Formulation of hesperidin-loaded in situ gel for ocular drug delivery: a comprehensive study.

BACKGROUND: Allergic conjunctivitis is one of the most common eye disorders. Different drugs are used for its treatment. Hesperidin is an active substance isolated from Citrus sinensis L. (Rutaceae) fruit peels, with known anti-inflammatory activity but low solubility. It was complexed with cyclodextrin and encapsulated in situ gel to extend its duration in the eye. RESULTS: The optimized formulation comprised 1% hesperidin, 1.5% hydroxyethyl cellulose, and 16% poloxamer 407. The viscosity at 25 °C was 492 ± 82 cP, and at 35 °C it was 8875 ± 248 cP, the pH was 7.01 ± 0.03, gelation temperature was 34 ± 1.3 °C, and gelation time was 33 ± 1.2 s. There was a 66% in vitro release in the initial 2 h, with a burst effect. A lipoxygenase (LOX) inhibition test determined that hesperidin was active at high doses on leukotyrens seen in the body in allergic diseases. In cell-culture studies, the hesperidin cyclodextrin complex loaded in situ gel, BRN9-CD (poloxamer 16%, hydroxy ethyl cellulose (HEC) 1.5%), enhanced cell viability in comparison with the hesperidin solution. It was determined that BRN9-CD did not cause any irritation in the ocular tissues in the Draize test. CONCLUSION: The findings of this study demonstrate the potential of the in situ gel formulation of hesperidin in terms of ease of application and residence time on the ocular surface. Due to its notable LOX inhibition activity and positive outcomes in the in vivo Draize test, it appears promising for incorporation into pharmaceutical formulations. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Phytochemical analysis and biological evaluation of Ferulago setifolia K. Koch.

BACKGROUND: Ferulago setifolia K. Koch (Apiaceae) has been the subject of this study, aiming to comprehensively determine its phenolic fingerprint and evaluate its various biological activities. The liquid chromatography-tandem mass spectrometry analysis of the 70% methanol extract of F. setifolia (FS) revealed the presence of 23 phytochemicals, among which chlorogenic acid, quinic acid, kaempferol-3-O-glucoside, and quercetin-3-O-glucoside were identified as the major phenolics in the extract. RESULTS: The biological screening included examinations of antioxidant, antibacterial, antiproliferative, and cytotoxic activities. The FS extract displayed moderate 2,2-diphenyl-1-picrylhydrazyl radical scavenging and ferric-reducing capacity, indicating moderate antioxidant activity. Furthermore, FS exhibited significant antiproliferative effects on cancer cells while showing low cytotoxicity on normal cells. The antibacterial activity findings revealed that FS demonstrated potent activity against Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus, and Escherichia coli. CONCLUSION: The findings of this study suggest that the methanolic extract of FS holds promise as a potential source of biologically active compounds. It can be utilized for the development of pharmaceutical formulations, thanks to its significant antiproliferative and antibacterial activities. Additionally, FS can serve as a valuable source of chlorogenic acid for industrial applications. © 2023 Society of Chemical Industry.

Evaluation of antidiabetic and antioxidant effects of Polygonum cognatum Meisn. and phytochemical analysis of effective extracts.

Polygonum cognatum Meisn. (Polygonaceae) is used both as food and as a folk medicine to treat diabetes. This study aimed to evaluate the effect of the extracts, along with isolated compounds, from P. cognatum aerial parts on diabetes. In vitro studies were conducted using an α-glucosidase inhibitory assay, while in vivo antidiabetic studies were carried out on streptozotocin-induced diabetic rats. Effective extracts were subjected to isolation studies, and structures of the compounds were elucidated by spectroscopic methods. The ethyl acetate and n-butanol extracts had the highest effect in both in vitro and in vivo experiments. They also decreased aspartate transaminase, alanine transaminase and malondialdehyde levels, while increasing glutathione and superoxide dismutase activity in rats. From the active extracts, 11 phenolic compounds were isolated and characterized. Among the isolated compounds, quercetin was found to be the most active according to α-glucosidase inhibitory activity studies. This study provided scientific evidence for the traditional use of P. cognatum as a folk medicine for treating diabetes. The findings suggest that the ethyl acetate and n-butanol extracts, as well as quercetin, have the potential for development as antidiabetic agents.

Antidiabetic and antioxidant properties of Paeonia mascula L.: In vitro and in vivo studies, and phytochemical analysis.

The medicinal plant Paeonia mascula L. is commonly used in Anatolian folk medicine for its antidiabetic properties. This study aimed to investigate the in vitro α-glucosidase enzyme inhibition effect, in vivo antidiabetic, and antioxidant activities of extracts obtained from P. mascula. The in vivo studies were conducted on diabetic rats induced with streptozotocin. The ethyl acetate and n-butanol extracts showed the highest efficacy in both in vitro and in vivo experiments, reducing AST, ALT, and MDA levels while increasing GSH and SOD activities in rats. In total, seven compounds were isolated from both extracts, and their structures were identified using spectroscopic methods such as 1D and 2D NMR and Mass Spectrometry. The in vitro α-glucosidase inhibition assay on purified compounds revealed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucose was the most effective compound. These findings support the traditional use of P. mascula as an antidiabetic agent.

Thermosensitive In situ Gelling System for Dermal Drug Delivery of Rutin.

Objectives: Rutin has been broadly applied for treating several diseases due to its pharmacological activities. However, its low aqueous solubility limits its absorption and bioavailability. This research aims to increase the solubility of rutin using cyclodextrin and to develop a temperature-triggered in situ gelling system for dermal application. Materials and Methods: The solubility of rutin was increased with sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD). Rutin- SBE-ß-CD inclusion complex was prepared by kneading and freeze dying method. Structural characterization was carried out using differential scanning calorimetry and fourier transform infrared spectroscopy. In situ gel formulations were prepared with pluronic F127 (PF127), a thermosensitive polymer, and chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer. In situ gel characteristics such as pH, clarity, gelation temperature, and viscosity were determined. Results: When the solubility diagrams were examined, it was concluded that SBE-ß-CD showed a linear increase, therefore, AL-type diagram was selected. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. Three in situ gels were evaluated for their pH, gelling temperature, and the rheological behaviors, and one formulation was selected. It was observed that the formulations had a pH between 6-6.1, and their gelation temperature decreased with increasing PF127 that was between 20°C to 34°C. For the selected formulation (formulation E3), 0.5% rutin and rutin/SBE-ß-CD were transferred to the in situ gelling system. Because of in vitro release studies, it was observed that the release of the rutin/SBE-ß-CD inclusion complex containing NZ formulation showed a higher burst effect than the others and the release continued for 6 hours. Conclusion: The results indicated that the combination of PF127 and CH can be a hopeful in situ gelling vehicle for dermal delivery of rutin and rutin/SBE-ß-CD.

Isolation and cytotoxic activities of undescribed iridoid and xanthone glycosides from Centaurium erythraea Rafn. (Gentianaceae).

Centaurium erythraea Rafn. (Gentianaceae) is used in internal traditional therapy as an anthelmintic, hypotensive, antipyretic, and antidiabetic. It is used externally for the treatment of wounds. Ursolic acid, maslinic acid, secologanin, secologanin dimethyl acetal, centauroside A, erythraeaxanthone I, erythraeaxanthone II, and demethyleustomin were isolated from aerial parts of Centaurium erythraea and were identified using spectroscopic methods, including NMR and mass spectrometry. The cytotoxic potency of undescribed compounds was evaluated by the XTT assay against human breast cancer MCF-7, MDA-MB-453 and mouse fibroblast 3T3-L1 cell lines. Erythraeaxanthone II was found to have the most potent cytotoxic activity.

Molecular Docking Study of Several Seconder Metabolites from Medicinal Plants as Potential Inhibitors of COVID-19 Main Protease.

Objectives: Coronaviruses (CoVs) cause infections that affect the respiratory tract, liver, central nervous, and the digestive systems in humans and animals. This study focused on the main protease (Mpro) in CoVs (PDB ID: 6LU7) that is used as a potential drug target to combat 2019-CoV. In this study, a total of 35 secondary metabolites from medical plants was selected and docked into the active site of 6LU7 by molecular docking studies to find a potential inhibitory compound that may be used to inhibit Coronavirus Disease-2019 (COVID-19) infection pathway. Materials and Methods: The chemical structures of the ligands were obtained from the Drug Bank (https://www.drugbank.ca/). AutoDockTools (ADT ver. 1.5.6) was used for molecular docking studies. The docking results were evaluated using BIOVIA Discovery Studio Visualizer and PyMOL (ver. 2.3.3, Schrodinger, LLC). Results: Pycnamine, tetrahydrocannabinol, oleuropein, quercetin, primulic acid, kaempferol, dicannabidiol, lobelin, colchicine, piperidine, medicagenic acid, and narcotine is found to be potential inhibitors of the COVID-19 Mpro. Among these compounds, pycnamine, which was evaluated against COVID-19 for the first time, showed a high affinity to the COVID-19 Mpro compared with other seconder metabolites and reference drugs. Conclusion: Our results obtained from docking studies suggest that pycnamine should be examined in vitro to combat 2019-CoV. Moreover, pycnamine might be a promising lead compound for anti-CoV drugs.

Evaluation of anticholinesterase effect of some Epilobium species and quantification of hyperoside by HPLC.

This article presents the evaluation of anticholinesterase effects of aerial parts of Epilobium angustifolium, E. stevenii and E. hirsutum and isolated flavonoids from E. angustifolium, and quantification of the flavonoids by HPLC. Besides, the highest acetylcholinesterase inhibition was seen in the EtOAc sub-extracts of E. angustifolium and E. stevenii (36.51 ± 1.88 and 39.89 ± 3.09%, respectively), whereas EtOAc sub-extract of E. angustifolium had the best butyrylcholinesterase inhibition (62.09 ± 1.98%). Hyperoside showed strong inhibition activity on both enzymes. The active EtOAc sub-extract of E. angustifolium was quantitatively analyzed for their content of hyperoside (quercetin-3-O-ß-D-galactoside) by HPLC. The content of hyperoside in EtOAc sub-extract of E. angustifolium was detected as 3.312%. The anatomical structures of the stem, leaf, sepal, petal, anther, and filament of E. angustifolium were investigated. The anatomical properties given in this study provide a description of E. angustifolium.[Formula: see text].

Simultaneous Determination of Arbutin and Hydroquinone in Different Herbal Slimming Products Using Gas Chromatography-mass Spectrometry.

OBJECTIVES: The aim of our study was to develop a simple, precise, sensitive and specific method for the simultaneous determination of arbutin and hydroquinone in different herbal slimming products using GC-MS. MATERIALS AND METHODS: The methanol and aqueous extracts of nine herbal slimming products in Turkey were evaluated for analysis of arbutin and hydroquinone using GC-MS method. RESULTS: The retention times of arbutin and hydroquinone were found as 11.32 and 5.44 min, respectively. The linear ranges in this method were 5-500 ng/mL for arbutin and hydroquinone, respectively. The intra- and inter-day precisions, expressed as the relative standard deviation, were less than 1.94 and 2.73%, determined from quality control samples for arbutin and hydroquinone, and accuracy was within 1.13 and 2.56% in terms of relative error, respectively. The limit of detection and quantification were 0.555 and 1.665 ng/mL for arbutin, and 0.031 and 0.093 ng/mL for hydroquinone, respectively. CONCLUSION: The developed method can be used for routine quality control analysis of arbutin and hydroquinone in different herbal slimming products.

The α-amylase and α-glucosidase inhibitory activities of the dichloromethane extracts and constituents of Ferulago bracteata roots.

CONTEXT: Ferulago (Apiaceae) species have been used since ancient times for the treatment of intestinal worms, hemorrhoids, and as a tonic, digestive, aphrodisiac, or sedative, as well as in salads or as a spice due to their special odors. OBJECTIVES: This study reports the α-amylase and α-glucosidase inhibitory activities of dichloromethane extract and bioactive compounds isolated from Ferulago bracteata Boiss. & Hausskn. roots. MATERIALS AND METHODS: The isolated compounds obtained from dichloromethane extract of Ferulago bracteata roots through bioassay-guided fractionation and isolation process were evaluated for their in vitro α-amylase and α-glucosidase inhibitory activities at 5000-400 µg/mL concentrations. Compound structures were elucidated by detailed analyses (NMR and MS). RESULTS: A new coumarin, peucedanol-2'-benzoate (1), along with nine known ones, osthole (2), imperatorin (3), bergapten (4), prantschimgin (5), grandivitinol (6), suberosin (7), xanthotoxin (8), felamidin (9), umbelliferone (10), and a sterol mixture consisted of stigmasterol (11), ß-sitosterol (12) was isolated from the roots of F. bracteata. Felamidin and suberosin showed significant α-glucosidase inhibitory activity (IC50 0.42 and 0.89 mg/mL, respectively) when compared to the reference standard acarbose (IC50 4.95 mg/mL). However, none of the tested extracts were found to be active on α-amylase inhibition. DISCUSSION AND CONCLUSIONS: The present study demonstrated that among the compounds isolated from CH2Cl2 fraction of F. bracteata roots, coumarins were determined as the main chemical constituents of this fraction. This is the first report on isolation and characterization of the bioactive compounds from root extracts of F. bracteata and on their α-amylase and α-glucosidase inhibitory activities.