Isolation of Chemical Constituents and Invitro Antidiabetic Activity of Mirabilis Jalapa Flower Extracts

Objectives: The present work was designed to investigate the phytochemical and in vitro screening of the flower extracts of Mirabilis jalapa. Materials and Methods: Phytochemical constituents were isolated using column chromatography and characterized of the compounds were carried out using IR, 1H NMR, 13C NMR and mass spectroscopy data. In vitro anti-diabetic activity was evaluated by alpha-amylase inhibition assay and Alpha-glucosidase inhibition assay. Results: Phytochemical investigation of the ethanol extract revealed the presence of a flavonoid Kaempferol and a triterpenoid Lupeol. In vitro investigation indicated that the Mirabilis jalapa flowers extracts has considerable anti-diabetic activity Conclusion: The anti-diabetic activity may due to the presence of phytoconstituents like flavonoids, triterpenoids, steroids.

Pharmacological Chaperone Therapy for Pompe Disease

Pompe disease (PD), a lysosomal storage disease, is caused by mutations of the GAA gene, inducing deficiency in the acid alpha-glucosidase (GAA). This enzymatic impairment causes glycogen burden in lysosomes and triggers cell malfunctions, especially in cardiac, smooth and skeletal muscle cells and motor neurons. To date, the only approved treatment available for PD is enzyme replacement therapy (ERT) consisting of intravenous administration of rhGAA. The limitations of ERT have motivated the investigation of new therapies. Pharmacological chaperone (PC) therapy aims at restoring enzymatic activity through protein stabilization by ligand binding. PCs are divided into two classes: active site-specific chaperones (ASSCs) and the non-inhibitory PCs. In this review, we summarize the different pharmacological chaperones reported against PD by specifying their PC class and activity. An emphasis is placed on the recent use of these chaperones in combination with ERT.

Metabolite Profiles of the Green Beans of Indonesian Arabica Coffee Varieties

The green beans of 3 Indonesian arabica coffee varieties, namely, ateng, buhun, and sigararutang, were analyzed with 1H NMR-based metabolomics coupled with alpha-glucosidase inhibitory activity assay. These coffees were cultivated in the same geographical conditions. The PLSDA model successfully classified the green coffee beans based on their varieties. To reveal the characteristic metabolites for each coffee variety, S-plot of two-class OPLSDA models was generated and analyzed. Ateng coffee was characterized with trigonelline, sucrose, 5-CQA, and acetic acid. The characteristic metabolites of buhun coffee were citric acid and malic acid. Meanwhile, the most discriminant compound of sigararutang coffee was quinic acid. HCA analysis revealed the lineage relationship of the 3 coffee varieties. Ateng coffee had closer lineage relationship to sigararutang compared to the buhun coffee. Alpha-glucosidase inhibitory activity of the coffee samples did not differ widely. I C 50 values of alpha-glucosidase inhibitory activity of ateng, sigararutang, and buhun coffees were 3.01 ± 0.16 , 3.14 ± 0.20 , and 5.05 ± 0.28 mg/mL, respectively. Although grown in the same geographical conditions, our results revealed that each coffee variety possessed a unique metabolome clarifying the diversity of Indonesian arabica coffees. This study verified that 1H NMR-based metabolomics is an excellence method for discovering the lineage relationship in the samples with different varieties or cultivars.

In silico Identification of Potential Inhibitor Targeting Streptococcus mutans and Lactobacillus Acidophilus for the Treatment of Dental Caries

Background: Dental caries is one of the most common chronic diseases, and it is caused by the acid fermentation of bacteria that have become attached to the teeth. Streptococcus mutans (S. mutans) and Lactobacillus acidophilus (L. acidophilus) anchor surface proteins to the cell wall and form a biofilm to aid adhesion to the tooth surface. Some natural plant products, particularly several flavonoids, are effective inhibitors. However, given the scarcity of inhibitors and the emergence of drug resistance, the development of new inhibitors is critical. The high-throughput virtual screening approach was used in this study to identify new potential inhibitor of against S. mutans and L. acidophilus by using ligand (Ellagic acid). Aim: To evaluate the drug interaction ligand (Ellagic acid) and protein [A3VP1 of AgI/II] of Streptococcus mutans (PDB ID: 3IPK), glucan-1,6 - alpha-glucosidase from Lactobacillus acidophilus NCFM (PDB ID: 4AIE). Materials and Methodology: The pdb format of two selected proteins was retrieved from the RCSB protein database. Then inhibitors were docked with protein (A3VP1 of AgI/II) and glucan-1,6-alpha-glucosidase to identify the potent inhibitor. An evaluation criterion was based on the binding affinities by using AutoDock. Results: The binding energy of Ellagic acid - Streptococcus mutans docked complex-10.63 kcal/mol and with Ellagic acid – Lactobacillus acidophilus docked complex was -7.30 kcal/mol. Conclusion: In this study, Showed that lesser binding energy better is the binding of the ligand and protein. These findings can provide a new strategy for dental caries disease therapy by using Ellagic acid as a inhibitor against Streptococcus mutans and Lactobacillus acidophilus

Antidiabetic Potential of Selected Medicinal Plants: A Literature Review

Aims: To investigated for any scientific evidence indicating traditional use of different plant species in the management of diabetes. Study Design: Review Article. Place and Duration of Study: Conducted in Saudi Arabia from December 2020 to August 2021. Methodology: The literature was thoroughly investigated for any scientific evidence indicating traditional use of different plant species in the management of diabetes. The search was done in databases of Google Scholar, Saudi Digital Library and PubMed. Accordingly, the used plant species are classified into six groups. These are: Plants with antidiabetic activity, Plants with hypoglycemic activity, plants with alpha-glucosidase activity, Plants with alpha-amylase activity, Plants with glucose tolerance test, Plants with hypolipemic, anti-cholesterol, LDL and HDL activity. Conclusion: We have done in vitro and in vivo evaluation of M. arvensis L. for antidiabetic activity. The leaves extracts of M. arvensis L. showed significant antioxidant potential and significantly inhibited protein glycation, which correlated well with its phenolics along with other phytoconstituents. the methanolic extract of M. arvensis L.

Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates

Pompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD is currently treated with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human GAA (rhGAA). Although the introduction of ERT represents a breakthrough in the management of PD, the approach suffers from several shortcomings. Here, we developed a mouse model of PD to compare the efficacy of hepatic gene transfer with adeno-associated virus (AAV) vectors expressing secretable GAA with long-term ERT. Liver expression of GAA results in enhanced pharmacokinetics and uptake of the enzyme in peripheral tissues compared to ERT. Combination of gene transfer with pharmacological chaperones boosts GAA bioavailability, resulting in improved rescue of the PD phenotype. Scale-up of hepatic gene transfer to non-human primates also successfully results in enzyme secretion in blood and uptake in key target tissues, supporting the ongoing clinical translation of the approach.