Mechanistic Insight into the Binding of Huperzine a with Human Transferrin: Computational, Spectroscopic and Calorimetric Approaches.

Huperzine A (HupA), an alkaloid found in the club moss Huperzia Serrata, has been in use for centuries in Chinese traditional medicine to treat dementia owing to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), thus acting as an acetylcholinesterase inhibitor (AChEI). An imbalance of metal ions in the brain is linked to Alzheimer's disease (AD) pathology. Transferrin (Tf) is a crucial player in iron homeostasis, thus highlighting its significance in AD. This study explores the plausible binding of HupA with Tf using molecular docking, molecular dynamics (MD) simulation, and free energy landscape (FEL) analyses. The docking results show that HupA binds to the functionally active region of Tf by forming three hydrogen bonds with Thr392, Glu394, and Ser688 and several hydrophobic interactions. The MD simulation analyses show that HupA binding is stable with Tf, causing minimal changes to the protein conformation. Moreover, principal component analysis (PCA) and FEL also depict the stable binding of HupA with Tf without any significant fluctuations. Further, fluorescence-based binding suggested excellent binding affinity of HupA with Tf affirming in silico observations. Isothermal titration calorimetry (ITC) advocated the spontaneous binding of HupA with Tf. This study provides an insight into the binding mechanism of HupA with Tf, and overall, the results show that HupA, after required experimentations, can be a better therapeutic agent for treating AD while targeting Tf.

Death-Associated Protein Kinase 3 Inhibitors Identified by Virtual Screening for Drug Discovery in Cancer and Hypertension.

Death-associated protein kinase 3 (DAPK3) is a serine/threonine protein kinase that regulates apoptosis, autophagy, transcription, and actin cytoskeleton reorganization. DAPK3 induces morphological alterations in apoptosis when overexpressed, and it is considered a potential drug target in antihypertensive and anticancer drug development. In this article, we report new findings from a structure-guided virtual screening for discovery of phytochemicals that could modulate the elevated expression of DAPK3, and with an eye to anticancer drug discovery. We used the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT), a curated database, as part of the methodology. The potential initial hits were identified based on their physicochemical properties and binding affinity toward DAPK3. Subsequently, various filters for drug likeness followed by interaction analysis and molecular dynamics (MD) simulations for 100 nsec were performed to explore the conformational sampling and stability of DAPK3 with the candidate molecules. Notably, the data from all-atom MD simulations and principal component analysis suggested that DAPK3 forms stable complexes with ketanserin and rotenone. In conclusion, this study supports the idea that ketanserin and rotenone bind to DAPK3, and show stability, which can be further explored as promising scaffolds in drug development and therapeutics innovation in clinical contexts such as hypertension and various types of cancer.

Knowledge, Attitude, and Practice of Bee Venom Acupuncture Therapy on Rheumatoid Arthritis Among Patients in Saudi Arabia.

INTRODUCTION: Bee venom acupuncture therapy (BVT) is an alternative therapy used worldwide by patients with different chronic diseases due to its therapeutic effects on conditions such as rheumatoid arthritis (RA). Previous studies have illustrated the clinical effects of BVT on RA, but such a study has yet to be performed in Saudi Arabia (SA). It is important to evaluate BVT awareness among citizens of SA to measure the feasibility of conducting clinical trials of BVT in patients with RA in SA. This study aims to measure the knowledge, attitude, and practice (KAP) of BVT on RA and other chronic diseases in SA. This will help determine whether patients with RA have sufficient knowledge to be enrolled in clinical trials. PATIENTS AND METHODS: A cross-sectional study of 180 patients with RA in SA was conducted using a KAP questionnaire on BVT. Individuals completed an online questionnaire using the Survey Monkey website. Data were obtained by self-completion of the online KAP questionnaire regarding BVT. RESULTS: A total of 180 patients with RA and other chronic diseases, with a mean age of 45 years (18-70 years), participated in the study. The results of the questionnaire showed that 55% of the participants demonstrated a good knowledge of BVT treatment; however, they also reported a poor attitude (55%) and practice (55%). Participants with RA demonstrated higher severity of disease (80%) than those with other chronic diseases. Participants with RA showed better KAP responses towards BVT than those with other chronic diseases. Participants with school education only and those who were beekeepers demonstrated significantly better KAP responses (P < 0.05) compared to participants who had received university education and those who were not beekeepers, respectively. CONCLUSION: Participants with strong RA knowledge may prove that patients from SA can be enrolled in BVT clinical trials. The participants' poor attitudes and practices may be due to BVT being expensive and unavailable in many cities in SA.