PHYTOCONSTITUENTS AND EVALUATION OF ACETYLCHOLINESTERASE INHIBITION BY METHANOL EXTRACT OF LIQUIDAMBAR STYRACIFLUA (L.) AERIAL PARTS
National Research Centre, Pharmacognosy Department, Dokki, Giza, Egypt.Federal University of Piaui, Laboratory of Natural Products, Chemistry Department, Ininga, 64049-550, Teresina-Pi, Brazil.
Keywords: Liquidamabar styraciflua, aerial parts, Anticholinesterase activity, Alzheimer’s disease, phytoconstitutents
Abstract

This study deals with evaluation of acetylcholinesterase activity of Liquidambar styraciflua aerial parts methanol 80% extract and identification of the bio-active phytoconstituents of the extract. The acetylcholinesterase inhibition was detected by Ellman’s method and the methanol extract was subjected for phytochemical analysis. The extract of L. styraciflua has shown (IC50 = 0.070 mg/mL), with a similar activity to neostigmine (IC50 = 1.87 µg/mL) and galanthamine (IC50 = 0.37 x10–3 mg/mL) which are the most effective compounds in the treatment of Alzheimer’s disease. Phytochemical investigation of methanol extract of L. styraciflua revealed the presence of triterpenes, flavonoids, tannins and carbohydrates and chromatographic separation and fractionation of methanol extract of L. styraciflua resulted in the isolation of ß-sitosterol, lupeol, oleanolic acid, ursolic acid, luteolin, orientin, isoorientin, kaempferol 3-O-a-rhamnoside and kaempferol 3-O-ß-glucoside. These results suggest that methanol extract of L. styraciflua is a good natural source for acetylcholinesterase inhibitor.

Article Information

Identifiers and Pagination:
Year:2014
Volume:6
First Page:123
Last Page:131
Publisher Id:19204159.6:3.2014
Article History:
Received:January 15, 2014
Accepted:January 27, 2014
Collection year:2014
First Published:April 1, 2014

INTRODUCTION

Alzheimer’s disease (AD) is one of the most widespread neurodegenerative diseases that involve dementia and mainly afflict people over 65 years of age. The therapy of early and moderate stages of AD is mainly based on acetylcholine esterase inhibitors such as synthetic donepezil and galanthamine. However, these licensed medicines have drawbacks of inducing severe peripheral and central side effects, including gastrointestinal disturbances, insomnia, fatigue or depression. On the other hand, since the butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activity in AD increases progressively as the severity of dementia progresses, researchers have investigated selective BuChE and AChE inhibitors in the treatment of AD as well [1]. The serious side effects caused by licensed drugs used to treat AD have forced researchers to investigate safer AChE inhibitors from natural sources. One of the best sources of new substances to treat AD are natural products and their derivatives. Traditionally, plants have been used to enhance memory and to alleviate other symptoms associated with AD [2]. Liquidambar styraciflua (L.) from Hamamelidaceae family, is known as sweet gum tree. It is native to southeastern, east-central, and south-central United States, southern Mexico and central America [3]. The bark is grayish brown, deeply furrowed into narrow, somewhat rounded ridges. The leaves are alternate, simple, dark green and lustrous above. Flowers are monoecious consisting of 2-beaker ovaries subtended by minute scales. The fruit is a dangling brown, woody spiny tipped “gum ball” with seeds brownish and winged [4, 5]. In traditional medicine, L. styraciflua is used in treatment of wounds, the roots were boiled into a strong tea to treat skin sores, diarrhea and dysentery [6]. The bark was used to make an infusion that was used as a sedative for nervous patients and for patients who were well in the day but sick during the night. The plant was used to treat colic, internal diseases and to “comfort the heart.”[6]. One report about cancer chemopreventive activity from triterpenoids from the cones of the plant [7]. The main aim of this present study is to evaluate acetylcholinesterase inhibitory activity of L. styraciflua aerial parts methanol extract and also investigate phytochemical content of the plant extract.

MATERIALS AND METHODS

General experimental procedures

UV/VIS: Shimadzu UV-visible recording spectrophotometer model-UV 240 (NRC, Egypt). 1H-NMR and 13C-NMR (Varian Unity Inova). MS (Finnigan MAT SSQ 7000, 70 ev). (Silica gel (0.063-0.200 mm for column chromatography) and Sephadex LH-20 (Pharmacia Fine Chemicals). Thin layer chromatography (TLC) F254 plates. Solvent mixtures, BAW (n-butanol: acetic acid: water 4:1:5 upper phase, 15% acetic acid: water: glacial acetic acid: 85:15). Paper Chromatography (PC) Whatman No.1 (Whatman Led.Maid Stone, Kent, England) sheets for qualitative detection of flavonoids and sugars were used in this study.

Plant identification and collection

Liquidambar styraciflua aerial parts were collected from Al-Zohiriya garden, Giza, Egypt in May 2011. The plant was identified by Dr. Mohammed El-Gebaly, department of botany, national research centre (NRC) and by Mrs. Tereeza Labib consultant of plant taxonomy at the ministry of agriculture and director of Orman botanical garden, Giza, Egypt. A voucher specimen was deposited in the herbarium  of Al-Zohiriya garden, Giza, Egypt.

Plant extract preparation

Air dried aerial parts of L. styraciflua (760 g) were extracted with methanol: distilled water 80:20 (v/v) several times at room temperature by maceration method. The extract was concentrated under reduced pressure to give 37 g of methanol extract. The extract was phytochemically screened according to that described by Yadav and Agarwala [8].

Isolation of the bioactive components of methanol extract of L. styraciflua

Liquidambar styraciflua (35 g) of  aerial parts methanol extract was subjected to silica gel column chromatography eluting with hexane, dichloromethane, ethyl acetate and methanol gradually.

One hundred and fifty fractions of 100 ml conical flask were collected. The fractions that showed similar Paper Chromatography (PC) in two solvent systems, butanol–acetic acid–water (BAW) 4:1:5 and 15% acetic acid were combined to give 4 fractions (I, II, III and IV). Fraction I (2.1 g) was subjected to sub–column of silica gel eluted with n-hexane: dichloromethane (50:50) gave compound 1 and elution with dichloromethane: n-hexane (80:20) gave compound 2.

Fraction II (1.45 mg) was subjected to sub–column of silica gel eluted with dichloromethane: ethyl acetate (90:10) yielded compound 3 and elution with dichloromethane: ethyl acetate (95:5) gave compound 4. Fraction III (1.85 g) was subjected to sub–column of silica gel eluted with ethyl acetate : methanol (95: 5) to give compound 5 while compound 6  was obtained from elution with ethyl acetate: methanol (90:10) and also compound 7 was obtained by elution with ethyl acetate: methanol (80:20). Fraction IV (1.25 g) was subjected to sub–column of silica gel eluted with ethyl acetate: methanol (70:30) gave compound 8 while compound 9 was obtained by elution with ethyl acetate: methanol (50:50). All the isolated compounds were purified on sephadex LH–20 column using different systems of methanol and distilled water.

General method for acid hydrolysis of flavonoid glycosides

5 mg of each flavonoid glycoside 6, 7, 8 and 9 in 5 ml 10% HCl was heated for 5 h. The aglycones were extracted with ethyl acetate and identified by co-TLC with authentic standards. The sugars in the aqueous layer were identified by co-paper chromatography (co-PC) with authentic markers on Whatman No. 1 sheets in solvent system (n-BuOH-AcOH-H2O 4:1:5 upper layer).

Acetylcholinesterase inhibition assay

The methanol extract of L. styraciflua was dissolved in methanol to prepare solution of 10 mg/mL. Then, 1.5 µL of the extract was spotted on silica gel TLC plate and developed with chloroform: methanol 9:1 after which the enzyme inhibitory activity was detected using Ellman’s method “in situ” on the plate [9, 10]. The developed plate was sprayed with 1 mM Ellman's reagent [5,5'-dithiobis-(2-nitrobenzoic acid)] (DTNB) and 1 mM acetylthiocholine iodide (ATCI) in buffer A. It dried for 3-5 minutes, then an enzyme solution of AChE from an electric eel (type VI-s lyophilized, 261 U/mg solid, 386 U/mg protein) dissolved in buffer A (500 U/mL stock solution) was diluted with buffer A to obtain 5 U/mL enzyme and was then sprayed on the plate [10]. Yellow background with white spot for inhibiting extract was visible after about 5 minutes. The observation must be recorded within 15 minutes because they fade after 20-30 minutes. To observe whether the positive results of the extract in TLC or the microplate assay are due to enzyme inhibition or to the inhibition of the chemical reaction between DTNB and thiocholine, (the product of the enzyme reaction), 5 units/mL of AChE was premixed with 1 mM ATCI in buffer A and incubated for 15 minutes at 37oC. This enzyme-substrate mixture was used as thiocholine spray [10]. The extract was spotted on the silica gel TLC plate developed as described above and sprayed with 1 mM solution DTNB followed by the thiocholine spray. White spot on a yellow background was observed for false positive extract.

The inhibitory effect quantitative of methanol extract of L. styraciflua on acetylcholinesterase activity is evaluated using and adaptation of the spectrophometric method of Ellman et al. [9] modified by Rhee et al. [10]. Five different concentrations were prepared in triplicate, starting from the methanol extract of L. styraciflua (1 mg/mL; 0.5 mg/ml; 0.25 mg/mL; 0.125 mg/mL and 0.0625 mg/mL). The reaction was monitored at 412 nm for 5 min in spectrophotometer.

In test tube is placed 100 µL of the extract (concentration 0.1% solution in 50 mM Tris-HCl pH 8, and  methanol 10%) was mixed with 100 µL of AChE 0.22 U / ml (22 U of enzyme diluted in 100 mL of 50 mM Tris-HCl pH 8, 0.1% BSA) and 200 µL of buffer (50 mM Tris-HCl, pH 8, BSA 0.1%). Incubating the mixture for 5 min at 30°C. Subsequently add, 500 µL of DTNB (concentration of the  3 mM in Tris-HCl pH 8, 0.1 M NaCl, 0.02 M MgCl2) and 100 µL of ATCI (4 mM in water). A blank should also be prepared by substituting AChE with 100 µL of buffer (50 mM Tris-HCl buffer pH 8, 0.1% BSA). The reaction is monitored for 5 min at 412 nm and initial velocity (V0) recorded. Anticholinesterase activity (%) was calculated:

I (%) = (1 – Vo  sample) x 100/ Vo white    

Sample Vo and Vo represents the initial rates blank samples and white.

Inhibition concentration 50% (IC50) values ??so obtained by plotting Log-Probit. Neostigmine (or other commercial acetylcholinesterase inhibitor) is used as positive control at the same. 

RESULTS

The present study was focused on the evaluation of acetylcholinesterase activity of L. styraciflua aerial parts methanol extract and the extract showed a significant inhibition for acetylcholinesterase. enzyme with (IC50 = 0.070 mg/mL). We investigated the presence of phytochemicals and bioactive constituents in L. styraciflua methanol extract. Phytoconstituents are shown in table 1. The major bioactive components of L. styraciflua aerial parts methanol extract are ß-sitosterol, lupeol, oleanolic acid, ursolic acid, luteolin, luteolin 8-C-ß-glucoside (orientin), luteolin 6-C-ß-glucoside (isoorientin), kaempferol 3-O-a-rhamnoside and kaempferol 3-O-ß-glucoside. The chemical structures of the bio-active components were elucidated by different spectroscopic analyses and shown in Figure 1. 

Table 1. Phytochemical analysis of the methanol extract of L. styraciflua aerial parts

Structure elucidation of the isolated compounds

Figure 1. Chemical structures of the compounds isolated of L. styraciflua methanol extract

Figure 2.  Acetylcholinesterase inhibition of L. styraciflua methanol extract (C-3) in TLC and caffeine is used as positive control for acetylcholinesterase inhibitor.

DISCUSSION

Plant extracts are of the most attractive sources of new drugs and have been shown to produce promising results in different pharmacological activities due to the presence of bioactive compounds. Nine compounds were isolated from L. styraciflua aerial parts methanol extract and their identification were elucidated by different spectroscopic tools (UV, IH-NMR, 13C-NMR, MS). Compound 1 (ß-sitosterol) which gave a dark spot under short UV light and changed to violet upon spraying with vanillin-sulphuric acid and heating in an oven at 110°C for 5 minutes. NMR spectral data showed signals very close to ß-sitosterol [11]. Compound 2 (lupeol) gave a dark spot under short UV light and changed to pink to violet upon spraying with vanillin-sulphuric acid and heating in an oven at 110°C for 5 min. NMR spectral data showed signals very similar to lupeol [12]. Compound 3 (oleanolic acid) and compound 4 (ursolic acid), both triterpenic acids were detected through spraying with vanillin sulphuric and heating in an oven at 110°C for 5 min and both compounds gave violet spot at visible light, also NMR and MS spectral data are in accordance with published literature [13]. Compound 5 (luteolin) showed a deep purple spot under UV light which changed to yellow with ammonia vapor indicating that a flavone with free 5-OH and 4'-OH  [14] and spectral data of compound 5 is very close to that of  Owen et al. 2003 [15]. Compound 6 (oientin) and compound 7 (isoorientin) showed a deep purple spot under UV light which changed to yellow with ammonia vapor indicating that they are flavones with free 5-OH and 4'-OH [14]. Complete acid hydrolysis of the two compounds revealed that no sugars were detected meaning that they  remained without change in addition to the appearance of an additional spot on the chromatogram (Wessely-Moeser rearrangement between C-6 and C-8), which may be due to acid isomerization [16], indicating that the compounds are mono C-glycosides. Thus, the compounds were subjected to ferric chloride degradation, and co-chromatographed with authentic sugars samples, where glucose was detected. UV spectral data, 1H NMR and 13C-NMR signals for the two compounds are very similar to the ones reported for orientin and isoorientin, respectively [17, 18]. Compound 8 (kaempferol 3-O-a-rhamnoside) and compound 9 (kaempferol 3-O-ß-glucoside) gave a deep purple spot under UV light which changed to yellow with ammonia vapor and spraying with AlCl3 and complete acid hydrolysis yielded kaempferol as an aglycone, rhamnose and glucose sugar moieties, respectively. The spectral data of both compounds 8, 9 are very similar to that of Amal et al. [19].

Acetylcholinesterase inhibition by methanol extract of L. styraciflua aerial parts

The qualitative results of inhibition of enzyme acetylcholinesterase in Thin Layer Chromatography (TLC) showed that the methanol extract the L. styraciflua significantly inhibited the enzyme by the appearance yellow backgrounds with white spots for inhibiting compounds were visible after about 5 minutes. This are the results of the first tests, yellow backgrounds with white spots for inhibiting compounds were visible after about 5 minutes for methanol extract of L. styraciflua apparently tested positive enzyme inhibition in concentration of 10 mg/mL (Figure 2). The results of acetylcholinesterase inhibition quantitative for methanol extract of L. styraciflua that presented strong activity in both tests, the IC50 values were determined (IC50 = 0.07 mg/mL). The concentration of  inhibition 50%  (CI50) was tested starting at five different concentrations (1 mg/mL; 0.5 mg/ml; 0.25 mg/mL; 0.125 mg/mL; 0.0625 mg/mL) tested in triplicate, showed that methanol extract of L. styraciflua has higher inhibition activity (L. styraciflua, IC50 = 0.07 mg/mL), in comparison to commonly used drugs neostigmine de (IC50 = 1.87 µg/mL)  and galanthamine (IC50 = 0.37 x10–3 mg/mL). Galanthamine which is alkaloid considered to be the most effective compound in the treatment of Alzheimer’s disease [20]. L. styraciflua aerial parts methanol extract seems of interest for further study. Plants that have shown favorable effects in relation to cognitive disorders, including anticholinesterase, anti-inflammatory and antioxidant activities or other relevant pharmacological activities are potentially of interest to clinical use for Alzheimer’s disease [21]. Eighteen medicinal plants of Brazil were screened for inhibitory activity on AChE, the results show that various plants are very interesting for further isolation of acetylcholinesterase inhibitors, which are widely used in the treatment of Alzheimer’s disease, galanthamine, an alkaloid from plants of the Amaryllidaceae family, is a selective reversible long-acting and competitive acetylcholinesterase inhibitor (AChEI). The extract is considered to be more effective in the treatment of Alzheimer’s disease (AD) and to have fewer limitations than physostigmine and tacrine are relevant in terms of searching for novel formulations or compounds for AD treatment [20]. This is the result of the first tests, yellow backgrounds with white spots for inhibiting extract was visible after about 5 minutes and so L. styraciflua aerial parts methanol extract apparently tested positive enzyme inhibition in concentration of 10 mg/mL. The activity of the methanol extract of L. styraciflua may be explained by the presence of carbohydrates, triterpenes, flavonoids and tannins and also for the isolated bioactive compounds where some of the isolated compounds (kaempferol sugars) showed a significant acetylcholinesterase inhibiton [22]. Also many plants as Sophora flavescens showed a significant acetylcholinesterase inhibition and this activity is due to prenylated flavonoid, 8-lavandulylkaempferol which exhibited significant inhibitory effects with IC50 values of 7.10 and 8.11µM for butyrylcholinesterase and acetylcholinesterase [23], also Inhibition of Acetyl Cholinesterase by Indigofera species extracts was due to the pote

CONCLUSION

The methanol extract of L. styraciflua apparently tested positive acetylcholinesterase enzyme inhibition, it has shown (IC50= 0.07 mg/mL). This activity may be due to the presence of bioactive compounds as (ß-sitosterol, lupeol, oleanolic acid, ursolic acid, luteolin, luteolin 8-C-ß-glucoside (orientin), luteolin 6-C-ß-glucoside (isoorientin), kaempferol 3-O-a-rhamnoside and kaempferol 3-O-ß-glucoside isolated from the extract. These active compounds have a similar activity to neostigmine (IC50 = 1.87 µg/mL) and galanthamine (IC50 = 0.37 x10 –3 mg/mL). These results prove that the extract can act as acetylcholinesterase inhibitor and can be widely used in the treatment of Alzheimer’s disease.

CONFLICT OF INTEREST

There is no conflict of interest associated with the authors of this paper.

REFERENCES

  1. Lane RM, Potkin SG, Enz A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia, Int. J. Neuropsychopharmacol 2006; 9: 101–124.
  2. Houghton PJ, Howes MJ. Natural products and derivatives affecting neurotransmission relevant to Alzheimer’s and Parkinson’s disease, Neurosignals 2005; 14: 2–22.
  3. Bailey LH, Bailey EZ. Hortus Third: A concise dictionary of plants cultivated in the United States and Canada. Simon and Schuster Macmillan Co., New York, New York. 1976; 1290-1297.
  4. Dirr MA.. Manual of woody landscape plants. Fifth Edition. Stipes Publishing, Champaign, Illinois. 1998; 1187-1194.
  5. Martin AC, Zim HS, Nelson AL. American wildlife and plants: A guide to wildlife food habits. Dover Publications, New York. 1951; 500-509.
  6. Hamel PB, Chiltoskey MU. Cherokee plants and their uses: A 400-year history. Herald Publishing Company, Sylva, North Carolina, 1975; 65-74.
  7. Yuko FA, Kuniyoshi S, Shunyo M, Harukuni T, Reiko T. Cancer chemopreventive activity of lupane- and oleanane-type triterpenoids from the cones of Liquidamber styraciflua. Chem Biodivers 2005;2(3):421-8.
  8. Yadav RNS, Agarwala M. Phytochemical analysis of some medicinal plants. Journal of Phytology 2011; 3(12): 10-14.
  9. Ellman GL, Courtney DK, Andres VJR, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology 1961; 7:88-95.
  10. Rhee, KI, Van RIJN, MR, Verpoorte R. Qualitative Determination of false-positive effects in acetylcholinesterase assay using thin-layer chromatography. Phytochemical Analalysis 2001; 14:127-131.
  11. Pateh UU, Haruna AK, Garba M, Iliya IM, Abubakar MS, Ambi AA. Isolation of stigmasterol, ß-sitosterol and 2-hydroxyhexadecanoic acid methyl ester from the rhizomes of Stylochiton lancifolius and Kotchy (Araceae). Nigerian Journal of Pharmaceutical Sciences 2009;7:19-25.
  12. Abdullahi SM, Musa AM, Abdullahi, MI, Sule MI, Sani YM. Isolation of Lupeol from the Stem-bark of Lonchocarpus sericeus (Papilionaceae). Scholars Academic Journal of Biosciences 2013; 1(1):18-19.
  13. Zuhal G, Nurcan K, Cavit K, Yusuf  K, Omur LD. Chemical Constituents of Galium tortumense. Turk J Chem 2006;30:515 – 523.
  14. Mabry TJ, Markham, KR, Thomas MB The Systematic Identification of Flavonoids. Springer-Verlag, Berlin, 1970;  119-292.
  15. Owen RW, Haubner R, Mier W, Giacosa A, Hull WE, Spiegelhalder B, Bartsch H. Isolation, structure elucidation and antioxidant potential of the major phenolic and flavonoid compounds in brined olive drupes. Food and Chemical Toxicology  2003; 41:703–717
  16. Harborne, JB, Mabry TJ, Mabry H. "The Flavonoids" Chapman and Hall Ltd, London, 1975.
  17. Agrawal, PK. “13C-NMR of Flavonoids”. Amesterdam Elsevier, 1989); Vol. 39. Thesis or Dissertation.
  18. Ayse K-U, Zuhal G, Karsten S, Omur LD, Axel Z. Antioxidant Potency of Flavonoids from Vitex agnus-castus L. growing in Turkey. FABAD J Pharm Sci. 2008;33:11–16.
  19. Amal MYM, Ahmed IK, Mahmoud AS. Isolation, structural elucidation of flavonoid constituents from Leptadenia pyrotechnica and evaluation of their toxicity and antitumor activity. Pharmaceutical Biology 2009; 47(6): 539–552
  20. Feitosa CM, Freitas RM, Luz NN, Bezerra MZB, Trevisan Maria TS. Acetylcholinesterase inhibition by somes promising Brazilian medicinal plants. Brazilian Journal of Biology 2011;71: 783-789.
  21. Houghton PJ, Howes, MJR. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacology Biochemistry and Behavior 2003;75: 513-527.
  22. Ilkay O, Murat K, Fatma T, Bilge S. Screening of Various Phenolic Acids and Flavonoid Derivatives for their Anticholinesterase Potential Z. Naturforsch 2007;62c:829-832.
  23. Jung HA, Takako Y, Byung-Woo K, Jee HJ, Jae Sue C. Selective Inhibition of Prenylated Flavonoids from Sophora flavescens against BACE1and Cholinesterases. The American Journal of Chinese Medicine 2010;38 (2): 415–429.
  24. Bakasso SA, Lamien-meda CE, Lamien MK, Coulibaly AY, Compaoré M, Meda NR, Nacoulma OG. In vitro Inhibition of Acetyl Cholinesterase, Lipoxygenase, Xanthine Oxidase and Antibacterial Activities of Five Indigofera (Fabaceae) Aqueous Acetone Extracts from Burkina Faso. Current Research Journal of Biological Sciences 2013; 5(3): 115-122. 


© 2016 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license. You are free to: Share — copy and redistribute the material in any medium or format Adapt — remix, transform, and build upon the material for any purpose, even commercially. The licensor cannot revoke these freedoms as long as you follow the license terms. Under the following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. No additional restrictions You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits
Editor in Chief
Prof. Dr. Cornelia M. Keck (Philipps-Universität Marburg)
Marburg, Germany

Bibliography

Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

Journal Highlights

Subject & Scope
  • Pharmaceutics
  • Physical Pharmacy 
  • Dosage Forms Science 
  • Pharmaceutical Microbiology & Immunology 
  • Industrial Pharmacy 
  • Bio-Pharmaceutics 
  • Pharmaceutical Chemistry 
  • Pharmaceutical Instrumentation 
  • Medicinal Chemistry 
  • Pharmacognosy 
  • Physiology &Histology 
  • Anatomy & Pathology 
  • Pharmacology & Therapeutics 
  • Pharmacy Practice 
  • Pharmaceutical Mathematics   
  • Biostatistics 
  • Dispensing 
  • Community Social & Administrative Pharmacy 
  • Hospital Pharmacy 
  • Clinical Pharmacy 
  • Pharmaceutical Quality Management 
  • Forensic Pharmacy 
  • Pharmaceutical Technology 
  • Pharmaceutical Management & Marketing

Consortium Publisher is an online publisher that enjoys global presence with International Journals

Follow Us

©2009 - 2019 Consortium Publisher Canada

Contact Info

6252 Lisgar Dr Mississauga Ontario L5N7V2 Canada
+1 (647) 526-0885
office@consortiumpublisher.ca
http://www.consortiumpublisher.ca/