Current Drug Discovery Technologies - Volume 20, Issue 3, 2023

Background: An ulcer is a condition characterized by inflammation, irritation, or erosion in the mucosal lining of the stomach or duodenum. Hence, peptic ulcer is the ulcer of both the stomach and the duodenum. 10% of the world’s population is affected by chronic peptic ulcers. The formation of peptic ulcers depends on gastric juice pH and the decrease in mucosal defenses. Nonsteroidal antiinflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two significant factors disrupting mucosal resistance to injury. Indian herbal plants are exceptional for their ethnic, ethnobotanical, and ethno-pharmaceutical use. In this review, attempts have been made to gain information regarding some plants that may be used to treat or prevent peptic ulcers. The ultimate goal of peptic ulcer disease treatment is to reduce pain, cure ulcers, and prevent recurrence. Objective: The aim of the study was to gain knowledge about several common medicinal plants employed in Ayurveda or contemporary science for the treatment or prevention of peptic ulcers and some natural and simple approaches to cure ulcers using readily available herbs. Methods: The literature search was carried out using search engines, like Google Scholar, Scopus, PubMed, Medline, Springer, etc. Results: The extensive literature search showed natural herbs to have potential anti-ulcer activity, including cabbage, bananas, liquorice, fenugreek, garlic, Terminalia chebula, Acacia arabica, Aegle marmelos, Aloe vera, Allium sativum, Plantago ispagula, Mimosa pudica, Annona squamosa, Azadirachta indica, and Galega purpurea. Conclusion: This study concluded several medicinal plants to effectively prevent or cure peptic ulcers caused by a variety of factors, including H. pylori, aspirin, indomethacin, alcohol, and others.

Background: Candidiasis is a serious problem in women's health that is caused by Candida species, especially Candida albicans. In this study, the effect of carotenoids in carrot extracts on Candida species including Candida albicans ATCC1677, Candida glabrata CBS2175, Candida parapsilosis ATCC2195, and Candida tropicalis CBS94 was investigated. Methods: In this descriptive study, the carrot plant was prepared from a carrot planting site in December 2012, and then the characteristics of the plant were determined. After extracting carotenoids from carrots, the susceptibility of different Candida species to carotenoids in carrot extract was determined. Also, the minimum inhibitory concentration and the minimum lethal concentration of the extracts were measured by the macro-dilution method. Finally, the data were analyzed by SPSS software using the Kruskal-Wallis test and Mann-Whitney post-hoc test with Bonferroni adjustment. Results: The highest growth inhibition zone was obtained for carrot extract at a concentration of 500 mg/ml for C. glabrata and C. tropicalis. The MFC of carrot extract on Candida species was 62.5 mg/ml for C. albicans, C. glabrata, and C. parapsilosis, and 125 mg/ml for C. tropicalis. The MFC of carrot extract on Candida species was 125 mg/ml for C. albicans, C. glabrata, and C. parapsilosis, and 250 mg/ml for C. tropicalis. Conclusion: The present study can be the starting point for research activities in this direction and promises new therapies based on the use of carotenoids.

Introduction: The root bark of Berberis aristata has been utilized by indigenous peoples for wound treatment for centuries. The mature root barks are crushed into a paste and applied to the wound's surface. Objective: The focus of this research is to analyse the wound healing activities of an ethanolic extract of Berberis aristata, as well as to use molecular docking to establish the likely mechanism of the potent phytochemical. There is no scientific evidence to support the usage of root bark extract of Berberis aristata. Methods: The Herbal ointment, which comprises (1%, 2%, and 4% w/w) ethanolic extract of root bark, was developed to test the wound healing ability of incision and excision wounds, and the molecular mechanism was established using Auto-Dock software. Results: Epithelization stage, wound index, % wound contraction area, hydroxyproline content, DNA estimate, and histopathological assessments were performed on the incision wound model. Tensile strength was assessed in an excision wound model. TLC was used to identify the samples after successive extractions with different solvents based on polarity. Conclusion: Berberine and tetrahydropalmatine were major active phytoconstituent found in root barks of Berberis aristata as secondary metabolites. Animals treated with 4% w/w formulation demonstrated considerable wound contraction, epithelization time, and wound index in the excision model. In contrast, to control and standardize the concentrations of hydroxyproline, total amino acids, and DNA in recovering tissue were higher. At 4% w/w extract formulation, the parameters studied indicated a substantial result. Berberine and tetrahydropalmatine, active metabolites which are present in the ethanolic extract of Berberis aristata, were found to be responsible for wound healing. Based on ligand interactions, the findings verified Berberis aristata ethnomedicinal claim in a wound healing capacity.

Background: Diabetes occurs due to insulin deficiency or less insulin. To manage this condition, insulin administration as well as increased insulin sensitivity is required, but exogeneous insulin cannot replace the sensitive and gentle regulation of blood glucose levels same as β cells of healthy individuals. By considering the ability of regeneration and differentiation of stem cells, the current study planned to evaluate the effect of metformin preconditioned buccal fat pad (BFP) derived mesenchymal stem cells (MSCs) on streptozotocin (STZ) induced diabetes mellitus in Wistar rats. Materials & Methods: The disease condition was established by using a diabetes-inducing agent STZ in Wistar rats. Then, the animals were grouped into disease control, blank, and test groups. Only the test group received the metformin-preconditioned cells. The total study period for this experiment was 33 days. During this period, the animals were monitored for blood glucose level, body weight, and food-water intake twice a week. At the end of 33 days, the biochemical estimations for serum insulin level and pancreatic insulin level were performed. Also, histopathology of the pancreas, liver and skeletal muscle was performed. Results: The test groups showed a decline in the blood glucose level and an increase in the serum pancreatic insulin level as compared to the disease group. No significant change in food and water intake was observed within the three groups, while body weight was significantly reduced in the test group when compared with the blank group, but the life span was increased when compared with the disease group. Conclusion: In the present study, we concluded that metformin preconditioned buccal fat pad-derived mesenchymal stem cells have the ability to regenerate damaged pancreatic β cells and have antidiabetic activity, and this therapy is a better choice for future research.

Background: Nanoemulsions are promising drug delivery systems for topical application owing to the high transdermal penetration. Objective: Due to the side effects of existing anti-inflammatory drugs, much attention has been paid to natural products such as flavonoids. The aim of this work was to formulate luteolin nanoemulsion (LNE) and to evaluate its anti-inflammatory effect. Methods: LNE was prepared using the low-energy spontaneous emulsion method and characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and dynamic light scattering (DLS). The anti-inflammatory effect of LNE was assessed in formalin and acetic acid-induced inflammation methods (Whittle test). Treatment with LNE (i.p, 4 consecutive days, 40 mg/kg) was compared with diclofenac 25 mg/kg and normal saline. In the formalin test, data were recorded at 1, 2 and 4 hours after formalin injection and in the Wittle test, the extent of Evans blue leakage in the peritoneal cavity was considered as vascular permeability. Results: Formalin-induced edema decreased in the LNE group, but this reduction was not significant (p > 0.05), however, in Whittle test, both LNE and diclofenac significantly reduced Evans blue leakage compared with the group treated with acetic acid alone (p < 0.05). Conclusion: Our results confirm the anti-inflammatory effect of LNE and give up a new platform for the design and development of bio-based carriers for more successful drug delivery.

Background: BACE1 (beta-site amyloid precursor protein (APP) cleaving enzyme) is a key target for Alzheimer's disease research because it catalyses the rate-limiting step in the formation of amyloid protein (Aβ). Natural dietary flavonoids have gained a lot of interest as potential Alzheimer's therapy candidates because of their anti-amyloidogenic, antioxidative, and anti-inflammatory properties. More research is needed, however, to learn more about the specific routes through which flavonoids may have neuroprotective benefits in Alzheimer's disease. Objective: Here, we report an in silico molecular modeling study for natural compounds, particularly flavonoids, as BACE-1 inhibitors. Methods: The interactions of flavonoids with the BACE-1 catalytic core were disclosed by demonstrating the predicted docking pose of flavonoids with BACE-1. The stability of flavonoids BACE-1 complex was analyzed by molecular dynamic simulation (standard dynamic cascade). Results: Our findings imply that these flavonoids, which have methoxy group instead of hydroxy may be promising BACE1 inhibitors that could reduce Aβ formation in Alzheimer's disease. The molecular docking study revealed that flavonoids e bind with the BACE1’s wide active site along with the catalytic residues Asp32 and Asp228. Further molecular dynamic investigation revealed that the average RMSD for all complexes ranged from 2.05 to 2.32 Å, indicating that the molecules were relatively stable during MD simulation. The RMSD analyses demonstrate that the flavonoids were structurally stable during the MD simulation. The RMSF was utilised to study the time-dependent fluctuation of the complexes. The N-terminal (~2.5 Å) fluctuates less than the C-terminal (~6.5 Å). Rutin and Hesperidin were highly stable in the catalytic region as compared to other flavonoids like Rhoifolin, Hesperidin, Methylchalcone, Phlorizin and Naringin. Conclusion: We were able to justify the flavonoids' selectivity for BACE-1 and crossing BBB for the treatment of Alzheimer's disease by using a combination of molecular modelling tools.

Introduction: Diabetes is the most common component of metabolic syndrome, including abdominal obesity, insulin resistance, hypertension, and dyslipoproteinemia. Objective: This study aims to determine whether vanillic acid has antihyperlipidemic properties in diabetic hypertensive rats. Methods: For this study healthy male albino Wister rats (180-220 gm) were selected. A 20-week highfat diet (HFD) was given to produce diabetic hypertension in Wister rats. Control and diabetic hypertensive rats were treated with vanillic acid. Vanillic acid effects on lipid profiles (cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoproteins (HDL)) and lipid metabolizing enzymes LPL, LCAT, and HMG CoA reductase studied by a conventional method. To understand the effect of vanillic acid control, experimental rat lipid and metabolic enzymes were studied and treated and controlled animal liver tissues were observed using the different histology staining agents. Results: Vanillic acid caused considerable lipid profile reductions except for HDL and increased plasma HDL levels. After eight weeks of vanillic acid administration also boosts lipid marker enzyme activity (HMG CoA reductase, LPL, and LCAT). In addition, vanillic acid reduces the accumulation of collagen in liver tissues. Conclusion: These research studies suggest that vanillic acid has antihyperlipidemic effects in diabetic hypertensive rats fed an HFD.

Background: Green strategy involves the design, synthesis, processing, and use of chemical substances by eliminating the generation of chemical hazards. This approach focuses on atom economy, use of safer solvents or chemicals, consumption of energy, and decomposition of the chemical substances to non-toxic materials which are eco-friendly. Objective: So, the microwave irradiated heating method is considered a green and sustainable technique for the development of novel heterocyclic scaffold-like isoxazole derivatives via chalcones. Isoxazole derivatives play a vital role due to their diverse pharmacological activities such as antibiotic (Sulfamethoxazole, Cloxacillin, Flucloxacillin, Cycloserine), anti-fungal (Drazoxolon), Antirheumatic (Leflunomide), antidepressant (Isocarboxazid), antineoplastic (Acivicin), anticonvulsant (Zonisamide), antipsychotic (Risperidone) and anti-inflammatory drugs (Valdecoxib), etc. Methods: The isoxazole derivatives were synthesized with the help of microwave irradiation that follows green chemistry protocol. Results: The titled compounds were subjected to antiepileptic evaluation to determine their therapeutic potential. Conclusion: The use of microwave radiation enhances the rate of the reaction which leads to high selectivity with improved product yields in comparison with the traditional heating methods. The tested compounds exhibited promising antiepileptic activity as compared to the standard drug (Phenytoin).