A mechanistic insight into the anticancer potentials of resveratrol: Current perspectives.

Resveratrol is a widely recognized polyphenolic phytochemical found in various plants and their fruits, such as peanuts, grapes, and berry fruits. It is renowned for its several health advantages. The phytochemical is well known for its anticancer properties, and a substantial amount of clinical evidence has also established its promise as a chemotherapeutic agent. This study focuses on assessing the anticancer properties of resveratrol and gaining insight into the underlying molecular mechanisms. It also evaluates the biopharmaceutical, toxicological characteristics, and clinical utilization of resveratrol to determine its suitability for further development as a reliable anticancer agent. Therefore, the information about preclinical and clinical studies was collected from different electronic databases up-to-date (2018-2023). Findings from this study revealed that resveratrol has potent therapeutic benefits against various cancers involving different molecular mechanisms, such as induction of oxidative stress, cytotoxicity, inhibition of cell migration and invasion, autophagy, arresting of the S phase of the cell cycle, apoptotic, anti-angiogenic, and antiproliferative effects by regulating different molecular pathways including PI3K/AKT, p38/MAPK/ERK, NGFR-AMPK-mTOR, and so on. However, the compound has poor oral bioavailability due to reduced absorption; this limitation is overcome by applying nanotechnology (nanoformulation of resveratrol). Clinical application also showed therapeutic benefits in several types of cancer with no serious adverse effects. We suggest additional extensive studies to further check the efficacy, safety, and long-term hazards. This could involve a larger number of clinical samples to establish the compound as a reliable drug in the treatment of cancer.

Antiemetic activity of abietic acid possibly through the 5HT3 and muscarinic receptors interaction pathways.

The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO4⋅5H2O) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D2, D3, 5HT3, H1, and M1-M5). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (- 10.2 kcal/mol) toward the M4 receptors and an elevated binding affinity toward the receptors 5HT3 (- 8.1 kcal/mol), M1 (- 7.7 kcal/mol), M2 (- 8.7 kcal/mol), and H1 (- 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH3 and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA.

Anti-diarrheal effect of piperine possibly through the interaction with inflammation inducing enzymes: In vivo and in silico studies.

Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.