Background: Alzheimer’s disease (AD), a progressive neurodegenerative disease for which there is no effective cure is among the leading causes of death worldwide. Objectives: To investigate the potential anti-AD activity of berberine (BBR). Methods: In silico assessment included molecular docking and ADMET prediction. BBR’s in vitro inhibitory activity of the target selected from docking results was assessed via colorimetric inhibitor screening assay. BBR’s LC50 in adult zebrafish was determined via an Acute Toxicity Study. ZnCl2 concentration for AD induction was determined via toxicity study and T-maze test. Finally, zebrafish were treated with ZnCl2 alone or simultaneously with either BBR or donepezil and assessed via the inhibitory avoidance task, followed by ELISA of AD-related biomarker levels in brain tissue. Results: The in silico assessment showed BBR’s desirable drug properties and binding affinity on selected AD-related targets, which was the greatest docking score with AChE. The in vitro IC50 on AChE was 3.45 μM. The LC50 in adult zebrafish was calculated at 366 ppm. In the T-maze test, ZnCl2 at 2.5 ppm caused the greatest cognitive impairment accompanied by moderate freezing. In the inhibitory avoidance test, fish treated with either 100 ppm BBR or 2.5 ppm donepezil had significantly better performance than ZnCl2-treated fish. ZnCl2-treated zebrafish brain tissue had the highest Aβ levels and AChE activity of all groups, but these were significantly lower in donepeziland BBR-treated fish. ZnCl2- and donepezil-treated fish had similar TNF-α levels, whereas BBR treatment significantly lowered them close to those of untreated fish. Conclusion: BBR showed anti-amyloidogenic, anti-AChE, and anti-inflammatory effects, which support its potential use in AD therapy.

: Memory loss or dementia is the key symptom of Alzheimer's disease (AD). In AD, significant interference in a progressive manner is observed in memory, behaviour, and cognitive abilities that affect the daily life of a person. At present, more than 50 million people are affected worldwide with Alzheimer's disease. Urgent attention is needed for the symptomatic regulation and management of this disease. The significant pharmacotherapy research in the last two decades gave only four drug compounds galanthamine, donepezil, rivastigmine, and memantine that inhibit the enzyme acetylcholinesterase (AChE) to elevate the availability of acetylcholine in the brain for symptomatic relief in AD patients. Plant-based AChE inhibitors from many plant families, mainly including Rutaceae, Papaveraceae, Apocynaceae, Rubiaceae, Amaryllidaceae, Liliaceae, Lycopodiaceae, Fabaceae, Lamiaceae, etc., have been characterized for the management of AD progression. AD progression is described by cholinergic, amyloid, Tau protein, oxidative stress, and neuroinflammatory hypothesis. To date, there is no comprehensive review in the literature that combined all plants of the Apocynaceae family showing anti-AChE activity. Therefore, the current review aims to present significant literature, especially on plant-derived compounds from the Apocynaceae family that inhibit AChE. The review compiled all plants showing potent anti-acetylcholinesterase activity. The anti-AChE activity of more than 30 plants is described, which may be potential targets to find new drug molecules by attracting the attention of researchers toward the Apocynaceae family. More than 8 species of genus Tabernaemontana of Apocynaceae have been investigated for indole alkaloids, demonstrating AChE inhibitory activity. The majority of anti-AChE compounds belong to the class of alkaloids.

Abstract: Enzyme inhibition stands as a crucial strategy in tackling cardiovascular diseases (CVDs), countering their significant global impact on health. Targeting key enzymes involved in critical disease pathways has emerged as a pivotal pharmacological approach across various cardiovascular conditions. In hypertension, ACE inhibitors effectively lower blood pressure by impeding the conversion of angiotensin I to angiotensin II, promoting vasodilation and reducing cardiac workload. CAD management often involves statins, which competitively inhibit 3-hydroxy-3-methylglutarylcoenzyme A reductase, thereby lowering cholesterol levels and curbing plaque formation in coronary arteries. For heart failure, neprilysin inhibitors combined with ARBs exhibit promise by preserving beneficial peptides, supporting heart function and regulating fluid balance. Aspirin, an irreversible COX enzyme inhibitor, reduces platelet aggregation, mitigating thromboxane A2 formation and lowering the risk of clot-related complications in atherosclerosis. Managing dyslipidemia involves drugs like ezetimibe, targeting cholesterol absorption in the intestines and reducing LDL cholesterol levels. However, administering these drugs mandates careful consideration of patient-specific factors, potential side effects, and contraindications. Integrating lifestyle changes, such as a healthy diet and regular exercise remains integral to CVD management. The potential of enzyme inhibition in disrupting disease pathways and addressing key factors in CVD progression is evident. Yet, it necessitates ongoing research for refining existing therapies and developing novel inhibitors to augment cardiovascular outcomes and elevate patients' quality of life.

Introduction: Recent studies have shown modified cyclobutene derivatives as potent anti- tubercular agents, and the discovery of drugs against strains of Mycobacterium tuberculosis is still a crucial challenge in the modern world. Objective: The objective of the present study is to design and perform molecular docking studies and in-silico analysis of some novel cyclobut-3-ene-1,2 Dione derivatives with the aim of creating new, potential Mtb ATP synthase inhibitors. Materials and Methods: The structures of 24 compounds of diamino-substituted cyclobut-3-ene-1,2 Dione derivatives against Mtb ATP synthase were drawn using ChemSketch. Further, molecular docking and in-silico studies for the prediction of drug-likeness and pharmacokinetic parameters were carried out. Results: The docking studies of the novel compounds were done, and they had a better docking score with a good binding affinity towards the protein molecule. The synthesized compounds also comply with the in-silico prediction of drug-likeness and pharmacokinetic parameters and have shown good activity against Mtb ATP synthase. Conclusion: The current study shows that the cyclobut-3-ene-1,2 Dione derivatives can serve as a better lead molecule against Mtb ATP synthase and can be involved in further drug discovery

Background: Hyperpigmentation is a growing problem worldwide among various skin diseases and directly relates to the quality of life. The factors causing hyperpigmentation may range from excess exposure to sunlight, pollution, underlying disease conditions, adverse effects of a medication, modified lifestyle, and oxidative stress. Treatment includes the use of hydroquinone, retinoids, corticosteroids, and kojic acid along with anti-inflammatory drugs. However, these medications are preferred for short-term treatment under acute conditions, while in the case of long-term treatment, botanical extracts are a safe choice for a majority of the population for the treatment of hyperpigmentation. Formulation with plant extracts/oil enriched with polyphenols, vitamin C, and vitamin E are reported to be safe and effective in inhibiting melanogenesis. Objective: Seed oils composed of polyphenols, vitamins and unsaturated fatty acids were selected to evaluate their antioxidant property and tyrosinase enzyme inhibitory activity. Methods: Grape seed oil (GSO), papaya seed oil (PSO), and carrot seed oil (CSO) were evaluated for their total phenolic and flavonoid content , in-vitro antioxidant activity was done using DPPH assay and anti-tyrosinase activity was done usingMushroomtyrosinaseinhibition assay. Results: Total phenolic content for PSO was 0.936 mg/gm. Gallic acid equivalent (GAE) was highest when compared to GSO and CSO, while CSO had a higher total flavonoid concentration, 0.945 mg/gm as quercetin equivalent (QE). Free radical scavenging activity was comparable to standard and tyrosinase inhibitory activity for grape and carrot seed oils were 80.10 % and 76.52 % at 100µg/ml, respectively and was comparable to kojic acid used as standard. Conclusion: The results obtained suggest that the oils can be formulated as a topical depigmenting product and used for skin care and skin glow

Abstract: Enzyme inhibition is a crucial pharmacological approach for treating various diseases as it targets enzymes involved in disease pathogenesis. This review explores the fundamental concepts of enzyme inhibition, including reversible and irreversible mechanisms, and the various types of enzymes, such as proteases, kinases, and polymerases, and their contributions to different disease states. The review discusses the design and production of enzyme inhibitors using methods like structurebased drug design, high-throughput screening, and rational drug design. The review also discusses the challenges and successes encountered in discovering and optimizing potent and selective enzyme inhibitors. Examples of enzyme inhibition's therapeutic benefits include protease inhibitors in HIV/AIDS therapy, kinase inhibitors in cancer treatment, and acetylcholinesterase inhibitors in Alzheimer's disease management. The review also examines possible side effects and limits of enzyme inhibition, focusing on ways to reduce off-target effects and make drugs more specific. At the end of the review, new trends and future possibilities in enzyme inhibition for treating diseases are talked about. These include personalized medicine, combination therapies, and new ways to get drugs into the body. By shedding light on the latest developments, challenges, and future directions, the review aims to contribute to the advancement of this vital field and revolutionize disease treatment modalities.

Background:: To search for antifungal bioactive molecules from Ocimum sanctum, we used a molecular docking approach to identify the natural compound responsible for the property with a specific target. Our goal is to identify the potential antifungal compounds based on computational screening from reported chemical constituents of Tulsi as potential inhibitors of 14α- demethylase. Method:: Molecular docking was performed using Molergo Virtual docker software and validated based on the Root Mean Square Deviation (RMSD) value. Result:: The compounds were docked to the pocket of the enzyme, and the docking results depicted that only oxygenated compounds were important for an antifungal profile with a good docking score and interaction with the enzyme molecule. Conclusion:: The results suggest the availability of significant compounds with high potential for antifungal properties from O. sanctum. This suggests isolating these compounds for further lead identification to develop new antifungal compounds with specific targets.

Background:: The neuroprotective effect of bioflavonoids has been demonstrated in epileptic disorder. Objective:: The objective of this study was to investigate the anticonvulsant and adjuvant effects of the bioflavonoid and explore behavioural responses of orientin (Ore) on kindled mice induced by pentylenetetrazole [PTZ]. Methods:: Albino Swiss mice weighing 20-30 g were divided into nine groups [n=6]. Prior to the PTZ dose, alternatively, ore [10 mg/kg, i.p.] was given for 7 days, dissolved in 6% w/v carboxymethylcellulose [CMC] salt. On the 7th day, saline was solubilized with Lamotrigine [Lmt], Phenobarbital [Pb], and Gabapentin [Gbp] and administered as separate intraperitoneal [i.p.] injections 30 minutes prior to the PTZ dose. For the development of kindling seizures in mice, PTZ [30 mg/kg, i.p.] was delivered to all the mice for 12 days, alternatively until the animals appeared to develop full motor muscle jerking seizures. Mice who survived from complete motor seizures were selected for further experimentation. Results:: Data showed that anticonvulsive activity was exhibited by the control. Ore [10 mg/kg] with PB [40 mg/kg, i.p.] was administered on the 12th day and showed an increase in transfer delays [ITL and RTL]. Conclusion:: Anti-seizure efficacy of drugs was investigated at the effective dose of ore at 10 mg/kg + PB 40mg/kg in group 7 and was found to have promising therapeutic outcomes and potency in therapeutic strategies and associated concerns.

Abstract: The present study examines the potential effect of Calendula monardii (Boiss. & Reut.) on inhibiting various enzymes involved in many diseases. Background: Calendula suffruticosa subsp. monardii (Boiss. & Reut.) Ohle, a medicinal plant from the Mediterranean region and, more precisely, from the extreme northeast of Algeria, is characterized by its wide use in the traditional medicine of the local population. This is what prompted us to investigate some pharmacological benefits such as anti-diabetes and Alzheimer's activities, in addition to antioxidant activity. The effects of extraction methods and solvents on the amount of phenolic profiles and the biological activity of the different parts of this plant were studied, where the aim was to obtain a high extraction yield of bioactive compounds and consequently high biological activities. Methods: In vitro standard procedures were used to assess enzyme inhibitory activity (AChE, BChE, α- Amylase and α-Glucosidase) of Calendula monadii, and the antioxidant activity was assessed using the DPPH, ABTS, CUPRAC, Reducing power and Ferrous ions assays. Results: When using ultrasound, a significant increase in the amounts of (TPC, TFC and TFlas) and antioxidant activity (DPPH, ABTS, CUPRAC, Reducing power and Ferrous ions cheating assay) in addition to the inhibitory activity of enzymes (AChE, BChE, α-Amylase α-Glucosidase) was found, compared to the results of conventional extraction. Furthermore, the aqueous solvent of ethanol 70% is the very effective solvent for extraction compared to methanol 70% aqueous solvent. Conclusion: Based on these results, it can be said that this plant contains important biological activities, so it can be used in phytotherapy.

Background: The imbalance between free radical formation and antioxidant defence leads to the development of oxidative stress. The search for substances that would mitigate or prevent the effects of oxidative stress remains relevant. Objective: Our goal was to compare the antioxidant and mitigation effects of L-glutamic acid (LGlu) and N-acetylcysteine (NAC) alone or in combination using a battery of biomarkers of oxidative stress such as reduced glutathione (GSH) superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST) and lipid peroxidation, determined as a content of lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS). Histopathological examination of the liver was also performed. Methods: Experimental rats were divided into five experimental groups. Exp.1: was treated with CCl4 only, Exp. 2: was treated with CCl4/L-Glu, Exp. 3: was treated with CCl4/Glu/NAC. Exp. 4: was treated with CCl4/NAC, Control 5: served as the control rats. Results: These findings suggest that the CCl4 leads to oxidative stress by depleting the antioxidant enzyme activities and increasing peroxidation products. The studied biochemical parameters were altered by the introduction of CCl4, which was normalised (to one degree or another) by L-Glu, LGlu/ NAC and NAC treatment. Conclusion: The most remarkable protective effect was observed in groups of rats that were treated with L-Glu only. This conclusion was confirmed by histopathological findings which showed less severe hepatocellular necrosis, fibrosis and inflammation in CCl4/L- Glu and CCl4/L-Glu/NAC treated group, compared to the CCl4 group.