TIRESIA: An eXplainable Artificial Intelligence Platform for Predicting Developmental Toxicity.

Herein, a robust and reproducible eXplainable Artificial Intelligence (XAI) approach is presented, which allows prediction of developmental toxicity, a challenging human-health endpoint in toxicology. The application of XAI as an alternative method is of the utmost importance with developmental toxicity being one of the most animal-intensive areas of regulatory toxicology. In this work, the established CAESAR (Computer Assisted Evaluation of industrial chemical Substances According to Regulations) training set made of 234 chemicals for model learning is employed. Two test sets, including as a whole 585 chemicals, were instead used for validation and generalization purposes. The proposed framework favorably compares with the state-of-the-art approaches in terms of accuracy, sensitivity, and specificity, thus resulting in a reliable support system for developmental toxicity ensuring informativeness, uncertainty estimation, generalization, and transparency. Based on the eXtreme Gradient Boosting (XGB) algorithm, our predictive model provides easy interpretative keys based on specific molecular descriptors and structural alerts enabling one to distinguish toxic and nontoxic chemicals. Inspired by the Organisation for Economic Co-operation and Development (OECD) principles for the validation of Quantitative Structure-Activity Relationships (QSARs) for regulatory purposes, the results are summarized in a standard report in portable document format, enclosing also details concerned with a density-based model applicability domain and SHAP (SHapley Additive exPlanations) explainability, the latter particularly useful to better understand the effective roles played by molecular features. Notably, our model has been implemented in TIRESIA (Toxicology Intelligence and Regulatory Evaluations for Scientific and Industry Applications), a free of charge web platform available at http://tiresia.uniba.it.

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs.

Multicomponent reactions (MCRs) have emerged as a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery and development. MCRs are flexible transformations in which three or more substrates react to form structurally complex products with high atomic efficiency. They are being increasingly appreciated as a highly exploratory and evolutionary tool by the medicinal chemistry community, opening the door to more sustainable, cost-effective and rapid synthesis of biologically active molecules. In recent years, MCR-based synthetic strategies have found extensive application in the field of drug discovery, and several anticancer drugs have been synthesized through MCRs. In this review, we present an overview of representative and recent literature examples documenting different approaches and applications of MCRs in the development of new anticancer drugs.

Bcr-Abl Tyrosine Kinase Inhibitors in the Treatment of Pediatric CML.

The therapeutic approach to Chronic Myeloid Leukemia (CML) has changed since the advent of the tyrosine kinase inhibitor (TKI) imatinib, which was then followed by the second generation TKIs dasatinib, nilotinib, and, finally, by ponatinib, a third-generation drug. At present, these therapeutic options represent the first-line treatment for adults. Based on clinical experience, imatinb, dasatinib, and nilotinib have been approved for children even though the studies that were concerned with efficacy and safety toward pediatric patients are still awaiting more specific and high-quality data. In this scenario, it is of utmost importance to prospectively validate data extrapolated from adult studies to set a standard therapeutic management for pediatric CML by employing appropriate formulations on the basis of pediatric clinical trials, which allow a careful monitoring of TKI-induced adverse effects especially in growing children exposed to long-term therapy.

Hydroxy-Propil-ß-Cyclodextrin Inclusion Complexes of two Biphenylnicotinamide Derivatives: Formulation and Anti-Proliferative Activity Evaluation in Pancreatic Cancer Cell Models.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with poor outcomes largely due to its unique microenvironment, which is responsible for the low response to drugs and drug-resistance phenomena. This clinical need led us to explore new therapeutic approaches for systemic PDAC treatment by the utilization of two newly synthesized biphenylnicotinamide derivatives, PTA73 and PTA34, with remarkable antitumor activity in an in vitro PDAC model. Given their poor water solubility, inclusion complexes of PTA34 and PTA73 in Hydroxy-Propil-ß-Cyclodextrin (HP-ß-CD) were prepared in solution and at the solid state. Complexation studies demonstrated that HP-ß-CD is able to form stable host-guest inclusion complexes with PTA34 and PTA73, characterized by a 1:1 apparent formation constant of 503.9 M-1 and 369.2 M-1, respectively (also demonstrated by the Job plot), and by an increase in aqueous solubility of about 150 times (from 1.95 µg/mL to 292.5 µg/mL) and 106 times (from 7.16 µg/mL to 762.5 µg/mL), in the presence of 45% w/v of HP-ß-CD, respectively. In vitro studies confirmed the high antitumor activity of the complexed PTA34 and PTA73 towards PDAC cells, the strong G2/M phase arrest followed by induction of apoptosis, and thus their eligibility for PDAC therapy.

Bcr-Abl Allosteric Inhibitors: Where We Are and Where We Are Going to.

The fusion oncoprotein Bcr-Abl is an aberrant tyrosine kinase responsible for chronic myeloid leukemia and acute lymphoblastic leukemia. The auto-inhibition regulatory module observed in the progenitor kinase c-Abl is lost in the aberrant Bcr-Abl, because of the lack of the N-myristoylated cap able to bind the myristoyl binding pocket also conserved in the Bcr-Abl kinase domain. A way to overcome the occurrence of resistance phenomena frequently observed for Bcr-Abl orthosteric drugs is the rational design of allosteric ligands approaching the so-called myristoyl binding pocket. The discovery of these allosteric inhibitors although very difficult and extremely challenging, represents a valuable option to minimize drug resistance, mostly due to the occurrence of mutations more frequently affecting orthosteric pockets, and to enhance target selectivity with lower off-target effects. In this perspective, we will elucidate at a molecular level the structural bases behind the Bcr-Abl allosteric control and will show how artificial intelligence can be effective to drive the automated de novo design towards off-patent regions of the chemical space.

A New Approach for Drug Target and Bioactivity Prediction: The Multifingerprint Similarity Search Algorithm (MuSSeL).

We present MuSSeL, a multifingerprint similarity search algorithm, able to predict putative drug targets for a given query small molecule as well as to return a quantitative assessment of its bioactivity in terms of Ki or IC50 values. Predictions are automatically made exploiting a large collection of high quality experimental bioactivity data available from ChEMBL (version 22.1) combining, in a consensus-like approach, predictions resulting from a similarity search performed using 13 different fingerprint definitions. Importantly, the herein proposed algorithm is also effective in detecting and handling activity cliffs. A calibration set including small molecules present in the last updated version of ChEMBL (version 23) was employed to properly tune the algorithm parameters. Three randomly built external sets were instead challenged for model performances. The potential use of MuSSeL was also challenged by a prospective exercise for the prediction of five bioactive compounds taken from articles published in the Journal of Medicinal Chemistry just few months ago. The paper emphasizes the importance of implementing multifingerprint consensus strategies to increase the confidence in prediction of similarity search algorithms and provides a fast and easy-to-run tool for drug target and bioactivity prediction.

Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds.

Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer's and Parkinson's diseases. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases.

Studying Chondrichthyans Using Baited Remote Underwater Video Systems: A Review.

Cartilaginous fish face significant threats due to overfishing and slow reproductive rates, leading to rapid declines in their populations globally. Traditional capture-based surveys, while valuable for gathering ecological information, pose risks to the health and survival of these species. Baited Remote Underwater Video Systems (BRUVS) offer a non-invasive alternative, allowing for standardized surveys across various habitats with minimal disturbance to marine life. This study presents a comprehensive review of BRUVS applications in studying cartilaginous fish, examining 81 peer-reviewed papers spanning from 1990 to 2023. The analysis reveals a significant increase in BRUVS usage over the past three decades, particularly in Australia, South Africa, and Central America. The most common BRUVS configurations include benthic setups, mono-camera systems, and the use of fish from the Clupeidae and Scombridae families as bait. BRUVS have been instrumental in studying 195 chondrichthyan species, providing insights into up to thirteen different aspects of the life histories. Moreover, BRUVS facilitate the monitoring of endangered and data-deficient species, contributing crucial data for conservation efforts. Overall, this study underscores the value of BRUVS as a powerful tool for studying and conserving cartilaginous fish populations worldwide.

Small Molecules for the Treatment of Long-COVID-Related Vascular Damage and Abnormal Blood Clotting: A Patent-Based Appraisal.

People affected by COVID-19 are exposed to, among others, abnormal clotting and endothelial dysfunction, which may result in deep vein thrombosis, cerebrovascular disorders, and ischemic and non-ischemic heart diseases, to mention a few. Treatments for COVID-19 include antiplatelet (e.g., aspirin, clopidogrel) and anticoagulant agents, but their impact on morbidity and mortality has not been proven. In addition, due to viremia-associated interconnected prothrombotic and proinflammatory events, anti-inflammatory drugs have also been investigated for their ability to mitigate against immune dysregulation due to the cytokine storm. By retrieving patent literature published in the last two years, small molecules patented for long-COVID-related blood clotting and hematological complications are herein examined, along with supporting evidence from preclinical and clinical studies. An overview of the main features and therapeutic potentials of small molecules is provided for the thromboxane receptor antagonist ramatroban, the pan-caspase inhibitor emricasan, and the sodium-hydrogen antiporter 1 (NHE-1) inhibitor rimeporide, as well as natural polyphenolic compounds.

The Community Pharmacy as a Study Center for the Epidemiological Analysis of the Population Vaccination against SARS-CoV-2: Evaluation of Vaccine Safety and Pharmaceutical Service.

We conducted a monocentric observational study aimed at evaluating the vaccine safety and the pharmaceutical service provided at a community pharmacy (C.PHARM) in the Puglia Region in the period from 29 December 2021 to 12 March 2022 using data from 550 patients of various ages and sexes and with concomitant diseases. We collected anamnestic data, the number of hospitalizations, and any post-vaccination adverse reactions. Interviews using the integrated EQ5 method were also performed to evaluate the quality of the service offered and any therapy preference. As expected, the vaccines were reactogenic after the first dose in the patients with mild-moderate reactions, with younger age and female gender as risk factors. Immune-allergic reactions of a moderate-severe degree were observed in adult females. In the elderly, the vaccination was well tolerated. Comirnaty® showed a favorable O.R. < 1 vs. other vaccines. No cardiovascular events or hospitalizations were observed up to May 2023. Regional data indicate that all treatments during May 2023 were correlated with the viremia. PaxlovidTM was prescribed in 3% of the patients in our center and in 1.46% in the region, and distributed/dispensed on behalf of third parties in accordance with a novel distribution/dispensation protocol of the C.PHARM that resulted in a safe vaccination center providing appropriate patient inclusion during vaccination.

Structure-based design of multitargeting ChEs-MAO B inhibitors based on phenyl ring bioisosteres: AChE/BChE selectivity switch and drug-like characterization.

A structure-based drug design approach was focused on incorporating phenyl ring heterocyclic bioisosteres into coumarin derivative 1, previously reported as potent dual AChE-MAO B inhibitor, with the aim of improving drug-like features. Structure-activity relationships highlighted that bioisosteric rings were tolerated by hMAO B enzymatic cleft more than hAChE. Interestingly, linker homologation at the basic nitrogen enabled selectivity to switch from hAChE to hBChE. In the present work, we identified thiophene-based isosteres 7 and 15 as dual AChE-MAO B (IC50 = 261 and 15 nM, respectively) and BChE-MAO B (IC50 = 375 and 20 nM, respectively) inhibitors, respectively. Both 7 and 15 were moderately water-soluble and membrane-permeant agents by passive diffusion (PAMPA-HDM). Moreover, they were able to counteract oxidative damage induced by both H2O2 and 6-OHDA in SH-SY5Y cells and predicted to penetrate into CNS in a cell-based model mimicking blood-brain barrier. Molecular dynamics (MD) simulations shed light on key differences in AChE and BChE recognition processes promoted by the basic chain homologation from 7 to 15.

Design, synthesis and biological evaluation of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase.

Acetylcholinesterase inhibitors (AChEIs) are currently the drugs of choice, although only symptomatic and palliative, for the treatment of Alzheimer's disease (AD). Donepezil is one of most used AChEIs in AD therapy, acting as a dual binding site, reversible inhibitor of AChE with high selectivity over butyrylcholinesterase (BChE). Through a combined target- and ligand-based approach, a series of coumarin alkylamines matching the structural determinants of donepezil were designed and prepared. 6,7-Dimethoxycoumarin derivatives carrying a protonatable benzylamino group, linked to position 3 by suitable linkers, exhibited fairly good AChE inhibitory activity and a high selectivity over BChE. The inhibitory potency was strongly influenced by the length and shape of the spacer and by the methoxy substituents on the coumarin scaffold. The inhibition mechanism, assessed for the most active compound 13 (IC(50) 7.6 nM) resulted in a mixed-type, thus confirming its binding at both the catalytic and peripheral binding sites of AChE.

Virtual Reverse Screening Approach to Target Type 2 Cannabinoid Receptor.

A screening pool consisting of 617710 drug-like query molecules properly filtered from the ChEMBL database was employed for a ligand-based reverse screening toward the type 2 cannabinoid receptor (CB2) target. By using our recently developed PLATO polypharmacological web platform, 233 out of 617710 drug-like molecules were prioritized on the basis of the predicted bioactivity values, better than 0.2 µM with a probability of about 98%, toward the CB2 target. Building on these results, the occurrence of putative CB2-related targets was also investigated for prospective repurposing studies.

Contamination by Trace Elements and Oxidative Stress in the Skeletal Muscle of Scyliorhinus canicula from the Central Tyrrhenian Sea.

Marine pollution, due to the regular discharge of contaminants by various anthropogenic sources, is a growing problem that imposes detrimental influences on natural species. Sharks, because of a diet based on smaller polluted animals, are exposed to the risk of water contamination and the subsequent bioaccumulation and biomagnification. Trace elements are very diffuse water pollutants and able to induce oxidative stress in a variety of marine organisms. However, to date, studies on sharks are rather scarce and often limited to mercury. In this context, the present study aimed to analyze the accumulation of trace elements and their putative correlation with the onset of an oxidative status in the muscle of the lesser spotted dogfish Scyliorhinus canicula, from the Central Mediterranean Sea. Ecotoxicological analysis detected the presence of Pb, As, Cd, Mn, Zn, Ni, Cu, and Fe; no significant differences were observed between sexes, while a negative correlation was found between Pb and animal length. Analysis of oxidative stress markers showed either positive or negative correlation with respect to the presence of trace elements. Lipid peroxidation (TBARS) positively correlated with Zn, Ni, and Fe; SOD enzyme activity negatively correlated with Cu and Ni; LDH was negatively correlated with Fe and positively correlated with Pb. Moreover, positive correlations between the leukocyte count and Mn and Zn, as well as with LDH activity, were also observed. The data suggested that, in sharks, trace elements accumulation may affect oxidant and antioxidant processes with important outcomes for their physiology and health.

Molecular Composition and Biological Activity of a Novel Acetonitrile-Water Extract of Lens Culinaris Medik in Murine Native Cells and Cell Lines Exposed to Different Chemotherapeutics Using Mass Spectrometry.

We evaluated the effects of a new extract (70% acetonitrile, 2E0217022196DIPFARMTDA) of Lens culinaris Medik (Terre di Altamura SRL, Altamura BA) to prevent cytotoxic damage from cisplatin, staurosporine, irinotecan, doxorubicin, and the glucocorticoid dexamethasone. The acetonitrile-water extract (range 0.1-5 mg/mL) was obtained by extracting 10 g of lentil flour with 50 milliliters of the acetonitrile-water extraction mixture in a 70:30 ratio, first for 3 h and then overnight in a shaker at room temperature. The next day, the extract was filtered and passed through a Rotavapor to obtain only the aqueous component and eliminate that with acetonitrile, and then freeze-dried to finally have the powdered extract. In vitro experiments showed that the extract prevented the cytotoxic damage induced by cisplatin, irinotecan, and doxorubicin on HEK293 and SHSY5Y cell lines after 24-96 h. In murine osteoblasts after 24-72 h of incubation time, the extract was cytoprotective against all chemicals. The extract was effective against dexamethasone, leading to synergic cell proliferation in all cell types. In bone marrow cells, the extract is cytoprotective after 72 h against doxorubicin, staurosporine, and dexamethasone. Instead, on muscle fibers, the extract has a synergic effect with chemotherapeutics, increasing cytotoxicity induced by doxorubicin and staurosporine. LC-MS attested to the existence of several phenolic structures in the extract. The most abundant families of compounds were flavonoids (25.7%) and mellitic acid (18%). Thus, the development of this extract could be implemented in the area of research related to the chemoprevention of damage to renal, neuronal, bone marrow cells, and osteoblasts by chemotherapeutics; moreover, it could be used as a reinforcer of cytotoxic action of chemotherapeutics on muscle fibers.

Diet and Plastic Ingestion in the Blackmouth Catshark Galeus melastomus, Rafinesque 1810, in Italian Waters.

Galeus melastomus is the most common Pentanchidae in the Mediterranean Sea. A scavenger and opportunistic feeder, and despite the wide distribution, little is known about its feeding habits in Italian waters. The main purpose of this study was to investigate the diet of the blackmouth catshark by analysing the stomach contents. The specimens analysed were obtained from five populations of the Tyrrhenian and of the Ionian Seas, collected from a depth between 40 and 700 m. A total of 259 stomachs were analysed. The stomach contents were grouped into macro-categories and identified to the lowest taxonomic level possible. Crustaceans such as Parapenaeus longirostris, the Cephalopods Heteroteuthis dispar and Onychoteuthis banksii, and Osteichthyes, mostly Myctophidae, were identified. Plastic debris was also found among the stomach contents and classified according to its colour and shape. Osteichthyes represent the most abundant item (44%), above all the Myctophidae family, except for the catshark population from Tuscany, in which the most frequent species were Cephalopods, such as Abralia veranyi and Heteroteuthis dispar. Differences in the plastic debris contents were also observed between the Tuscany population and other populations. These could be explained as a probable consequence of the different depths at which the blackmouth catshark populations were sampled.

N-adamantyl-anthranil amide derivatives: New selective ligands for the cannabinoid receptor subtype 2 (CB2R).

Cannabinoid type 2 receptor (CB2R) is a G-protein-coupled receptor that, together with Cannabinoid type 1 receptor (CB1R), endogenous cannabinoids and enzymes responsible for their synthesis and degradation, forms the EndoCannabinoid System (ECS). In the last decade, several studies have shown that CB2R is overexpressed in activated central nervous system (CNS) microglia cells, in disorders based on an inflammatory state, such as neurodegenerative diseases, neuropathic pain, and cancer. For this reason, the anti-inflammatory and immune-modulatory potentials of CB2R ligands are emerging as a novel therapeutic approach. The design of selective ligands is however hampered by the high sequence homology of transmembrane domains of CB1R and CB2R. Based on a recent three-arm pharmacophore hypothesis and latest CB2R crystal structures, we designed, synthesized, and evaluated a series of new N-adamantyl-anthranil amide derivatives as CB2R selective ligands. Interestingly, this new class of compounds displayed a high affinity for human CB2R along with an excellent selectivity respect to CB1R. In this respect, compounds exhibiting the best pharmacodynamic profile in terms of CB2R affinity were also evaluated for the functional behavior and molecular docking simulations provided a sound rationale by highlighting the relevance of the arm 1 substitution to prompt CB2R action. Moreover, the modulation of the pro- and anti-inflammatory cytokines production was also investigated to exert the ability of the best compounds to modulate the inflammatory cascade.

Development of N-(1-Adamantyl)benzamides as Novel Anti-Inflammatory Multitarget Agents Acting as Dual Modulators of the Cannabinoid CB2 Receptor and Fatty Acid Amide Hydrolase.

Cannabinoid type 2 receptor (CB2R), belonging to the endocannabinoid system, is overexpressed in pathologies characterized by inflammation, and its activation counteracts inflammatory states. Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the degradation of the main endocannabinoid anandamide; thus, the simultaneous CB2R activation and FAAH inhibition may be a synergistic anti-inflammatory strategy. Encouraged by principal component analysis (PCA) data identifying a wide chemical space shared by CB2R and FAAH ligands, we designed a small library of adamantyl-benzamides, as potential dual agents, CB2R agonists, and FAAH inhibitors. The new compounds were tested for their CB2R affinity/selectivity and CB2R and FAAH activity. Derivatives 13, 26, and 27, displaying the best pharmacodynamic profile as CB2R full agonists and FAAH inhibitors, decreased pro-inflammatory and increased anti-inflammatory cytokines production. Molecular docking simulations complemented the experimental findings by providing a molecular rationale behind the observed activities. These multitarget ligands constitute promising anti-inflammatory agents.

Bioaccumulation of Trace Elements in the Muscle of the Blackmouth Catshark Galeus melastomus from Mediterranean Waters.

Environmental pollution, particularly in the marine environment, has become a significant concern due to the increasing presence of pollutants and their adverse effects on ecosystems and human health. This study focuses on the bioaccumulation of trace elements in the muscle tissue of the blackmouth catshark (Galeus melastomus) from different areas in the Mediterranean Sea. Trace elements are of interest due to their persistence, toxicity, and potential for bioaccumulation. This research aims to assess the distribution and accumulation of trace elements in the muscle tissue of G. melastomus and investigate their potential impact on the deep-sea environment of the Mediterranean. The focused areas include the Ligurian Sea, the northern and central Tyrrhenian Sea, the southern Tyrrhenian Sea, the Ionian Sea, the Pantelleria Waters, and the Gela Waters. Samples were collected following established protocols, and trace element analysis was conducted using inductively coupled plasma mass spectrometry. The study provides data on the concentrations of 17 trace elements, namely aluminum, arsenic, cadmium, cobalt, copper, manganese, molybdenum, nickel, zinc, selenium, strontium, lead, chromium, iron, barium, bismuth, and uranium. The findings contribute to a better understanding of trace element bioaccumulation patterns in elasmobranch species, specifically G. melastomus, and highlight the potential risks associated with chemical contamination in the Mediterranean Sea. This research emphasizes the importance of studying the impacts of pollutants on marine organisms, particularly those occupying key ecological roles, like sharks, to support effective conservation and management strategies.

Counteractions of a Novel Hydroalcoholic Extract from Lens Culinaria against the Dexamethasone-Induced Osteoblast Loss of Native Murine Cells.

The cytoprotective effects of a novel hydroalcoholic extract (0.01-5 mg/mL) from Lens culinaria (Terre di Altamura Srl) were investigated within murine native skeletal muscle fibers, bone marrow cells, and osteoblasts, and in cell lines treated with the apoptotic agent staurosporine (2.14 × 10-6 M), the alkylating drug cisplatin (10-4 M), the topoisomerase I inhibitor irinotecan (10-4 M), the antimitotic pro-oxidant doxorubicin (10-6 M), and the immunosuppressant dexamethasone (2 × 10-6 M). An amount of 10g of plant material was used to obtain a 70% ethanol/water product, following two-step extraction, evaporation, lyophilization, and storage at -20 °C. For the murine osteoblasts, doxorubicin reduced survival by -65%, dexamethasone by -32% and -60% after 24 and 48 h of incubation time, respectively. The extract was effective in preventing the osteoblast count-reduction induced by dexamethasone; it was also effective at preventing the inhibition of mineralization induced by dexamethasone. Doxorubicin and cisplatin caused a significant reduction in cell growth by -77% for bone marrow cells, -43% for irinotecan, and -60% for dexamethasone, but there was no evidence for the cytoprotective effects of the extract in these cells. Staurosporine and doxorubicin caused a fiber death rate of >-40% after 18 and 24 h of incubation, yet the extract was not effective at preventing these effects. The extract was effective in preventing the staurosporine-induced reduction of HEK293 proliferation and colony formation in the crystal violet DNA staining and the clonogenic assays. It was also effective for the cisplatin-induced reduction in HEK293 cell proliferation. The extract, however, failed to protect the SHSY5Y neurons against cisplatin and irinotecan-induced cytotoxicity. A UV/VIS spectroscopy analysis showed three peaks at the wavelengths of 350, 260, and 190 nm, which correspond to flavonoids, proanthocyanins, salicylates, and AA, constituting the extract. These data suggest the possible development of this extract for use against dexamethasone-induced bone loss and renal chemotherapy-induced damage.