Triterpenoids Biosynthesis Regulation for Leaf Coloring of Wheel Wingnut (Cyclocaryapaliurus)

Cyclocaryapaliurus leaves are rich in triterpenoids with positive results in the treatment of diabetes, antioxidation, and scavenging free radicals. C. paliurus red leaves have been found to contain higher flavonoids including anthocyanin, however, the triterpenoids accumulation pattern is still unclear. For the purpose of researching the triterpenoid accumulating mechanism during red new leaf development, transcriptome and metabolome analysis was conducted during C. paliurus the red leaf development process. The results uncovered that most triterpenoid ingredients were found to accumulate during leaves turning green, while the unique ingredients content including cyclocaric acid A, cyclocarioside I, cyclocarioside Ⅱand cyclocarioside Ⅲ decreased or remained unchanged. Functional structure genes (hydroxymethylglutaryl-CoA synthase, hydroxymethylglutaryl-CoA reductase, and farnesyl-diphosphate synthase) were identified for promoting triterpenoids accumulation mainly in the mevalonic acid pathway (MVA). Moreover, glycosyltransferase (UGT73C, UGT85A, and UGT85K) was also found attributed to triterpenoids accumulation. These findings provide information for a better understanding of the triterpenoid biosynthesis mechanism during leaf development and will be useful for targeted breeding.

New players in the treatment of hypercholesterolaemia: focus on bempedoic acid and inclisiran

Dyslipidaemias and in particular elevated plasma low-density lipoprotein cholesterol (LDL-C) levels are major risk factors for atherosclerotic cardiovascular disease (ASCVD). Indeed, the more LDL-C is reduced the larger will be the ASCVD risk reduction. Although statins represent the first-line intervention to reduce the atherosclerotic burden driven by raised levels of LDL-C, adherence is not optimal and most patients do not follow guidelines and recommended doses. Thus, to achieve optimal LDL-C goals, especially in very high-risk patients, there is a need for new and safe agents, more tolerable than statins with low risk of myalgia. Thus, the present review will address the most recent clinical trials with bempedoic acid and inclisiran. Bempedoic acid is an oral drug acting at a biochemical step preceding hydroxymethylglutaryl-CoA reductase and not associated with muscular side effects. Inclisiran, the first-in-class small interfering RNA-based approach, has the ability to effectively reduce LDL-C by inhibiting the hepatic synthesis of proprotein convertase subtilisin/kexin type 9, with the advantage of requiring subcutaneous of a single dose on Day 1, Day 90, and every 6 months thereafter.

Polyphenols from Citrus Tacle® Extract Endowed with HMGCR Inhibitory Activity: An Antihypercholesterolemia Natural Remedy

Tacle® is a citrus fruit obtained from the crossbreeding of Clementine and Tarocco cultivars. This fruit retains a promising nutraceutical potential most likely due to a high content in polyphenols, among which the main constituents are the two glycosides naringin and hesperidin. Herein, we evaluated, through an in vitro assay, the capability of Tacle extracts to inhibit the hydroxymethylglutaryl-CoA reductase enzyme, which plays a key role in cholesterol biosynthesis. The results obtained spurred us to investigate whether the anti-enzymatic activity observed may be due to a direct interaction of aglycones naringenin and hesperetin with the enzyme catalytic site. Molecular docking simulations indicated that these two compounds are able to anchor to the protein with binding modes and affinities similar to those found for statins, which represent mainstream medications against hypercholesterolemia. The overall results showed an interesting nutraceutical potential of Tacle, suggesting that its extract could be used for dietary supplementation in the treatment of moderate hypercholesterolemia.

Pathology Features of Immune and Inflammatory Myopathies, Including a Polymyositis Pattern, Relate Strongly to Serum Autoantibodies

We asked whether myopathology features of immune or inflammatory myopathies (IIM), without reference to clinical or laboratory attributes, correlate with serum autoantibodies. Retrospective study included 148 muscle biopsies with: B-cell inflammatory foci (BIM), myovasculopathy, perimysial pathology (IMPP), myofiber necrosis without perimysial or vessel damage or inflammation (MNec), inflammation and myofiber vacuoles or mitochondrial pathology (IM-VAMP), granulomas, chronic graft-versus-host disease, or none of these criteria. 18 IIM-related serum autoantibodies were tested. Strong associations between myopathology and autoantibodies included: BIM with PM/Scl-100 (63%; odds ratio [OR] = 72); myovasculopathies with TIF1-γ or NXP2 (70%; OR = 72); IMPP with Jo-1 (33%; OR = 28); MNec with SRP54 (23%; OR = 37); IM-VAMP with NT5C1a (95%; OR = 83). Hydroxymethylglutaryl-CoA reductase (HMGCR) antibodies related to presence of myofiber necrosis across all groups (82%; OR = 9), but not to one IIM pathology group. Our results validate characterizations of IIM by myopathology features, showing strong associations with some serum autoantibodies, another objective IIM-related marker. BIM with PM/Scl-100 antibodies can be described pathologically as polymyositis. Tif1-γ and NXP2 antibodies are both common in myovasculopathies. HMGCR antibodies associate with myofiber necrosis, but not one IIM pathology subtype. Relative association strengths of IIM-related autoantibodies to IIM myopathology features versus clinical characteristics require further study.

Statins Attenuate Fibrotic Manifestations of Cardiac Tissue Damage

: Cardiac fibrosis is a maladaptive condition secondary to cardiomyopathy caused by a wide spectrum of stimuli includingmyocardial infarction (MI), pressure overload, hyperglycemia, aging, and other factors.Despite having been supposed to be a reparative mechanism, the development of cardiac fibrosis can result inundesirable outcomes likedisruption of excitation-contraction coupling and ventricular hypertrophy leading finallyto heart failure (HF).Statins are known as potent cardioprotective agents widely used to control dyslipidemia; these drugs have exhibited protective effects against manifestations of cardiac fibrosis and hypertrophy.Cumulative evidence have suggested that statins attenuate the severity of fibrotic and hypertrophic manifestations of cardiac damage by affecting a variety of mechanisms like differentiation of myofibroblasts and cross-talk between cells in cardiac tissue as well as altering the expression and function of different molecules involved in cardiac remodelingincluding inflammatory cytokines and signaling molecules.It seems that statins can inhibit cardiac fibrosis and hypertrophy not only through their ability to inhibit hydroxymethylglutaryl-CoA reductase, but also by their pleiotropic properties.This review aims to discuss the effects of statins on molecular pathways involved inthe inhibition of fibrotic and hypertrophic remodeling in the heart, therebypotentially helping to recover proper cardiac size, plasticity, and functioning.

The Natural Products as Hydroxymethylglutaryl-Coa Reductase Inhibitors

High cholesterol and triglyceride levels are mainly related to further generation of lifethreating metabolism disorders including cardiovascular system diseases. Therefore, hypercholesterolemia (i.e., also referred to as hyperlipoproteinemia) is a serious disease state, which must be controlled. Currently, the treatment of hypercholesterolemia is mainly achieved through the employment of statins in the clinic, although there are alternative drugs (e.g., ezetimibe, cholestyramine). In fact, the original statins are natural products directly obtained from fungi-like molds and mushrooms and they are potent inhibitors of hydroxymethylglutaryl-CoA reductase, the key enzyme in the biosynthesis of cholesterol. This review focuses on the first identification of natural statins, their synthetic and semi-synthetic analogues, and the validation of hydroxymethylglutaryl-CoA reductase as a target in the treatment of hypercholesterolemia. Furthermore, other natural products that have been shown to possess the potential to inhibit hydroxymethylglutaryl-CoA reductase are also reviewed with respect to their chemical structures.