To restore the integrity of the skin and subcutaneous tissue, the wound healing process involves a complex series of well-orchestrated biochemical and cellular events. Due to the existence of various active components, accessibility and few side effects, some plant extracts and their phytoconstituents are recognised as viable options for wound healing agents. To find possible inhibitors of diabetic wound healing, four main constituents of aloe vera were identified from the literature. TGF-β1 and the compounds were studied using molecular docking to see how they interacted with the active site of target protein (PDB ID: 6B8Y). The pharmacokinetics investigation of the aloe emodin with the highest dock score complied with all the Lipinski's rule of five and pharmacokinetics criteria. Conformational change in the docked complex of Aloe emodin was investigated with the Amber simulation software, via a molecular dynamic (MD) simulation. The MD simulations of aloe emodin bound to TGF-β1 showed the significant structural rotations and twists occurring from 0 to 200 ns. The estimate of the aloe emodin-TGF-β1 complex's binding free energy has also been done using MM-PBSA/GBSA techniques. Additionally, aloe emodin has a wide range of enzymatic activities since their probability active (Pa) values is >0.700. 'Aloe emodin', an active extract of aloe vera, has been identified as the key chemical in the current investigation that can inhibit diabetic wound healing. Both in-vitro and in-vivo experiments will be used in a wet lab to confirm the current computational findings.Communicated by Ramaswamy H. Sarma.
Diabetes mellitus (DM) is a long-term metabolic disease characterised by a controlled metabolism of fat, carbohydrates, and proteins. In recent decades, it has grown into a significant global public health issue. According to the International Diabetes Federation, there were 425 million DM globally in 2017, and the number might be increased to 629 million by 2045 (a global 48% increase). Approximately 4.2 million deaths globally attributed to DM occur before the age of 60. The existing class of anti-diabetic medications is limited by side effects, which has led to the hunt for novel inhibitors that specifically target the α-amylase and α-glucosidase enzymes. Curcumin is a small-molecular-weight compound found in the roots of the Curcuma longa L (C. longa). plant, which has been used for culinary, medicinal, and other purposes throughout Asia for thousands of years. Curcumin has potent anti-inflammatory, anti-cancer, anti-angiogenic, antispasmodic, antibacterial, and anti-parasitic qualities. Even though the potential of curcumin to cure DM has been well investigated, its low solubility, rapid metabolism, and short plasma half-life have limited its application in DM. Therefore, the objectives of this review were to review the chemical composition of C. longa, the structure of curcumin, the degradation of curcumin, and the effects of curcumin derivatives on anti-diabetic properties against α-amylase and α-glucosidase enzymes. The results showed that C. longa contains carbohydrates, moisture, protein, fat, minerals, volatiles, fibre, and curcuminoids. Among the curcuminoids, curcumin is 60-70% present in C. longa. Moreover, curcumin and its derivatives have a lot of potential for treating DM, which was highlighted in this review. This review emphasises the several biological applications of curcumin, which collectively establish the foundation for its anti-diabetic characteristics. Considering these results, curcumin derivatives may be considered as potential agents in the pharmacotherapeutic management of patients with DM.
Aedes aegypti is the primary vector for the transmission of the dengue virus, which causes dengue fever, dengue hemorrhagic illness and dengue shock syndrome. There is now no antiviral medication available to treat DENV, which kills thousands of people each year and infects millions of individuals. A possible target for the creation of fresh and efficient dengue treatments is the DENV-3 NS5 MTase. So, Nigella sativa quinones were examined using in silico methods to find natural anti-DENV compounds. The in silico docking was conducted utilising the Discovery Studio software on the quinones of N. sativa and the active site of the target protein DENV-3 NS5 MTase. In addition, the druggability and pharmacokinetics of the lead compound were assessed. Dithymoquinone was comparable to the reference compound in terms of its ability to bind to the active site of target protein. Dithymoquinone met the requirements for drug likeness and Lipinski's principles, as demonstrated by the ADMET analysis and drug likeness results. The current study indicated that the dithymoquinone from N. sativa had anti-DENV activity, suggesting further drug development and dengue treatment optimisation.Communicated by Ramaswamy H. Sarma.
The goal of this work is to use a variety of in-silico techniques to identify anti-diabetic agents against DPP-IV enzyme from five main curcumin analogues. To produce the successful molecules, five main curcumin analogues were docked into the active site of DPP-IV enzyme. In comparison to the control molecule (Saxagliptin, -6.9 kcal/mol), all the compounds have the highest binding affinity (-7.6 to -7.7 kcal/mol) for the DPP-IV enzyme. These compounds underwent further testing for studies on drug-likeness, pharmacokinetics, and acute toxicity to see the efficacy and safety of compounds. To assess the stability of the docking complex and the binding posture identified during the docking experiment, our study got THC as the lead compound, which was then exposed to 200 ns of molecular dynamic simulation and PCA analysis. Additionally, DFT calculations were conducted to determine the thermodynamic, molecular orbital, and electrostatic potential characteristics of lead compound. Overall, the lead chemical has shown strong drug-like properties, is non-toxic, and has a sizable affinity for the DPP-IV enzyme.
Diabetes mellitus (DM) a metabolic disorder characterized by high blood sugar levels causing damage to various organs over time. Current anti-diabetic drugs have limitations and side effects, prompting a search for new inhibitors targeting the α-amylase enzyme. This study aims to discover such inhibitors from thirty isoxazole derivatives of usnic acid using in silico approaches. The potential inhibitory effects of compounds were investigated using ADMET, molecular docking, molecular dynamic simulation, principal component analysis and density functional theory studies. ADMET analysis exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities with no significant side effects which were then investigated using molecular docking experiment to determine the lead compound with the best binding affinity for the α-amylase enzyme. All compounds showed good binding affinity against α-amylase enzyme (-7.9 to -9.2 kcal/mol) where compound-13 showed the best binding affinity of -9.2 kcal/mol forming hydrogen bonds with Leu162, Tyr62, Glu233 and Asp300 amino acids. Furthermore, the binding posture and the stability of the compound-13-α-amylase enzyme complex was confirmed by molecular dynamic simulation experiment. Moreover, compound-13 showed binding energy value of -27.92 ± 5.61 kcal/mol, which indicated it could be an α-amylase inhibitor. Additionally, the reactivity of compound-13 was further confirmed by density functional theory analysis. The above findings suggest compound-13 to be a potential α-amylase inhibitor in DM. And setting the stage for further in vitro and in vivo experimental validation.