Isolation, crystal structure, DFT calculation and molecular docking of uncinatine-A isolated from Delphinium uncinatum.

The main objective of our present research work was to explore molecular insight for potentially active new acetylcholinesterase inhibitor from the aerial parts of Delphinium uncinatum. New norditerpenoid alkaloids, uncinatine-A, was isolated from the basic alkaloidal fraction of D. uncinatum, based on bioactivity guided isolation. The structure of uncinatine-A was determined through latest spectroscopic techniques including single X-Ray diffraction technique. The structural data and electronic properties of uncinatine-A was also calculated by Density Functional Theory (DFT) using B3LYP/6-31þ G (p) basis set. The isolated natural product was evaluated for their acetyl cholinesterase inhibitory potential in dose dependent protocol (62.5-1000 µg/mL), followed by molecular docking studies. Significant competitive type inhibition activity (IC50 = 207.73 ± 0.3) was shown by isolated natural norditerpenoid against cholinesterase targets in comparison with standard drugs available in the market such as galanthamine. The molecular docking results showed that isolated natural product was well accommodated by AChE in the active site with docking scores -11.0326. This is the first report indicating uncinatine-A as a potent acetylcholinesterase inhibitor and can be used as a target drug in cerebral dementia and Alzheimer diseases.

Effect of Application of Treadmill Training on Metabolic Control and Vitamin D Level in Saudi Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus type 2 and vitamin D deficiency are both prevalent in the Saudi Arabia. Vitamin D deficiency treatment with supplements carries a risk of intoxication. AIM: The present study is aimed at elucidating the effect of exercise on modulation of metabolic status and vitamin D level in patients with type 2 diabetes mellitus (T2DM). METHODS: A sum of 110 type 2 diabetic patients were voluntarily enrolled for the present investigation by dividing them into two separate groups (55 individuals for each group), the diabetic study group and diabetic control group. The diabetic study group was engaged in the training program using treadmill exercise. Laboratory parameters were monitored before and after the training program. RESULTS: There were significant elevation in the diabetic study group compared to diabetic control group regarding postexercise vitamin D level, high-density lipoprotein (HDL) (p value ≤ 0.001, 0.045; respectively). In addition, triglycerides, low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1C), and homeostatic model assessment-insulin resistance (HOMA-IR) were significantly decreased (p value < 0.001 for all mentioned parameters). Moreover, there were significant higher level in postexercise parameters as compared to preexercise level in the diabetic study group. CONCLUSION: The exercise training program improved the metabolic control and vitamin D level after three months of intervention.

Effect of Application of Different Exercise Intensities on Vitamin D and Parathormone in Children with Down's Syndrome.

BACKGROUND: Children with Down's syndrome are more liable to vitamin D deficiency. Treating this deficiency with supplements is associated with the risk of intoxication. AIM: The study is aimed at comparing the effect of two exercise intensities on the modulation of vitamin D and parathormone levels in children with DS. METHODS: Forty-four DS male children aged from 8 to 12 years participated in the study. They were assigned randomly into two equal groups. Group I received high-intensity treadmill aerobic exercises, and group II received moderate-intensity T-AE, three times per week for three months. The blood samples were collected from both groups before the intervention, after one month of intervention, then after three months of intervention to assess serum 25(OH)D and PTH levels. RESULTS: Repeated measure MANOVA revealed that the high-intensity T-AE induced a significant increase in 25(OH)D after one month and after three months while it significantly decreased PTH only after three months. Moderate-intensity T-AE had a nonsignificant effect on both hormones. CONCLUSION: The current study concluded that the high-intensity T-AE improved both vitamin D and parathormone serum levels after three months of intervention.

Structure-based investigation of MARK4 inhibitory potential of Naringenin for therapeutic management of cancer and neurodegenerative diseases.

MAP/microtubule affinity-regulating kinase 4 (MARK4) is a member of serine/threonine kinase family and considered an attractive drug target for many diseases. Screening of Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) using virtual high-throughput screening coupled with enzyme assay suggested that Naringenin (NAG) could be a potent inhibitor of MARK4. Structure-based molecular docking analysis showed that NAG binds to the critical residues found in the active site pocket of MARK4. Furthermore, molecular dynamics (MD) simulation studies for 100 ns have delineated the binding mechanism of NAG to MARK4. Results of MD simulation suggested that binding of NAG further stabilizes the structure of MARK4 by forming a stable complex. In addition, no significant conformational change in the MARK4 structure was observed. Fluorescence binding and isothermal titration calorimetric measurements revealed an excellent binding affinity of NAG to MARK4 with a binding constant (K) = 0.13 × 106 M-1 obtained from fluorescence binding studies. Further, enzyme inhibition studies showed that NAG has an admirable IC50 value of 4.11 µM for MARK4. Together, these findings suggest that NAG could be an effective MARK4 inhibitor that can potentially be used to treat cancer and neurodegenerative diseases.