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SWERTISIN AMELIORATES COGNITIVE IMPAIRMENT INDUCED BY SCOPOLAMINE OR MK-801 AND PREPULSE INHIBITION DEFICITS INDUCED BY MK-801 IN MICE
© Hee Kyong Oh13, Ho Jung Bae2 3, Hyung Eun Lee2 3, Se Jin Jeon2 3, Se Jin Park4, Jae Hoon Cheong5, Dae Sik Jang2,3, Jong Hoon Ryu12,3
1 Department of oriental Pharmaceutical Science;
2 Department of Life and Nanopharmaceutical Science;
3 Kyung Hee East- West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea;
4 Department of Biological Environment, Kangwon National University, Republic of Korea;
5 Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul, Republic of Korea
Swertisin, a C-glucosylflavone isolated from Swertia japonica, has been known to have antiinflammatory or antidiabetic activities. In the present study, we investigated the effects of swertisin on cholinergic blockade- or hypoglutamatergic-induced memory impairment and prepulse inhibition deficit induced by glutamatergic dysfunction mediated by dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate receptor antagonist, in mice. Swertisin (5 or 10 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in the several behavioral tasks. Also, single administration of swertisin (10 mg/ kg, p.o.) in normal naive mice enhanced the latency time in the passive avoidance task. In addition, in the novel
object recognition test, recognition memory impairments that were induced by MK-801 (0.2 mg/kg, i.p.) were also reversed by administration of swertisin (30 mg/kg, p.o.). In the acoustic startle response test, MK-801 (0.2 mg/kg, i.p.)-induced prepulse inhibition deficit was significantly attenuated by the administration of swertisin (30 mg/ kg, p.o.). In addition, swertisin normalized MK-801-induced elevation of the phosphorylation levels of Akt and GSK-3ß signaling molecules in the prefrontal cortex. These results indicate that swertisin may be useful in managing the symptoms of schizophrenia, including sensorimotor gating disruption and cognitive impairment, and that these behavioral outcomes may be related to Akt-GSK-3ß signaling in the prefrontal cortex.
GC/MS ANALYSIS AND IN VITRO ANTIMICROBIAL ACTIVITY OF THE ESSENTIAL OILS AND VARIOUS EXTRACTS OF THREE ACHILLEA SPECIES
© Sabanoalu S.1, Eryilmaz M.2, Asian Erdem S.1, Altun M.L.1
1 Department of Pharmacognosy, Ankara University Faculty of Pharmacy, Ankara, Turkey;
2 Department of Pharamceutical Microbiology, Ankara University Faculty of Pharmacy, Ankara, Turkey
The genus Achillea belongs to the Asteraceae family, comprises more than 100 species throughout the world, mainly distributed in Northern hemisphere as a mythological plant [1]. The genus is represented by 47 species and 24 of them are endemic in Turkey [2]. Achillea species have several components such as essential oils, phenolic acids, flavonoids, terpenes, lignans. Thanks to including of these components, Achillea species have been used in traditional medicine as antimicrobial, antioxidant, antispasmodic, estrogenic, antiulser agents [3]. In this study, essential oils of the air-dried aerial parts of A. biebersteinii, A. setacea. and A. wilhelmsii were obtained by hydrodistillation, and analyzied using GC/MS. The major compounds of the essential oils were identified as 1,8-cineol (23%), camphor (19%) and piperiton (12%) for A. biebersteinii; 1,8-cineol (23%), camphor (10%) and a-thujone (9%) for A. setacea; camphor (30%) and 1,8-cineol (17%) for A. wilhelmsii. On
the other hand, the air dried and milled flowers, leaves and roots of plants were extracted separately with aqueous and ethanol (96%). After all, aqueous and ethanol extracts of plants were investigated for their antimicrobial activities against in a broth dilution method against two Gram (+) bacteria (Staphyococcus aureus ATCC25923, Bacillus subtilis ATCC6633), two Gram (-) bacteria (Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27853) and one fungi (Candida albicans ATCC10231), but activity of essential oils were investigated only against C. albicans. No antimicrobial activity was observed with the aqueous extracts, whereas the ethanol extracts possessed activity having MIC values of 0.125-1 mg/ml against all the tested microorganisms. Among all the investigated extracts, root ethanol extract of A. setacea has the strongest activity against the C. Albicans with MIC values of 0.125 mg/ml. As for essential oils, the strongest activity was observed with essential oil of A. biebersteinii having MIC value 0.78 p.l.
Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] vol. 15/2017/suppLement 1
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References: 3. Si XT, Zhang ML, Shi QW, Kiyota H. 2006. Chemistry
1. Akkol EK, Koca U, Pesin I, Yilmazer D. 2011. Evid & Biodiversity. 3:1163-1180. Based Complement Alternat Med. 2011:1-7.
2. Turkmenoglu FP, Agar OT, Akaydin G, Hayran M, Demirci B. 2015. Molecules. 20:11432-11458.
SYNERGISTIC EFFECTS - A NEW APPROACH IN COMBINATION THERAPY
© Harald Schweim
Drug Regulatory Affairs, Rheinische Friedrich-Wilhelms-University, Bonn, Germany
At the end of all drug research stands the "approval of the (new) drug". Therefore, it is un-avoidable for scientists to think about the process of regulation although during the development. Textbooks are full of negative interactions effects of medicines in in combination treatment, but due to lack of ethic to make RTCs, mainly discovered by chance. The result over years, common knowledge of classical pharmacology is: "Avoid Combination!" Moreover, to be frank, there have been and are several inacceptable combinations on the market. If new ideas like "synergy" comes up -among regulators - in "slow motion".
A major argument was that different ingredients of a fixed combination could have different courses or durations of action, e.g. the synchronization of the bioavailability of the substances. However, this is only convincing, if the mode of action is needed simultaneously, not, if there are different targets etc. Nevertheless, even in therapy with chemically defined medicine, we are reaching borders.
First: There are serious diseases, from which since a long time, is known that they cannot sufficiently be influenced (or cured) with one drug alone. In addition, in the last years the disease needing combination-therapy increased.
Second: The ageing society brings up more and more "multi-morbidity" patients needing polypharmacy where the influences of different drugs to each other are mainly unknown but the combination is unavoidable, caused by the severity of the diseases. It's typical that problems arises, when new or additional medicines are
needed, or different physicians, not knowing from each other prescription, prescribe different drugs.
Third: In the fighting with bacteria etc., we are close to the end of effective antibiotics. We urgently need new substances OR new ideas of treatment; less side effects and eradication should result in less resistance. However, up to today this is only a dream.
Fourth: We have many problems with (tropical) diseases e.g. in Africa. Of course, we have some effective (chemically defined) medicines e.g. against malaria, but in poorer countries they are too expensive and we need (cheaper) alternatives, e.g. plants like Artemisia annua.
Combinations are used commonly for many different indications. To cover all the individual needs of the patients a wide range of different combinations with different content of active substances need to be marketed.
New pathways for the authorisation of combinations need to be introduced. The next logical step in the regulatory framework is the co-approval of combination therapies based on target-ed approaches, which so far does not exist. The approach introduced in this thesis recommends this additional new way of drug approval to overcome this gap. The development and approval of novel therapeutic concepts would be a consistent step towards a better health care. A clear regulatory pathway towards an approval of drug combinations could help agencies, health care professionals and patients to gain safer therapies and clear recommendations for medical practice.
Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy]
vol. 15/2Q17/suppLeMEnt 1
