Current Bioactive Compounds - Volume 20, Issue 7, 2024

Background: One of the frequent side effects of cancer treatment is chemotherapyinduced alopecia (CIA). The psychological discomfort of hair loss may cause patients to stop receiving chemotherapy, lowering the therapy's effectiveness. Finasteride (FNS), a JAK inhibitor, has shown tremendous promise in therapeutic uses for treating baldness. Still, systemic side effects constrained its broad use in alopecia from oral treatment and a low absorption rate at the target site-PLGA-loaded nanoparticles (NPs) for topical delivery of FNS-to overcome these issues. Methods: The nano-precipitation process was used to make FNS-NPs. The independent variables (stabiliser and polymer) were PLGA (X1), P407 (X2), and sonication time (X3). Based on the point prediction method obtainable by the Box Behnken design software, the best FNS-NPs composition was selected. Entrapment efficiency, particle size, zeta potential, and polydispersity index were used to characterize the nanoparticles. Using Carbopol as a polymer, the ideal FNS-NPs composition was further transformed into a gel formulation. The prepared topical gel formulation (FNS-NPs gel) included gel characterization, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), in vitro and in vivo studies. Results: Optimized FNS-NPs (F13) had particle sizes of 175.26±3.85 nm, 0.241±0.11 PDI, 71.04±1.35 % EE, and -33.27±0.39 surface charges. There is no interaction between the drug and the excipients, according to FTIR studies. The FNS were visible in the X-ray diffractogram enclosed in a polymer matrix. The developed FNS-NPs gel formulation shows ideal drug content, viscosity, pH, and spreadability. According to the release and permeation investigation findings, FNS released slowly (68.73±0.94%) but significantly permeated the membrane more than before. In a dose- and time-dependent manner, the produced nanoparticles considerably (p ≤0.05) increased FNS delivery compared to the FNS solution. The FNS-NPs gel therapy significantly increases the quantity and size of hair follicles dose-dependently. The effectiveness of the 1% FNSNPs gel and the 2% minoxidil solution were comparable. After 72 hours, the FNS-NPs gel showed no signs of skin irritation. The outcomes, therefore, showed that the trans follicular delivery mechanism of the FNS-NPs gel might stimulate hair growth. Conclusion: These findings imply that the innovative formulation that has been developed has several beneficial properties that make it suitable for FNS dermal delivery in the treatment of alopecia areata.

The present review describes the biological essence of pyridazine scaffold. Around 142 biologically potential pyridazine entities are gathered in a pile from documented literature. Some of them are commercially available drugs, few are naturally occurring pyridazine compounds, and a wide variety of compounds containing pyridazine moiety are biologically tested, and some are under clinical trials. Rather than collecting large quantities of data, an attempt is made to compile valuable entities. However, efforts have been made to compile the maximum literature in brief. The main motto of this review is to provide a combination of therapeutically active pyridazine containing compounds for further drug design, discovery, and development to contribute to future medicinal chemistry. Our approach is to bring the most biologically potent pyridazine derivatives to medicinal chemists, biologists, pharmacists, and organic chemists. The present work encompasses the literature from 2000-2022 from different and authentic sources. The work is divided according to the bioactive nature of pyridazine nucleus.

A large class of substances known as polysaccharides have a wide range of advantageous therapeutic and nutritional properties. Polysaccharides found in plants and plant components are extracted for the use in treating a number of diseases. Since ancient times, these polysaccharides have been utilized for human wellness. With no or minimal adverse effects, the polysaccharides that were extracted and refined from the fruits exhibit strong antioxidant, antiinflammatory, immunoregulatory, and hepatoprotective action. These fruit polysaccharides are isolated and purified using numerous chromatographic methods. In this review, the polysaccharide obtained from sources such as Rubus chingii, Mulberry, Glycyrrhiza glabra, Lilium davidii, Flammulina velutipes, Angelica sinesis, and Diospyros kaki have been discussed along with their biological activities including DPPH radical scavenging activity, ABTS free radical scavenging assay, Hydroxyl radical scavenging activity and assay for oxygen free radical absorption capacity (ORAC) listed in various studies.

1, 2, 3-traizole is five-membered heterocyclic compounds having three nitrogen at 1, 2 and 3 positions. 1, 2, 3-triazoles are important five-membered heterocyclic scaffolds due to their widespread biological activities. 1, 2, 3-triazole derivative can be readily obtained in good to excellent yields through click chemistry, 1, 3-dipolar cycloaddition, Metal Catalysed azide-alyne cycloaddition method. 1, 2, 3-triazoles showed various biological activities, such as antiinflammatory, anticonvulsant, antineoplastic, antimicrobial, analgesic, antimalarial, antiviral, antiproliferative, and anticancer activities. The objective of this review is to synthesize pharmacological activity of 1,2,3-triazole derivatives documented in recent literature.

Aims: To investigate the autophagy-inducing and tumoricidal efficacy of Theaflavins on Ehrlich’s Ascites Carcinoma (EAC) cells. Background: The apoptosis-inducing role of Theaflavins against cancer is reported. Autophagy, a cellular mechanism under stress, occurs either as a survival process or Type-II programmed-cell death in the presence/absence of apoptosis. The report of Theaflavins inducing autophagy against cancer is poor. Objective: Here, for the first time, the investigation for the anti-tumor efficacy of Theaflavins via autophagy in EAC was attempted. Methods: EAC-bearing mice were treated orally with Theaflavins (10 mg/kg b.w.) every alternate day with a total of 27 doses. Body weight, tumor volume and survivability were recorded. Tumoricidal and cellular dehydrogenase activity, in vivo and in vitro, were studied using Trypan-blue exclusion and MTT assay respectively. Theaflavins-treated EAC cells were subjected to Monodansylcadaverine- staining. LC3II turnover and LC3I conversion were detected by western blotting. Apoptosis up to 12 h TF-treatment was estimated by AnnexinV binding. Results: This is the first report of Theaflavins inducing autophagy in EAC cells in vivo and in vitro. Oral Theaflavins treatment restricted excessive body-weight increase due to tumors, reduced tumor volume, and increased survivability of tumor-bearing mice. Theaflavins caused EAC cell death (~8% in vitro, ~30% in vivo), significantly reduced metabolic activity, and created conspicuous vacuolization in surviving cells. Resultant vacuoles (in vitro, 6 h) were marked as autophagosomes by Monodansylcadaverine-staining. Autophagy was confirmed by LC3II augmentation. No significant apoptosis was observed up to 12 h TF-treatment in vitro. Conclusion: Theaflavins were efficient inducing autophagy and Type-II PCD in EAC cells. Notably, Theaflavins induced autophagy prior to apoptosis in vitro.