A systematic analysis of anti-diabetic medicinal plants from cells to clinical trials.

Background: Diabetes is one of the fastest-growing health emergencies of the 21st century, placing a severe economic burden on many countries. Current management approaches have improved diabetic care, but several limitations still exist, such as decreased efficacy, adverse effects, and the high cost of treatment, particularly for developing nations. There is, therefore, a need for more cost-effective therapies for diabetes management. The evidence-based application of phytochemicals from plants in the management of diseases is gaining traction. Methodology: Various plants and plant parts have been investigated as antidiabetic agents. This review sought to collate and discuss published data on the cellular and molecular effects of medicinal plants and phytochemicals on insulin signaling pathways to better understand the current trend in using plant products in the management of diabetes. Furthermore, we explored available information on medicinal plants that consistently produced hypoglycemic effects from isolated cells to animal studies and clinical trials. Results: There is substantial literature describing the effects of a range of plant extracts on insulin action and insulin signaling, revealing a depth in knowledge of molecular detail. Our exploration also reveals effective antidiabetic actions in animal studies, and clear translational potential evidenced by clinical trials. Conclusion: We suggest that this area of research should be further exploited in the search for novel therapeutics for diabetes.

Protective capacity of carotenoid trans-astaxanthin in rotenone-induced toxicity in Drosophila melanogaster.

Trans-astaxanthin (TA), a keto-carotenoid found in aquatic invertebrates, possesses anti-oxidative and anti-inflammatory activities. Rotenone is used to induce oxidative stress-mediated Parkinson's disease (PD) in animals. We probed if TA would protect against rotenone-induced toxicity in Drosophila melanogaster. Trans-astaxanthin (0, 0.1, 0.5, 1.0, 2.5, 10, and 20 mg/10 g diet) and rotenone (0, 250 and 500 µM) were separately orally exposed to flies in the diet to evaluate longevity and survival rates, respectively. Consequently, we evaluated the ameliorative actions of TA (1.0 mg/10 g diet) on rotenone (500 µM)-induced toxicity in Drosophila after 7 days' exposure. Additionally, we performed molecular docking of TA against selected pro-inflammatory protein targets. We observed that TA (0.5 and 1.0 mg/10 g diet) increased the lifespan of D. melanogaster by 36.36%. Moreover, TA (1.0 mg/10 g diet) ameliorated rotenone-mediated inhibition of Catalase, Glutathione-S-transferase and Acetylcholinesterase activities, and depletion of Total Thiols and Non-Protein Thiols contents. Trans-astaxanthin prevented behavioural dysfunction and accumulation of Hydrogen Peroxide, Malondialdehyde, Protein Carbonyls and Nitric Oxide in D. melanogaster (p < 0.05). Trans-astaxanthin showed higher docking scores against the pro-inflammatory protein targets evaluated than the standard inhibitors. Conclusively, the structural features of TA might have contributed to its protective actions against rotenone-induced toxicity.

Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2.

Owing to the urgent need for therapeutic interventions against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potentials of the compounds against SARS-CoV-2 drug targets - main protease (Mpro), spike protein (Spro) and RNA-dependent RNA polymerase (RdRp) were investigated through molecular docking analysis. The binding free energy of the protein-ligand complexes were estimated, pharmacophore models were generated and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the compounds were determined. The compounds displayed various levels of binding affinities for the SARS-CoV-2 drug targets. Bisimidazole C2 scored highest against all the targets, with its aromatic rings including the two imidazole groups contributing to the binding. Among the phenyl-substituted 1H-imidazoles, C9 scored highest against all targets. C11 scored highest against Spro and C12 against Mpro and RdRp among the thiophene-imidazoles. The compounds interacted with HIS 41 - CYS 145 and GLU 288 - ASP 289 - GLU 290 of Mpro, ASN 501 of Spro receptor binding motif and some active site amino acids of RdRp. These novel imidazole compounds could be further developed as drug candidates against SARS-CoV-2 following lead optimization and experimental studies.

In vitro and in vivo analysis of the anti-plasmodial activity of ethanol extract of Phyllanthus nivosus W. Bull leaf.

Antimalarial agents are necessary tools in the global malaria eradication agenda and plants used traditionally in the treatment of malaria are indispensable sources of antimalarial compounds. The aim of this study was to evaluate the antiplasmodial potential of Phyllanthus nivosus leaf. In vitro antiplasmodial assay was conducted using Plasmodium falciparum infected erythrocytes incubated at 37 °C in modified RPMI 1640 culture media. The inhibitory effect of the ethanol extract on plasmodium lactate dehydrogenase (pLDH) activity was determined as a measure of antiplasmodial activity. In vivo study was done using mice infected with chloroquine sensitive P. berghei (NK-65 strain). Parasitemia, packed cell volume (PCV), hemoglobin (Hb) and liver lipid peroxidation (MDA) levels were determined after a 4 day treatment. Chloroquine was used as standard drug for both assays. The extract reduced pLDH activity by 39.52, 42.07 and 43.87% at 12, 25 and 50 µg/mL respectively. 100 and 200 mg/kg body weight of extract and 10 mg/kg chloroquine suppressed parasitemia of infected mice by 82.76, 81.11 and 86.87% respectively. Furthermore, the extract significantly reduced (p < 0.05) the elevated MDA level and reversed PCV and Hb levels of infected mice to normal values. Phytochemical screening of the extract revealed the presence of alkaloids, tannins, flavonoids, cardiac glycosides, anthraquinones, steroids and terpenes. Gas chromatography-mass spectrometry (GC-MS) analysis showed the presence of ten compounds, the most abundant of which is Methyl linoleate (35.77%). This study demonstrated that P. nivosus leaf possesses antimalarial potential and contains bioactive compounds that could be beneficial in the development of new antimalarial agents.