Central JSM Alzheimer’s Disease and Related Dementia

Research Article *Corresponding author Hanna Rosenmann, Department of Neurology, Hadassah University Hospital, Ein Karem, Jerusalem 91120, Anti Alzheimer’s Disease Israel, Tel: 972-2-6776954; Fax: 972-3-7256022; Email: Related Activities of Israeli Submitted: 03 December 2014 Accepted: 24 February 2015 Published: 26 February 2015 Medicinal Copyright Lea Tsalkovich1, Sarah Sallon2, Helen Paavilainen2 and Hanna © 2015 Rosenmann et al. Rosenmann1* OPEN ACCESS 1Department of Neurology, Hadassah Hebrew University Medical Center, Israel 2The Louis Borick Natural Medicine Research Center, Hadassah Hebrew University Medical Center, Israel

Abstract Medicinal plants may provide a potential source of therapeutic agents against Alzheimer’s-disease (AD) and other dementias. In the current study medical plants with an historical/traditional use for improving memory were evaluated for anti-AD activity. Plants were collected mainly from wild species growing in Israel and tested for their protective properties against toxicity of amyloid-beta (Aβ) and a decrease in its secretion by neuronal cells (SHSY5Y and PC12). Of 20 plants tested, 5 plants: Citrullus colocynthis, tubulosa, Paronychia argentea, Sisymbrium irio and Origanum dayi Post, showed rescue of cells from amyloid toxicity of 205%, 177%, 42.5%, 40%, and22.7%, respectively. Citrullus colocynthis and Cistanche tubulosa also demonstrated a decreasing trend of 19% and 25%, respectively in Aβ levels secreted by cells. Two additional plants, Varthemia iphionoides and Anchusa strigosa, showed a decreasing trend in secreted amyloid levels of 32% and 34% and a decrease of 23 and 31% in γ-secretase activity respectively. These results point to a potential therapeutic use of medicinal plantssome of which has a long historical/ traditional use for improving memory and should be the basis of further investigation for neurodegenerative diseases such as AD.

INTRODUCTION its progress. An effective treatment able to postpone onset by an

Alzheimer’s Disease (AD) is a progressive neurodegenerative nearly 50% [3]. disorder occurring predominantly in the aging population and average of five years would reduce associated costs to society by representing the commonest cause of dementia. The risk of AD rises sharply with advancing age currently affecting over 20 molecules that have been widely used in the search for effective Medicinal plants constitute an important source of bio-active million people worldwide [1]. With a further increase in life expectancy the number of AD patients is predicted to increase therapies in many diseases including cancer, infections, rheumatic dramatically. a source of innovative molecules for neurodegenerative diseases hasconditions not been etc. widely [4,5]. exploited.Until now however the potential of plants as The main neuro pathological hall marks of AD in the brain plaques result from the accumulation of several proteins and are amyloid plaques and neuro fibrillary tangles (NFTs). Amyloid regionsIsrael possesses with its variedsome 2600 climate and species geography belonging situated to in 130 a transition zone between Mediterranean, desert and sub-tropical form of the different families ranging from alpine plants in the north to an inflammatory reaction around deposits of amyloid-beta processes(Aβ); NFTs asare well the aggregated as oxidative and stress phosphorylated are implicated in the area [6]. With a long history of traditional use spanning millennia desert and salt plants in the south, many endemic only to the pathogenesis.microtubule-associated As these tau cellular protein. changes Inflammatory progress and neurons apoptotic are lost in the brain (reviewed in [2]). Although impressive advances the medicinal plants of Israel present a unique opportunity for in understanding AD have been made over the past decade the focused screening based on their ethno-botanical use. mechanisms of brain degeneration remain to be resolved with the Middle Eastern Medicinal Plant Project (MEMP effective drug therapy still not available. There is thus a real In the current study plants were investigated as part of ), an ethno- botanical initiative of The Natural Medicine Research Center need to find drugs to prevent AD, delay its onset and/or retard (NMRC) dedicated to the preservation of traditional knowledge, Cite this article: Tsalkovich L, Sallon S, Paavilainen H, Rosenmann H (2015) Anti Alzheimer’s Disease Related Activities of Israeli Medicinal Plants. JSM Alzheimer’s Dis Related Dementia 2(1): 1015. Rosenmann et al. (2015) Email: Central

Plant collection: by the above method for screening were collected from wild , domestication, conservation and re-introduction of selected The majority (18) of the plants selected speciesEthanol and focused extracts screening of whole of Israeli plants flora traditionally [7,8]. used to enhance memory were evaluated on AD related pathogenesis. sources (Judean Hills) in Israel. Two species (extract #114 and Aravaextract region. #63) were Domestication harvested offrom these domesticated plants derived wild originally plants at the MEMP cultivation site, Kibbutz Ketura in Israel’s southern Investigations included neuroprotective activity against Aβ from seeds obtained from wild sources took place without the peptide in neuronal cell lines, ability to reduce amyloid levels use of fertilizers or pesticides using shaded net houses and drip irrigation. proteinsecreted (APP). by these cells and reduction in activity of γ-secretase, an enzyme catalyzing cleavage of Aβ from its amyloid precursor Screening of 20 herbal extracts demonstrated rescue of (seeAll acknowledgements) plants from wild and withdomesticated voucher sources herbarium were specimens identified by botanists Dr. Ori Fragman-Sapir and Ms. Hagar Leschner neuronal cells from amyloid toxicity in 5 extracts, decrease in amyloid levels secreted by treated neuronal cells in 4 extracts, of Jerusalem. These results point to the potential therapeutic value deposited at NMRC officers in Hadassah Medical Organization, which 2 were also associated with lower activity of γ-secretase. Plant Extracts (Ethanol extraction) neurodegenerative disorders particularly against amyloid All reagents used in the study were purchased from Sigma relatedof selected pathology plants in AD. found in Israel in the treatment of were air dried at room temperature and extracted with ethanol MATERIALS AND METHODS (St. Louis, MO) unless otherwise stated. Freshly harvested plants Plants beaker for 24 h at room temperature after which the process was repeated.(50% v/v, 10v per gram weight) by vigorous stirring in a covered Plant Selection: Plants were selected for screening using

evaporated in a chemical hood for 4 days with the evaporated techniquesa focused method and was based derived on fromtheir a historical/traditional variety of sources. Theseethno The supernatant of° both extracts was filtered and ethanol botanical use. Information was obtained by data mining The dried extract was kept at 4° extract frozen at ‑70 C followed by lyophilization till dryness. plantsincluded (SS the unpublished ethno botanical data). database of NMRC containing the C. Stock solutions of the plant traditional and folk medicine use of over 500 Israeli medicinal extracts (200 mg/ml) were prepared by weighing the powder and dissolving° in 10% dimethyl sulphoxide/ phosphate buffered saline (DMSO/PBS). The solution was divided to aliquots and In addition the following sources were also consulted: animal products and their medical effects and usages) and keptCells at and ‑20 C,cell until viability used. assessment medicalmedieval encyclopaedias pharmacopoeias (describing (texts diseases listing herbs, with therapeutic minerals, Human neuroblastoma cells SHSY5Y cells (105 recommendations including drugs useful for the problem). These cells/ml) Hebrew and Arabic sources range from the 1st th century. Any were grown in RPMI medium supplemented with L-Glutamine referencetexts translated to a plant when or remedy necessary being by used author in a way (HP) that from indicates Latin, 1%, FCS 10% and Gentamicine 50mg/ml in CO2 10%. PC12 it could have psychotropic or neurological effects -16 particularly a pheochromocytoma of the rat adrenal medulla cells (105cells/ memory improving effect e.g. “against loss of memory” was noted. ml) were grown in DMEM, FCS 7.5%, horse serum 7.5%, Penstrep To evaluate the relative reliability of this information and provide 1% and L-Glut 1%. The cell reagents were purchased from Biological° Industries Israel Beit Haemek Ltd. Cells were exposed 25−35 drugs described in these texts were assessed in the following wereor non-exposed treated concomitantly to Aβ (10µM) with each (amyloid of the was extracts first incubated dissolved inat a criteria for inclusion in focused screening (below), plants 25−35 10%37 c forDMSO 1h toor allowwith vehicle its aggregation). only as controls Cells exposedand further to the incubated Aβ way (by author HP, unpublished data): (a) the frequency with which authors mention particular plants/drugs; (b) the plants/ overnight. In one set of experiments the extract was added to the drugs mentioned by most of the authors; (c) the exact indication cells at the following different time points for comparison: 2h for which they were used (which will show if a plant/drug has memory loss or if its effect could be assumed to be more general plantbefore extracts exposure were to administeredamyloid, concomitantly to the cells concomitantly.with amyloid, or After 2h a specific effect against the given problem, for example, against anafter overnight amyloid incubationwas added. cellsIn all were other washed experiments and lysed amyloid and and cell viability estimated by the Methyl Thiazolyl Tetrazolium bromide e.g. improving the patient’s general physical condition); (d) the (MTT) assay (a sensitive measure of the normal metabolic status inpercentage question ofis stressedthe texts in the the plant/ text (i.e. drug how in questionoften it appears is mentioned in the as having the quality or effect sought; (e) how highly the quality between different texts over time. of cells particularly mitochondria and reflecting early cellular same description); (f) how continuously the drug is referenced redox changes), expressed as Optical Density (OD) units at 595 Aβnm 1-42as previously levels secreted tested by by us the [9]. cells (ELISA)

On the basis of these assessments, a list of plant species / secreted drugs and/or plant genus were compiled as being the most likely amnesic properties. of the SHSY5Y cells grown with 1−42the tested plant extracts or with to possess potentially psychotropic, neurologic and/or anti- To determine the level of Aβ by cells, the medium

JSM Alzheimer’s Dis Related Dementia 2(1): 1015 (2015) 2/7 Rosenmann et al. (2015) Email: Central

vehicleresults wereonly (controls) normalized were for collected protein concentration and submitted in to the ELISA cell (205% ), 1.047±0.153 and 0.978±0.007 for concentrations of (Aβ1−42 kit, Covance Laboratories Inc., Chantilly, Virginia). The 0.01, 0.1, 1, and 5µg/ml (p=0.0001, p=0.04, p=0.015, p=0.002 respectively), reaching OD values similar and even higher to Preparationlysates, determined of with detergent-solubilized BCA protein assay. membrane cells not exposed to amyloid (Figure 1a). A similar protective fractions and γ-secretase activity assays effect in higher concentrations of extract #63 was demonstrated in PC12 cells: exposure to amyloid reduced cell viability from Secretase activity was determined in membrane fractions of 0.797±0.053 to 0.3625±0.053 (p=0.0005); treating cells with extract #63 increased cell viability to 0.585±0.046 (p=0.005) and the cells grown with or without plant extracts using Fluorescence 0.452±0.066 for concentrations of 30 and 60µg/ml, respectively. exposure to amyloid also showed robust neuroprotection [while Resonance Energy Transfer (FRET) assay based on published Treating amyloid exposed cells with extract #63 2 h before protocols [9,10] with some modifications, as follows: The cells in 10 cm dishes (3 dishes per sample) were collected and re- exposure to amyloid reduced cell viability from 0.818 ±0.184 to suspended in homogenization buffer (50 mm Hepes, pH 7.0, 0.308±0.019 (p=0.039), treating cells with this extract increased 250 mm sucrose, 5 mm EDTA) containing complete protease smallercell viability neuroprotective to 0.647±0.029 trend was (p=0.0001) demonstrated and 0.389±0.019 even when inhibitor mixture (Roche Applied Science, Indianapolis, IN). (0.007) at concentrations of 30 and 60µg/ml, respectively]. A The re-suspended cells were homogenized by Tissue Grinders × g for 10 min. The supernatants were further centrifuged at to amyloid [while exposure to amyloid reduced cell viability from homogenizer and the cell debris and nuclei removed at 3,000 treatment with extract #63 was initiated 2 h following exposure

100,000 × g for 1 h. The membrane pellets were solubilized with 0.711±0.05 to 0.3359±0.048, treatment with 30µg/ml of the 1% digitonin or CHAPSO in homogenization buffer for 90 min extractThese increased results viability suggest to that 0.3894±0.054]. the protective effect of plant on ice and then centrifuged at 100,000 × g for 1h. The protein concentration of the supernatant was determined with BCA effect seems more pronounced when used as a prophylactic. protein assay reagent. CHAPSO-solubilized membrane fractions extract #63 may have potential therapeutic activity although its All other extracts were tested for rescuing cells from amyloid were diluted to 0.25% CHAPSO and then incubated with 8 μm toxicity exposed concomitantly with each extract. inhibitorpeptide γ-secretase substrate, Fluorogenic° (Millipore, Billerica, Massachusetts) in the absence or presence of the γ-secretase Cistanche tubulosa (Schenk) Hook, f) rescued DAPT (10 μm) at 37 C overnight. After incubation, reactions were centrifuged at 16,100 × g for 15 min and placed Extract #106 ( on ice. Supernatants were transferred to a 96-well plate (Black, amyloid exposed SHSY5Y cells from cell viability of 0.198±0.003 (relative to 0.368±0.023 of cells not exposed to amyloid, p=0.005) emissionNunclon, wavelengthNunc) and fluorescence at 460 nm. The measured results wereusing normalized a plate reader for to 0.433±0.044, 0.549±0.085 (177%) and 0.509±0.092 at protein(Fluorstar concentration Galaxy) with in the excitation cell lysates. wavelength at 320 nm and concentrations of 1, 5, and 50 µg/ml (p=0.011, p=0.018, p=0.027) showed a Statistical analysis respectively (Figure 1b).Paronychia argentea Lam) protective effect against amyloid with cell viability increased fromExtract #120 (

Results are presented as Mean ± SEM. The unpaired t-test 0.439±0.032 (relative to 0.850±0.1 of cells not exposed was used for comparing results of MTT assay, amyloid levels and to amyloid, p=0.013) to 0.626±0.032 (42.5%) (p=0.002), and enzyme activity assays between study groups (p values of ≥ 0.05 0.571±0.109 when treated with 1 and 10µg/ml of the extract; wereRESULTS considered significant). and from 0.781±0.097 under amyloid exposure to 1.014±0.096 (Sisymbrium irio L) rescued amyloid exposed Herbal extracts demonstrating neuroprotective (p=0.042) when treated with 50µg/ml of the extract. activity against amyloid toxicity Extract #107 cells from cell viability of 0.927±0.06 (relative to 1.379±0.015 in A total of 20 plant extracts were screened for potency cells not exposed to amyloid, p=0.06) to 1.023±0.09 in 1µg/ml peptide exposed extract; and of 0.992±0.06 to 1.392±0.131 (40%) (p=0.019) in 50 25−35 Origanum dayi Post) showed a dose response in rescuing cells from toxicity of Aβ µg/ml extract. trend of protecting cells against amyloid toxicity although not propertiesconcomitantly some with of each them extract. presenting Of these a very 5 extracts robust (#63, statistically #106, Extract #114 ( #120, #107 and #114) showed anti-amyloid neuroprotective others demonstrated a more modest trend of neuroprotection reaching statistical significance: from cell viability 0.308±0.04 significant effect of increased cell viability (177-205%), while under amyloid exposure (relative to 0.4511±0.052 in cells not exposed to amyloid, p=0.024) treated cells showed an increase Citrullus (22.7-42.5%). of viability to 0.335±0.027, 0.378±0.008 (22.7%), 0.365±0.075, colocynthis (L) Schrad) showed a robust dose dependent effect These included the following: extract #63 ( 0.368±0.036, 0.318±0.069 and 0.335±0.027 at concentrations of 0.01,Herbal 0.1, 1, extracts 10, 50µg/ml associated respectively. with reduced levels of of rescuing SHSY5Y cells, as follows: while exposure to amyloid amyloid secretion from cells reduced cell viability from 1.167±0.17 to 0.465±0.048 OD units (p=0.014), treating the amyloid exposed cells with the plant extract increased cell viability to: 1.288±0.069, 1.422±0.127 Screening 8 plant extracts for their ability to reduce the levels JSM Alzheimer’s Dis Related Dementia 2(1): 1015 (2015) 3/7 Rosenmann et al. (2015) Email: Central

Figure 1a ⊥ The herbal extracts #63 and #106 rescued the SHSY5Y from Aβ toxicity in MTT assay. (a) Aβ exposed1 cells showed2 significantly3 lower4 viability than cells not exposed to Aβ ( p=0.014). Aβ exposed cells treated with extract #63 showed significant increase in viability relative to Aβ exposed cells treated with vehicle only [controls (Aβ cont)], at concentrations of 0.01, 0.1, 1 and 5µg/ml (∗ p=0.0001, ∗ p=0.04, ∗ p=0.015, ∗ p=0.002, respectively.

Figure 1b ⊥ 1 2 Aβ3 exposed cells showed significantly lower viability than cells not exposed to Aβ ( p=0.005). Aβ exposed cells treated with extract #106 showed significant increase in viability relative to Aβ exposed cells treated with vehicle only, at concentrations of 1, 10 and 50µg/ml (∗ p=0.011, ∗ p= 0.018, ∗ p= 0.027, respectively). peptide secreted Cistanche of them showed1−42 trends in reducing amyloid levels in the medium tubulosa) of thecells Aβ grown with the extracts. by the SHSY5Y cells, revealed that 4 treated with 0.1, 1, 10 and 50µg/ml of extract #106 ( [decrease of 25.36% (p=0.044), -10.32%,Citrullus 16.87%, colocynthis) and Varthemia iphionoides Boiss (21.95%, respectively, relative to vehicle-treated controls] as well & Blanche as with 0.01, 0.1, 1, 10µg/ml of extract #63 ( Cells treated with extract #123 ( decrease of 19.09%, -2.28%, 6.23% and 13.54% respectively, ) showed amyloid levels as expressed by Relative Light relative to vehicle-treated controls). Units (RLU) of 49065.58±6858.36, 52922.57±18107.16 and cells treated with plant extracts was obtained by demonstrating 59396.84±15677.59 for 1, 10 and 50µg/ml of extract, respectively Further confirmation for a decrease in secretion of amyloid by vs. 72357.65±20595.59 RLU in vehicle-treated controls (a presented below. 1−42, decrease of 32.19%, 26.84% and 17.93% respectively). reduced activity of the enzyme catalyzing formation of Aβ (Anchusa strigosa Banks &Sol) also showed lower amyloid levels Plant extracts associated with reduced γ-secretase At similar concentrations cells treated with extract #124 activity

(decrease of 27.06%, 34.38%, and 11.20%, respectively relative to vehicle-treated controls) (Figure 2). neuronal cells treated with selected plant extracts suggests that The decrease demonstrated above in Aβ levels secreted by Some beneficial trends were also detected when cells were JSM Alzheimer’s Dis Related Dementia 2(1): 1015 (2015) 4/7 Rosenmann et al. (2015) Email: Central

1 2 0

1 0 0

8 0 l ve le blevel level 6 0 fAβ β o %4 0 % of of % % A A

2 0

0 c o n t 1 µ g /m l 1 0 µg /m l 5 0 µg /m l 1 µ g /m l 1 0 µg /m l 5 0 µ g /m l extract # 1 2 3 extract # 1 2 4

Figure 2 Trends were detected

The herbal extracts #123 and #124 reduced the level of Aβ1−42 secreted by the SHSY5Y cells, detected by ELISA. showing that at concentrations of 1-50 µg/ml extract #123 and extract #124 reduced the Aβ level relative to vehicle treated control cells (cont) (by 32% at 1µg/ml, and by 34% at 10µg/ml, respectively).

Figure 3 At concentrations 1 p=0.003) The2 herbal extracts #123 and #124 reduced the activity of the γ-secretase in SHSY5Y cells, detected by FRET analysis. ⊥ ofrelative 10µg/ml, to vehicle extract treated #123 and control extract cells. #124 reduced each the γ-secretase activity relative to vehicle treated control cells (cont) by 23% (∗ and 31% (∗ p=0.04), respectively. For comparison we used the γ-secretase inhibitor DAPT, which reduced the enzyme activity by 45% ( p=0.02), these extracts may interfere with the formation of this toxic

By comparison, reduced γ-secretase activity was peptide. To test this possibility activity of γ-secretase (catalyzing demonstrated using γ-secretase inhibitor DAPT [55.51%±12.42% cleavage of APP to generate Aβ peptide following cleavage by of activity in vehicle-treated control cells (p=0.025) (decrease of SHSY5Y cells treated with 2 plant extracts that were associated β-secretase in the amyloidogenic pathway) was tested in the 44.49%)].DISCUSSION (Varthemia iphionoides) & These results point to the largely unexplored therapeutic (Anchusa strigosa). with a decrease in Aβ levels: #123 #124 demonstratedpotential of selectedboth prior plants to and with concomitantly activity againstwith exposure amyloid- to A significant decrease in enzyme activity was demonstrated: pathology associated with AD. Significant effects were cells treated with 10µg/ml of extract #123 showed a lower ) associated secretase activity: 76.73%±2.5% of activity in vehicle-treated amyloid-toxicity. Cistanche tubulosa (Schenk) Hook, f in this study with both a neuroprotective effect and reduction control cells (p=0.003) (decrease of 23.27%). In cells treated with in amyloidExtract #106 secretion ( belongs to a worldwide genus of 22 extract #124 activity was 68.89%±3.08% (decrease of 31.11%) (p=0.04) (Figure 3a). JSM Alzheimer’s Dis Related Dementia 2(1): 1015 (2015) 5/7 Rosenmann et al. (2015) Email: Central holoparasitic desert plants in the family . Plants a related species Anchusa italica [32] no studies until now have in this genus are widely used in traditional and folk medicine Anchusa strigosa.

demonstratedThree other an species anti-Alzheimer’s in this study effect were for also associated with (Paronychia thoseparticularly used in in treating China “amnesia” (where 5 and species memory are problems. found) forming Previous an argentea Lam), Sisymbrium irio L) (Origanum chemicalimportant analysis component of C. in tubulosa a number as of well Chinese as several medicines other including plants dayineuroprotection Post). Of these against only Paronychia amyloid toxicity:argentea #120has demonstrated #107 ( and #114 inhibitory oligosaccharidesin the genus indicate and thepolysaccharides main constituents [11]. are essential species oils, Cistanche consideredpotentially relevanta promising activity strategy with for acetyl-cholinesterase the treatment of neurological havephenyl demonstrated ethanoid glycosides a variety of (PhGs), activities iridoids, including lignans, vasorelaxation alditols, disordersactivity, the such key as enzyme AD [33]. in the breakdown of acetylcholine, and (C. deserticola)

[12], hepatoprotective [13], sedative [14] anti- protection against amyloid cellular toxicity as well as inhibition The wide spectrum of effects noted in this study, including theallergic potential [15], of anti-nociceptive Cistanche species and to anti-inflammatory improve memory [16], has of enzymatic pathways involved in amyloid formation makes indicatedhypocholesterolemia that echinacoside [17] and and acteoside anti-oxidant fractions [18]. isolated Recently from several of these plants both interesting and potentially valuable C.tubulosa . to analyze the active constituents responsible for these effects are associated with memory-improving effects in in the treatment and prevention of AD. Further research is needed SAMP/8although micein other and Cistanche scopolamine-induced species (C. Herba amnesia) induction[19,20] of nerveUntil and evaluate their in-vivo efficacy and toxicity. Using whole plant now the mechanism of this effect [21]has suggestsnot been thatfully this evaluated, may be should also be considered in view of the increasing attention extracts as novel preventative and/or therapeutic agents in AD one possible mode of action. natural products have received in the last decades for their growth factor (NGF) in PC12 cells Citrullus colocynthis (L) Schrad) also time and lower costs required for them to become commercially demonstrated both neuroprotection and a reduction in amyloid available.potential in treating many diseases and the significantly shorter secretionExtract activity. #63 A ( member of the family Cucurbitaciae the fruit and roots of this small perennial creeping herb has been ACKNOWLEDGMENTS

powerfulused medicinally purgative since [22]. ancient Phytochemical times for analysis infections, has indicated jaundice, We are most grateful to Louise and Gigi Gartner and the diabetes urinary problems, nerve pain and particularly as a supportLouise of Gartner this research. Philanthropic We also want Fund, to Thethank Charles the following Wolfson for Charitable Trust and the Merrin Family Trust for their generous tertiary or quaternary alkaloids, glycosides, saponin as well as activityamino acids, of C. and colocynthis proteins [23]. although No relevant previous studies studies however have their assistance in collection and identification of wild plants: demonstratedcould be found numerous on the memory other activities enhancing including or anti-Alzheimer’s Ms.Hagar Leschner, Collection Manager, The Herbarium of The based on the presence of Cucurbitacin, Hebrew University, The National Natural History Collections at anti-tumor forthe providingHebrew University, 2 cultivated Dr. species Ori Fragman-Sapir, from the MEMP Head plantation Scientist, Thesite stimulating. [26]. glycosides [24], cytotoxic Jerusalem Botanical Gardens. We also thank Dr Elaine Solowey and anti-leismanial activity [22], anti-oxidant [25] and immune (Varthemia iphionoides Boiss & atREFERENCES Kibbutz Ketura. Blanche) (Anchusa strigosa Banks &Sol) were both associatedThe two in the extracts current #123 study with reduced amyloid secretion 1. and #124 Varthemia iphionoides a common herb in Mayeux R, Stern Y. Epidemiology of Alzheimer disease. Cold Spring the Eastern Mediterranean in the family Compositae (Asteraceae), 2. Harb Perspect Med. 2012; 2. and γ-secretase activity. Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010; commonly used as an aqueous extract in folk medicine for 3. is a bushy perennial with aromatic stems [27]. Its aerial parts, 362: 329-344. 4. Changing the Trajectory of Alzheimer’s Disease: A National Imperative diabetes and gastrointestinal disorders [28] have exhibited anti- Cassileth BR, Deng G. Complementary and alternative therapies for fungal, anti-spasmodic, anti-platelet, cytotoxic, anti-oxidantV. iphionoides and 5. cancer. Oncologist. 2004; 9: 80-89. anti-bacterial activity [27,29,30].We believe however that this is on pathological elements associated with AD. Tascilar M, de Jong FA, Verweij J, Mathijssen RH. Complementary and the first study to demonstrate a potential effect of Anchusa strigosa alternative medicine during cancer treatment: beyond innocence. 6. Oncologist. 2006; 11: 732-741. spiny hairs is a member of the Borage ( ) family a herbaceous, perennial plant with stiff Fragman O, Uzi Plitmann, David Heller. Checklist and Ecological Mediterranean basin and Middle East [31]. CBoraginaceaehemical studies have Data-Base of the Flora of Israel and its Surroundings including Israel, Jordan, The Palestinian Autonomy, Golan Heights, Mt. Hermon and shownthat includes that Anchusa some 27–30 strigosa species mainly distributed in the Sinai. In: Israel Nature and National Parks Protection Authority and contains aliphatic hydrocarbons, ROTEM-Israel Plant Information Center Mifalot “Yeffe Nof” & The Middle East Nature Conservation Promotion. 1999. oil, proteins, pyrrolizidine alkaloids and polyphenols. 7. Sallon S, Solowey E, Cohen Y, Korchinsky R, Egli M, Woodhatch I, et al. enhancingPharmacological effect effectsin chronically include gastricstressed protective, mice has anti-microbial,been found in hypotensive and anti-diabetic activity [32]. Although a memory- Germination, genetics, and growth of an ancient date seed. Science. 2008; 320: 1464. JSM Alzheimer’s Dis Related Dementia 2(1): 1015 (2015) 6/7 Rosenmann et al. (2015) Email: Central

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Cite this article Tsalkovich L, Sallon S, Paavilainen H, Rosenmann H (2015) Anti Alzheimer’s Disease Related Activities of Israeli Medicinal Plants. JSM Alzheimer’s Dis Related Dementia 2(1): 1015.

JSM Alzheimer’s Dis Related Dementia 2(1): 1015 (2015) 7/7