Endoplasmic reticulum stress in pancreatic ß-cell dysfunction: The potential therapeutic role of dietary flavonoids.

Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic ß-cells. In pancreatic ß-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to ß-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic ß-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic ß-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic ß-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic ß-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic ß-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM.

Investigation into the role of phenolic compounds in the protection of citrus against Phyllosticta citricarpa.

INTRODUCTION: The use of chemical fungicides to combat disease has made a substantial contribution to food quality and security. Nonetheless, their applications have been limited due to environmental and health concerns, unaffordability, and the fact that pathogens have acquired resistance to some of these fungicides. Alternative eco-friendly and safe control methods should be explored. The current study investigated the influence of citrus rind phenolic compounds against Phyllosticta citricarpa infection by metabolic profiling of two citrus cultivars with varying degrees of susceptibility to infection. METHODS: Chromatographic data obtained by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC) was subjected to multivariate data analysis to identify biomarkers associated with the tolerant cultivar. The identified biomarkers were tested in vitro against P. citricarpa. RESULTS: Seville oranges, a tolerant cultivar, displayed higher levels of phenolic content and lower total sugar content, that are both associated with lower susceptibility to citrus black spot infection. The generated Principal Component Analysis (PCA) and Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA) models gave an overview of the data set and identified components that may be responsible for the differences in susceptibility between the two cultivars. Candidate biomarkers associated with tolerance were identified as naringin, neoeriocitrin, bruteiridin, melitidin, and lucenin-2. CONCLUSION: Naringin, a major candidate biomarker was able to inhibit the growth of the pathogen at 10 000 ppm.

Review on the Applications of Selected Metal-Based Complexes on Infectious Diseases.

Fatalities caused by infectious diseases (i.e., diseases caused by parasite, bacteria, and viruses) have become reinstated as a major public health threat globally. Factors such as antimicrobial resistance and viral complications are the key contributors to the death numbers. As a result, new compounds with structural diversity classes are critical for controlling the virulence of pathogens that are multi-drug resistant. Derivatization of bio-active organic molecules with organometallic synthons is a promising strategy for modifying the inherent and enhanced properties of biomolecules. Due to their redox chemistry, bioactivity, and structural diversity, organometallic moieties make excellent candidates for lead structures in drug development. Furthermore, organometallic compounds open an array of potential in therapy that existing organic molecules lack, i.e., their ability to fulfill drug availability and resolve the frequent succumbing of organic molecules to drug resistance. Additionally, metal complexes have the potential towards metal-specific modes of action, preventing bacteria from developing resistance mechanisms. This review's main contribution is to provide a thorough account of the biological efficacy (in vitro and in vitro) of metal-based complexes against infectious diseases. This resource can also be utilized in conjunction with corresponding journals on metal-based complexes investigated against infectious diseases.

Phytochemicals from Pterocarpus angolensis DC and Their Cytotoxic Activities against Breast Cancer Cells.

Pterocarpus anglonesis DC is an indigenous medicinal plant belonging to the Pterocarpus genus of the Fabaceae family. It is used to treat stomach problems, headaches, mouth ulcers, malaria, blackwater fever, gonorrhea, ringworm, diarrhea, heavy menstruation, and breast milk stimulation. Column chromatography of the stem bark extracts resulted in the isolation of eight compounds, which included friedelan-3-one (1), 3α-hydroxyfriedel-2-one (2), 3-hydroxyfriedel-3-en-2-one (3), lup-20(29)-en-3-ol (4), Stigmasta-5-22-dien-3-ol (5), 4-O-methylangolensis (6), (3ß)-3-acetoxyolean-12-en-28-oic acid (7), and tetradecyl (E)-ferulate (8). The structures were established based on NMR, IR, and MS spectroscopic analyses. Triple-negative breast cancer (HCC70), hormone receptor-positive breast cancer (MCF-7), and non-cancerous mammary epithelial cell lines (MCF-12A) were used to test the compounds' cytotoxicity. Overall, the compounds showed either no toxicity or very low toxicity to all three cell lines tested, except for the moderate toxicity displayed by lupeol (4) towards the non-cancerous MCF-12A cells, with an IC50 value of 36.60 µM. Compound (3ß)-3-acetoxyolean-12-en-28-oic acid (7) was more toxic towards hormone-responsive (MCF-7) breast cancer cells than either triple-negative breast cancer (HCC70) or non-cancerous breast epithelial (MCF-12A) cells (IC50 values of 83.06 vs. 146.80 and 143.00 µM, respectively).

Extractives from Artemisia afra with Anti-Bacterial and Anti-Fungal Properties.

Secondary metabolites were isolated using chromatographic techniques after being extracted sequentially from the roots of Artemisia afra using organic solvents such as ethanol, ethyl acetate, dichloromethane, and n-hexane. The isolated compounds were evaluated for anti-fungal, anti-bacterial, and cytotoxicity activities. Spectroscopic techniques, including Nuclear Magnetic Resonance (NMR), Fourier transform infrared (FTIR), and liquid chromatography-mass spectrometry (LC-MS), were used to elucidate the structures of the isolated compounds. The phytochemical investigation of A. afra led to the isolation of eight (A-H) compounds which were identified as 3ß-taraxerol (A), 3ß-taraxerol acetate (B), dodecyl-p-coumarate (C), ferulic acid (D), scopoletin (E), sitosterol-3-O-ß-D-glucopyranoside (F), 3,5-di-O-feruloylquinic acid (G) and Isofraxidin-7-O-ß-D-glucopyranoside (H) based on spectroscopic data. Compounds A, B, C, F, G, and H are known but were isolated for the first time from the roots of A. afra. The isolated compounds and extracts from A. afra exhibited good anti-fungal and anti-bacterial activity with dichloromethane and ethyl acetate crude extracts (0.078 mg/mL) and compound E (62.5 µg/mL) showed good activities against Escherichia coli. Compounds C and F also showed good activity against Enterococcus faecalis with minimum inhibitory concentration (MIC) values of 62.5 and 31.25 µg/mL, respectively. Extracts and compounds (A-H) exhibited anti-fungal and anti-bacterial properties and showed no toxicity when tested on Vero monkey kidney (Vero) cells.

Anticancer Activities of Re(I) Tricarbonyl and Its Imidazole-Based Ligands: Insight from a Theoretical Approach.

Rhenium complexes have been observed experimentally to exhibit good inhibitory activity against malignant cells. Hence, our motivation is to explore this activity from a theoretical perspective. In the present study, density functional theory (DFT) and in silico molecular docking approaches were utilized to unravel the unique properties of metal-based rhenium tricarbonyl complexes as effective anticancer drugs. All DFT calculations and geometric optimizations were conducted using the well-established hybrid functional B3LYP-GD(BJ)/Gen/6-311++G(d,p)/LanL2DZ computational method. The FT-IR spectroscopic characterization of the complexes: fac-[Re(Pico)(CO)3(Pz)] (R1), fac-[Re(Pico)(CO)3(Py)] (R2), fac-[Re(Dfpc)(CO)3(H2O)] (R3), fac-[Re(Dfpc)(CO)3(Pz)] (R4), fac-[Re(Dfpc)(CO)3(Py)] (R5), fac-[Re(Tfpc)(CO)3(H2O)] (R6), fac-[Re(Tfpc)(CO)3(Py)] (R7), and fac-[Re(Tfpc)(CO)3(Im)] (R8) was explored. To gain insights into the electronic structural properties, bioactivity, and stability of these complexes, the highest occupied molecular orbital-lowest unoccupied molecular orbital analysis, binding energy, and topological analysis based on quantum theory of atoms-in-molecules were considered. The anticancer activities of the complexes were measured via in silico molecular docking against human BCL-2 protein (IG5M) and proapoptotic (agonist) BAX 1 protein (450O). The results showed that the studied complexes exhibited good binding affinity (-3.25 to -10.16 kcal/mol) and could cause significant disruption of the normal physiological functions of the studied proteins. The results of DFT calculations also showed that the studied complexes exhibited good stability and are suitable candidates for the development of anticancer agents.

Exploring the in vitro anticancer activities of Re(I) picolinic acid and its fluorinated complex derivatives on lung cancer cells: a structural study.

Fifteen rhenium(I) tricarbonyl complexes of the form fac-[Re(N,O')(CO)3(X)], where N,O'-bidentate ligand = 2-picolinic acid (Pico); 3,5-difluoropyridine-2-carboxylic acid (Dfpc); 3-trifluoromethyl-pyridine-2-carboxylic acid (Tfpc) and X = H2O; pyrazole (Pz); pyridine (Py); imidazole (Im); and methanol (CH3OH) were synthesized using the '2 + 1' mixed ligand approach with an average yield of 84%. The complexes were characterized using the following spectroscopic techniques: IR, 1H and 13C NMR, UV/Vis, and single-crystal X-ray diffraction. The effect of the fluorine atoms on the backbone of the N,O'-bidentate ligand was investigated and a trend was noticed in the carbonyl stretching frequencies: with Pico < Tfpc < Dfpc. The in vitro biological screening on Vero (healthy mammalian), HeLa (cervical carcinoma) and A549 (lung cancer) cells revealed one toxic complex, fac-[Re(Pico)(CO)3(H2O)], with respective LC50 values of 9.0 ± 0.9, 15.8 ± 4.9 (SI = 0.570) and 20.9 ± 0.8 (SI = 0.430) µg/mL. As a result, it can be used as a positive control drug of toxicity.

The Use of Medicinal Plant-Derived Metallic Nanoparticles in Theranostics.

In the quest to effectively diagnose and treat the diseases that afflict mankind, the development of a tool capable of simultaneous detection and treatment would provide a significant cornerstone for the survival and control of these diseases. Theranostics denotes a portmanteau of therapeutics and diagnostics which simultaneously detect and treat ailments. Research advances have initiated the advent of theranostics in modern medicine. Overall, theranostics are drug delivery systems with molecular or targeted imaging agents integrated into their structure. The application of theranostics is rising exponentially due to the urgent need for treatments that can be utilized for diagnostic imaging as an aid in precision and personalised medicine. Subsequently, the emergence of nanobiotechnology and the green synthesis of metallic nanoparticles (MNPs) has provided one such avenue for nanoscale development and research. Of interest is the drastic rise in the use of medicinal plants in the synthesis of MNPs which have been reported to be potentially effective in the diagnosis and treatment of diseases. At present, medicinal plant-derived MNPs have been cited to have broad pharmacological applications and have been studied for their potential use in the treatment and management of cancer, malaria, microbial and cardiovascular diseases. The subject of this article regards the role of medicinal plants in the synthesis of MNPs and the potential role of MNPs in the field of theranostics.

Ent-abietane diterpenoids from Suregada zanzibariensis Baill. (Euphorbiaceae), their cytotoxic and anticancer properties.

The stem bark extract of Suregada zanzibariensis afforded a previously undescribed ent-abietane diterpenoid trivially named mangiolide (1) and a known jolkinolide B (2) via anticancer bioassay-guided fractionation. The CH2Cl2:MeOH extract of S. zanzibariensis was initially analysed for its anticancer properties against three cancer cell lines, renal (TK10), melanoma (UACC62), and breast (MCF7) and was found to be potent at low µg/mL ranges. Compound 1, 6α-acetoxy-14-keto-ent-abieta-7(8),13(15)-diene-16,12-olide (mangiolide) inhibited the growth of renal (TK10) with a GI50 of 0.02 µg/mL; a GI50 of 0.03 µg/mL for melanoma (UACC62) and a GI50 of 0.05 µg/mL for breast (MCF7) cancer cell lines. Compound 2, 8,13-diepoxy-13,15-ent-abietene-16,12-olide (jolkinolide B) inhibited the growth (GI50) of the cell lines at 3.31 µg/mL for renal (TK10), 0.94 µg/mL for melanoma (UACC62) and 2.99 µg/mL for the breast (MCF7). The structures were established on the basis of their spectroscopic analysis and the absolute stereostructures assigned using electronic circular dichroism (ECD).

Use of circular dichroism to determine the absolute configuration of a pimarane diterpenoid from the southern African Sclerocroton integerrimus (Euphorbiaceae).

From the stem bark and leaves of Sclerocroton integerrimus, eight compounds, including 17-hydroxy-ent-pimara-8(14),15-dien-3-one (1), were isolated. The structures of the compounds were determined on the basis of spectroscopic analysis. The absolute configuration of 17-hydroxy-ent-pimara-8(14),15-dien-3-one was confirmed from electronic circular dichroism studies.