Current Drug Therapy - Volume 18, Issue 5, 2023

Secondary metabolites of natural origin exhibit numerous pharmacological activities, like anti-inflammatory and anti-oxidant effects. Lipid peroxidation has been observed to be prevented by terminating free radical chains and chelating redox active metal ions. These properties of the secondary products can also aid in preventing carcinoma. Many traditional and emerging plants are blessed with plenty of unexplored phytometabolites, which contain the probability to carry huge antineoplastic potential. Acetogenins are anticancer compounds that kill tumor cells through a variety and series of developmental methods. They are very powerful apoptosis inducers that can regulate the exclusion of chemotherapy medicines from cancer cells. Chalcone is a pharmacologically active molecule that can be found in both natural and manufactured products. Marine species, which are also examples of naturally derived drug sources, such as algae, sponges, tunicates, and bryozoans, have emerged as important components of choice for the separation of novel anticancer drugs obtained from marine sources. Bacteria of marine origin are the source of new drug discoveries and therapeutic targets, which are being explored to unprecedented heights, and they have proven to be sources of various medicinal agents, such as antibiotics, etc. Numerous secondary metabolites have been isolated from marine fungi that were active biologically, structurally unique, and also therapeutically beneficial. So far, almost 1000 secondary metabolites have been found, the majority of which are exclusive to lichens. This mini-review discusses different aspects related to the natural derivatives obtained from various sources, which play a pivotal role as anti-neoplastic agents.

Background: Fascioliasis is a worldwide parasitic infection caused by a food-borne trematode called Fasciola, and Fasciola infection has been reported in more than 80 countries. Recently, the WHO has presented a roadmap for overlooked diseases from 2021 to 2030, which aims to increase the prevention and control of overlooked different diseases such as Fascioliasis. Methods: Our main objective was to conduct a systematic review aiming to summarize recent knowledge on the antiparasitic compounds against human fascioliasis. A keyword search was performed in PubMed, Web of Science, to gather relevant literature published between the 17th of April 1992 and the 23rd October 2022. A total of 329 records were initially retrieved, with 28 full-text articles retained for the qualitative synthesis. Results: Up to now, various antiparasitic drugs have been used to treat human fascioliasis, the most important of which are: Triclabendazole, Albendazole and Bithionol, Praziquantel, Emetine and Dehydroemetine, Mebendazole in combination with Metronidazole and Nitazoxanide, Chloroquine, Hexylresorcinol. From the past to the present, natural herbal medicines have traditionally been used in most countries to treat various parasitic diseases in humans and animals so that these are known as active anthelmintic phytochemicals such as Artemisinin, Mirazid, Plumbagin, Lycium chinense. Conclusion: Although Triclabendazole is an effective and useful drug of choice for the treatment of human fascioliasis, but due to the gradual resistance of fasciolas to Triclabendazole, further research is needed to find new drugs. Despite many advances in antiparasitic compounds used against human fascioliasis, a number of integrated control measures should be implemented as strong management strategies for fascioliasis.

Background: Skin pigmentation is one of the most serious problems in the adult population of all races. The underlying factors of skin pigmentation are excessive exposure to UV radiation, oxidative stress, and other provocative causes that cause melasma, black spots, and post-inflammatory hyperpigmentation. Hence, treating hyperpigmentation disorders is challenging. Objective: Skin pigmentation occurs as a process of melanin biosynthesis triggered by UV exposure. Tyrosinase, an enzyme that catalyzes the rate-confining step in melanogenesis, if inhibited, can cause skin hypopigmentation. This has evoked an interest in reviewing plant extracts/ phytoconstituents, which can serve the purpose of sun protection and treat hyperpigmentation, ensuring skin glow for a better quality of life. Methods: A literature search on Medline, PubMed, Embase, and Scopus databases was done using various keywords like hyperpigmentation, melasma, skin-lightening agents, and sunscreen. Result: Sun protection products for canopy with photo-aging and skin pigmentation are recommended. Tyrosinase inhibitors are first-line topical medicines available as single or combined topical formulations. Hydroquinone, retinoids, corticosteroids, and kojic acid are clinically proven as exceptionally powerful. However, the adverse effects reported with these small molecules largely impact skin appearance, dermatitis, and exogenous ochronosis. Currently, there is a rising trend towards comfortable, fascinating, and well-endured skin depigmenting agents from natural products that might be utilized by a wide populace. Conclusion: This present study aimed at exploring plant and fruit extracts together with their active ingredients as potential multitargeted anti-hyperpigmentation agents with sunscreen properties, tyrosinase inhibition, and skin whitening effects.

The green synthesis approach using plants for the formation of metal/metal oxide nanoparticles is biologically safe and environment-friendly as compared to various physical and chemical methods. Various phytoconstituents present in the plants, such as phenols, flavonoids, alkaloids, tannins, and proteins, act as potential bioresources for the formation of metal/metal oxide nanoparticles. The most common metals/metal oxides used are silver (Ag), copper (Cu), zinc, iron, and gold. Amongst them, copper is a comparably cheap metal than gold and silver. Copper oxide nanoparticles have diverse applications in various fields of therapeutics. This review provides insights regarding the bio-mediated synthesis of copper/copper oxide nanoparticles, factors affecting the synthesis, their characterization, and the biomedical applications, mainly the antibacterial, antifungal, and anticancer activity. Although many trials and research have already been conducted, indicating the potential for developing copper and copper oxide nanoparticles as a future drug, still, more research is needed focusing on different ways to minimize their toxicity and improve biological efficacy.

Background: The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anticancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and antiapoptotic properties used to prevent and treat some cancers. Objectives: In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined. Methods: In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group in which HCT116 cells were not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT, and GPX was measured by a colorimetric method in HCT116 cells. Results: Different treatments reduced the cell viability and increased apoptotic cells in a timedependent manner, which was significant for beta-lactoglobulin nanocapsules treatment (P <0.05). It means receiving more 5-FU or ATX in the encapsulated form by HCT116 cells. The antioxidant enzyme activity of SOD, CAT, and GPX in HCT116 cells treated with beta-lactoglobulin nanocapsule treatment significantly increased compared to the control group (P <0.001). Moreover, the antioxidant activity of these enzymes in different treatments containing ATX (free or encapsulation) was significantly higher than in other treatments (P <0.05). The most increase in the activity of antioxidant enzymes is recorded in the treatment of nanocapsules containing ATX and 5-FU simultaneously. Conclusion: Increased activity of antioxidant enzymes in addition to the induction of apoptosis in colorectal cancer cells by various treatments of beta-lactoglobulin nanocapsules indicates more effective drug administration in encapsulated form as well as synergistic thera[peutic effects of ATX and 5-FU. Moreover, the main increase in antioxidant enzyme activity may be related to ATX.

Background: Presently, only four drugs have been approved by FDA for Alzheimer’s disease (AD). A drug repurposing approach can be fruitful in searching for promising candidates for AD. Objective: The objective of the work was to evaluate the neuroprotective effect of levetiracetam (LEV) in combination with berberine (BER) in scopolamine-induced cognitive impairment in mice by applying a drug repositioning approach owing to their antioxidant potential. Methods: Cognitive impairment was induced in mice by scopolamine. Morris water maze, elevated plus maze, and Y-maze were used to evaluate behavioral parameters. Assays for acetylcholinesterase (AChE), reduced glutathione (GSH), malondialdehyde (MDA), catalase, nitrite, TNF-α, and brain histopathology were performed. Results: The transfer latency time and percentage of spontaneous alternation were significantly reduced and significant alterations in AChE and MDA levels, GSH concentration, and improvement in nitrite and catalase levels were also evidenced after the treatment of mice with a combination of LEV and BER in comparison to independent drugs, standard and disease control groups. The antioxidant defense was also improved and TNF-α levels were significantly reduced by a combination of LEV and BER. Improvement in neuronal damage by restoration of the cytoarchitecture of the brain was also seen in the histopathological study of the brain of treatment groups. Conclusion: The present study has demonstrated that the combination of LEV and BER has significantly improved cognition in mice by lipid peroxidation inhibition, augmentation of endogenous antioxidant enzymes, the decline in TNF- α levels, and AChE activity in the brain when compared to individual drugs, standard and disease control owing to their strong antioxidant and anti-inflammatory potentials.

Background: Febuxostat is a BCS class-II drug, used in the treatment of gout. However, because of its lower solubility, a higher and more frequent dose of the drug is required in the treatment. Objective: The objective of this research was to develop and evaluate febuxostat-loaded floating beads as a gastro-retentive drug delivery system (GRDDS) to target drug release up to 24hr in order to enhance bioavailability. Methodology: Gastro-retentive floating beads were formulated using the ionotropic gelation method. Screening of lipids was carried out based on the shape and texture of floating beads. Drug-excipient compatibility study was done using DSC analysis. Further optimization of gastro-retentive floating beads of febuxostat was performed by Box-Behnken design using gelucire 43/01, lactose, and soluplus as independent variables and %drug entrapment and %drug release after 24 hr as dependent variables. Evaluation of the optimized batch was performed for in vitro buoyancy, %drug entrapment, %drug release, FTIR, and SEM study. Result and Discussion: In the ANOVA, contour plots, and 3D surface plots, the optimized batch showed 93.95±0.29 % drug entrapment and 88.14±0.58 % drug release after 24 hr with 98%±1% invitro buoyancy. Overlay plots and checkpoint batches were accompanied to confirm the optimization. Polynomial equations proved the positive effect of lipids on drug entrapment and drug release. SEM images explained porous and microstructures on beads. Conclusion: In conclusion, gastro-retentive febuxostat floating beads were successfully developed and characterized for once a daily dose with enhanced bioavailability and reduced cost of therapy.