Molnupiravir increases SARS-CoV-2 genome diversity and complexity: A case-control cohort study.

Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies.

7-O-tyrosyl Silybin Derivatives as a Novel Set of Anti-Prostate Cancer Compounds.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anticancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O-alkyl silybins derivatives were synthesized by the Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4), and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of eighteen new derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by the DPPH assay showed a very pronounced activity depending on the tyrosyl moiety (HTYR > MTYR >> TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin-based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a, and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a, and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, Western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

Proteolysis Targeting Chimera Degraders of the METTL3-14 m6A-RNA Methyltransferase.

Methylation of adenine N6 (m6A) is the most frequent RNA modification. On mRNA, it is catalyzed by the METTL3-14 heterodimer complex, which plays a key role in acute myeloid leukemia (AML) and other types of blood cancers and solid tumors. Here, we disclose the first proteolysis targeting chimeras (PROTACs) for an epitranscriptomics protein. For designing the PROTACs, we made use of the crystal structure of the complex of METTL3-14 with a potent and selective small-molecule inhibitor (called UZH2). The optimization of the linker started from a desfluoro precursor of UZH2 whose synthesis is more efficient than that of UZH2. The first nine PROTAC molecules featured PEG- or alkyl-based linkers, but only the latter showed cell penetration. With this information in hand, we synthesized 26 PROTACs based on UZH2 and alkyl linkers of different lengths and rigidity. The formation of the ternary complex was validated by a FRET-based biochemical assay and an in vitro ubiquitination assay. The PROTACs 14, 20, 22, 24, and 30, featuring different linker types and lengths, showed 50% or higher degradation of METTL3 and/or METTL14 measured by Western blot in MOLM-13 cells. They also showed substantial degradation on three other AML cell lines and prostate cancer cell line PC3.

Lingual laser frenotomy in newborns with ankyloglossia: a prospective cohort study.

BACKGROUND: The study aims to describe the lingual laser frenotomy perioperative protocol for newborns with ankyloglossia with or without breastfeeding difficulties developed by Odontostomatology and Neonatology and Neonatal Intensive Care Units of the Aldo Moro University of Bari. METHODS: Authors carried out a prospective observational cohort study. Newborns with ankyloglossia (classified by using both Coryllos' and Hazelbaker's criteria) with or without difficult breastfeeding (according to Infant Breastfeeding Assessment Tool) underwent diode laser frenotomy (800 ± 10 nm; 5 W; continuous wave mode; contact technique; under topical anesthesia) and follow-up visits after seven and thirty days postoperatively. The authors analyzed as main outcomes the perioperative pain intensity measured by the C.R.I.E.S. scale, the occurrence of complications and quality of healing, the quality of breastfeeding, newborn's postoperative weight gain, maternal nipple pain, and the presence of lesions as secondary outcomes. RESULTS: Fifty-six newborns were included in the current study. Intraoperative mean pain intensity was 5.7 ± 0.5 points, resolved within thirty postoperative minutes. Observed complications were mild punctuating bleeding, carbonization of the irradiated site, and transitory restlessness. All wounds were completely healed within the thirtieth postoperative day. During follow-up, a significant breastfeeding improvement was evident with satisfactory newborns' weight gain and a significant reduction of nipple pain and lesions (p < .05). CONCLUSION: Our lingual laser frenotomy protocol provided significant breastfeeding improvement in the mother-newborn dyads with low intraoperative pain and no significant complications.

Silybins inhibit human IAPP amyloid growth and toxicity through stereospecific interactions.

Type 2 Diabetes is a major public health threat, and its prevalence is increasing worldwide. The abnormal accumulation of islet amyloid polypeptide (IAPP) in pancreatic ß-cells is associated with the onset of the disease. Therefore, the design of small molecules able to inhibit IAPP aggregation represents a promising strategy in the development of new therapies. Here we employ in vitro, biophysical, and computational methods to inspect the ability of Silybin A and Silybin B, two natural diastereoisomers extracted from milk thistle, to interfere with the toxic self-assembly of human IAPP (hIAPP). We show that Silybin B inhibits amyloid aggregation and protects INS-1 cells from hIAPP toxicity more than Silybin A. Molecular dynamics simulations revealed that the higher efficiency of Silybin B is ascribable to its interactions with precise hIAPP regions that are notoriously involved in hIAPP self-assembly i.e., the S20-S29 amyloidogenic core, H18, the N-terminal domain, and N35. These results highlight the importance of stereospecific ligand-peptide interactions in regulating amyloid aggregation and provide a blueprint for future studies aimed at designing Silybin derivatives with enhanced drug-like properties.

Phosphodiester Silybin Dimers Powerful Radical Scavengers: A Antiproliferative Activity on Different Cancer Cell Lines.

Silibinin is the main biologically active component of silymarin extract and consists of a mixture 1:1 of two diastereoisomeric flavonolignans, namely silybin A (1a) and silybin B (1b), which we call here silybins. Despite the high interest in the activity of this flavonolignan, there are still few studies that give due attention to the role of its stereochemistry and, there is still today a strong need to investigate in this area. In this regard, here we report a study concerning the radical scavenger ability and the antiproliferative activity on different cell lines, both of silybins and phosphodiester-linked silybin dimers. An efficient synthetic strategy to obtain silybin dimers in an optical pure form (6aa, 6ab and 6bb) starting from a suitable building block of silybin A and silybin B, obtained by us from natural extract silibinin, was proposed. New dimers show strong antioxidant properties, determined through hydroxyl radical (HO●) scavenging ability, comparable to the value reported for known potent antioxidants such as quercetin. A preliminary screening was performed by treating cells with 10 and 50 µM concentrations for 48 h to identify the most sensitive cell lines. The results show that silibinin compounds were active on Jurkat, A375, WM266, and HeLa, but at the tested concentrations, they did not interfere with the growth of PANC, MCF-7, HDF or U87. In particular, both monomers (1a and 1b) and dimers (6aa, 6ab and 6bb) present selective anti-proliferative activity towards leukemia cells in the mid-micromolar range and are poorly active on normal cells. They exhibit different mechanisms of action in fact all the cells treated with the 1a and 1b go completely into apoptosis, whereas only part of the cells treated with 6aa and 6ab were found to be in apoptosis.

Cytotoxicity of an Innovative Pressurised Cyclic Solid-Liquid (PCSL) Extract from Artemisia annua.

Therapeutic treatments with Artemisia annua have a long-established tradition in various diseases due to its antibacterial, antioxidant, antiviral, anti-malaria and anti-cancer effects. However, in relation to the latter, virtually all reports focused on toxic effects of A. annua extracts were obtained mostly through conventional maceration methods. In the present study, an innovative extraction procedure from A. annua, based on pressurised cyclic solid-liquid (PCSL) extraction, resulted in the production of a new phytocomplex with enhanced anti-cancer properties. This extraction procedure generated a pressure gradient due to compressions and following decompressions, allowing to directly perform the extraction without any maceration. The toxic effects of A. annua PCSL extract were tested on different cells, including three cancer cell lines. The results of this study clearly indicate that the exposure of human, murine and canine cancer cells to serial dilutions of PCSL extract resulted in higher toxicity and stronger propensity to induce apoptosis than that detected by subjecting the same cells to Artemisia extracts obtained through canonical extraction by maceration. Collected data suggest that PCSL extract of A. annua could be a promising and economic new therapeutic tool to treat human and animal tumours.

Maximizing cancer therapy via complementary mechanisms of immune activation: PD-1 blockade, neoantigen vaccination, and Tregs depletion.

BACKGROUND: A number of different immune pathways are involved in the effective killing of cancer cells, collectively named as the 'Cancer Immunity Cycle'. Anti-PD-1 checkpoint blockade (CPB) therapy is active on one of these pathways and reinvigorates anticancer T cell immunity, leading to long-term responses in a limited fraction of patients with cancer. We have previously shown that neoantigens-based adenovirus vectored vaccine in combination with anti-PD-1 further expands pre-existing anticancer immunity and elicits novel neoantigen-specific T cells thereby increasing efficacy to 50% of tumor clearance in mice. Here we added a third component to the CPB plus vaccine combination, which is able to modify the suppressive tumor microenvironment by reducing the number of tumor-infiltrating regulatory T cells (Tregs), as strategy for improving the therapeutic efficacy and overcoming resistance. METHODS: The antitumor efficacy of anti-PD-1, neoantigen vaccine and Treg modulating agents, either Bempegaldesleukin (BEMPEG: NKTR-214) or an anti-CTLA-4 mAb with Treg-depleting activity, was investigated in murine tumor models. We evaluated tumor growth in treated animals, neoantigen-specific T cells in tumors, tumor-infiltrating lymphocytes (TILs) and intratumoral Tregs. RESULTS: The addition of BEMPEG or anti-CTLA-4 to the combination of vaccine and anti-PD-1 led to complete eradication of large tumors in nearby 100% of treated animals, in association with expansion and activation of cancer neoantigen-specific T cells and reduction of tumor-infiltrating Tregs. CONCLUSION: These data support the notion that the integrated regulation of three steps of the cancer immunity cycle, including expansion of neoantigen-specific T cells, reversal of the exhausted T cell phenotype together with the reduction of intratumoral Tregs may represent a novel rationally designed drug combination approach to achieve higher cure rates.

Investigation on the solid-phase synthesis of silybin prodrugs and their timed-release.

Prodrugs are ingenious derivatives of therapeutic agents designed to improve the pharmacokinetic profile of the drug. Here, we report an efficient and regioselective solid phase approach for obtaining new prodrugs of 9″-silybins conjugated with 3'-ribonucleotide units (uridine and adenosine) as pro-moieties. Uridine and adenosine conjugates were obtained in good yields (41-50%), beginning with silibinin and its diastereomers (silybin A and silybin B), using a NovaSyn® support functionalized with an ad hoc linker, which allowed selective detachment of only the desired products. As expected, the solubility of both uridine and adenosine conjugates was higher than that of the parental natural product (5 mg/mL and 3 mg/mL for uridine and adenosine, respectively). Our investigations revealed that uridine conjugates were quickly cleaved by RNase A, releasing silybin drugs, even at low enzyme concentrations. No toxic effects were found for any ribonucleotide conjugate on differentiated neuroblastoma SH-SY5Y cells when tested at increasing concentrations. All results strongly encourage further investigations of uridine-silybin prodrugs as potential therapeutic agents for both oral and intravenous administration. The present synthetic approach represents a valuable strategy to the future design of new prodrugs with modified nucleoside pro-moieties to modulate the pharmacokinetics of silybins or different natural products with strong pharmacological activities but poor bioavailability.

VENUS, a Novel Selection Approach to Improve the Accuracy of Neoantigens' Prediction.

Neoantigens are tumor-specific antigens able to induce T-cell responses, generated by mutations in protein-coding regions of expressed genes. Previous studies demonstrated that only a limited subset of mutations generates neoantigens in microsatellite stable tumors. We developed a method, called VENUS (Vaccine-Encoded Neoantigens Unrestricted Selection), to prioritize mutated peptides with high potential to be neoantigens. Our method assigns to each mutation a weighted score that combines the mutation allelic frequency, the abundance of the transcript coding for the mutation, and the likelihood to bind the patient's class-I major histocompatibility complex alleles. By ranking mutated peptides encoded by mutations detected in nine cancer patients, VENUS was able to select in the top 60 ranked peptides, the 95% of neoantigens experimentally validated including both CD8 and CD4 T cell specificities. VENUS was evaluated in a murine model in the context of vaccination with an adeno vector encoding the top ranked mutations prioritized in the MC38 cell line. Efficacy studies demonstrated anti tumoral activity of the vaccine when used in combination with checkpoint inhibitors. The results obtained highlight the importance of a combined scoring system taking into account multiple features of each tumor mutation to improve the accuracy of neoantigen prediction.

Solid-phase synthesis of curcumin mimics and their anticancer activity against human pancreatic, prostate, and colorectal cancer cell lines.

Curcumin is a bioactive natural compound with a wide range of pharmacological properties, including antitumor activity; however, its clinical application has been limited because of its low solubility, stability, and bioavailability. In this study, a solid phase approach was proposed for the combinatorial synthesis of a mini library of the mimics of curcumin in good purity and yield. The non-effective findings in pancreatic cancer cells switched to strong growth inhibition and cell death efficacy for PC3 prostate cancer cells, and mimic 9, in which tyrosol (TYR) and homovanillyl alcohol (HVA) units were linked by a phosphodiester bond, was quite effective not only in cell growth inhibition but also in causing strong cell death under the study conditions and treatments that were not effective in PANC1 cells. The results got more exciting when we also consider the findings in SW480 human colorectal carcinoma cell line, where the growth inhibitor effects were more in line with that of the PC3 cells, but the lack of cell death effect was more in line with the PANC1 cells.

Antioxidant Effect of Beer Polyphenols and Their Bioavailability in Dental-Derived Stem Cells (D-dSCs) and Human Intestinal Epithelial Lines (Caco-2) Cells.

Beer is one of the most consumed alcoholic beverages in the world, rich in chemical compounds of natural origin with high nutritional and biological value. It is made up of water, barley malt, hops, and yeast. The main nutrients are carbohydrates, amino acids, minerals, vitamins, and other compounds such as polyphenols which are responsible for the many health benefits associated with this consumption of drinks. Hops and malt are one of the raw materials for beer and are a source of phenolic compounds. In fact, about 30% of the polyphenols in beer comes from hops and 70%-80% from malt. Natural compounds of foods or plants exert an important antioxidant activity, counteracting the formation of harmful free radicals. In the presence of an intense stressing event, cells activate specific responses to counteract cell death or senescence which is known to act as a key-task in the onset of age-related pathologies and in the loss of tissue homeostasis. Many studies have shown positive effects of natural compounds as beer polyphenols on biological systems. The main aims of our research were to determine the polyphenolic profile of three fractions, coming from stages of beer production, the mashing process (must), the filtration process (prehopping solution), and the boiling process with the addition of hops (posthopping solution), and to evaluate the effects of these fractions on Dental-derived Stem Cells (D-dSCs) and human intestinal epithelial lines (Caco-2 cells). Furthermore, we underline the bioavailability of beer fraction polyphenols by carrying out the in vitro intestinal absorption using the Caco-2 cell model. We found an antioxidant, proliferating, and antisenescent effects of the fractions deriving from the brewing process on D-dSCs and Caco-2 cells. Finally, our results demonstrated that the bioavailability of polyphenols is greater in beer than in the control standards used, supporting the future clinical application of these compounds as potential therapeutic tools in precision and translational medicine.

A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors with Microsatellite Instability.

Tumors with microsatellite instability (MSI) are caused by a defective DNA mismatch repair system that leads to the accumulation of mutations within microsatellite regions. Indels in microsatellites of coding genes can result in the synthesis of frameshift peptides (FSP). FSPs are tumor-specific neoantigens shared across patients with MSI. In this study, we developed a neoantigen-based vaccine for the treatment of MSI tumors. Genetic sequences from 320 MSI tumor biopsies and matched healthy tissues in The Cancer Genome Atlas database were analyzed to select shared FSPs. Two hundred nine FSPs were selected and cloned into nonhuman Great Ape Adenoviral and Modified Vaccinia Ankara vectors to generate a viral-vectored vaccine, referred to as Nous-209. Sequencing tumor biopsies of 20 independent patients with MSI colorectal cancer revealed that a median number of 31 FSPs out of the 209 encoded by the vaccine was detected both in DNA and mRNA extracted from each tumor biopsy. A relevant number of peptides encoded by the vaccine were predicted to bind patient HLA haplotypes. Vaccine immunogenicity was demonstrated in mice with potent and broad induction of FSP-specific CD8 and CD4 T-cell responses. Moreover, a vaccine-encoded FSP was processed in vitro by human antigen-presenting cells and was subsequently able to activate human CD8 T cells. Nous-209 is an "off-the-shelf" cancer vaccine encoding many neoantigens shared across sporadic and hereditary MSI tumors. These results indicate that Nous-209 can induce the optimal breadth of immune responses that might achieve clinical benefit to treat and prevent MSI tumors. SIGNIFICANCE: These findings demonstrate the feasibility of an "off-the-shelf" vaccine for treatment and prevention of tumors harboring frameshift mutations and neoantigenic peptides as a result of microsatellite instability.

Contrast-induced nephropathy after cardiac resynchronization therapy implant impairs the recovery of ejection fraction in responders.

AIMS: Data regarding contrast-induced nephropathy (CIN) after cardiac resynchronization therapy (CRT) implant are limited. We aimed to investigate the incidence and determinants of CIN and its impact on CRT response and outcomes. METHODS AND RESULTS: Patients who underwent CRT implant were retrospectively analysed, and CIN was defined as an increase of serum creatinine ≥0.3 mg/dL or ≥1.5 times the baseline value. Response to CRT was defined as a reduction of left ventricle end-systolic volume (LVESV) of 15% or the increase of five percentage points in ejection fraction (EF) as assessed by echocardiography at 6 months. Follow-up visits were scheduled at 3, 6, and 12 months. Contrast-induced nephropathy occurred in 13/107 patients (12%). Among baseline clinical, echocardiographic, and laboratory characteristics, only a high baseline serum creatinine was associated with the occurrence of CIN. Symptoms, EF, and LVESV at 6 months improved in both CIN and non-CIN patients, and the rate of responders to CRT was similar. Among responders, at 6 months, those with CIN had significantly lower EF (28.5% vs. 35.7% P = 0.003). At a median follow-up of 112 weeks, 43% of patients experienced a clinical event with similar incidence in CIN and non-CIN patients, and likewise survival was similar. Non-responders to CRT had worse survival while among responders those with CIN had worse survival than non-CIN patients (71% vs. 90%, P = 0.0035). CONCLUSIONS: The incidence of CIN is rather high. Although CIN does not influence response to CRT overall, however among responders impairs the recovery of EF and survival.

Adenoviral vaccine targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint blockade.

Neoantigens (nAgs) are promising tumor antigens for cancer vaccination with the potential of inducing robust and selective T cell responses. Genetic vaccines based on Adenoviruses derived from non-human Great Apes (GAd) elicit strong and effective T cell-mediated immunity in humans. Here, we investigate for the first time the potency and efficacy of a novel GAd encoding multiple neoantigens. Prophylactic or early therapeutic vaccination with GAd efficiently control tumor growth in mice. In contrast, combination of the vaccine with checkpoint inhibitors is required to eradicate large tumors. Gene expression profile of tumors in regression shows abundance of activated tumor infiltrating T cells with a more diversified TCR repertoire in animals treated with GAd and anti-PD1 compared to anti-PD1. Data suggest that effectiveness of vaccination in the presence of high tumor burden correlates with the breadth of nAgs-specific T cells and requires concomitant reversal of tumor suppression by checkpoint blockade.

Silibinin phosphodiester glyco-conjugates: Synthesis, redox behaviour and biological investigations.

New silibinin phosphodiester glyco-conjugates were synthesized by efficient phosphoramidite chemistry and were fully characterized by 2D-NMR. A wide-ranging study focused on the determination of their pKa and E° values as well as on their radical scavenging activities by different assays (DPPH, ABTS+ and HRSA) was conducted. The new glyco-conjugates are more water-soluble than silibinin, and their radical scavenging activities are higher than those of silibinin. The conjugation therefore improves both the water solubilities and antioxidant activities of the flavonolignan moieties. The serum stability was evaluated under physiological conditions, and the glyco-conjugates degraded with half-lives of 40-70 h, making them useful in pro-drug approaches. We started by treating androgen-dependent prostate cancer (PCa) LNCaP cells and then expanded our studies to androgen-independent PCa PC3 and DU145 cells. In most cases, the new derivatives significantly reduced both total and live cell numbers, albeit at different levels. Anti-HIV activities were evaluated and the glucosamine-phosphate silibinin derivative showed higher activity (IC50 = 73 µM) than silibinin.

A New Class of Synthetic Flavonolignan-Like Dimers: Still Few Molecules, but with Attractive Properties.

In recent years, there has been increasing interest in dimeric molecules due to reports of their promising therapeutic value in the treatment of numerous diseases (such as cancer, HIV, Alzheimer's and, malaria). Many reports in the literature have highlighted the ability of these molecules to interact not only with specific biologic receptors but also to induce a biological response that more than doubles the results of the corresponding monomeric counterpart. In this regard, flavonolignan dimers or simply bi-flavonolignans are an emerging class of dimeric compounds that unlike bi-flavonoids, which are very widespread in nature, consist of synthetic dimers of some flavonolignans isolated from the milk thistle Silybum marianum [L. Gaertn. (Asteraceae)]. This mini-review will discuss recent developments in the synthesis, characterization and antioxidant activity of new families of flavonolignan dimers, in light of emerging medicinal chemistry strategies.

Phosphate-Linked Silibinin Dimers (PLSd): New Promising Modified Metabolites.

By exploiting the regioselective protection of the hydroxyl groups of silibinin along with the well-known phosphoramidite chemistry, we have developed an efficient strategy for the synthesis of new silibinin-modified species, which we have named Phosphate-Linked Silibinin Dimers (PLSd), in which the monomer units are linked by phosphodiester bonds. The antioxidant abilities of the new PLSd were estimated on HepG2 cells using DPPH free radical scavenging and xanthine/xanthine oxidase assays. The new phosphate-metabolites showed a higher anti-oxidant activity than the silibinin, as well as very low toxicity. The ability to scavenge reactive oxygen species (ROS) such as singlet oxygen () and hydroxyl radical () reveals that the two dimers are able to scavenge about two times more effectively than silibinin. Finally, solubility studies have shown that the PLSd present good water solubility (more than 20 mg·L-1) under circumneutral pH values, whereas the silibinin was found to be very poorly soluble (less than 0.4 mg·L-1) and not stable under alkaline conditions. Together, the above promising results warrant further investigation of the future potential of the PLSd as anti-oxidant metabolites within the large synthetic polyphenols field.

Traditional uses, chemical composition and biological activities of Sideritis raeseri Boiss. & Heldr.

Sideritis species have been used in folk medicine for their antimicrobial, antiulcerogenic, digestive and anti-inflammatory properties. Over the years, the phytochemistry of the genus Sideritis has been studied, and various terpenoids, sterols, coumarins and especially flavonoid aglycones and glycosides have been identified. In particular, species from the Balkan Peninsula have been studied and were found to be rich in flavonoids, with valuable antioxidant activity. In the folk medicine of the Balkan countries, Sideritis raeseri is used as a herbal tea in the treatment of inflammation, gastrointestinal disorders and coughs, and also as a tonic, whereas extracts are used as a component of dietary supplements for anaemia. Its dried inflorescences are used to prepare a beverage called 'mountain tea'. In light of the considerable interest generated in the chemistry, pharmacological properties and commercial value of S. raeseri Boiss. & Heldr., we review and summarise the available literature on these plants. The review details the chemical composition of the essential oil, its mineral and polyphenol contents, the naming of these plants and their physicochemical characterisation, and the nuclear magnetic resonance spectral data and biological properties associated with the plant extracts, with a focus on their potential chemotherapeutic applications. © 2016 Society of Chemical Industry.

Bioactive Compounds of Aristotelia chilensis Stuntz and their Pharmacological Effects.

Aristotelia chilensis ([Molina], Stuntz) a member of the family Eleocarpaceae, is a plant native to Chile that is distributed in tropical and temperate Asia, Australia, the Pacific Area, and South America. The juice of its berries has important medicinal properties, as an astringent, tonic, and antidiarrhoeal. Its many qualities make the maqui berry the undisputed sovereign of the family of so-called "superfruits", as well as a valuable tool to combat cellular inflammation of bones and joints. Recently, it is discovered that the leaves of the maqui berry have important antibacterial and antitumour activities. This review provides a comprehensive overview of the traditional use, phytochemistry, and biological activity of A. chilensis using information collected from scientific journals, books, and electronic searches. Anthocyanins, other flavonoids, alkaloids, cinnamic acid derivatives, benzoic acid derivatives, other bioactive molecules, and mineral elements are summarized. A broad range of activities of plant extracts and fractions are presented, including antioxidant activity, inhibition of visible light-induced damage of photoreceptor cells, inhibition of α-glucosidase, inhibition of pancreatic lipase, anti-diabetic effects, anti-inflammatory effects, analgesic effects, anti-diabetes, effective prevention of atherosclerosis, promotion of hair growth, anti-photo ageing of the skin, and inhibition of lipid peroxidation. Although some ethnobotanical uses have been supported in in vitro experiments, further studies of the individual compounds or chemical classes of compounds responsible for the pharmacological effects and the mechanisms of action are necessary. In addition, the toxicity and the side effects from the use of A. chilensis, as well as clinical trials, require attention.