Flavonoids are found in natural health products and plant-based foods. The flavonoid molecules contain a 15-carbon skeleton with the particular structural construction of subclasses. The most flavonoid’s critical subclasses with improved health properties are the catechins or flavonols (e.g., epigallocatechin 3-gallate from green tea), the flavones (e.g., apigenin from celery), the flavanones (e.g., naringenin from citrus), the flavanols (e.g., quercetin glycosides from berries, onion, and apples), the isoflavones (e.g., genistein from soya beans) and the anthocyanins (e.g., cyanidin-3-O-glucoside from berries). Scientific data conclusively demonstrates that frequent intake of efficient amounts of dietary flavonoids decreases chronic inflammation and the chance of oxidative stress expressing the pathogenesis of human diseases like cardiovascular diseases (CVDs). The endoplasmic reticulum (ER) is a critical organelle that plays a role in protein folding, post-transcriptional conversion, and transportation, which plays a critical part in maintaining cell homeostasis. Various stimuli can lead to the creation of unfolded or misfolded proteins in the endoplasmic reticulum and then arise in endoplasmic reticulum stress. Constant endoplasmic reticulum stress triggers unfolded protein response (UPR), which ultimately causes apoptosis. Research has shown that endoplasmic reticulum stress plays a critical part in the pathogenesis of several cardiovascular diseases, including diabetic cardiomyopathy, ischemic heart disease, heart failure, aortic aneurysm, and hypertension. Endoplasmic reticulum stress could be one of the crucial points in treating multiple cardiovascular diseases. In this review, we summarized findings on flavonoids’ effects on the endoplasmic reticulum and their role in the prevention and treatment of cardiovascular diseases.

Background and aims: The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied were as follows: LDL, HDL, TG, Total Cholesterol, and Remnant Cholesterol. Method: We carried out a systematic search in multiple databases, including PubMed, Google Scholar, and Scopus, up to September 2022. Finally, after omitting the duplicates, 2724 studies were left, 104 related articles were extracted from the databases, and five articles were included in the study after screening the title, abstract and full text. Result: Five studies (4 cohorts and one cross-sectional) with a total population of 138664 were reviewed. These studies were done in China, Japan, Hong Kong, Taiwan, and Italy. The average age of the patients varied from 45 to 84 years. The follow-up duration of cohort studies ranged from 4 to 7 years. These studies have shown that higher LDL, HDL, and TG variability adversely affect microvascular complications, especially nephropathy and neuropathic complications. TG and LDL variability was associated with developing albuminuria and GFR decline. In another study, a lower HDL variation had a protective effect on microalbuminuria. In contrast, another study has shown no evidence of a relationship between lipid variation and microvascular complications such as retinopathy. Conclusion: The relationship between lipid variation (LDL, HDL, and TG) (adverse effects) on microvascular complications, especially nephropathy and neuropathic (and maybe not retinopathy), is proven. Physicians and health policymakers should be highly vigilant to lipid variation in a general population.

Flavonoids are classified into subclasses of polyphenols, a multipurpose category of natural compounds which comprises secondary metabolites extracted from vascular plants and are plentiful in the human diet. Although the details of flavonoid mechanisms are still not realized correctly, they are generally regarded as anti-microbial, anti-fungal, anti-inflammatory, anti-oxidative; anti-mutagenic; anti-neoplastic; anti-aging; anti-diabetic, cardio-protective, etc. The anti-cancer; properties of flavonoids are evident in functions such as prevention of proliferation, metastasis, invasion, inflammation and activation; of cell death. Tumors growth and enlargement expose cells to acidosis, hypoxia, and lack of nutrients which result in endoplasmic reticulum (ER) stress; it triggers the unfolded protein response (UPR), which reclaims homeostasis or activates autophagy. Steady stimulation of ER stress can switch autophagy to apoptosis. The connection between ER stress and cancer, in association with UPR, has been explained. The signals provided by UPR can activate or inhibit anti-apoptotic or apoptotic pathways depending on the period and grade of ER stress. In this review, we will peruse the link between flavonoids and their impact on the endoplasmic reticulum in association with cancer therapy.