Elastase Inhibitory Activity Research Articles

Spectrofluorimetric and Computational Investigation of New Phthalimide Derivatives towards Human Neutrophil Elastase Inhibition and Antiproliferative Activity

Herein, nine phthalimide-based thiazoles (4a-4i) were synthesized and investigated as new human neutrophil elastase (HNE) inhibitors using spectrofluorimetric and computational methods. The most active compounds containing 4-trifluoromethyl (4c), 4-naphthyl (4e) and 2,4,6-trichloro (4h) substituents in the phenyl ring exhibited high HNE inhibitory activity with IC50 values of 12.98-16.62 µM. Additionally, compound 4c exhibited mixed mechanism of action. Computational investigation provided a consistent picture of the ligand-receptor pattern of inter-actions, common for the whole considered group of compounds. Moreover, compounds 4b, 4c, 4d and 4f showed high antiproliferative activity against human cancer cells lines MV4-11, and A549 with IC50 values of 8.21 to 25.57 µM. Additionally, compound 4g showed high activity against MDA-MB-231 and UMUC-3 with IC50 values of 9.66 and 19.81 µM, respectively. Spectrophotometric analysis showed that the most active compound 4c demonstrated high stability under physiological conditions.

Salicornia ramosissima: A New Green Cosmetic Ingredient with Promising Skin Effects.

This study aims to validate a new cosmetic ingredient from Salicornia ramosissima S J. Woods through in vitro and ex vivo assays. The halophyte extracts were obtained by subcritical water extraction (SWE) at different temperatures (110, 120, 140, 160 and 180 °C). The antioxidant/radical scavenging activities and the phenolic profile were screened for all extracts. The optimal extract was assessed in keratinocytes and fibroblasts, while permeation assays were performed in Franz cells. The inhibitory activity of hyaluronidase and elastase was also evaluated. The sample extracted at 180 °C presented the highest phenolic content (1739.28 mg/100 g of dry weight (dw)). Despite not being efficient in the sequestration of ABTS•+, this extract scavenged the DPPH• (IC50 = 824.57 µg/mL). The scavenging capacity of superoxide (O2•-) and hypochlorous acid (HOCl) was also considerable (respectively, IC50 = 158.87 µg/mL and IC50 = 5.80 µg/mL). The cell viability assays confirmed the absence of negative effects on keratinocytes, while the fibroblasts' viability slightly decreased. The ex vivo permeation of rutin, quercetin and syringic acid after 24 h was, respectively, 11, 20 and 11%. Additionally, the extract showed a good elastase and hyaluronidase inhibitory activity. The results obtained support the S. ramosissima bioactivity as a cosmetic ingredient.

In Vitro and In Silico Evaluations of Boswellia carterii Resin Dermocosmetic Activities

Boswellia carterii is a plant species belonging to the Burseraceae family. It grows up in trees or shrubs, and it is known for producing an aromatic resin commonly named frankincense or olibanum. This resin has been used in traditional medicine to treat various conditions such as inflammations, gastrointestinal disorders and traumatic injuries. Virtual screening and molecular docking are two in silico approaches used to predict potential interactions between ligands and the active site of a protein. These approaches are mainly used in natural product chemistry and pharmacology as a screening tool to select plant extracts or fractions for in vitro testing, as well as for the prediction of mechanisms of action. The aim of this research is the in silico and in vitro evaluations of the potential collagenase and elastase inhibitory activities of Boswellia carterii resin organic extracts (viz., methanol, n-hexane and ethyl acetate). The obtained results revealed that methanol and n-hexane exhibited the best collagenase inhibitory activity with values superior to 85%, whereas the methanol and ethyl acetate showed the highest elastase inhibition activity with inhibition values ranging between 40 and 60%. The molecular docking prediction confirmed the experimental results; moreover, the visualization of the ligand–protein interactions showed that the main compounds of the organic extracts may have mechanisms of action similar to the positive controls. Those findings are very promising and open new perspectives for the exploitation of Boswellia carterii resin as active agents for the development of anti-aging cosmeceuticals.

By-Product of the Red Ginseng Manufacturing Process as Potential Material for Use as Cosmetics: Chemical Profiling and in Vitro Antioxidant and Whitening Activities

Red ginseng (RG), which is obtained from heated Panax ginseng and is produced by steaming followed by drying, is a valuable herb in Asian countries. Steamed ginseng dew (SGD) is a by-product produced in processing red ginseng. In the present study, phytochemical profiling of extracts of red ginseng and steamed ginseng dew was carried out using gas chromatography-mass spectrometry (GC-MS) and rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS) analysis. Additionally, antioxidant activities (DPPH, ·OH, and ABTS scavenging ability) and whitening activities (tyrosinase and elastase inhibitory activity) were analyzed. Phytochemical profiling revealed the presence of 66 and 28 compounds that were non-saponin components in chloroform extracts of red ginseng and steamed ginseng dew (RG-CE and SGD-CE), respectively. Meanwhile, there were 20 ginsenosides identified in n-butanol extracts of red ginseng and steamed ginseng dew (RG-NBE and SGD-NBE). By comparing the different polar extracts of red ginseng and steamed ginseng dew, it was found that the ethyl acetate extract of red ginseng (RG-EAE) had the best antioxidant capacity and whitening effect, the water extract of steamed ginseng dew (SGD-WE) had stronger antioxidant capacity, and the SGD-NBE and SGD-CE had a better whitening effect. This study shows that RG and SGD have tremendous potential to be used in the cosmetic industries.

Bioactive Saponins of Primula vulgaris Huds. Promote Wound Healing through Inhibition of Collagenase and Elastase Enzymes: in Vivo, in Vitro and in Silico Evaluations.

Primula vulgaris Huds. leaves and roots were used to treat skin damage and inflammation in Anatolian Folk Medicine. This study aimed to assess the ethnopharmacological use of the plant using in vivo, in vitro, and in silico test models. Linear incision and circular excision wound models were used to determine the in vivo wound-healing potential of the plant extracts and fractions. In vitro assays including hyaluronidase, collagenase, and elastase inhibitory activities were carried out for the active compounds to discover their activity pathways. Structure-based molecular modeling was performed to understand inhibitory mechanisms regarding collagenase and elastase at the molecular level. The butanol fraction of the roots of P. vulgaris showed the highest wound-healing activity. Through activity-guided fractionation and isolation techniques, primulasaponin I (1) and primulasaponin I methyl ester (2) were stated as the major active compounds. These compounds exerted their activities through the inhibition of collagenase and elastase enzymes. Primulasaponin I methyl ester isolated from butanol fraction was found to be the strongest agent, especially with the values of 29.65 % on collagenase and 38.92 % on elastase inhibitory activity assays, as well as molecular docking studies. The present study supports scientific data for the traditional use of P. vulgaris and the wound healing properties of the plant can be referred to secondary metabolites as especially saponins found in the roots.

차나무 부위별 추출물의 미백, 주름 개선과 피부보호 효과

Background: Camellia sinensis is globally cultivated, principally for the leaves which are used as a green tea. Green tea made from C. sinensis leaves contains various physiologically active ingredients and is used for health and beauty purposes; however, most parts of the plant are discarded. In this experiment the physiological activity of each part of the C. sinensis was analyzed to confirm its potential for use as a cosmetic raw material.BR Methods and Results: Leaves, flowers, roots, branches, and seeds were extracted with 70% ethyl alcohol. Experiments were performed to measure, tyrosinase inhibitory activity, elastase inhibitory activity, antibacterial activity, and cell viability upon ultraviolet B (UVB)-induced cell damage. Tyrosinase inhibitory activity was high in leaves, flowers, and roots, and elastase inhibitory activity showed high inhibition rates in roots, leaves, and branches. Antibacterial activity against Propionibacterium acnes was highest in leaves and roots, followed by branches and flowers, with no antibacterial activity found in seeds. In terms of the protective effect from UVB irradiation induced damage, the experimental group treated with the seed extract in HaCaT cells showed a high survival rate. In Detroit cells, an increased survival rate was observed in most of the experimental groups treated with the extracts, particularly those treated with the seed and flower extracts.BR Conclusions: Experiment results suggest various parts of the C. sinensis, could be used as raw materials for cosmetics.

Diapin®: A food supplement with diverse therapeutic potentials

Background and Aims: For many centuries herbs and spices have traditionally been used to treat or manage a variety of diseases. The formulation of food supplements containing single or multiple herbs or spices is now popular. These formulations provide biochemical, pharmacological and medicinal benefits due to their diverse phytochemical constituents. Methods: In the present study, Diapin® – a food supplement containing Olea europaea L. leaves extract, Cinnamomum cassia (L.) J. Presl stem extract, Nigella sativa L. seed oil, Cocos nucifera L. oil and vitamin D3 – dissolved in absolute ethanol was evaluated for α-amylase, α-glucosidase, acetylcholinesterase, elastase, neuraminidase, adenosine deaminase and arginase inhibitory activity. Results: The supplement strongly inhibited neuraminidase (IC50 = 0.272 ± 0.007 mg/mL), while adenosine deaminase, acetylcholinesterase, elastase and arginase were moderately inhibited (with an IC50 of 4.562 ± 0.052, 5.396 ± 0.563, 5.783 ± 0.058 and 6.800 ± 0.067 mg/mL respectively). The less inhibition activity was on α-amylase and α-glucosidase (IC50 = 9.593 ± 0.582 and 14.010 ± 2.280 mg/mL respectively). Conclusion: The pharmacological activities of Diapin® can be attributed to its opulent phytochemical composition. The present findings support the folkloric claim of Diapin® supplement having antidiabetic, anticancer, anti-inflammatory, antimicrobial, anti-ageing, and immune bolstering properties, in addition to the mitigation of Alzheimer’s disease and the alleviation of neurological dysfunction.

Preparation, identification, and molecular docking of novel elastase inhibitory peptide from walnut (Juglans regia L.) meal

This study aimed to isolate bioactive peptides with elastase inhibitory activity from walnut meal via ultrasonic enzymatic hydrolysis. The optimal hydrolysis conditions of walnut meal protein hydrolysates (WMPHs) were obtained by response surface methodology (RSM), while a molecular weight of<3 kDa fraction was analyzed by LC-MS/MS, and 556 peptides were identified. PyRx virtual screening and Autodock Vina molecular docking revealed that the pentapeptide Phe-Phe-Val-Pro-Phe (FFVPF) could interact with elastase primarily through hydrophobic interactions, hydrogen bonds, and π-sulfur bonds, with a binding energy of −5.22 kcal/mol. The verification results of inhibitory activity showed that FFVPF had better elastase inhibitory activity, with IC50 values of 0.469 ± 0.01 mg/mL. Furthermore, FFVPF exhibited specific stability in the gastric environment. These findings suggest that the pentapeptide FFVPF from defatted walnut meal could serve as a potential source of elastase inhibitors in the food, medical, and cosmetics industries.

Process Optimization Based on Biological Effects and Biomarker Contents of Camellia japonica L. for the Development of Anti-Hyperuricemic and Anti-Wrinkle Source

The purpose of this study was to simultaneously develop anti-hyperuricemic and anti-wrinkle source using Camellia japonica leaf (CJ). CJ extract was prepared. Its contents of biomarkers and biological activities were then analyzed. First, we investigated the extraction efficiency. The extraction rate was 10% or less with hot water or 80% ethanol. HPLC analysis revealed that CJ extract contained rutin, hyperoside, isoquercitrin, chlorogenic acid (CGA), gallocatechin gallate (GCG), and phillygenin. As a result of measuring contents of biomarkers in the extract, CGA was detected in 20, 40, and 60% ethanol extracts. GCG showed the highest content in the hot water extract. Hyperoside and isoquercitrin showed the highest contents in the 80% ethanol extract. Philligenin showed an even content of 0.1% or more in all samples except for 40% ethanol extract. Rutin showed the highest content in 80% ethanol extract. Elastase inhibitory abilities of six extracts and PPRM were investigated at a concentration of 0.5 mg/mL. Results revealed that PPRM and 80% ethanol extract showed about 80% and 62% inhibition, respectively. As a result of comparing elastase inhibitory activities of biomarkers, hyperoside, isoquercitrin, and philligenin showed higher activities. Among six extracts, the extract that could be used as an anti-hyperuricemic source was 80% ethanol extract. When xanthine oxidase (XO) inhibitory activities of biomarkers were evaluated, rutin and hyperoside showed excellent activities. In particular, when XO activity was measured by mixing rutin and hyperoside with 80% ethanol extract, the same efficacy as 80% ethanol extract was obtained. It was predicted that 80% ethanol extract could be used simultaneously as an anti-hyperuricemic and anti-wrinkle source. Further studies are needed to determine anti-hyperuricemic activities of rutin and hyeproside in vivo.

Extraction Preparation and Anti-Wrinkle Biomarkers from Ilex x wandoensis C. F. Miller and M. Kim Hybrid nov., a New Plant

Ilex x wandoensis and M. Kim hybrid nov. (IW) is a new variety formed through the natural hybridization of Ilex. cornuta Thunb and Iles. integra Thunb. It was first discovered on Wando Island, Korea. IW has not been studied to date; we investigated the industrial application potential of IW leaf for the first time. We prepared hot water and solvent extracts and tested for biological activity. IW extract was confirmed to have antioxidant and anti-wrinkle effects. The hot water extract had a high antioxidant effect, and the hexane, ethyl acetate, and acetone extracts showed excellent elastase inhibitory activity. The HPLC and GC-MS analyses of β-amyrin and erythrodiol identified them as biomarkers for anti-wrinkle activity. Here, we report for the first time the active ingredients in IW leaf, representing a new plant variety, and suggest that IW extract could be developed as a cosmetic material.

Effect of Different Solvents on the Extraction of Compounds from Different Parts of Undaria pinnatifida (Harvey) Suringar

Asian kelp (Undaria pinnatifida) is a brown alga mainly grown and consumed in East Asian countries such as China, Japan, and Korea. To date, studies on the various biological activities of Asian kelp have been conducted; however, studies focusing on the different parts of Asian kelp and their use for other than food are limited. Therefore, in this study, different parts of Asian kelp, namely, whole U. pinnatifida (UP), U. pinnatifida blade (UPB), U. pinnatifida stipe (UPS), and U. pinnatifida sporophylls (UPSP), were extracted by using different solvents including ethanol, methanol, and hot water. The antioxidant activity, antiaging effect, and phenolic content of the extracts were investigated. The results revealed that the UPB methanolic extract had significantly higher polyphenol and flavonoid contents, with the respective values of 5.61 mg TAN/g and 7.80 mg QUE/g, than the other extracts. The DPPH and ABTS radical scavenging activities and FRAP values were the highest in the 95% ethanolic (IC50 12.73 mg/mL), methanolic (63.83%), and ethanolic (75.75%) extracts of UPB, respectively. Superoxide dismutase, catalase, and ascorbate peroxidase enzymatic activities were also measured, and the results showed that the activities of these enzymes were higher in the UPB methanolic extract than in the other extracts. Similarly, the highest elastase and tyrosinase inhibitory activity was observed in the UPB methanolic extract. The highest phenolic content was found in the hot water extract of UP (4-hydroxybenzoic acid) and the ethanolic extracts of all parts (naringin and naringenin). The phenolic content of the Asian kelp differed depending on the parts and extraction solvents used. Finally, the antioxidant activity of the UPB extract showed a close correlation with the polyphenol and flavonoid contents. The methanol extract of UPB exhibited excellent antioxidant and antiaging activities, indicating its potential use in the development of functional materials using Asian kelp and in other new applications.

Bio-guided Studies of Lotus maritimus Aerial Parts and Investigation of their Antioxidant, Tyrosinase and Elastase Inhibitory Activities

Background: Lotus maritimus L. (Fabaceae) is a perennial herb species with yellow flowers, growing in Europe, Asia, Middle East and Maghreb. Some flavones and flavonols have been identified in their leaves and flowers. Their leaf extract was used as a cellulolytic and antiaging cosmetic ingredient. Objective: The aim of this work was to perform antioxidant, anti-tyrosinase and anti-elastase properties of L. maritimus aerial parts and their chemical profile. Methods: A 13C NMR-based dereplication method combined with a bio-guided purification was used for metabolite identification. Chemical structures were determined by NMR and ESI-MS spectroscopic methods. The antioxidant properties of the fractions and purified compounds were measured using CUPRAC, DPPH and hydroxyl radical scavenging assays. Their inhibitory activities against the fungal tyrosinase and human neutrophil elastase enzymes were also evaluated. Results: EtOAc and n-BF fractions were characterized as the most active parts. Twenty-two compounds were identified from these fractions by using a 13C NMR-based dereplication method. This process was completed by the purification of minor compounds in the n-BuOH fraction. Eight known compounds were isolated, including many mono-glycosylated flavonoids with variable substitutions on the B-ring, allowing structure-activity relationships. Conclusion: Twenty-two compounds, including phenolic acids, flavonoids and glycoside derivatives, were firstly described in L. maritimus. Three quercetin and myricetin-type flavonoids exhibited good antioxidant activities and all flavonoids tested have moderate effects on elastase inhibition.

Comprehensive study of chemical composition and biological activity of Thymus pubescens Boiss. et Kotschy ex Čelak.

The use of Thymus species amongst the public and their importance in the scientific world is increasing day by day. In addition to being consumed as tea and spice, Thymus species are used as folk medicine for respiratory, digestive, skin, circulatory, genital, nervous, visual and urinary diseases. In this study, it was aimed to examine the essential oil and ethanol extract of the root and aerial parts of Thymus pubescens Boiss. et Kotschy ex Celak in the terms of their biological activity and chemical content. The phenolic content of the species was determined by LC-MS/MS, while triterpenoid content, the chemical composition of the essential oil as well as flavour was determined by GC–MS. In addition, their antioxidant and cytotoxic activities, as well as acetyl- (AChE) and butyrylcholinesterase (BChE), urease, tyrosinase, elastase, collagenase, HMG-CoA reductase and angiotensin-converting enzyme (ACE) inhibitory activities were studied. Thymol (53.33%) was determined as the major component in the essential oil, while β-fenchyl alcohol (43.87%) was determined as the major component of the flavour. According to the LC-MS/MS and GC–MS results, it was found that especially the aerial parts of the species have a high amount of rosmarinic acid (3875.76 µg analyte/g extract), quinic acid (2392.55), naringenin (970.39), oleanolic (92785.96) and ursolic (63373.32) acids. The essential oil of T. pubescens species was observed to show high activity in four antioxidant assays, e.g. inhibition of lipid peroxidation, DPPH and ABTS radical scavenging activity as well as CUPRAC, while the ethanol extracts showed moderate antioxidant activity. In enzyme inhibition assays, the aerial parts exerted marked BChE, elastase, and collagenase inhibitory activities (92.43±1.28%, 42.59±0.56, and 48.61±0.39 at 100 µg/mL, respectively). On the other hand, AChE, urease, tyrosinase, HMG-CoA reductase and ACE inhibitory activities of all extracts were from low to moderate levels. In particular, the aerial parts of the species displayed a high cytotoxic effect (vitality%: 6.82±0.01 at 200 µg/mL) in breast cancer (MCF-7) cell line. Due to its remarkable antioxidant capacity, high content of rosmarinic, oleanolic, and ursolic acids and especially BChE, elastase, and collagenase inhibitory activity, T. pubescens has the potential for using in food supplements, food preservatives, cosmetics, and pharmaceutical industries.

Labdanum Resin from Cistus ladanifer L.: A Natural and Sustainable Ingredient for Skin Care Cosmetics with Relevant Cosmeceutical Bioactivities.

Labdanum resin from Cistus ladanifer L. (Cistaceae) is an abundant natural resource in the Iberian Peninsula worth being explored in a sustainable manner. It is already used in the cosmetic industry; mainly by the fragrances/perfumery sector. However, given the highest market share and traditional uses, labdanum resin also has the potential to be used and valued as a cosmetic ingredient for skincare. Aiming to evaluate this potential, labdanum methanolic absolute and fractions purified by column chromatography were characterized by UPLC-DAD-ESI-MS and then evaluated for UV-protection, antioxidant, anti-elastase, anti-inflammatory, and antimicrobial activities. Labdanum absolute represented ~70% of the resin; diterpenoid and flavonoid fractions represented ~75% and 15% of the absolute, respectively. Labdane-type diterpenoids and methylated flavonoids were the main compounds in labdanum absolute and in diterpenoid and flavonoid fractions, respectively. Labdanum absolute showed a spectrophotometric sun protection factor (SPF) near 5, which is mainly due to flavonoids, as the flavonoids’ SPF was 13. Low antioxidant activity was observed, with ABTS radical scavenging being the most significant (0.142 ± 0.017, 0.379 ± 0.039 and 0.010 ± 0.003 mgTE/mgExt, for the absolute and flavonoid and terpene fractions, respectively). Anti-aging and anti-inflammatory activity are reported here for the first time, by the inhibition of elastase activity (22% and 13%, by absolute and flavonoid extract at 1 mg/mL), and by the inhibition of nitric oxide production in LPS-induced RAW 264.7 cells (84% to 98%, at 15 µg/mL extracts, flavonoid fraction the most active), respectively. Antimicrobial activity, against relevant skin and cosmetic product microorganisms, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Escherichia coli, revealed that only S. aureus was susceptible to labdanum absolute (MIC: 1.2 mg/mL) and its fractions (MIC: <0.3 mg/mL). In conclusion, labdanum resin showed potential to be used in sunscreen cosmetics, anti-inflammatory skincare cosmeceuticals or medicines but has low potential as a cosmetic product preservative given the low antioxidant and low-spectrum antimicrobial activities.

Evaluation of the EtOAc Extract of Lemongrass (Cymbopogon citratus) as a Potential Skincare Cosmetic Material for Acne Vulgaris.

This study evaluated the biological properties of lemongrass (Cymbopogon citratus) extracts. The EtOAc extract of lemongrass had DPPH, TEAC, and nitric oxide-scavenging activity assay results of 58.06, 44.14, and 41.08% at the concentration of 50, 10, and 50 μg/ml, respectively. The EtOAc extract had higher elastase and collagenase inhibitory activities than the 80% MeOH, n-hexane, BuOH, and water extracts and comparable whitening activity toward monophenolase or diphenolase. Also, the EtOAc fraction had higher lipase inhibitory and antimicrobial activities against Cutibacterium acnes among extracts which is known to an important contributor to the progression of inflammatory acne vulgaris, and an opportunistic pathogen present in human skin. Total phenolic and flavonoid concentrations in the EtOAc extract were 132.31 mg CAE/g extract and 104.50 mg NE/g extract, respectively. Biologically active compounds in lemongrass extracts were analyzed by LC-MS. This study confirms that lemongrass extracts have potential use as cosmetic skincare ingredients. Thus, lemongrass can be considered a promising natural source of readily available, low-cost extracts rich in antioxidant, skincare, and antimicrobial compounds that might be suitable for replacing synthetic compounds in the cosmeceutical industry.

Bioactive constituents isolated from the Sri Lankan endemic plant Artocarpus nobilis and their potential to use in novel cosmeceuticals

Two novel compounds, dicarbonyl ester (2) and artolankanin A (3) were isolated from the sequential ethyl acetate and ethanol extracts of stem bark of A. nobilis along with the known compounds, artonin E (1) and artobiloxanthone (4) by bioassay-guided fractionation using a combination of normal phase and size exclusion column chromatography. Their structures were elucidated by spectroscopic techniques, including NMR (1H, 13C, APT, 1H–1H COSY, HSQC, and HMBC), Mass, IR, and UV. The isolated compounds were evaluated for DPPH free radical scavenging activity, tyrosinase, elastase, hyaluronidase, and A5-lipoxygenase enzyme inhibitory activities lipopolysaccharide-induced nitric oxide production inhibitory activity in SIM-A9 microglial cells. Artonin E exhibited marked tyrosinase and A5-lipoxygenase enzyme inhibitory activities and NO inhibition activity in LPS-stimulated microglia cells having IC50 values of 60.92 ± 3.45, 56.38 ± 1.05, and 23.94 ± 1.08 µg/mL, respectively. Kinetic studies showed that the tyrosinase inhibitory activity of artonin E is via a noncompetitive inhibition mechanism. Further, artolankanin A and artobiloxanthone exhibited good A5-lipoxygenase enzyme inhibitory activity having IC50 values of 59.48 ± 1.06 and 62.45 ± 2.25 µg/mL, respectively. Insights from molecular docking and molecular dynamics simulations align with these experimental observations and propose plausible mechanisms of inhibition. Collectively these results suggest that these compounds have the potential to be used as depigmenting and anti-inflammatory agents.

Abstract 451: Enrichment Of High Density Lipoprotein-Associated Protease Inhibitor Activity Prevents Atherosclerosis Progression

Background: Atherosclerotic lesions contain inflammatory cells which secrete a variety of proteolytic enzymes that contribute to lesion progression. The relative contributions of specific proteases to lesion progression is not well understood. The serine protease elastase is produced by neutrophils and macrophages in atherosclerotic lesions and may contribute to plaque progression and destabilization. We have reported significant enrichment of protease inhibitor proteins associated with plasma high density lipoprotein (HDL), including the elastase inhibitor alpha-1-antitrypsin, suggesting a potential role for HDL as an endogenous modulator of protease activity. Hypothesis: We hypothesized that protease inhibition is a mechanism for HDL-mediated protection against atherosclerosis that is independent of HDL cholesterol content. Methods and Results: We developed an HDL-targeting protease inhibitor (HTPI) peptide to allow for synthetic enrichment of HDL-associated elastase inhibitor activity. The small (1 kDa) peptide has an HDL-targeting domain, a soluble linker, and an elastase inhibitor motif. Using a fluorescent version, we demonstrated preferential binding to HDL in human plasma ex vivo . When injected into mice, we observed binding to plasma HDL and increased elastase inhibitor activity on HDL isolated from plasma of mice that received HTPI. Injection into mouse models of atherosclerosis resulted in accumulation of HTPI within lesions. To examine the impact of HTPI treatment on established atherosclerosis, Ldlr -/- mice were maintained on Western diet for 12 weeks, then administered vehicle or HTPI (2.5 mg/kg) three times per week for two weeks while remaining on diet. Lesion quantification by en face analysis and aortic root sections demonstrated that HTPI prevented additional lipid deposition in established lesions. The impact of HTPI on lesion morphology and inflammatory features was examined by histology and immunofluorescence staining of aortic root sections. Conclusions: Targeted enrichment of HDL-associated elastase inhibitor activity using a synthetic peptide prevented atherosclerotic lesion progression. These findings support a possible role for the endogenous antiprotease activity of HDL in atheroprotection.

Coriander (Coriandrum sativum L.) essential oil and oil-loaded nano-formulations as an anti-aging potentiality via TGF\u03b2/SMAD pathway

Aging has become a concern for many people, especially women. Given that high-quality anti-aging products are of high cost; it has imperative to search for other economical sources. Essential oils are frequently used in cosmetics products due to a wide range of biological activities as well as their pleasant odor. The current study aimed to investigate the biochemical effect of the cosmetic potential of selected Apiaceous essential oils, traditionally used for skincare, by evaluating their anti-wrinkle activity. It is worth noting that, coriander essential oil showed the highest collagenase, elastase, tyrosinase, and hyaluronidase inhibitory activities compared to other Apiaceous oils (fennel, anise, and cumin). GC–MS proved that coriander essential oil showed a very high level of oxygenated monoterpenes, with linalool (81.29%) as the most abundant constituent. Intriguingly, coriander oil cream and Coriander Essential Oil-loaded Lipid Nanoparticles (CEOLNs) formulations attenuated in vivo UV-induced skin photoaging that was manifested by significantly decreased MDA, COX-2, PGE-2, MMP-1, JNK, and AP-1 levels. Moreover, these pharmaceutical dosage forms significantly increased skin collagen content compared to UV-injured group. Also, coriander essential oil significantly increased TGFβ, TGFβII, and SMAD3 protein expression levels compared to UV-injured group. In conclusion, the pharmaceutical dosage forms of coriander oil possess anti-wrinkle activities that could have an auspicious role in amending extrinsic aging.

Elastase inhibitory activity of quinoline Analogues: Synthesis, kinetic mechanism, cytotoxicity, chemoinformatics and molecular docking studies

Herein, we have synthesized quinoline united various Schiff base derivatives (Q1-Q13) and systematically characterized them using diverse analytical practices such as 1H NMR, 13C NMR, FT-IR and LC-MS respectively. All of the target compounds that have been synthesized were tested for elastase inhibition, and the findings were compared to the standard drug oleanolic acid. Among the entire series, compound Q11 (IC50 = 0.897 ± 0.015 µM) exhibit most promising elastase inhibitory activity than oleanolic acid (Standard) having an IC50 value of 13.426 ± 0.015 µM. Also, the utmost effectivecompound Q11 was used for kinetic mechanism investigation based on in-vitro data, from which it has been concluded that compound Q11 inhibits elastase competitively. Furthermore, utilizing the MTT test approach, the most effective compounds were assessed for cytotoxicity on B16F10 melanoma cells. From the cytotoxicity experiment, the most potent compound did not display any hazardous response against B16F10 melanoma cells despite being treated at high concentrations. Additionally, the molecular docking study was settled to govern the binding interaction pattern among an enzyme and inhibitors.

Anti-Inflammatory, Antiallergic and COVID-19 Main Protease (Mpro) Inhibitory Activities of Butenolides from a Marine-Derived Fungus Aspergillus costaricaensis.

Amid the current COVID‐19 pandemic, the emergence of several variants in a relatively high mutation rate (twice per month) strengthened the importance of finding out a chemical entity that can be potential for developing an effective medicine. In this study, we explored ethyl acetate (EtOAc) extract of a marine‐derived fungus Aspergillus cosatricaensis afforded three butenolide derivatives, butyrolactones I, VI and V (1–3), two naphtho‐γ‐pyrones, TMC‐256 A1 (4) and rubrofusarin B (5) and methyl p‐hydroxyphenyl acetate (6). Structure identification was unambiguously determined based on exhaustive spectral analyses including 1D/2D NMR and mass spectrometry. The isolated compounds (1–6) were assessed for their in vitro anti‐inflammatory, antiallergic, elastase inhibitory activities and in silico SARS‐CoV‐2 main protease (Mpro). Results exhibited that only butenolides (1 and 2) revealed potent activities similar to or more than reference drugs unlike butyrolactone V (3) suggesting them as plausible chemical entities for developing lead molecules.