Therapeutic Promises of Bioactive Rosavin: A Comprehensive Review with Mechanistic Insight.

Rosavin is an alkylbenzene diglycoside primarily found in Rhodiola rosea (L.), demonstrating various pharmacological properties in a number of preclinical test systems. This study focuses on evaluating the pharmacological effects of rosavin and the underlying molecular mechanisms based on different preclinical and non-clinical investigations. The findings revealed that rosavin has anti-microbial, antioxidant, and different protective effects, including neuroprotective effects against various neurodegenerative ailments such as mild cognitive disorders, neuropathic pain, depression, and stress, as well as gastroprotective, osteoprotective, pulmoprotective, and hepatoprotective activities. This protective effect of rosavin is due to its capability to diminish inflammation and oxidative stress. The compound also manifested anticancer properties against various cancer via exerting cytotoxicity, apoptotic cell death, arresting the different phases (G0/G1) of the cancerous cell cycle, inhibiting migration, and invading other organs. Rosavin also regulated MAPK/ERK signaling pathways to exert suppressing effect of cancer cell. However, because of its high-water solubility, which lowers its permeability, the phytochemical has low oral bioavailability. The compound's relevant drug likeness was evaluated by the in silico ADME, revealing appropriate drug likeness. We suggest more extensive investigation and clinical studies to determine safety, efficacy, and human dose to establish the compound as a reliable therapeutic agent.

Pharmacological Activities of Plant-Derived Fraxin with Molecular Mechanisms: A Comprehensive Review.

Fruits and vegetables serve not only as sources of nutrition but also as medicinal agents for the treatment of diverse diseases and maladies. These dietary components are significant resources of phytochemicals that demonstrate therapeutic properties against many illnesses. Fraxin is a naturally occurring coumarin glycoside mainly present in various species of Fraxinus genera, having a multitude of therapeutic uses against various diseases and disorders. This study focuses to investigate the pharmacological activities, botanical sources, and biopharmaceutical profile of the phytochemical fraxin based on different preclinical and non-clinical studies to show the scientific evidence and to evaluate the underlying molecular mechanisms of the therapeutic effects against various ailments. For this, data was searched and collected (as of February 15, 2024) in a variety of credible electronic databases, including PubMed/Medline, Scopus, Springer Link, ScienceDirect, Wiley Online, Web of Science, and Google Scholar. The findings demonstrated favorable outcomes in relation to a range of diseases or medical conditions, including inflammation, neurodegenerative disorders such as cerebral ischemia-reperfusion (I/R) and depression, viral infection, as well as diabetic nephropathy. The phytochemical also showed protective effects such as osteoprotective, renoprotective, pulmoprotective, hepatoprotective, and gastroprotective effects due to its antioxidant capacity. Fraxin has a great capability to diminish oxidative stress-related damage in different organs by stimulating the antioxidant enzymes, downregulating nuclear factor kappa B and NLRP3, and triggering the Nrf2/ARE signaling pathways. Fraxin exhibited poor oral bioavailability because of reduced absorption and a wide distribution into tissues of different organs. However, extensive research is required to decipher the biopharmaceutical profiles, and clinical studies are necessary to establish the efficacy of the natural compound as a reliable therapeutic agent.

Anticonvulsant effect of (±) citronellal possibly through the GABAergic and voltage-gated sodium channel receptor interaction pathways: In vivo and in silico studies.

This study aimed to investigate the anticonvulsant effects of citronellal (CIT) and possible underlying mechanisms through an isoniazid (INH)-induced seizure (convulsion) via in vivo and in silico studies. For this, convulsions were induced by the oral administration of INH (300 mg/kg) to the mice. The animals were treated orally with different doses of CIT (50, 100, and 200 mg/kg). Vehicle served as a negative control (NC), while diazepam (DZP) (2 mg/kg) and carbamazepine (CAR) (80 mg/kg) were provided (p.o.) as positive controls (PC). A combination therapy of CIT (middle dose) with DZP and CAR was also given to two separate groups of animals to estimate the synergistic or antagonistic effects. Molecular docking and visualization of ligand-receptor interactions are also estimated through different computational tools. The results of the in vivo study showed that CIT dose-dependently significantly (p < 0.05) exhibited a higher onset of seizures while reducing the frequency and duration of seizures in mice compared to the NC group. Besides these, in combination therapy, CIT significantly antagonized the activity of CAR and DZP, leading to a reduction in the onset of seizures and an increase in their frequency and duration compared to treatment with CAR and DZP alone. Additionally, molecular docking revealed that the CIT exhibited a moderate binding affinity (-5.8 kcal/mol) towards the GABAA receptor and a relative binding affinity (-5.3 kcal/mol) towards the voltage-gated sodium channel receptor by forming several bonds. In conclusion, CIT showed moderate anticonvulsant activity in INH-induced convulsion animals, possibly by enhancing GABAA receptor activity and inhibiting the voltage-gated sodium channel receptor.

Anxiolytic-like Effects by trans-Ferulic Acid Possibly Occur through GABAergic Interaction Pathways.

Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of trans-ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to Swiss albino mice, and various behavioral methods of open field, hole board, swing box, and light-dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABAA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABAA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABAA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent.