Apart from reducing the circulating LDL-c and the number of cardiovascular cases as well as fatalities, statins have auxiliary non-lipid-related or cholesterol independent effects, the pleiotropic effects. The aim of the present review is to understand the pleotropic effects of statins.

Cardiovascular disease (CVD) is presently the major cause of patient misery as well as mortality among non-communicable diseases (NCDs) in the world. Despite the fact that statins are the most extensively affirmed, prescribed and evidence-based lipid-lowering medicine worldwide that curtail low density lipoprotein cholesterol (LDL-c) levels and the number of cardiovascular cases as well as deaths, statins also elicit auxiliary non-lipid-related or cholesterol independent effects, the pleiotropic effects. Improved endothelial function, significantly lowered oxidative stress, atherosclerotic plaque stabilization, immunomodulatory, cessation of vascular smooth muscle proliferation, effects on bone metabolism, anti-inflammatory, antithrombotic effects, and reduced risk of dementia are among these pleotropic effects. Statins have also been explored for its uses in life threatening diseases like cancer and inflammatory bowel disease. They have been demonstrated to revamp vascular tone. Many research and review articles have been thoroughly studied for this systematic review.

Statins have not only shown to be benefitial in lowering the levels of LDL-C but have also been established to be advantageous in the treatment of cancer, neurological conditions like dementia, multiple sclerosis, inflammatory bowel disease. Future high-quality trials are needed to include statins in the treatment of these conditions as per guidelines.

Cistanche deserticola Y.C. Ma (CD) possesses hepatoprotective activity, while the active ingredients and involved mechanisms have not been fully explored. The objective of this study was to investigate the chemical composition and hepatoprotective mechanisms of CD. We primarily used ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) to identify the phenylethanoid glycoside (PhG) components of CD. Then, network analysis was used to correlate and predict the pharmacology of the identified active components of PhGs with hepatoprotection. Next, the mechanisms of the core components and targets of action were explored by cellular assays and toll-like receptor 4 (TLR4) target competition assays. Finally, its hepatoprotective effects were further validated in in vivo experiments. The results showed that a total of 34 PhGs were identified based on the UPLC-Q-TOF-MS/MS method. Echinacoside (ECH) was identified as the key ingredient, and TLR4 and nuclear factor-kappa B (NF-κB) were speculated as the core targets of the hepatoprotective effect of CD via network analysis. The cellular assays confirmed that PhGs had significant anti-inflammatory activity. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot indicated that ECH notably reduced the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), as well as the mRNA expression of TLR4, TNF-α, and IL-6, and decreased the high expression of the TLR4 protein, which in turn downregulated the myeloid differentiation factor 88 (MyD88), p-P65 and TNF-α proteins in the inflammatory model. The target competition experiments suggested that ECH and LPS could competitively bind to the TLR4 receptor, thereby reducing the expression of TLR4 downstream proteins. The results of in vivo studies showed that ECH significantly ameliorated LPS-induced hepatic inflammatory infiltration and liver tissue damage and reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice. Moreover, ECH remarkably inhibited the release of inflammatory factors such as TNF-α, IL-6, IL-1β, and MCP-1 in the serum of mice, exerting the hepatoprotective effect by the TLR4/NF-κB signaling pathway. More importantly, ECH could act as a potential inhibitor of TLR4 and deserves further in-depth study. Our results could provide a basis for exploring the hepatoprotective properties of CD.

In the past few decades, the increasing socioeconomic burden of acute diverticulitis (AD) has become evident, and with the growth of the population age, this significant economic impact will likely continue to rise. Furthermore, recent evidence showed an increased rate of hospital admissions especially evident among women and younger individuals. The natural history and pathophysiology of this clinical condition is still to be fully defined, and efforts continue to be made in the identification of risk factors and the establishment of relative preventive strategies. The actual therapeutic strategies aimed to modulate gut microbiota, such as rifaximin or probiotics, or to reduce mucosal inflammation, such as mesalazine, present a relatively poor efficacy for both the prevention of the first AD episode (primary prevention) and its recurrence (secondary prevention). In the last few years, the main goal achieved has been in the management of AD in that uncomplicated AD can, to a larger extent, be managed in an outpatient setting with no or little supportive therapy, a strategy that will certainly impact on the health costs of this disease. The problem of AD recurrence remains a topic of debate. The aim of this review is to present updated evidence on AD epidemiology and relative open clinical questions and to analyze in detail predisposing and protective factors with an attempt to integrate their possible modes of action into the several pathogenic mechanisms that have been suggested to contribute to this multifactorial disease. A unifying hypothesis dealing with the colonic luminal and extra-luminal microenvironments separately is provided. Finally, evidence-based changes in therapeutic management will be summarized. Because of an ascertained multifactorial pathogenesis of uncomplicated and complicated AD, it is probable that a single 'causa prima' will not be identifiable, and a better stratification of patients could allow one to pursue tailored therapeutic algorithm strategies.