosis and decrease the production of ROS. Compared with normal group, the protein levels of Bax, caspase-3, caspase-9, GRP78, p-eIF2α, and CHOP were enhanced in the hypoxia group, whereas the protein level of Bcl-2 was dramatically reduced. Compared with hypoxia group, AST markedly inhibited the phosphorylation of eIF2α and the expression of caspase-3, caspase-9 and CHOP, and promoted the protein expression of Bcl-2. Thus, AST can inhibit the ER stress-mediated apoptosis, partly through the eIF2α/CHOP pathway suppression to inhibit ER stress.

Efficacy and potential mechanisms of Chinese herbal compounds in coronavirus disease 2019: advances of laboratory and clinical studies.

The Coronavirus disease 2019 (COVID-19) pandemic is still spread and has made a severe public health threat around the world. To improve disease progression, emerging Chinese herbal compounds were used in clinical practice and some agents have proven beneficial in treating COVID-19. Here, the relevant literature from basic researches to clinical application were identified and comprehensively assessed. A variety of Chinese herbal compounds have been reported to be effective in improving symptoms and outcomes in patients with COVID-19, particularly together with routine treatment strategy. The pharmacological activities were mainly attributed to the relief of clinical symptoms, inhibition of cytokine storm, and improvement of organ function. Besides, the development of novel antiviral drugs from medicinal herbs were further discussed. The updated laboratory and clinical studies provided the evidence of Chinese herbal compounds such as Lianhua Qingwen prescription, Shufeng Jiedu prescription, and Qingfei Paidu Tang for the relief of COVID-19. However, both of the randomized controlled trials and real world researches need to be done for supporting the evidence including the efficacy and safety in fighting COVID-19.

Beetroot as a functional food with huge health benefits: Antioxidant, antitumor, physical function, and chronic metabolomics activity.

Previously, beetroot is mainly consumed as a food additive. In recent years, the beetroot, especially the betalains (betanin) and nitrates it contains, now has received increasing attention for their effective biological activity. Betalains have been proven to eliminate oxidative and nitrative stress by scavenging DPPH, preventing DNA damage, and reducing LDL. It also has been found to exert antitumor activity by inhibiting cell proliferation, angiogenesis, inducing cell apoptosis, and autophagy. In some chronic diseases, nitrate is the main component for lowing blood lipids, glucose, and pressure, while its role in treating hypertension and hyperglycemia has not been clearly stated. Moreover, the intake of nitrate-rich beetroot could enhance athletic performance and attenuate muscle soreness in certain types of exercise. The objective of this review is to provide sufficient evidence for the clarification of health benefits of beetroot, especially in the aspect of biooxidation, neoplastic diseases, some chronic diseases, and energy supplementation.

IGF-1 induces iNOS expression via the p38 MAPK signal pathway in the anti-apoptotic process in pulmonary artery smooth muscle cells during PAH.

Apoptosis and cell proliferation are two important cellular processes that determine the accumulation of pulmonary artery smooth muscle cells (PASMC) during pulmonary arterial hypertension (PAH). Insulin-like growth factor 1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that circulates at high levels in the plasma and is expressed in most cell types. IGF-1 has major effects on development, cell growth and differentiation, also tissue repair. Inducible nitric oxide synthase (iNOS) has been shown to serve many vasoprotective roles in vascular smooth muscle cells (VSMCs) including inhibition of VSMC proliferation and migration and stimulation of endothelial cell growth. In this study, we investigated the involvement of iNOS in the process of IGF-1-induced inhibition of PASMC apoptosis. We also examined the role of p38 mitogen-activated protein kinase (MAPK) in the IGF-1-induced iNOS activation. Our results show that exogenous IGF-1 induced the up-regulation of iNOS in PASMC. Immunofluorescence of IGF-1 and iNOS showed a decreased immunostaining of both IGF-1 and iNOS in the cytoplasm and the perinucleus under serum deprivation condition. iNOS inhibition in PASMC in vitro markedly induced IGF-1-mediated anti-apoptosis as assessed by the cell viability measurement, Western blot, mitochondrial potential analysis and nuclear morphology determination. A p38 MAPK inhibitor blocked all the effects of IGF-1 on iNOS. Our findings suggest that IGF-1 inhibits cells apoptosis in PASMC by activating the p38 MAPK-iNOS transduction pathway. This mechanism may contribute to the accumulation of PASMC in early human PAH.

Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population.

OBJECTIVE: To investigate associations between single nucleotide polymorphisms (SNPs) rs2228314 and rs2267443 in the sterol regulatory element binding protein-2 gene (SREBP-2) and knee osteoarthritis (OA) susceptibility in a Chinese Han population. METHODS: SREBP-2 rs2228314 and rs2267443 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. RESULTS: A total of 402 patients with knee OA and 410 controls were enrolled in the study. GC and CC genotypes of rs2228314, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs2228314 GC heterozygotes compared with GG homozygotes was stronger in females and those aged >65 years. In contrast, the GA and AA genotypes of rs2267443 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. CONCLUSIONS: SREBP-2 rs2228314 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.