The recent novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV) has caused a large number of deaths around the globe. There is an urgent need to understand this ...new virus and develop prophylactic and therapeutic drugs. Since drug development is an expensive, intense and time-consuming path, timely repurposing of the existing drugs is often explored wherein the research avenues including genomics, bioinformatics, molecular modeling approaches offer valuable strengths. Here, we have examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) (active withanolides of Ashwagandha) and Caffeic Acid Phenethyl Ester (CAPE, bioactive ingredient of propolis) to a highly conserved protein, M
pro
of SARS-CoV-2. We found that Wi-N and CAPE, but not Wi-A, bind to the substrate-binding pocket of SARS-CoV-2 M
pro
with efficacy and binding energies equivalent to an already claimed N3 protease inhibitor. Similar to N3 inhibitor, Wi-N and CAPE were interacting with the highly conserved residues of the proteases of coronaviruses. The binding stability of these molecules was further analyzed using molecular dynamics simulations. The binding free energies calculated using MM/GBSA for N3 inhibitor, CAPE and Wi-N were also comparable. Data presented here predicted that these natural compounds may possess the potential to inhibit the functional activity of SARS-CoV-2 protease (an essential protein for virus survival), and hence (i) may connect to save time and cost required for designing/development, and initial screening for anti-COVID drugs, (ii) may offer some therapeutic value for the management of novel fatal coronavirus disease, (iii) warrants prioritized further validation in the laboratory and clinical tests.
Communicated by Ramaswamy H. Sarma
Exposure to nonbiodegradable cadmium (Cd) causes many health problems including the damage to the nervous system. This study aimed to increase knowledge about its neurotoxic effects and the ...neuroprotective potential of caffeic acid phenethyl ester (CAPE, a polyphenol abundant in honeybee propolis). In mice, CAPE (10 μmol/kg/day body weight) attenuated significantly learning and memory deficits induced by CdCl2 (1.5 mg/kg/day body weight). For the CdCl2-treated mice, CAPE increased crossing number in open field test, decreased the alternation in Y-maze test, and increased the latency time and error number in step down test. CAPE also inhibited CdCl2-initiated Aβ accumulation and activation of pro-inflammatory factors and microglia in the brains. Therefore, CAPE could be a food-derived neuroprotective agent against Cd-induced neurotoxicity and neurodegenerative disorders, through attenuating neuronal apoptosis and neuroinflammation via the AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis.
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•CAPE has protective effect on CdCl2-induced neurotoxicity and neurodegenerative disorders.•CAPE plays a protective role through attenuating neuronal apoptosis and neuroinflammation.•AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis involve in the protection of CAPE.
Dental caries is the most common disease in the human mouth.
is the primary cariogenic bacterium. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. ...The polyphenol-rich extract from propolis inhibits
growth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases (GTF). However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. Caffeic acid phenethyl ester (CAPE) is abundant in the polyphenolic compounds from propolis, and it has many pharmacological effects. In this study, we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria (
,
,
, and
) and its effects on the biofilm-forming and cariogenic abilities of
CAPE shows remarkable antimicrobial activity against cariogenic bacteria. Moreover, CAPE also inhibits the formation of
biofilms and their metabolic activity in mature biofilms. Furthermore, CAPE can inhibit the key virulence factors of
associated with cariogenicity, including acid production, acid tolerance, and the bacterium's ability to produce extracellular polysaccharides (EPS), without affecting bacterial viability at subinhibitory levels. In conclusion, CAPE appears to be a new agent with anticariogenic potential, not only via inhibition of the growth of cariogenic bacteria.
•Caffeic acid phenethyl ester (CAPE) loaded Zinc oxide nanoparticles/Chitosan (ZnONPs/CS) formulation was prepared.•The prostate cancer treatment effectiveness of this formulation was evaluated.•The ...hybrid ZnONPs/CS-CAPE system can kill prostate cancer cells at concentrations as low as 3 μg/mL.•The significant changes are observed in the cellular macromolecules of HCA, LnCaP and PC-3 cancer cells incubated with ZnONPs/CS-CAPE sample.
The synthesis of zinc oxide nanoparticles/chitosan (ZnONPs/CS) formulation loaded with Caffeic acid phenethyl ester (CAPE) was performed to evaluate its prostate cancer treatment efficiency within the scope of this research. It has been hypothesized that a dual active materials delivery system containing ZnO and CAPE loaded Chitosan (CS) nanoparticles has better bioavailability compared to single one against to cancer cells. ZnONPs were synthesized between 45 and 60 nm particle sizes and then they were capped with CS biodegradable polymer prior to load with CAPE bioactive molecule. ZnONPs/CS-CAPE system was characterized by using Fourier Transform Infrared (FTIR) for structural elucidation, Scanning Electron Microscope (SEM) for particle size determination, High Performance Liquid Chromatography (HPLC) system for determination of CAPE amount. 131I CAPE and 131I ZnONPs/CS-CAPE labeled by the Iodogen method with 131I were used in-vitro cell culture experiments. Cell viabilities (%) of CAPE and ZnONPs/CS-CAPE were examined using Cell Counting Kit-8 assay on PC-3 (human adenocarcinoma prostate), LnCaP (human carcinoma prostate), and RWPE-1 (human normal prostate). IC50 values of ZnONPs /CS -CAPE on all cells were found 2-fold lower than neat CAPE. Based on the FTIR data, the most significant spectral changes (lipid, protein, nucleic acids, glycogen) were monitored for the PC-3 and LnCaP cancer cells incubated with ZnONPs/CS-CAPE samples while being exposed to neat CAPE molecules caused small cellular changes when compared to RWPE-1 healthy cell lines.
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Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a ...novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated world-wide, in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use.
Communicated by Ramaswamy H. Sarma
Organophosphate (Op)-containing herbicides continue to be widely used in the world. Although its usage and intoxication are widespread, the studies on organophosphate-induced neurotoxicity and ...treatment protocols are very few in the literature.
This study aimed to investigate any potential effects of caffeic acid phenyl ester with/without intralipid on neurotoxicity produced by acute intoxication of glyphosate isopropylamine in an experimental rat model.
Forty-nine wistar albino rats were randomly allotted into seven experimental groups: I, control; II, intralipid (IL); III, caffeic acid phenyl esther (CAPE); IV, glyphosate isopropylamine (GI); V, GI + IL; VI, GI + CAPE; and VII, GI + IL + CAPE. Total antioxidant and oxidant status levels were gauged, and the oxidative stress index was calculated in the serum samples. On the other hand, the tissues were analyzed with hematoxylin-eosin (HE) staining protocol and counted up by immunohistochemical method. Statistical evaluations were conducted using SPSS 11.5 for Windows (SPSS, Chicago, IL, USA).
Compared to the control, IL, and GI + IL + CAPE groups, the GI group significantly decreased the total antioxidant levels in brain tissues. In a supportive nature, a significant increase in the oxidative site index (OSI) in the GI group compared to other groups. Especially standing out point of these findings is the significant difference between the GI + IL + CAPE and the GI group. Parallelly, histopathological analysis extended severe neurotoxicity in the GI group. Neurotoxic status was reduced significantly in the GI + CAPE + IL group. The histopathologic examinations confirmed biochemical results. The results also revealed that CAPE and IL, probably their antioxidant effects, have a rehabilitative effect on neurotoxicity caused by GI.
Therefore, CAPE and IL may function as potential cleansing and scavenger agents for supportive therapy regarding tissue damage or facilitate the therapeutic effects of the routine treatment of the patient with GI poisoning.
Caffeic acid phenethyl ester (CAPE), an active polyphenolic component of honeybee propolis, has been demonstrated to have many medicinal properties. However, the antitumor effect and mechanism of ...CAPE on laryngeal carcinoma cells have not been examined. In this study, we treated HEp2 cells with various concentration of CAPE, and the results showed that CAPE can reduce the viability of HEp2 cells with IC50 values of 23.8+-0.7μM for 72 h. Meanwhile, CAPE significantly inhibited activation of signal transducer and activator of transcription (Stat)3 in a concentration dependent manner in HEp2 cells and regulated the expression and transcription of Plk1. AG490, a specific Stat3 inhibitor, not only inhibited the activation and expression of Stat3, but also inhibited the expression of PIk1 in HEp2 cells, so Stat3 was probably involved in the regulation of Plk1 in HEp2 cells. In addition, treatment of CAPE leaded to a blockage of cell cycle in S phase in HEp2 cells. Therefore, CAPE inhibited the proliferation of HEp2 Cells probably by regulating Stat3/Plk1 pathway and inducing S phase arrest.
With the increasing clinical application of dental and orthopedic implants, the problem of peri-implant osteolysis has attracted attention. The inflammatory response and osteoclast differentiation ...induced by wear particles play an important role in peri-implant bone loss. However, the treatment of peri-implant osteolysis is still lacking. In the present study, we investigated the effect of caffeic acid phenethyl ester (CAPE) on titanium particles induced bone loss in a mouse model. We found that CAPE significantly suppressed titanium particle-induced bone loss in vivo. CAPE treatment decreased ratio of nuclear factor kappa B receptor activator ligand (RANKL)/osteoprotegerin (OPG) and subsequently reduced osteoclastogenesis in the mouse model. In addition, CAPE downregulated the expression and secretion of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) stimulated by titanium particles in vivo. In summary, we conclude that CAPE prevent the titanium particles-induced bone loss.
•Titanium particles induced osteolysis and secretion of proinflammatory cytokines in vivo.•Caffeic acid phenethyl ester (CAPE) inhibited secretion of IL-6, IL-1β, TNF-α.•CAPE suppressed osteoclastogenesis in a murine calvarial osteolysis model.
Caffeic acid phenethyl ester (CAPE) is a natural compound with anticancer activities but has low water solubility. In this work, sucrose fatty acid ester (SFAE) was used to nanoencapsulate CAPE in ...aqueous propylene glycol (PG) with a temperature-cycle method by heating at 90 °C for 20 min and cooling to 21 °C, followed by additional heating at 90 °C for 5 min and cooling to 21 °C. A higher amount of PG facilitated encapsulation with up to 0.1%w/w CAPE in 1.0% w/w SFAE. Additional 0.3%w/w thymol further improved the CAPE loading capability to 0.15%w/w to form nanoparticles smaller than 100 nm and stable in 30 days at 21 °C. Nanoencapsulation enhanced cytotoxicity of CAPE against colon cancer HCT-116 and breast cancer MCF-7 cells, and thymol additionally enhanced the cytotoxicity of CAPE dispersions. This work provides a new approach to nanoencapsulate CAPE in stable aqueous dispersions with improved cytotoxicity.
•Caffeic acid phenethyl ester (CAPE) was loaded in sucrose fatty acid ester (SFAE) micelles.•Propylene glycol was a co-surfactant to load CAPE in SFAE micelles.•Thymol increased the loading of CAPE in SFAE micelles by functioning as another co-surfactant.•Encapsulated CAPE showed similar antioxidant capacity as free CAPE.•Encapsulated CAPE showed the improved cytotoxicity against cancer cells than free CAPE.
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