Vascular diseases, such as peripheral artery disease (PAD), are associated with diabetes mellitus and a higher risk of cardiovascular disease and even death. Surgical revascularization and pharmacological treatments (mainly antiplatelet, lipid-lowering drugs, and antidiabetic agents) have some effectiveness, but the response and efficacy of therapy are overly dependent on the patient’s conditions. Thus, the demand for new cures exists. In this regard, new studies on natural polyphenols that act on key points involved in the pathogenesis of vascular diseases and, thus, on PAD are of great urgency. The purpose of this review is to take into account the mechanisms that lead to endothelium dysfunction, such as the glycoxidation process and the production of advanced glycation end-products (AGEs) that result in protein misfolding, and to suggest plant-derived polyphenols that could be useful in PAD. Thus, five polyphenols are considered, baicalein, curcumin, mangiferin, quercetin and resveratrol, reviewing the literature in PubMed. The key molecular mechanisms and preclinical and clinical studies of each selected compound are examined. Furthermore, the safety profiles of the polyphenols are outlined, together with the unwanted effects reported in humans, also by searching the WHO database (VigiBase).

/pdf/selected-plant-derived-polyphenols-as-potential-therapeutic-vczv7emt.pdf

Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety

Herb-drug interaction of Xingnaojing injection and Edaravone via pharmacokinetics, mixed inhibition of UGTs, and molecular docking.

A frequent ailment in infants, neonatal jaundice is characterized by high bilirubin levels and yellowing of the skin and eyes. It needs to be carefully managed to avoid serious consequences like kernicterus. The principles of bilirubinometry are examined in this review paper, with particular attention paid to different evaluation techniques, the value of prompt monitoring, and modern intervention approaches. Newborns may find it uncomfortable to undergo intrusive blood drawing as part of traditional bilirubin measurement methods. Transcutaneous bilirubinometry (TcB), on the other hand, provides a non-invasive substitute that improves monitoring effectiveness and lessens patient pain. The mainstay of care for newborn jaundice is still phototherapy, which uses light to change bilirubin into a form that is easier to excrete. The efficacy and safety of phototherapy have been enhanced by recent developments, especially about LED-based technology. The evaluation also looks at integrated phototherapy options that optimize therapeutic results and improve neonatal safety by combining automated treatment modifications with real-time bilirubin monitoring. To improve neonatal health outcomes and lessen difficulties related to hyperbilirubinemia, this review emphasizes the significance of timely and effective care of neonatal jaundice by synthesizing existing achievements and highlighting the incorporation of technology innovations 

Exploring the Fundamentals of Bilirubinometry: Methods of Assessment, Timely Monitoring, and Intervention in Neonatal Jaundice with Integrated Phototherapy Solutions—A Review

The relevance of this study lies in the lack of reliable information on the key aspects of the molecular mechanisms of fatty hepatosis, a common mammalian disease, and its dangerous complications, such as fibrosis, cirrhosis, and hepatocellular carcinoma. These circumstances substantially complicate the prompt diagnosis of this hepatopathology and reduce the effectiveness of treatment. The metabolism of the heme derivative bilirubin is unique and inherent in the liver, which undergoes transformation due to hepatocyte enzyme systems to form neutral compounds, such as glucurono-conjugates and sulphoconjugates, which undergoes changes and requires analysis in fatty hepatosis in animals. The aim of the study was to determine the characteristic changes in the content of unconjugated bilirubin and its sulphoconjugate, glucuronide, monoglucuronide, monoglucoside, and diglucuronide in the blood, bile, and liver of rats under the modelling of fatty hepatosis and the administration of rehabilitation therapy. For this, the thin-layer chromatography method was used. It was found that under tetracycline-induced fatty hepatosis in laboratory rats, the concentration of unconjugated bilirubin in the blood decreased by 39.3%, bilirubin glucuronide by 44.4%, and the total fraction of bilirubin monoglucuronide and monoglycoside by 78.9%. Oral administration of the milk phospholipid complex in the composition of the BAS “FLP-MD” to sick animals ensured the maintenance of these indicators at the control level. The content of bilirubin glucuronide and bilirubin diglucuronide decreased in the liver tissue of the treated rats. When these animals were administered a phospholipid-containing bioadditives, the level of unconjugated bilirubin in the liver tissue increased by 22.2%, but the content of its conjugated forms decreased. The content of all the studied bilirubin fractions decreased in the bile of sick rats during self-rehabilitation. The components of the BAS “FLP-MD” in fatty hepatosis in rats did not affect the reduction of unconjugated bilirubin in bile but eliminated the inhibitory effect of the modelled pathology on the content of all conjugated forms of bilirubin. The findings can be used as biochemical markers to monitor the pigment metabolism in the development of fatty hepatosis in mammals 

Bilirubin derivatives in bile, blood, and liver of rats upon correction of experimental fatty hepatosis

Integration of pharmacodynamics, network pharmacology and metabolomics to elucidate effect and mechanism of Artemisia capillaris Thunb. in the treatment of jaundice.

Bilirubin-related adverse drug reactions (ADRs) or malady (e.g., jaundice) induced by some herbs rich in certain flavonoids have been widely reported. However, the causes and mechanisms of the ADRs are not well understood. The aim of this paper was to explore the mechanism of Shuang-huang-lian (SHL) injections and its major constituents-induced jaundice via inhibiting human UDP-glucuronosyltransferases1A1 (hUGT1A1)-mediated bilirubin glucuronidation. The inhibitory effects of SHL and its major constituents in the herbal medicine, including baicalein (BAI), baicalin (BA), and hyperoside (HYP), on bilirubin glucuroBBREVInidation were investigated. This study indicated that the average formation rates of bilirubin glucuronides [i.e., mono-glucuronide 1 (BMG1), BMG2, and bilirubin diglucuronide] displayed significant differences (P < 0.05). Specifically, the formation of BMGs was favored regardless of whether an inhibitor was absent or present. SHL, BAI, BA, and HYP dose-dependently inhibit bilirubin glucuronidation, showing the IC50 values against total bilirubin glucuronidation were in the range of (7.69 ± 0.94)–(37.09 ± 2.03) μg/ml, (4.51 ± 0.27)–(20.84 ± 1.99) μM, (22.36 ± 5.74)–(41.35 ± 2.40) μM, and (15.16 ± 1.12)–(42.80 ± 2.63) μM for SHL, BAI, BA, and HYP, respectively. Both inhibition kinetics assays and molecular docking simulations suggested that SHL, BAI, BA, and HYP significantly inhibited hUGT1A1-mediated bilirubin glucuronidation via a mixed-type inhibition. Collectively, some naturally occurring flavonoids (BAI, BA, and HYP) in SHL have been identified as the inhibitors against hUGT1A1-mediated bilirubin glucuronidation, which well explains the bilirubin-related ADRs or malady triggered by SHL in clinical settings. SIGNIFICANCE STATEMENT Herbal products and their components (e.g., flavonoids), which been widely used across the entire world, may cause liver injury. As a commonly used herbal products rich in flavonoids, SHL injections easily lead to symptoms of liver injury (e.g., jaundice) owing to significant inhibition of hUGT1A1-mediated bilirubin glucuronidation by its flavonoid components (i.e., baicalein, baicalin, and hyperoside). Herb-induced bilirubin-related ADRs and the associated clinical significance should be seriously considered.

Inhibition of Human UDP-Glucuronosyltransferases1A1–Mediated Bilirubin Glucuronidation by the Popular Flavonoids Baicalein, Baicalin, and Hyperoside Is Responsible for Herb (Shuang-Huang-Lian)-Induced Jaundice

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Inhibition of Human UDP-Glucuronosyltransferases1A1–Mediated Bilirubin Glucuronidation by the Popular Flavonoids Baicalein, Baicalin, and Hyperoside Is Responsible for Herb (Shuang-Huang-Lian)-Induced Jaundice