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Tuberculosis is a highly infectious ailment worldwide. The emergence of multi-drug resistance and serious adverse effects of anti-TB drugs have led to the continuous search of natural candidates. This study aimed to analyse the chemical profile of Vitex pinnata (VP) bark lipophilic extract using GC-MS also evaluating its anti-TB and cytotoxic activities. GC-MS revealed a total of 81 compounds which representing 86% identified compounds. In vitro anti-TB of VP lipophilic extract was evaluated using the Microplate Alamar Blue Assay which exhibited MIC value of 62.5 µg/mL. In vitro cytotoxicity was evaluated using Water Soluble formazan assay recording IC50 > 100 and 200 µg/mL using Vero and A-549 cell lines, respectively. In silico docking study was performed on the major identified compounds, n-nonane showed the most favourable binding affinity (ΔG) equals to −33.34 Kcal/mol. The results obtained herein unravelled the potential use of VP n-hexane extract as a natural anti-TB.

Red and purple grape juices (GJs) have long been consumed worldwide for their unique taste and nutritive value. Moreover, grape is postulated to play an important role in the improvement of cardiovascular risk factors owing to its rich polyphenol content. Little is known regarding GJ’s holistic chemistry and functionality as compared to those of other fruit juices. This review aims to compile the state-of-the art chemistry of colored grape juices and in context to its analysis and nutritional values. Further, a review of potential contaminants to be introduced during manufacturing and other factors that influence juice quality and or health effects are presented to help maximize GJ’s quality. A comparison between analytical methods for juice QC establishment is presented employing hyphenated platforms versus direct spectroscopic techniques. The enrichment of the colored skin with a myriad of phenolics poses it as a functional beverage compared to that of skinless juice. Graphical abstract

Background: Essential oils represent a major class of natural products which are known for their antimicrobial activity. This study aimed to determine the composition of four Piper essential oils by gas chromatography mass spectrometry, attenuated total reflection infrared, and chemometric analysis. Results: Monoterpene was the most predominant class in Piper nigrum and white pepper (87.6 and 80%, respectively) with the dominance of α-pinene, β-pinene, 3-carene, limonene, and β-caryophyllene. Sesquiterpenes represented 50, 19.6, and 12.3% of the essential oils of Piper longum, white pepper, and P. nigrum, respectively. Unlike other species, Piper cubeba oil was found to be rich in aromatics (59%), with eugenol (10.7%) and methyl eugenol (47.4%) representing the major components along with β-myrcene (21.2%) and 1,8-cineole (6.4%). Only P. longum essential oil comprised about 18.2% of alkanes and 13.6% of alkenes. Application of chemometric analysis utilizing GC/MS and ATR-IR data displayed the same segregation pattern where both principal component analysis and hierarchal cluster analysis revealed that white pepper was most closely related to P. nigrum while being completely discriminated from other Piper species. The Piper oils showed promising inhibitory effects on Helicobacter pylori. P. longum oil recorded the most efficient anti-Helicobacter activity [minimum inhibitory concentration (MIC) value of 1.95 μg/ml, which is the same as the MIC of clarithromycin], followed by the oil of white pepper (MIC = 3.90 μg/ml), while P. cubeba and P. nigrum produced the lowest activity (MIC value of 7.81 μg/ml). Conclusion:Piper essential oils can be used as nutritional supplements or therapeutic drugs to protect against H. pylori infection.

Acylated flavonoids are widely distributed natural dietary bioactives with several health attributes. A large diversity of acylated flavonoids with interesting biological potentialities were reported. Of these, 123 compounds with potential antimicrobial, antiparasitic, anti-inflammatory, anti-nociceptive, analgesic and anti-complementary effects were selected from several databases. Based upon these data, the possible mechanistic evidence for their effects were reported. Generally, aromatic acyls i.e., galloyl derivatives appeared to improve efficacy through enhancement of the binding affinities to molecular targets due to plenty of donating and accepting centers. Docking simulations conducted by Molecular Operating Environment (MOE) of acylated flavonoids revealed that compound 12 is at the top of the list into the antibacterial target DNA gyrase subunit B (GyrB), from E. coli, followed by compounds 10, 4 and 23. Compounds 81, 88, 96, 92, 99, 100, 102 and 103 have the strongest binding affinities into Human matrix metallopeptidase (MMP) 2 and 9 catalytic domains. Compound 103 exerted the most balanced predicted dual MMP-2/MMP-9 inhibition action. Compound 95 recorded the strongest binding affinity into metabotropic glutamate receptor (mglur1) with the lowest energy conformer. The data presented in this review suggests that these candidate acylated flavonoids ought to be considered in future drug developments especially as anti-inflammatory and antimicrobial agents.

Diospyros species (DS), "Ebenaceae," were known for their therapeutic uses in folk medicine since days of yore. Thereafter, scientific evidence related their health benefits to a myriad of chemical classes, for instance, naphthoquinones, flavonoids, tannins, coumarins, norbergenin derivatives, sterols, secoiridoids, sesquiterpenes, diterpenoids, triterpenoids, volatile organic compounds (VOCs), and carotenoids. The available literature showed that more than 200 compounds were isolated and identified via spectroscopic techniques. Many pharmacological activities of DS have been previously described, such as antioxidant, neuroprotective, antibacterial, antiviral, antiprotozoal, antifungal, antiinflammatory, analgesic, antipyretic and cosmeceutical, investigated, and confirmed through versatile in vitro and in vivo assays. Previous studies proved that genus Diospyros is a rich reservoir of valuable bioactive compounds. However, further comparative studies among its different species are recommended for more precise natural source-based drug discovery and clinical application. Accordingly, this review is to recall the chemical abundance and diversity among different members of genus Diospyros and their ethnopharmacological and pharmacological uses. PRACTICAL APPLICATIONS: Practically, providing sufficient background on both secondary metabolites divergence and pharmacological properties of genus Diospyros has many fruitful aspects. As demonstrated below, extracts and many isolated compounds have significant curative properties, which can lead to the discovery of pharmaceutically relevant alternative substitutes to conventional medicine. Consequently, molecular docking on various receptors can be applied. On the grounds, Naoxinqing tablets, a standardized herbal product containing D. kaki leaves extract, have been patented and recorded in Chinese Pharmacopeia as an approved Traditional Chinese Medicine (TCM) for the treatment of cerebro- and cardiovascular diseases, although the underlying mechanism remains under advisement. Moreover, the antimicrobial applications of DS are of considerable concern; since the widespread use of antibiotics resulted in different forms of bacterial resistance, hence, limiting and compromising effective treatment. In addition, as a result of contemporary rampant memory disorders, neuroprotective activities of different extracts of DS became of great emphasis.

Noha M Badawi,1 Yasmeen M Attia,2 Dina M El-Kersh,3 Olfat A Hammam,4 Maha KA Khalifa5 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; 2Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; 3Department of Pharmacognosy, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; 4Department of Pathology, Theodor Bilharz Research Institute, Cairo, Egypt; 5Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, EgyptCorrespondence: Noha M Badawi, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, Suez Desert Road, P.O. Box 11562, El Sherouk City, Cairo, Egypt, Email Noha.alaa@bue.edu.egPurpose: To design and optimize trans-cinnamic acid-loaded PLGA nanoparticles (CIN-PLGA-NPs) and assess its inhibitory effect on epithelial-mesenchymal transition (EMT) in triple-negative breast cancer.Methods: The quality by design approach was used to correlate the formulation parameters (PLGA amount and Poloxamer188 concentration) and critical quality attributes (entrapment efficiency percent, particle size and zeta potential). Design of CIN-PLGA-NPs formulations was done based on central composite response surface design and formulated by nanoprecipitation method. In addition, the optimized CIN-PLGA-NPs formulation was further evaluated for morphology using transmission electron microscopy and in vitro dissolution test. The cytotoxicity of CIN-PLGA-NPs optimized formula in comparison to the free trans-cinnamic acid (CIN-Free) was investigated in vitro using MDA-MB-231, triple-negative breast cancer cells, followed by scratch wound assay for evaluating the impact on the migratory potential of MDA-MB-231 cells. In vivo antitumor activity was evaluated using Ehrlich ascites carcinoma solid tumor animal model where tumor volumes were measured at different time points and necrotic/apoptotic indices were estimated in tumor sections. EMT markers, E- and N-cadherin, were assessed in solid tumors as well.Results: The optimized formulation showed entrapment efficiency of 76.98%, particle size of 186.3 nm with a smooth spherical surface and zeta potential of − 28.47 mV indicating its stability. Furthermore, CIN-PLGA-NPs optimized formula released 60.8± 1.89% of the total CIN-Free within 24 hours compared to 29± 1.25% of the raw CIN-Free indicating improved dissolution rate. The optimized formula showed superior cytotoxicity on MDA-MB-231 cells compared to its free counterpart as well as increased wound closure percentage along with reduced tumor size in mice and increased necrotic and apoptotic indices. Tumor levels of E-cadherin and N-cadherin were indicative of EMT inhibition.Conclusion: Our findings proved the capability of PLGA nanoparticles in loading trans-cinnamic acid in addition to enhancing its antitumor efficacy in triple-negative breast cancer possibly via inhibiting EMT.Keywords: trans-cinnamic acid, epithelial-mesenchymal transition, PLGA nanoparticles, quality by design, breast cancer

This study aims to identify the major phytochemical constituents in

Benincasa hispida (Thunb.) Cogn. (Cucurbitaceae) is an annual climbing plant, native to Asia with multiple therapeutic uses in traditional medicine. This updated review is aimed at discussing the ethnopharmacological, phytochemical, pharmacological properties, and molecular mechanisms highlighted in preclinical experimental studies and toxicological safety to evaluate the therapeutic potential of this genus. The literature from PubMed, Google Scholar, Elsevier, Springer, Science Direct, and database was analyzed using the basic keyword “Benincasa hispida.” Other searching strategies, including online resources, books, and journals, were used. The taxonomy of the plant has been made by consulting “The Plant List”. The results showed that B. hispida has been used in traditional medicine to treat neurological diseases, kidney disease, fever, and cough accompanied by thick mucus and to fight intestinal worms. The main bioactive compounds contained in Benincasa hispida have cytotoxic, anti-inflammatory, and anticancer properties. Further safety and efficacy investigations are needed to confirm these beneficial therapeutic effects and also future human clinical studies.

To design and optimizeThe quality by design approach was used to correlate the formulation parameters (PLGA amount and Poloxamer188 concentration) and critical quality attributes (entrapment efficiency percent, particle size and zeta potential). Design of CIN-PLGA-NPs formulations was done based on central composite response surface design and formulated by nanoprecipitation method. In addition, the optimized CIN-PLGA-NPs formulation was further evaluated for morphology using transmission electron microscopy and in vitro dissolution test. The cytotoxicity of CIN-PLGA-NPs optimized formula in comparison to the freeThe optimized formulation showed entrapment efficiency of 76.98%, particle size of 186.3 nm with a smooth spherical surface and zeta potential of -28.47 mV indicating its stability. Furthermore, CIN-PLGA-NPs optimized formula released 60.8±1.89% of the total CIN-Free within 24 hours compared to 29±1.25% of the raw CIN-Free indicating improved dissolution rate. The optimized formula showed superior cytotoxicity on MDA-MB-231 cells compared to its free counterpart as well as increased wound closure percentage along with reduced tumor size in mice and increased necrotic and apoptotic indices. Tumor levels of E-cadherin and N-cadherin were indicative of EMT inhibition.Our findings proved the capability of PLGA nanoparticles in loading

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.

Objectives: The aim of this study is to unravel the variabilities posed by alteration of the extraction technique employed on the contents and composition of essential oils derived from the same plant species Methods: Volatile oils of four different Ocimum species (Ocimum basilicum L., O. africanum Lour., O. americanum L. and O. minimum L. family Lamiaceae) were individually extracted from their fresh aerial parts using green microwave assisted extraction (MAE) method and conventional hydrodistillation (HD) and steam distillation (SD) methods. Extracted volatile oil samples were further analysed by GC-MS. Results: Qualitatively, distillation of the Ocimum samples resulted in higher yields of volatile oil than MAE (0.16-0.42%, 0.16-0.44% and 0.1-0.25% ml/g fresh weight for HD, SD and MAE, respectively). However, MAE technique was accomplished in a fraction of time (8 minutes) compared to distillation procedures (2 - 4 hours). GC-MS analysis of the Ocimum oils extracted using MAE method revealed higher enrichment of marker ingredients, viz. β-linalool and eucalyptol, over the distillation methods. Relative percentage of β-linalool in oil of O. basilicum and O. africanum was 76.9 & 72.2% versus 31.2 & 42.9% and 24.7 & 57.2%, whereas that of eucalyptol was 11.1 & 9.4% versus 6.2 & 4.5% and 4.8 & 4.2%, by MAE, SD and HD, respectively. Estragole, a natural volatile having safety concerns, was detected with appreciable amounts in the oil samples obtained by distillation. MAE extraction resulted in less than third the estragole content in oil of O.basilicum when compared to (HD) and (SD) methods (10.2%, 36.7% and 33.2%, respectively).Conclusions: MAE provides a rapid, power saving and green technique for extraction and preserving the valuable constituents of Ocimum essential oils. (MAE) produced an exceptionally β-linalool and eucalyptol enriched oil of sweet basil, much suitable for commercial and medicinal uses. Estragole contents were much reduced in (MAE) prepared oil samples comparable to distillation methods, a fact that prioritize selecting this technique for preparing Ocimum oils intended for systemic and/or pediatric applications.

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.

Several corona viral infections have created serious threats in the last couple of decades claiming the death of thousands of human beings. Recently, corona viral epidemic raised the issue of developing effective antiviral agents at the earliest to prevent further losses. Natural products have always played a crucial role in drug development process against various diseases, which resulted in screening of such agents to combat emergent mutants of corona virus. This review focuses on those natural compounds that showed promising results against corona viruses. Although inhibition of viral replication is often considered as a general mechanism for antiviral activity of most of the natural products, studies have shown that some natural products can interact with key viral proteins that are associated with virulence. In this context, some of the natural products have antiviral activity in the nanomolar concentration (e.g., lycorine, homoharringtonine, silvestrol, ouabain, tylophorine, and 7-methoxycryptopleurine) and could be leads for further drug development on their own or as a template for drug design. In addition, a good number of natural products with anti-corona virus activity are the major constituents of some common dietary supplements, which can be exploited to improve the immunity of the general population in certain epidemics.

The Aquilaria malaccensis species of the genus Aquilaria is an abundant source of agarwood resin and many bioactive phytochemicals. Recent data regarding the chemical constituents and biological activities of Aquilaria leaves led us to attempt to qualitatively profile the metabolites of Aquilaria malaccensis leaves from a healthy, noninoculated tree through phytochemical screening, GC-MS, and LC/Q-TOF-MS. The present work is also the first to report the antilipoxygenase activity of A. malaccensis leaves from healthy noninoculated tree and investigate its toxicity on oral mucosal cells. A total of 53 compounds were tentatively identified in the extract, some of which have been described in literature as exhibiting anti-inflammatory activity. A number of novel compounds were identified for the first time, including quercetin, quercetin-O-hexoside, kaempferol-O-dirhamnoside, isorhamnetin-O-hexoside, syringetin-O-hexoside, myricetin, tetrahydroxyflavanone, hesperetin, sissotrin, and lupeol. The antilipoxygenase assay was used to determine the lipoxygenase (LOX) inhibitory potential of the extract, while a WST-1 assay was conducted to investigate the effect of the extract on oral epithelial cells (OEC). The extract implied moderate anti-LOX activity with IC50 value of 71.6 &micro, g/mL. Meanwhile, the cell viability of OEC ranged between 92.55% (10 &micro, g/mL)&ndash, 76.06% &plusmn, (100 &micro, g/mL) upon treatment, indicating some potential toxicity risks. The results attained encourage future studies of the isolation of bioactive compounds from Aquilaria malaccensis leaves, as well as further investigation on the anti-inflammatory mechanisms and toxicity associated with their use.

Nigella sativa is a crop grown worldwide for its seeds oil production, nutritive value and health benefits. Despite extensive studies on Nigella seed non-volatile metabolites, much less is known regarding volatiles composition within that genus. To gain insight into Nigella species aroma, 34 volatile constituents from 12 Nigella accessions were profiled using headspace solid-phase microextraction (SPME) coupled to mass spectrometry. Aromatics amounted for the major volatile class among N. sativa accessions at ca. 99.8% with thymoquinone as a major component. Variation in thymoquinone levels were evident among N. sativa accessions and also recognized as potential marker for identifying N. sativa from its closely allied drugs. In contrast, sesquiterpenes dominated N. arvensis, N. damascena, N. nigellastrum and N. orientalis volatile blends. Compared to N. sativa fresh seeds, roasted seeds and fixed oil preparation were both found less enriched in thymoquinone and more dominated by its immediate precursor p-cymene.

Graphical abstract, Ceratonia siliqua is a legume tree of considerable commercial importance for the flavor and sweets industry cultivated mostly for its pods nutritive value and or several health benefits. Despite extensive studies on C. siliqua pod non-volatile metabolites, much less is known regarding volatiles composition which contributes to the flavor of its many food products. To gain insight into C. siliqua aroma, 31 volatile constituents from unroasted and roasted pods were profiled using headspace solid-phase micro extraction (HD-SPME) analyzed via quadruple mass spectrometer followed by multivariate data analyses. Short chain fatty acids amounted for the major volatile class at ca. (71–77%) with caproic acid (20%) and pentanoic acid (15–25%) as major components. Compared to ripe pod, roasted ripe pod was found less enriched in major volatile classes i.e., short chain fatty acids and aldehydes, except for higher pyranone levels. Volatiles mediating for unheated and hot carob fruit aroma is likely to be related to its (E)-cinnamaldehyde and pyranone content, respectively. Such knowledge is expected to be the key for understanding the olfactory and taste properties of C. siliqua and its various commercial food products.

Colorectal cancer (CRC) is the third most common cancer mortality worldwide. Although, 5-Fluorouracil (5-FU)-based chemotherapeutic regimens remain the mainstay for treatment of CRC, intrinsic and acquired resistance to 5-FU is the main reason for treatment failure and relapse. Adjunct or add-on therapy, therefore, should be thought of to enhance responsiveness to 5-FU. Verbascoside (VER) is a phenylethanoid glycoside ingredient present in many Plantago species and was widely used in traditional medicine. VER showed antiproliferative effects in many cancer types including CRC. In the present study, VER in Plantago seeds was identified using UPLC-MS/MS and quantified using newly developed and validated UPLC-DAD followed by investigating its potential sensitization of CRC cells to 5-FU in vitro. The potential impact on PI3K/AKT pathway was also investigated. A synergistic cytotoxic interaction between 5-FU and VER besides G1 cell cycle arrest were detected. Enhanced apoptosis mainly by affecting Bax and Bcl-2 and to a lesser extent Bcl-xL and p53 was also observed. Additionally, 5-FU combined to VER was capable of significantly reducing PI3K and p-AKT/total AKT ratio. Overall, these results suggest a potential role of VER as an adjuvant treatment to decrease the resistance of CRC cells to 5-FU possibly by targeting the PI3K/AKT pathway.

Treatment of breast cancer by paclitaxel (PAX) often encounters therapeutic failure most likely caused by innate/acquired resistance. Cancer stem cells (CSCs) and multidrug resistance complex (MDR-1 or P-glycoprotein) overexpression are main mechanisms implicated in chemoresistance. Increased aldehyde dehrogenase-1 (ALDH-1) was previously correlated with the stemness features of CSCs and hence is used as a marker for identification and CSCs targeting. The present study, therefore, aimed at investigating the effect of both curcumin (CUR) and vitamin D3 (D3) on MDR-1 and ALDH-1 expression and consequently the resistance to PAX both in vitro and in vivo. CUR was isolated from Turmeric rhizomes and identified using UPLC-ESI-MS/MS. For in vitro studies, the antiproliferative effect of PAX, CUR, 1,25(OH)2D3 (the active form of D3, also known as calcitriol) was determined, each alone and combined (PAX+CUR, PAX+1,25(OH)2D3, and PAX+CUR+1,25(OH)2D3) on MCF-7 breast cancer cells. Ehrlich ascites carcinoma solid tumor animal model was also used for in vivo studies. Combining CUR and/or 1,25(OH)2D3 to PAX showed synergistic cytotoxic interaction on MCF-7 cells. The apoptotic potential was also enhanced, as evidenced by a significant increase in caspase-7 and -9 as well as the pro-apoptotic Bax whereas a decrease in Bcl-2 levels was reported. Combining CUR and 1,25(OH)2D3 to PAX caused a downregulation in both MDR-1 and ALDH-1 gene expression in MCF-7 besides a decrease in their protein levels. In vivo, the triple therapy group (PAX+CUR+D3) showed the least tumor size. It also showed the lowest levels of MDR-1 and ALDH-1. PAX alone, however, showed increased levels of MDR-1 and ALDH-1 compared to control. Overall, the present study showed that PAX, as a monotherapy, demonstrated acquired resistance possibly by increasing MDR-1 expression and enriching CSCs population, as evidenced by increased ALDH-1. However, using CUR and D3 enhanced tumor response to PAX.

Ceratonia siliqua (Carob); is a Mediterranean legume globally recognized for its commercial value, being used as a cold beverage, in bakery and confectionary products. It is widely used as a Cocoa substitute not only due to its richness in sugar but rather the absence of caffeine and theobromine stimulant action. Both fruit pulp and seeds are of potential nutritive and medicinal values. The pulp comprises a high sugar content dominantly sucrose as well as polyphenols viz. phenolic acids, flavonoids and tannins. Seeds potential usage is attributed to its locust bean gum (LBG), commercially and pharmaceutically used as gelling and stiffening agent. Carob syrup is a traditional product native to the Mediterranean region, enriched in D-pinitol sugar of anti-diabetic effect. Considering the diversity of carob active constituents’ classes, a myriad of biological effects is recorded to include antioxidant, anticancer, antimicrobial and anti-hyperlipidemic effects. This book chapter presents up to date information on carob usage and chemistry while providing insight on research questions or applications yet to be addressed.

Oromuco-adhesive films for buccal delivery of Propolis extract (PPE) entrapped in niosomes, were prepared to treat oral recurrent aphthous ulcer (RAU). PPE was investigated for antimicrobial compounds. Niosomes composed of span60 and cholesterol were evaluated for particles size, polydispersity index (PDI), zeta-potential, entrapment efficiency and in vitro release. The formed oromuco-adhesive films containing niosomal PPE were evaluated for swelling, mucoadhesion and elasticity. 24 patients suffering from RAU were divided equally into medicated and placebo groups and participated in this study to examine the onset of ulcer size reduction, complete healing and pain relief. Ultra-performance liquid chromatography-high resolution mass spectrometry revealed the presence of pinocembrin, pinobanksin, chrysin and galangin as antimicrobial flavonoids with total content of 158.7 ± 0.15 µg quercetin equivalents and phenolic content of 180.8 ± 0.11 µg gallic acid equivalents/mg. Multilamellar niosomes of 176–333 nm displayed entrapment efficiency of 91 ± 0.48%, PDI of 0.676 and zeta potential of −4.99. In vitro release after 8 h from niosomal dispersion and films were 64.05% and 29.09 ± 0.13% respectively. Clinical results revealed duration of film adherence from 2–4 h in the two groups. The onset of ulcer size reduction in medicated group was attained within second and third day, complete healing was achieved within first 10 days of treatment and pain relief lasted for more than 4–5 h, in contrast to the placebo group. This oromuco-adhesive films which offer controlled and targeting drug delivery can be proposed as a new therapeutic strategy in the treatment of oral recurrent aphthous ulcer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Colorectal cancer (CRC) is the third most common cancer mortality worldwide. Although, 5-Fluorouracil (5-FU)-based chemotherapeutic regimens remain the mainstay for treatment of CRC, intrinsic and acquired resistance to 5-FU is the main reason for treatment failure and relapse. Adjunct or add-on therapy, therefore, should be thought of to enhance responsiveness to 5-FU. Verbascoside (VER) is a phenylethanoid glycoside ingredient present in many Plantago species and was widely used in traditional medicine. VER showed antiproliferative effects in many cancer types including CRC. In the present study, VER in Plantago seeds was identified using UPLC-MS/MS and quantified using newly developed and validated UPLC-DAD followed by investigating its potential sensitization of CRC cells to 5-FU in vitro. The potential impact on PI3K/AKT pathway was also investigated. A synergistic cytotoxic interaction between 5-FU and VER besides G1 cell cycle arrest were detected. Enhanced apoptosis mainly by affecting Bax and Bcl-2 and to a lesser extent Bcl-xL and p53 was also observed. Additionally, 5-FU combined to VER was capable of significantly reducing PI3K and p-AKT/total AKT ratio. Overall, these results suggest a potential role of VER as an adjuvant treatment to decrease the resistance of CRC cells to 5-FU possibly by targeting the PI3K/AKT pathway.

Carob is a legume tree of a considerable commercial importance for the flavor and sweet industry. In this context, it is cultivated mostly for its pods, which are known for their nutritive value and multiple health benefits. However, metabolite patterns, underlying these properties are still mostly uncharacterized. In this study, the role of geographical origin, ontogenetic changes and thermal processing on the Ceratonia siliqua pod metabolome was assessed by mass spectrometry (MS)-based metabolomics. Thereby, a total of 70 fruits primary metabolites, represented mainly by carbohydrates, organic and amino acids were detected. Analysis of secondary bioactive metabolites assessed by ultra-high-performance liquid chromatography-electrospray ionization high resolution mass spectrometry (UHPLC-ESI-HR-MS) revealed in total 83 signals. The major signals, most significantly contributing in discrimination of C. siliqua specimens were assigned to tannins and flavonoids. PCA models derived from either UHPLC-MS or GC-MS proved to be powerful tools for discrimination of C. siliqua specimens.