Therapeutic Interventions for Diabetes Mellitus-Associated Complications.

BACKGROUND: Diabetes Mellitus (DM) is an alarming health concern, affecting approximately 537 million people worldwide. As a leading cause of morbidity and mortality, DM demands a comprehensive understanding of its diverse pathophysiological mechanisms and disease progression. METHODS: This traditional review has consolidated literature on the pathogenesis of hyperglycemia, its progression into complications, and advances in optimal treatment strategies. The literature in the last two decades has been reviewed using several keywords, including "diabetes," "diabetes-associated complications", "novel therapeutic interventions for diabetes-associated diseases", "phyto-extracts as antidiabetic drugs", etc. in prominent databases, such as PubMed, Scopus, Google Scholar, Web of Science, and ClinicalTrials.gov. RESULTS: We have discussed macrovascular and microvascular complications, such as atherosclerosis, cardiovascular disease, Peripheral Arterial Disease (PAD), stroke, diabetic nephropathy, retinopathy, and neuropathy, as well as various pharmacological and non-pharmacological interventions that are currently available for the management of DM. We have also focused on the potential of natural products in targeting molecular mechanisms involved in carbohydrate metabolism, insulin production, repair of pancreatic cells, and reduction of oxidative stress, thereby contributing to their antidiabetic activity. Additionally, novel therapeutic approaches, like genetic, stem cell, and immunomodulatory therapies, have been explored. We have also discussed the benefits and limitations of each intervention, emerging research and technologies, and precision medicine interventions. CONCLUSION: This review has emphasized the need for an improved understanding of these advancements, which is essential to enhance clinicians' ability to identify the most effective therapeutic interventions.

Scirpusin B isolated from Passiflora edulis Var. flavicarpa attenuates carbohydrate digestive enzymes, pathogenic bacteria and oral squamous cell carcinoma.

Passiflora edulis Var. flavicarpa (passion fruit) generates vast waste (60-70%) in the form of peel and seed after the juice extraction. The study aimed to isolate Scirpusin B (SB) from passion fruit (PF) seed waste collected from Northeast India and to analyse its anti-radical, antibacterial, anti-diabetic, and anti-oral cancer activities. Scirpusin B was isolated following hydro-alcoholic extraction, fractionation, and column chromatography. The isolated fraction was further identified through NMR and mass spectroscopy. SB exhibited significant antiradical activity against six standard antioxidant compounds, indicating its commercial application. SB inhibited α-amylase (IC50 Value: 76.38 ± 0.25 µg/mL) and α-glucosidase digestive enzymes (IC50 Value: 2.32 ± 0.04 µg/mL), signifying its antidiabetic properties. In addition, SB showed profound antibacterial activity against eight gram-positive and gram-negative bacteria reported for the first time. Furthermore, SB inhibited SAS and TTN oral cancer cell proliferation up to 95% and 83%, respectively. SB significantly inhibited colonies of SAS and TTn cells in the clonogenic assay, attributing to its anticancer properties. The PI-FACS assay confirmed the ability of SB (75 µM) to kill SAS and TTn cells by 40.26 and 44.3% in 72 h. The mechanism of SB inhibiting oral cancer cell proliferation was understood through western blot analysis, where SB significantly suppressed different cancer hallmark proteins, such as TNF-α, survivin, COX-2, cyclin D1, and VEGF-A. The present study suggests that SB isolated from PF seed can add noteworthy value to the waste biomass for various industrial and medical applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03876-6.

Dietary and bioactive properties of the berries and leaves from the underutilized Hippophae salicifolia D. Don grown in Northeast India.

The physico-chemical, polyphenols, antioxidant and antibacterial properties of berries and mixture of male and female leaves of Hippophae salicifolia were investigated. The mineral, vitamin C, sugar, total protein, and total tannin contents of the berries and the leaves were evaluated. Further, the extracts of berries and mixture of leaves samples obtained by successive solvent extraction were investigated for their polyphenols, antioxidant and antibacterial properties. Total phenolic content was highest in leaves-methanol extract (157.97 ± 2.09 mg GAE/g) followed by berries-aqueous extract (48.45 ± 1.94 mg GAE/g), while total flavonoid was predominant in leaves-acetone extract (75.64 ± 3.21 mg QE/g) and berries-methanol extract (28.93 ± 2.08 mg QE/g). Gallic acid, caffeic acid, and rutin were the major polyphenols confirmed by HPLC analysis. Berries-aqueous and leaves-methanol extracts showed excellent global antioxidant score. Best antibacterial activity was observed by methanol extracts against eight different strains. Overall, the leaves and berries of Hippophae salicifolia collected from Northeast India exhibited good antioxidant and antibacterial activity and can be utilized by food and pharmaceutical sectors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00988-8.

Effective control of Salmonella infections by employing combinations of recombinant antimicrobial human ß-defensins hBD-1 and hBD-2.

We successfully produced two human ß-defensins (hBD-1 and hBD-2) in bacteria as functional peptides and tested their antibacterial activities against Salmonella enterica serovar Typhi, Escherichia coli, and Staphylococcus aureus employing both spectroscopic and viable CFU count methods. Purified peptides showed approximately 50% inhibition of the bacterial population when used individually and up to 90% when used in combination. The 50% lethal doses (LD50) of hBD-1 against S. Typhi, E. coli, and S. aureus were 0.36, 0.40, and 0.69 µg/µl, respectively, while those for hBD-2 against the same bacteria were 0.38, 0.36, and 0.66 µg/µl, respectively. Moreover, we observed that bacterium-derived antimicrobial peptides were also effective in increasing survival time and decreasing bacterial loads in the peritoneal fluid, liver, and spleen of a mouse intraperitoneally infected with S. Typhi. The 1:1 hBD-1/hBD-2 combination showed maximum effectiveness in challenging the Salmonella infection in vitro and in vivo. We also observed less tissue damage and sepsis formation in the livers of infected mice after treatment with hBD-1 and hBD-2 peptides individually or in combination. Based on these findings, we conclude that bacterium-derived recombinant ß-defensins (hBD-1 and hBD-2) are promising antimicrobial peptide (AMP)-based substances for the development of new therapeutics against typhoid fever.

Development of an intra-molecularly shuffled efficient chimeric plant promoter from plant infecting Mirabilis mosaic virus promoter sequence.

We developed an efficient chimeric promoter, MUASMSCP, with enhanced activity and salicylic acid (SA)/abscisic acid (ABA) inducibility, incorporating the upstream activation sequence (UAS) of Mirabilis mosaic virus full-length transcript (MUAS, -297 to -38) to the 5' end of Mirabilis mosaic virus sub-genomic transcript (MSCP, -306 to -125) promoter-fragment containing the TATA element. We compared the transient activity of the MUASMSCP promoter in tobacco/Arabidopsis protoplasts and in whole plant (Petunia hybrida) with the same that obtained from CaMV35S and MUAS35SCP promoters individually. The MUASMSCP promoter showed 1.1 and 1.5 times stronger GUS-activities over that obtained from MUAS35SCP and CaMV35S promoters respectively, in tobacco (Xanthi Brad) protoplasts. In transgenic tobacco (Nicotiana tabacum, var. Samsun NN), the MUASMSCP promoter showed 1.1 and 2.2 times stronger activities than MUAS35SCP and CaMV35S(2) promoters respectively. We observed a fair correlation between MUASMSCP-, MUAS35SCP- and CaMV35S(2)-driven GUS activities with the corresponding uidA-mRNA level in transgenic plants. X-gluc staining of transgenic germinating seed-sections and whole seedlings also support above findings. Protein-extracts made from tobacco protoplasts expressing GFP and human-IL-24 genes driven individually by the MUASMSCP promoter showed enhanced expression of the reporters compared to that obtained from the CaMV35S promoter. Furthermore, MUASMSCP-driven protoplast-derived human IL-24 showed enhanced cell inhibitory activity in DU-145 prostate cancer cells compared to that obtained from the CaMV35S promoter. We propose chimeric MUASMSCP promoter developed in the study could be useful for strong constitutive expression of transgenes in both plant/animal cells and it may become an efficient substitute for CaMV35S/CaMV35S(2) promoter.