Herbal Nanoformulations for Diabetes: Mechanisms, Formulations, and Clinical Impact.

BACKGROUND: Diabetes mellitus remains a global health challenge, demanding innovative therapeutic strategies. Herbal remedies have garnered attention for their potential in diabetes management, and recent advancements in nanotechnology have enabled the development of herbal nanoformulations with enhanced efficacy and bioavailability. OBJECTIVE: This review aimed to comprehensively analyze the mechanisms, formulations, and clinical impact of herbal nanoformulations in managing diabetes mellitus. METHOD: A systematic literature search was conducted to identify relevant studies exploring the mechanisms of action, various formulations, and clinical outcomes of herbal nanoformulations in diabetes management. RESULT: Herbal nanoformulations exert their anti-diabetic effects through multiple mechanisms, including enhanced bioavailability, improved tissue targeting, and potentiation of insulin signaling pathways. Various herbal ingredients, such as bitter melon, fenugreek, and Gymnema sylvestre, have been encapsulated into nanocarriers, like liposomes, polymeric nanoparticles, and solid lipid nanoparticles, to enhance their therapeutic potential. Clinical studies have demonstrated promising results, showing improvements in glycemic control, lipid profile, and antioxidant status with minimal adverse effects. CONCLUSION: Herbal nanoformulations represent a promising avenue for the management of diabetes mellitus, offering improved therapeutic outcomes compared to conventional herbal preparations. Further research is warranted to optimize formulation strategies, elucidate long-term safety profiles, and explore the potential synergistic effects of herbal nanoformulations in combination therapies for diabetes management.

ProFitFun: a protein tertiary structure fitness function for quantifying the accuracies of model structures.

MOTIVATION: An accurate estimation of the quality of protein model structures typifies as a cornerstone in protein structure prediction regimes. Despite the recent groundbreaking success in the field of protein structure prediction, there are certain prospects for the improvement in model quality estimation at multiple stages of protein structure prediction and thus, to further push the prediction accuracy. Here, a novel approach, named ProFitFun, for assessing the quality of protein models is proposed by harnessing the sequence and structural features of experimental protein structures in terms of the preferences of backbone dihedral angles and relative surface accessibility of their amino acid residues at the tripeptide level. The proposed approach leverages upon the backbone dihedral angle and surface accessibility preferences of the residues by accounting for its N-terminal and C-terminal neighbors in the protein structure. These preferences are used to evaluate protein structures through a machine learning approach and tested on an extensive dataset of diverse proteins. RESULTS: The approach was extensively validated on a large test dataset (n = 25 005) of protein structures, comprising 23 661 models of 82 non-homologous proteins and 1344 non-homologous experimental structures. In addition, an external dataset of 40 000 models of 200 non-homologous proteins was also used for the validation of the proposed method. Both datasets were further used for benchmarking the proposed method with four different state-of-the-art methods for protein structure quality assessment. In the benchmarking, the proposed method outperformed some state-of-the-art methods in terms of Spearman's and Pearson's correlation coefficients, average GDT-TS loss, sum of z-scores and average absolute difference of predictions over corresponding observed values. The high accuracy of the proposed approach promises a potential use of the sequence and structural features in computational protein design. AVAILABILITY AND IMPLEMENTATION: http://github.com/KYZ-LSB/ProTerS-FitFun. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Traditional Japanese Herbal Medicine Yokukansan Targets Distinct but Overlapping Mechanisms in Aged Mice and in the 5xFAD Mouse Model of Alzheimer's Disease.

Yokukansan (YKS) is a traditional Japanese herbal medicine that has been used in humans for the treatment of several neurological conditions, such as age-related anxiety and behavioral and psychological symptoms (BPSD) related to multiple forms of dementia, including Alzheimer's disease (AD). However, the cellular and molecular mechanisms targeted by YKS in the brain are not completely understood. Here, we compared the efficacy of YKS in ameliorating the age- and early-onset familial AD-related behavioral and cellular defects in two groups of animals: 18- to 22-month-old C57BL6/J wild-type mice and 6- to 9-month-old 5xFAD mice, as a transgenic mouse model of this form of AD. Animals were fed food pellets that contained YKS or vehicle. After 1-2 months of YKS treatment, we evaluated the cognitive improvements in both the aged and 5xFAD transgenic mice, and their brain tissues were further investigated to assess the molecular and cellular changes that occurred following YKS intake. Our results show that both the aged and 5xFAD mice exhibited impaired behavioral performance in novel object recognition and contextual fear conditioning (CFC) tasks, which was significantly improved by YKS. Further analyses of the brain tissue from these animals indicated that in aged mice, this improvement was associated with a reduction in astrogliosis, microglia activation and downregulation of the extracellular matrix (ECM), whereas in 5xFAD mice, none of these mechanisms were evident. These results show the differential action of YKS in healthy aged and 5xFAD mice. However, both aged and 5xFAD YKS-treated mice showed increased neuroprotective signaling through protein kinase B/Akt as the common mode of action. Our data suggest that YKS may impart its beneficial effects through Akt signaling in both 5xFAD mice and aged mice, with multiple additional mechanisms potentially contributing to its beneficial effects in aged animals.