Therapeutic application of carvacrol: A comprehensive review.

Carvacrol is a major natural constituent and is significantly present as an essential oil in aromatic plants and is well known for its numerous biological activities. Therapeutic properties of carvacrol have been demonstrated as anti-oxidant, anticancer, diabetes prevention, cardioprotective, anti-obesity, hepatoprotective and reproductive role, antiaging, antimicrobial, and immunomodulatory properties. The carvacrol biosynthesis has been mediated through mevalonate pathway. Carvacrol has the anticancer ability against malignant cells via decreasing the expressions of matrix metalloprotease 2 and 9, inducing apoptosis, enhancing the expression of pro-apoptotic proteins, disrupting mitochondrial membrane, suppressing extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signal transduction, and also decreasing the phosphoinositide 3-kinase/protein kinase B. It also decreased the concentrations of alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase, and gamma-glutamyl transpeptidase as well as also restored liver function, insulin level, and plasma glucose level. Carvacrol also has been found to exert antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Coagulase-negative staphylococcus, Salmonella spp., Enterococcus sp. Shigella, and Escherichia coli. The current review article summarizes the health-promoting perspectives of carvacrol through various pathways.

Efficiency of Multiple Extraction Solvents on Antioxidant, Cytotoxic, and Phytotoxic Potential of Taraxacum officinale (L.) Weber ex F.H. Wigg. from Poonch Valley, Azad Kashmir, Pakistan.

Background: Different parts of Taraxacum officinale (L.) were used in traditional medicine in various parts of the world for the treatment of health problems, and they possess significant biological activities. The present study aimed to estimate phytochemical and biological activities of T. officinale using different extraction solvents. Methods: Methanolic, acetone, and n-hexane extracts of selected species were prepared, and ten secondary metabolites were examined using standard protocols. The antioxidant activity was performed using three in vitro methods, namely, DPPH assay, total reducing power (TRP) assay, and total antioxidant capacity (TAC). Toxicological analysis was done using the brine shrimp cytotoxic assay and radish seed phytotoxic assay. Results: The T. officinale methanolic extract showed the highest phenolic (178.27 ± 17.17 mg/GAE/g) and flavonoid (18.50 ± 1.64 mg QE/g) contents. Similarly, the methanolic extract also revealed the highest DPPH activity (32.80 ± 9.66 IC50), reducing potential (0.53 ± 0.02 mg/g), and TAC (19.42 ± 0.97 mg/g) as compared to the acetone and n-hexane extracts. The Pearson correlation analysis confirmed a strong positive correlation (r > 0.9) between total phenolic content (TPC), total flavonoid content (TFC), and all antioxidant assays. Furthermore, a heat map displayed the methanolic extract (red color) as a valuable source of phytochemicals and antioxidant agents. Moreover, the T. officinale methanolic extract also showed the highest (7.12 ppm) cytotoxic potential whereas both methanolic and acetone extracts were revealed as moderate phytotoxic agents when compared with the standard. Conclusion: The T. officinale methanolic extract exhibited comparatively notable phytochemicals that are actively involved in antioxidant activities and possess toxicological properties. This upholds the folkloric use of T. officinale as a possible source to develop natural plant-based drugs. Further investigations to isolate bioactive compounds and elements and on their safety need to be conducted.

Toward the Identification of Natural Antiviral Drug Candidates against Merkel Cell Polyomavirus: Computational Drug Design Approaches.

Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell polyomavirus (MCPyV). Most MCC tumors express MCPyV large T (LT) antigens and play an important role in the growth-promoting activities of oncoproteins. Truncated LT promotes tumorigenicity as well as host cell proliferation by activating the viral replication machinery, and inhibition of this protein in humans drastically lowers cellular growth linked to the corresponding cancer. Our study was designed with the aim of identifying small molecular-like natural antiviral candidates that are able to inhibit the proliferation of malignant tumors, especially those that are aggressive, by blocking the activity of viral LT protein. To identify potential compounds against the target protein, a computational drug design including molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) approaches were applied in this study. Initially, a total of 2190 phytochemicals isolated from 104 medicinal plants were screened using the molecular docking simulation method, resulting in the identification of the top five compounds having the highest binding energy, ranging between -6.5 and -7.6 kcal/mol. The effectiveness and safety of the selected compounds were evaluated based on ADME and toxicity features. A 250 ns MD simulation confirmed the stability of the selected compounds bind to the active site (AS) of the target protein. Additionally, MM-GBSA analysis was used to determine the high values of binding free energy (ΔG bind) of the compounds binding to the target protein. The five compounds identified by computational approaches, Paulownin (CID: 3084131), Actaealactone (CID: 11537736), Epigallocatechin 3-O-cinnamate (CID: 21629801), Cirsilineol (CID: 162464), and Lycoricidine (CID: 73065), can be used in therapy as lead compounds to combat MCPyV-related cancer. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the virus.

Ethnobotanical and Biochemical Study of Berberis lycium Royle Collected from Different Areas of Azad Jammu and Kashmir.

Berberis lycium Royle has a long history of medicinal uses to treat different diseases. It naturally grows on the mountains of Indian subcontinent. Its ethnobotanical and biochemical study from the state of Azad Jammu and Kashmir (AJ&K) was not previously explored. So, the objective of the current study was to explore the ethnobotanical and biochemical properties of the B. lycium Royle population of AJ&K. For this purpose, samples of B. lycium Royle were randomly collected from five districts of Azad Jammu and Kashmir, including thirty-five locations. Demographic features of informants such as plant part used, methods of preparation, modes of administration, conservation status, and ethnomedicinal uses were documented. It was used for treating different diseases such as diabetes, arthritis, joint pain, and stomach ulcer. This plant is very famous for providing medicinal roots, leaves, and fruits which are extensively used in many parts of the world. The biochemical analysis was conducted for total phenolic contents (TPC), chlorophyll contents, and antioxidant activity. The highest level of TPC found was 88.66 ± 1.07 µg/g of gallic acid equivalent phenolic (GAE) from leaves collected from Patikka (Chanjhal), Muzaffarabad District, AJ&K. The highest total chlorophyll contents (3.75 ± 0.53 µg/ml) were found in samples collected from Sathrian, Neelum District. The highest antioxidant activity with lowest IC50 value (33.26 µg/ml) was obtained from the root of sample collected from Bakreyali, Muzaffarabad District, as compared with other districts. The concentration of berberine was found to be 4.76 percent in the root bark of B. lycium Royle, estimated by high-performance liquid chromatography (HPLC). In syrup composition, 0.95 mg/5 ml of berberine was used. Hence, it is concluded that amongst the five districts, the plant parts (stem, fruits, and root) collected from Muzaffarabad District, AJ&K, showed the highest medicinal potential due to its unique climatic conditions.

Development of omega-3 loxoprofen-loaded nanoemulsion to limit the side effect associated with NSAIDs in treatment of tooth pain.

The majority of newly developed drugs need to be incorporated with delivery systems to maximize their effect and minimize side effects. Nanoemulsions (NEs) are one type of delivery system that helps to improve the solubility and dissolution of drugs, attempting to enhance their bioavailability and onset of action. The objective of this investigation was to develop an omega-3 oil-based NE loaded with loxoprofen (LXP) to enhance its dissolution, in vitro release, and mucosal penetration and decrease its mucosal ulcerative effects when applied in an oral treatment. LXP-loaded NEs were formulated with varying levels of omega-3 oil (10-30%), surfactant polyoxyethylene-C21-ethers (laureth-21) (40-60%), and co-surfactant polyethylene glycol-40 hydrogenated castor oil (HCO-40) (30-50%) using an extreme vertices mixture design. The developed NEs were characterized for globule size and drug loading capacity. The optimal formulation was tested for in vitro drug release, ex vivo permeation, and ulcer index value. The developed NE acquired a globule size ranging 71-195 nm and drug loading capacity of 43-87%. Considering the results of the in vitro release study, the optimized NE formulation achieved 2.45-fold and 2-fold increases in drug permeation across tested mucosa compared to a marketed tablet and drug aqueous dispersion, respectively. Moreover, the optimum NE exhibited the best ulcer index in comparison to drug aqueous suspension and different formulations when tested in rats. Overall, this research highlights the capacity of NEs to deliver LXP with enhanced solubility, drug release, and permeation while effectively protecting the application site from side effects of the model drug.

Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization.

BACKGROUND: Fungal keratitis (FK) is a serious pathogenic condition usually associated with significant ocular morbidity. Natamycin (NAT) is the first-line and only medication approved by the Food and Drug Administration for the treatment of FK. However, NAT suffers from poor corneal penetration, which limits its efficacy for treating deep keratitis. PURPOSE: The objective of this work was to prepare NAT solid lipid nanoparticles (NAT-SLNs) to achieve sustained drug release and increased corneal penetration. METHODS: NAT-SLNs were prepared using the emulsification-ultrasonication technique. Box- Behnken experimental design was applied to optimize the effects of independent processing variables (lipid concentration [X1], surfactant concentration [X2], and sonication frequency [X3]) on particle size (R1), zeta potential (ZP; R2), and drug entrapment efficiency (EE%) (R3) as responses. Drug release profile, ex vivo corneal permeation, antifungal susceptibility, and cytotoxicity of the optimized formula were evaluated. RESULTS: The optimized formula had a mean particle size of 42 r.nm (radius in nanometers), ZP of 26 mV, and EE% reached ~85%. NAT-SLNs showed an extended drug release profile of 10 hours, with enhanced corneal permeation in which the apparent permeability coefficient (Papp) and steady-state flux (Jss) reached 11.59×10-2 cm h-1 and 3.94 mol h-1, respectively, in comparison with 7.28×10-2 cm h-1 and 2.48 mol h-1 for the unformulated drug, respectively. Antifungal activity was significantly improved, as indicated by increases in the inhibition zone of 8 and 6 mm against Aspergillus fumigatus ATCC 1022 and a Candida albicans clinical isolate, respectively, and minimum inhibitory concentration values that were decreased 2.5-times against both of these pathogenic strains. NAT-SLNs were found to be non-irritating to corneal tissue. NAT-SLNs had a prolonged drug release rate, that improved corneal penetration, and increased antifungal activity without cytotoxic effects on corneal tissues. CONCLUSION: Thus, NAT-SLNs represent a promising ocular delivery system for treatment of deep corneal keratitis.