Shimon Ben-Shabat's research while affiliated with Ben-Gurion University of the Negev and other places

Publications (78)

Article
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Oral medication with activity specifically at the inflamed sites throughout the gastrointestinal tract and limited systemic exposure would be a major advance in our therapeutic approach to inflammatory bowel disease (IBD). For this purpose, we have designed a prodrug by linking active drug moiety to phospholipid (PL), the substrate of phospholipase...
Article
Full-text available
Therapeutics with activity specifically at the inflamed sites throughout the gastrointestinal tract (GIT) would be a major advance in our therapeutic approach to inflammatory bowel disease (IBD). We aimed to develop the prodrug approach that can allow such site-specific drug delivery. Currently, using cyclosporine as a drug of choice in IBD is limi...
Article
Current strategies of combating bacterial infections are limited and involve the use of antibiotics and preservatives. Each of these agents has generally inadequate efficacy and a number of serious adverse effects. Thus, there is an urgent need for new antimicrobial drugs and food preservatives with higher efficacy and lower toxicity. Edible plants...
Article
The aim of this research was to investigate an influence of flow velocity on the main parameters (retention time, tailing factor, relative area and number of theoretical plates) of peaks belonging to volatile compounds in the GC- Flame ionization detector analysis. Our results showed that as the flow increases, the retention time declines significa...
Article
We have developed an ethyl cellulose-based nanoparticulate system for encapsulation of sparingly soluble active pharmaceutical ingredients. Cannabidiol (CBD) and curcumin (CUR) were selected as model active ingredients. Using the nanoprecipitation method, nanoparticles ranged between 150­250nm were obtained with an entrapment efficiency of >80%. It...
Article
A new curcuminoid, quinone methide cyclopentadione (QMC), was synthesized by oxidation of curcumin (CUR) in the presence of potassium ferricyanide, and further isolated and analyzed. QMC was found to be a relatively water-soluble curcuminoid, and more stable than CUR in citric-phosphate buffer solutions. Unlike CUR, QMC possesses a pH-independent s...
Article
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Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimi...
Poster
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Purpose: To date, drug delivery strategies in inflammatory bowel disease (IBD) target a general intestinal region (i.e. colon) regardless of where the inflammation is located. An orally delivered compound with activity specifically at inflamed sites in the gastrointestinal tract (GIT) and limited systemic absorption would be a major advance in the...
Article
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Lilium candidum L., known as Madonna, meadow, or white lily, is a bulbous plant from the Liliaceae family, originating in the Middle East. L. candidum has been abundantly used in folk medicine since ancient times to relieve a variety of ailments, including age-related diseases, burns, ulcers, and coughs. The aim of this article is to investigate th...
Article
Novel phospholipid (PL)‐cyclosporine conjugates, were prepared and studied as potential prodrugs for IBD. Our approach relies on Phospholipase A 2 (PLA 2 ), which is overexpressed in the inflamed intestinal tissues, as the prodrug‐activator to potentially release cyclosporine at the site of inflammation. PL‐cyclosporine prodrug conjugates with vary...
Article
Full-text available
Prodrugs are designed to improve pharmaceutical/biopharmaceutical characteristics, pharmacokinetic/pharmacodynamic properties, site-specificity, and more. A crucial step in successful prodrug is its activation, which releases the active parent drug, exerting a therapeutic effect. Prodrug activation can be based on oxidation/reduction processes, or...
Chapter
The lipidic prodrug approach that resulted in lymphatic transport includes a number of drugs; some examples are testosterone, L-dopa, and bexaroten. Special liker design and drug delivery system can significantly improve drug delivery; lipid-based conjugates and drug delivery systems can form hydrophobic interactions, stabilizing the drug loading a...
Article
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The aim of this work is to analyze relevant endogenous lipid processing pathways, in the context of the impact that lipids have on drug absorption, their therapeutic use, and utilization in drug delivery. Lipids may serve as biomarkers of some diseases, but they can also provide endogenous therapeutic effects for certain pathological conditions. Cu...
Article
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Phlomis viscosa Poiret is an evergreen shrub growing in Israel, Turkey, Lebanon, and Syria with acknowledged pro-wound healing (WH) properties. In this study, we evaluated the pro-WH potential of selected compounds found in this plant. Among the pro-WH compounds (identified by us) was a combination of three chemicals-diosmin, 1-octen-3-ol, and hima...
Article
Viral infections affect three to five million patients annually. While commonly used antivirals often show limited efficacy and serious adverse effects, herbal extracts have been in use for medicinal purposes since ancient times and are known for their antiviral properties and more tolerable side effects. Thus, naturally based pharmacotherapy may b...
Article
Nowadays, prodrugs are no longer used as a last resort, rather, they are intentionally designed at the early stages of drug development. Lipidic prodrug strategy, where a drug moiety is covalently bound to a lipid carrier, was initially proposed half a century ago, yet, this approach still remains to be explored. Lipidic prodrugs can join physiolog...
Article
Full-text available
The lipidic prodrug approach is an emerging field for improving a number of biopharmaceutical and drug delivery aspects. Owing to their structure and nature, phospholipid (PL)-based prodrugs may join endogenous lipid processing pathways, and hence significantly improve the pharmacokinetics and/or bioavailability of the drug. Additional advantages o...
Article
Full-text available
In ulcerative colitis (UC), the inflammation is localized in the colon, and one of the successful strategies for colon-targeting drug delivery is the prodrug approach. In this work, we present a novel phospholipid (PL)-based prodrug approach, as a tool for colonic drug targeting in UC. We aim to use the phospholipase A2 (PLA2), an enzyme that is ov...
Article
In the past, a prodrug design was used as a last option to improve bioavailability through controlling transport, distribution, metabolism, or other mechanisms. Prodrugs are currently used even in early stages of drug development, and a significant percentage of all drugs in the market are prodrugs. The focus of this article is lipidic prodrugs, a...
Article
Full-text available
Nowadays, the prodrug approach is used already at the early stages of drug development. Lipidic prodrug approach is a growing field for improving a number of drug properties/delivery/therapy aspects, and can offer solutions for various unmet needs. This approach includes drug moiety bound to the lipid carrier, which can be triglyceride, fatty acids...
Article
Crude ethanolic extracts from Phlomis viscosa Poiret leaves from the Judea region (Israel) are renowned for their remarkable geroprotective properties: anti-inflammatory, anti-diabetic, and anti-cancer. A phytochemical investigation carried out in this study revealed that the tested plant might belong to a particular distinct chemotype because its...
Poster
Full-text available
Purpose: Current therapies of inflammatory bowel diseases (IBD) target a particular segment in the gastrointestinal tract regardless of where the inflammation is actually localized. We propose a novel prodrug approach that may address this issue by using phospholipase A2 (PLA2), an enzyme that hydrolyses the sn-2 position of phospholipids (PL) and...
Article
Full-text available
Targeting drugs to the inflamed intestinal tissue(s) represents a major advancement in the treatment of inflammatory bowel disease (IBD). In this work we present a powerful in-silico modeling approach to guide the molecular design of novel prodrugs targeting the enzyme PLA2, which is overexpressed in the inflamed tissues of IBD patients. The prodru...
Article
The enzyme phospholipase A2 (PLA2) is overexpressed in the inflamed intestine in inflammatory bowel disease (IBD) patients, and in this work we aimed to exploit PLA2 as a prodrug-activating enzyme for a novel PL-drug conjugate, thereby liberating the free drug specifically in the targeted diseased tissue(s). The proposed prodrug contains a drug moi...
Article
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Our “diabetogenic diet” composition [1] was indeed based on the one described by Funda et al. [2] with regards to dietary requirements.[...]
Article
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Nutrition, especially wheat consumption, is a major factor involved in the onset of type 1 diabetes (T1D) and other autoimmune diseases such as celiac. While modern wheat cultivars possess similar gliadin proteins associated with the onset of celiac disease and T1D, alternative dietary wheat sources from Israeli landraces and native ancestral speci...
Article
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The ectendomycorrhizal fungus Terfezia boudieri is known to secrete auxin. While some of the effects of fungal auxin on the plant root system have been described, a comprehensive understanding is still lacking. A dual culture system to study pre mycorrhizal signal exchange revealed previously unrecognized root-fungus interaction mediated by the fun...
Article
In inflammatory bowel disease (IBD) patients, the enzyme phospholipase A2 (PLA2) is overexpressed in the inflamed intestinal tissue, and hence may be exploited as a prodrug-activating enzyme allowing drug targeting to the site(s) of gut inflammation. The purpose of this work was to develop powerful modern computational approaches, to allow optimize...
Article
Full-text available
The traditional preparation process of Nigella sativa (NS) oil starts with roasting of the seeds, an allegedly unnecessary step that was never skipped. The aims of this study were to investigate the role and boundaries of thermal processing of NS seeds in the preparation of therapeutic extracts and to elucidate the underlying mechanism. NS extracts...
Article
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The present study was aimed at investigating the anti-cancer properties of the unique chemotype of Varthemia iphionoides (V. iphionoides) growing in the Judaea region (Israel). Specifically, we determined the effects of the crude ethanolic extract of V. iphionoides on the growth and viability of human cancer cell lines (SKOV3 ovarian carcinoma cell...
Article
In the United States alone chronic wounds affect 6.5 million patients. It is expected that the number of chronic wounds will increase worldwide due to the increase in age-related conditions and pathologies such as diabetes, obesity, and cardiovascular diseases. An estimated excess of US$25 billion is spent annually on treatment of chronic wounds, a...
Article
Full-text available
The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodru...
Chapter
Khat (Catha edulis Forsk., Celastraceae) is a flowering perennial shrub with a long history of use and cultivation in East Africa and the Arabian Peninsula. Young khat leaves are traditionally chewed in social gatherings to attain special states of mind, aimed especially at awakeness and enhanced mind focus. Since khat chewing contains amphetamine-...
Article
Calcitriol, the hormonally active form of vitamin D, is well known for its diverse pharmacological activities, including modulation of cell growth, neuromuscular and immune function and reduction of inflammation. Calcitriol and its analogs exert potent effects on cellular differentiation and proliferation, regulate apoptosis and produce immunomodul...
Chapter
Viral infection is an important health problem worldwide due to the rapid development of resistant mutants against current therapeutic agents. There are only a few antiviral drugs available for the treatment of viral diseases and they have generally inadequate efficacy and a number of serious adverse effects. Medicinal plants may be an alternative...
Article
Introduction: Inflammatory bowel disease (IBD) is an exceptional scenario with regard to drug targeting, as oral administration has the potential to deliver the drug directly to the site(s) of action. Consequently, retention of the drug within the intestinal lumen and tissue, rather than systemic absorption, is frequently desirable. Areas covered...
Article
The aim of this work was to investigate new pro-vitamins based on α-tocopherol (α-Toc) and fatty acids, and to compare their properties with those of α-tocopherol acetate (α-TAc). Skin levels of α-Toc-fatty acid ester conjugates, total α-Toc and endogenous α-Toc were measured in skin samples taken from separate groups of treated and untreated rats....
Article
Medicinal plants from the Mediterranean region have been used in medicine since ancient times and are well known for their successful therapeutic activity. Many glycosides isolated from these plants showed various medicinal properties. The purpose of this review is to provide the verified data on the anti-viral, anti-microbial, anti-cancer, anti-in...
Article
Ephedrine and pseudoephedrine are phenylpropylamino alkaloids widely used in modern medicine. Some Ephedra species such as E. sinica Stapf (Ephedraceae), a widely used Chinese medicinal plant (Chinese name: Ma Huang), accumulate ephedrine alkaloids as active constituents. Other Ephedra species, such as E. foeminea Forssk. (syn. E. campylopoda C.A....
Article
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One of the most innovative approaches to the treatment of cancer entails the use of 1α,25-dihydroxyvitamin D(3) (calcitriol) analogs to inhibit cancer cell growth. We demonstrate here that BGP-13, a new calcipotriene-based 1α,25-dihydroxyvitamin D(3) analog that we synthesized in our laboratory, inhibits the growth of prostate cancer (LNCaP), breas...
Article
Khat (Catha edulis Forsk.) is a perennial shrub whose young leaves are chewed for their psychostimulating and anorectic properties. The main active principles of khat are believed to be the phenylpropylamino alkaloids, primarily (-)-cathinone [(S)-α-aminopropiophenone], (+)-cathine [(1S)(2S)-norpseudoephedrine], and (-)-norephedrine [(1R)(2S)-norep...
Article
Crude ethanol extracts from Ficus benjamina leaves strongly inhibit Herpes Simplex Virus 1 and 2 (HSV-1/2) as well as Varicella Zoster Virus (VZV) cell infection in vitro. Bioassay-guided fractionation of the crude extract demonstrated that the most efficient inhibition of HSV-1 and HSV-2 was obtained with the flavonoid fraction. The present study...
Article
Saponins are well known as plant stress-induced protective agents. Saponin compounds are also considered responsible for numerous pharmacological properties including anticarcinogenic activity. This paper evaluates the antiproliferative activity and mode of action of spirostane (SAP-1016 and SAP-884) and furostane (KE-1046 and KE-1064) saponins we...
Article
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The antiviral activity of Callissia fragrans and Simnondsia chinensis aquatic and ethanol leaf extracts, as well as purified fractions from these extracts was studied against herpetic viruses in vitro. Ethanol extract of C. fragrans effectively inhibited the infection of Vero cells by HSV-1, HSV-2 in vitro, while its aquatic extract inhibited only...
Article
Ephedra sinica Stapf (Ephedraceae) is a widely used Chinese medicinal plant (Chinese name: Ma Huang). The main active constituents of E. sinica are the unique and taxonomically restricted adrenergic agonists phenylpropylamino alkaloids, also known as ephedrine alkaloids: (1R,2S)-norephedrine (1S,2S)-norpseudoephedrine, (1R,2S)-ephedrine, (1S,2S)-ps...
Article
A series of new biodegradable copolymers and copolyanhydrides built of trimers of fumaric and succinic acid and propylene glycol, covering a wide range of compositions, were prepared and characterized for use as drug carriers. The polymers were found to degrade within a period of weeks. Polyanhydrides loaded with ibuprofen as a model drug released...
Article
The role of vitamin D3 in cancer prevention and its potential as an anticancer therapeutic agent have been researched and are well established. However, the clinical use of the natural vitamin D3 metabolite, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3 or calcitriol] is limited by a possible cause of hypercalcemia and hypercalciuria. A new 24-chloro...
Article
The antiviral activity of plant ethanol extracts against Herpes Simplex Virus-1 and -2 (HSV-1 and HSV-2) and Varicella-Zoster Virus (VZV) was investigated in vitro. Ficus binjamina, resistant to plant viruses, and Lilium candidum, which has a high susceptibility to plant viruses were used. Leaf extracts of F. binjamina inhibited all studied viruses...
Article
Chronic inflammation and oxidative stress have been implicated in the pathogenesis of neurodegenerative diseases. A growing body of research focuses on the role of microglia, the primary immune cells in the brain, in modulating brain inflammation and oxidative stress. One of the most abundant antioxidants in the brain, particularly in glia, is the...
Article
The aim of the present study was to evaluate the antiviral activity of ethanol extracts from Ficus binjamina and Lilium candidum in vitro. Ficus binjamina is known to be resistant to various plant viruses, while Lilium candidum has a high susceptibility to plant viruses [1]. Vero cells and Herpes Simplex Virus -1 and 2 (HSV-1, HSV-2) and Varicella-...
Chapter
The endocannabinoid system (ECS) including its receptors, endogenous ligands ("endocannabinoids"), synthesizing and degradating enzymes, and transporter molecules has been detected from the earliest embryonal stages and throughout pre- and postnatal development; endocannabinoids, notably 2-arachidonoylglycerol, are also present in maternal milk. Du...
Article
Fatty acids (FA) are well known as efficient enhancers for transdermal delivery of drugs; however, their frequent dermal toxicity limits their regular use. In order to utilize the fatty acid as a safe enhancer devoid of its irritant effect, we have synthesized and evaluated a series of fatty acids conjugated to propylene glycol (FA-PG). Each one of...
Article
Antidepressant pharmacotherapy has dramatically improved the quality of life for many patients. However, prolonged use may induce weight gain, resulting in enhanced risk for treatment noncompliance. Cannabinoid CB(1) receptor antagonists decrease food intake and body weight, but may also affect mood. We investigated in female Sabra mice first, whet...
Article
Diblock and multiblock copolymers composed of a poly(D,L-lactide) (PLA) or poly(trimethylene carbonate) (PTMC) core with a hydrophilic chain of poly(ethylene glycol) (PEG) were prepared. These copolymers, in which the core is connected to PEG through a polyfunctional molecule such as citric, mucic, or tartaric acid, may be used to form nanoparticle...
Article
We have reviewed the effects of two endogenous cannabinoid constituents, anandamide and 2-Ara-G1, and of two synthetic cannabinoids, HU-211 and HU- 210. Anandamide partly parallels THC in most CNS activities; the lack of published data prevents comparison of 2-Ara-G1 with THC. Anandamide probably serves as a mediator in motor functions, in memory a...
Article
Full-text available
Cannabidiol (CBD) and cannabidiol dimethyl hephtyl (CBD-DMH) were hydrogenated to give four different epimers. The new derivatives were evaluated for their ability to modulate the production of reactive oxygen intermediates (ROI), nitric oxide (NO), and tumor necrosis factor (TNF-alpha) by murine macrophages, and for their binding to the cannabinoi...
Article
The development of topical and transdermal drug delivery systems has aimed at overcoming the remarkably efficient barrier property of human skin by nontoxic and nonirritant methods. Numerous chemical and physical approaches have been investigated to overcome the skin's formidable barrier function. This article reviews two types of drug delivery app...
Article
The goals of the experiments reported in this paper were to explore skin bioavailability and cell growth inhibitory activity of new vitamin D3-based conjugates studied as a potential drug complex for psoriasis. Conjugation was made between polyunsaturated fatty acids (PUFAs), such as linolenic acid or gamma-linolenic acid, and calcipotriol--a vitam...
Article
Biodegradable polymers based on a blend of polycaprolactone (PCL) and aliphatic polyanhydrides with various monomer lengths were prepared to obtain desired polymer blends for use as drug carriers. The physicochemical, mechanical, and drug-release properties of these blends were investigated by various techniques to evaluate the uniformity degree of...
Article
Full-text available
Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage. Protective mechanisms to attenuate damage are also set in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery and in the brain, but its physiological roles have been only partially clarified. Her...
Article
The production of 2-arachidonoyl glycerol, an endogenous cannabinoid, is enhanced in normal, but not in endothelium-denuded rat aorta on stimulation with carbachol, an acetylcholine receptor agonist. 2-Arachidonoyl glycerol potently reduces blood pressure in rats and may represent an endothelium-derived hypotensive factor.