Mushrooms can be employed as functional foods or medicines for the prevention and treatment of several chronic diseases, since they are rich sources of bioactive metabolites. Nonetheless, the therapeutic value of Algerian mushrooms remains largely unexplored. To date, there are no published studies concerning the different medicinal properties of endemic Ganoderma lucidum in Algeria. This study aimed to compare the antioxidant potential of an endemic specimen collected in the Lake Tonga Forest of El Kala National Park in Northeast Algeria with findings from other countries. To this end, phenolic and flavonoid contents were determined using three solvents of increasing polarity (chloroform, ethyl acetate, and butanol). The mushroom specimen was identified as G. lucidum based on strong molecular evidence using internal transcribed spacer, large subunit, and small subunit sequences. Our study showed that ethyl acetate extract contained higher total phenolic content (171.1 ± 1.06 μg gallic acid equivalents/mg and 102.5 ± 0.69 μg pyrocatechol equivalents/mg extract) and total flavonoid content (25.48 ± 0.13 μg quercetin equivalents/mg and 40.45 ± 0.83 μg rutin equivalents/mg extract) than the other mushroom extracts (chloroform and butanolic). The ethyl acetate extract also showed good antioxidant activity in DPPH (28.51 ± 0.24 μg/mL), ABTS^·+ (10.06 ± 0.13 μg/mL), galvinoxyl radical (15.46 ± 0.48 μg/mL), reducing power (22.74 ± 0.30 μg/mL), cupric reducing antioxidant capacity (21.36 ± 0.04 μg/mL), and phenanthroline (12.87 ± 0.26 μg/mL) assays. These results suggest that G. lucidum could be used as a source of strong natural antioxidants for the food and pharmaceutical industries.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs commonly used worldwide for their analgesic and antipyretic effects. However, an overdose of NSAIDs can have negative effects on various systems, including the cardiovascular, gastrointestinal, hepatic, renal, and neural systems. The search for new, safer, and more effective anti-inflammatory agents has now become a necessity. The aim of the present study is to identify new natural compounds that act against cyclooxygenase-2 (COX-2), one of the main anti-inflammatory targets, using computational approaches. For this purpose, molecular docking and MM/GBSA binding free energy calculations were utilized to discover new natural inhibitors for COX-2. In addition, several prediction tools, such as SwissADME server, QikProp, and Pro-Tox II, were used in this study to elucidate the pharmacokinetic properties, drug-likeness ability, safety, and the lethal dose (LD₅₀) of the studied compounds. The results of molecular docking have indicated that among all phytochemicals under examination, canniprene, oroxylin A and luteolin show high docking scores and binding affinities toward COX-2 (−10.587, −10.254, and −9.494 Kcal.mol⁻¹, respectively) when compared with the reference inhibitor. Moreover, the top hits demonstrated stability during molecular dynamics simulation and were found to conform to drug-like rules with good bioavailability. Toxicity parameters of the best hits indicate that these compounds could be safe COX-2 inhibitors, but further in vitro and in vivo studies are needed to confirm these findings.

Existing inhibitors of kynurenine-3-monooxygenase (KMO) have side effects and poorly cross the blood-brain barrier. Therefore, the discovery of new molecules targeting KMO isnecessary.This study aims to develop a novel therapeutic drug targeting KMO using computational methods and experimental validation of natural compounds.The results of our study show that the top four compounds, namely, 3′-Hydroxy-alpha-naphthoflavone exhibited the best docking scores with KMO (−10.0 kcal/mol), followed by 3′-Hydroxy-ss-naphthoflavone (−9.9 kcal/mol), genkwanin (−9.2 kcal/mol) and apigenin(-9.1 kcal/mol) respectively. Molecular dynamics was used to assess the stability of the primary target, KMO, and inhibitor complexes. We found stable interactions of 3′-Hydroxy-ss-naphthoflavone and apigenin with KMO up to 100 ns. Further, kinetic measurements showed that 3′-Hydroxy-alpha-naphthoflavone and 3′-Hydroxy-ss-naphthoflavone induce competitive inhibition with a good IC₅₀ activity (15.85 ± 0.98 μM and 18.71 ± 0.78, respectively), while Genkwanin and Apigenin exhibit non-competitive inhibition mechanism (21.61 ± 0.97 μM and 24.14 ± 1.00 μM, respectively).Drug-likeness features and ADME analysis features also showed that the top four compounds could be used as potential candidates to replace the synthetic KMO inhibitor drugs with known side effects and poor brain-blood barrier penetration.

Background/Objectives: Kynurenine aminotransferase II (KAT-II) is a target for treating several diseases characterized by an excess of kynurenic acid (KYNA). Although KAT-II inactivators are available, they often lead to adverse side effects due to their irreversible inhibition mechanism. This study aimed to identify potent and safe inhibitors of KAT-II using computational and in vitro approaches. Methods: Virtual screening, MM/GBSA, and molecular dynamics simulations were conducted to identify the top drug candidates, followed by kinetic measurements and in vitro cytotoxicity evaluation. Results: The study showed that two compounds, herbacetin and (-)-Epicatechin exhibited the best scores. Their Glide docking scores are −8.66 kcal/mol and −8.16 kcal/mol, respectively, and their MM/GBSA binding energies are −50.30 kcal/mol and −51.35 kcal/mol, respectively. These scores are superior to those of the standard inhibitor, PF-04859989, which has docking scores of −7.12 kcal/mol and binding energy of −38.41 kcal/mol. ADMET analysis revealed that the selected compounds have favorable pharmacokinetic parameters, moderate bioavailability, and a safe toxicity profile, which supports their potential use. Further, the kinetic study showed that herbacetin and (-)-Epicatechin are reversible KAT-II inhibitors and exhibit a competitive inhibition mechanism. Their half-maximal inhibitory concentrations (IC50) are 5.98 ± 0.18 µM and 8.76 ± 0.76 µM, respectively. The MTT assay for cell toxicity indicated that the two compounds do not affect HepG2 cell viability at the necessary concentration for KAT-II inhibition. Conclusions: These results suggest that herbacetin and (-)-Epicatechin are suitable for KAT-II inhibition and are promising candidates for further development of KAT-II inhibitors.

Background/Objectives: Essential oils are increasingly recognized for their therapeutic potential, yet Ammoides verticillata essential oil (AVEO) remains relatively unexplored, particularly for its anti-inflammatory and analgesic properties. This study aimed to profile AVEO’s chemical composition and evaluate its antioxidant, anti-inflammatory, and analgesic effects, with a focus on its novel pharmacological actions. Methods: The chemical composition of AVEO was determined using GC-MS analysis, and antioxidant capacity was assessed through in vitro assays. Furthermore, the anti-inflammatory potential was investigated using a carrageenan-induced paw edema model in rats, complemented by the inhibition assays of cyclooxygenase (COX) enzymes. The analgesic effects were evaluated through acetic acid-induced writhing and tail immersion tests. Additionally, a computational study was performed to explore the binding affinity of AVEO’s major constituents to COX-2. Results: GC-MS analysis revealed a rich monoterpene profile dominated by carvacrol (32.51%). It was found that AVEO exhibited significant antioxidant activity. Similarly, in vivo, AVEO showed significant anti-inflammatory effects, achieving a percentage inhibition of 52.23% at 200 mg/kg, comparable to diclofenac, along with potent COX-2 inhibition observed (IC50 = 1.51 ± 0.20, SI = 5.56). Moreover, analgesic tests demonstrated dose-dependent pain relief, in which the dose of 200 mg/kg significantly prolonged tail latency to 14.00 ± 1.45 s and markedly reduced abdominal constriction to 21.17 ± 1.62. Computational analysis further corroborated the high binding affinity of carvacrol and thymol with COX-2 (−7.381 and −6.939 Kcal/mol, respectively). Conclusions: These findings underscore AVEO’s potential as a promising therapeutic agent for managing inflammation and pain.

Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of α-amylase and α-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 µg/g extract) and quinic acid (797.18 µg/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both α-amylase and α-glucosidase (IC₅₀ = 239.30 ± 7.40 and 192.60 ± 15.51 μg/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (−12.935 and −8.073 Kcal/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-α, IL-1β, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM.