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.

Inhibitory effect of Newtonia extracts and myricetin-3-o-rhamnoside (myricitrin) on bacterial biofilm formation.

BACKGROUND: Diarrhoea is a major health issue in both humans and animals and may be caused by bacterial, viral and fungal infections. Previous studies highlighted excellent activity of Newtonia buchananii and N. hildebrandtii leaf extracts against bacterial and fungal organisms related to diarrhoea-causing pathogens. The aim of this study was to isolate the compound(s) responsible for antimicrobial activity and to investigate efficacy of the extracts and purified compound against bacterial biofilms. METHODS: The acetone extract of N. buchananii leaf powder was separated by solvent-solvent partitioning into eight fractions, followed by bioassay-guided fractionation for isolation of antimicrobial compounds. Antibacterial activity testing was performed using a broth microdilution assay. The cytotoxicity was evaluated against Vero cells using a colorimetric MTT assay. A crystal violet method was employed to test the inhibitory effect of acetone, methanol: dichloromethane and water (cold and hot) extracts of N. buchananii and N. hildebrandtii leaves and the purified compound on biofilm formation of Pseudomonas aeruginosa, Escherichia coli, Salmonella Typhimurium, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus. RESULTS: Myricetin-3-o-rhamnoside (myricitrin) was isolated for the first time from N. buchananii. Myricitrin was active against B. cereus, E. coli and S. aureus (MIC = 62.5 µg/ml in all cases). Additionally, myricitrin had relatively low cytotoxicity with IC50 = 104 µg/ml. Extracts of both plant species had stronger biofilm inhibitory activity against Gram-positive than Gram-negative bacteria. The most sensitive bacterial strains were E. faecalis and S. aureus. The cold and hot water leaf extracts of N. buchananii had antibacterial activity and were relatively non-cytotoxic with selectivity index values of 1.98-11.44. CONCLUSIONS: The purified compound, myricitrin, contributed to the activity of N. buchananii but it is likely that synergistic effects play a role in the antibacterial and antibiofilm efficacy of the plant extract. The cold and hot water leaf extracts of N. buchananii may be developed as potential antibacterial and antibiofilm agents in the natural treatment of gastrointestinal disorders including diarrhoea in both human and veterinary medicine.

Flavonoids isolated from the South African weed Chromolaena odorata (Asteraceae) have pharmacological activity against uropathogens.

BACKGROUND: Urinary tract infections (UTIs) caused by opportunistic pathogens are among the leading health challenges globally. Most available treatment options are failing as a result of antibiotic resistance and adverse effects. Natural sources such as plants may serve as promising alternatives. METHODS: Compounds were isolated from the South African weed Chromolaena odorata through column chromatography. Purified compounds were tested for antimicrobial activity using the p-iodonitrotetrazolium chloride (INT) colorimetric method, against uropathogenic Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Aspergillus fumigatus and Cryptococcus neoformans. Anti-biofilm, anti-adhesion and metabolic inhibition activities were investigated against selected strains. Safety of the compounds was determined against Vero monkey kidney, C3A human liver and colon (Caco2) cells. RESULTS: Four compounds identified as pectolinaringenin (1), (±)-4',5,7-trimethoxy flavanone (2), 5-hydroxy-3,7,4'-trimethoxyflavone (3) and 3,5,7-trihydroxy-4'-methoxyflavone) (4) were isolated. Minimum inhibitory concentration (MIC) varied between 0.016 and 0.25 mg/mL. Compounds 2 and 3 showed promising antimicrobial activity against E. coli, S. aureus, K. pneumoniae, A. fumigatus and C. neoformans with MIC between 0.016 and 0.125 mg/mL, comparable to gentamicin, ciprofloxacin and amphotericin B used as positive controls. Compounds 2 and 3 showed good anti-biofilm and metabolic inhibition activities against E. coli and S. aureus but weak anti-adhesion activity against the organisms. Low toxicity with selectivity indexes between 1 and 12.625 were recorded with the compounds, indicating that the compounds were rather toxic to the microbial strains and not to the human and animal cells. CONCLUSION: Pharmacological activities displayed by compounds 2 and 3 isolated from C. odorata and low toxicity recorded credits it as a potential lead for the development of useful prophylactic treatments and anti-infective drugs against UTIs. Although known compounds, this is the first time these compounds have been isolated from the South African weed C. odorata and tested for antimicrobial, anti-biofilm, metabolic inhibition and anti-adhesion activities.

Warburgia: a comprehensive review of the botany, traditional uses and phytochemistry.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Warburgia (Canellaceae) is represented by several medicinal trees found exclusively on the African continent. Traditionally, extracts and products produced from Warburgia species are regarded as important natural African antibiotics and have been used extensively as part of traditional healing practices for the treatment of fungal, bacterial and protozoal infections in both humans and animals. We here aim to collate and review the fragmented information on the ethnobotany, phytochemistry and biological activities of ethnomedicinally important Warburgia species and present recommendations for future research. MATERIALS AND METHODS: Peer-reviewed articles using "Warburgia" as search term ("all fields") were retrieved from Scopus, ScienceDirect, SciFinder and Google Scholar with no specific time frame set for the search. In addition, various books were consulted that contained botanical and ethnopharmacological information. RESULTS: The ethnopharmacology, phytochemistry and biological activity of Warburgia are reviewed. Most of the biological activities are attributed to the drimane sesquiterpenoids, including polygodial, warburganal, muzigadial, mukaadial and ugandensial, flavonoids and miscellaneous compounds present in the various species. In addition to anti-infective properties, Warburgia extracts are also used to treat a wide range of ailments, including stomach aches, fever and headaches, which may also be a manifestation of infections. The need to record anecdotal evidence is emphasised and conservation efforts are highlighted to contribute to the protection and preservation of one of Africa's most coveted botanical resources.

Bioactivities of Plectranthus ecklonii constituents.

Plectranthus ecklonii Benth. is traditionally used in South Africa for treating stomach aches, nausea, vomiting and meningitis. Bioassay-guided fractionation of the ethyl acetate extract of the plant led to the isolation of two known compounds, parvifloron D and parvifloron F, neither of which has been previously reported for this species. The compounds exhibited minimum inhibitory concentrations of 15.6 and 31.2 microg/mL, respectively against Listeria monocytogenes, whereas the values against a drug-sensitive strain of Mycobacterium tuberculosis were 190 and 95 microg/mL, respectively. The ethyl acetate extract of P. ecklonii and its isolated compounds were tested for their activity on tyrosinase inhibition. The concentration at which half the tyrosinase activity was inhibited (IC50) by the extract was found to be 61.7 +/- 2.7 microg/mL. The antibacterial activity of the extract and its isolated compounds correlates with the traditional use of the plant for various ailments such as stomach aches, diarrhea and skin diseases. The fifty percent inhibitory concentrations of parvifloron D and parvifloron F against vero cell lines were found to be 2.9 microg/mL and 1.6 microg/mL, respectively. This is the first report of the bioactivity of P. ecklonii extract and its constituents.