Научная статья на тему 'Isolation of bergamottin and rare lucidafuranocoumarin a from Peucedanum alsaticum fruits using high performance counter current chromatography'

Isolation of bergamottin and rare lucidafuranocoumarin a from Peucedanum alsaticum fruits using high performance counter current chromatography Текст научной статьи по специальности «Фундаментальная медицина»

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Текст научной работы на тему «Isolation of bergamottin and rare lucidafuranocoumarin a from Peucedanum alsaticum fruits using high performance counter current chromatography»

ADAPTOGENS: PAST, TODAY AND FUTURE

© Shikov A.N., Pozharitskaya O.N., Makarov V.G.

Saint-Petersburg Institute of Pharmacy, Leningrad region, Kuzmolovo, Russia

In the recent decades adaptogens have gained dramatically popularity all over the world. The number of references for the term "adaptogen" has increased in Google search engine tenfold since 2009.

The era of adaptogens has begun in the middle of the XX century. On March 4, 1943, J. Stalin signed Order No 4654-p of the People's Commissars Council of the USSR concerning research work "with the purpose of finding tonic ... substances" for both soldiers and persons working in the USSR defense industry during the Second World War. As a result of intensive work, the concept of herbal substances that would increase "the state of non-specific resistance" under stress conditions was developed, and the term "adaptogen" was introduced in 1947 by N.V. Lazarev. Later, I.I. Brekhman and I.V. Dardymov have claimed that an adaptogen must produce a nonspecific response against multiple stressors; have a normalizing effect, irrespective of the nature of the pathology; and be nontoxic, innocuous and not influence normal body functions more than required. According to modern definition adaptogens are metabolic regulators which increase the ability of an organism to adapt to environmental stressors and prevent damage to the organism by such stressors. Since 1997, the term "adaptogen" has been used as a functional term by Russian health-regulatory authorities, in 1998 this term was allowed by the FDA, and in 2008 was approved by EMEA.

Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., Leuzea carthamoides Willd., Oplopanax elatus (Nakai) Nakai, Panax ginseng C. A. Mey., Schisandra chinensis (Turkz.) Baill., and Sedum roseum (L.) Scop. were considered as classical adaptogens in result of intensive studies.

The main active compounds of adaptogens as such as tetracyclic triterpenes, polyphenols, unsaturated tri- and polyhydroxi fatty acids, etc. are close related to the unique regulatory molecules existing in the human body.

Number of important pharmacological activities (stress protective, increase of concentration, performance and endurance during fatigue, improves some aspects of mental health and social functioning, antihypoxant, antioxidant, treatment of impotence, normalization of sleep, improving of appetite, improving of night vision, geroprotective, improving of quality of life) are documented for adaptogens. The most effects have been proved in the clinical trials.

The normal paradigm "one drug for one disease" is not ap propriate for adaptogens as they can have numerous pharmacological effects and mechanisms. The activity of adaptogens is associated with the regulation of homeostasis on both the system level via several mechanisms of action that are linked to the hypothalamic-pituitary-adrenal axis and the cellular level via activation of molecular chaperones, mainly hsp70 proteins; regulation of key mediators of the stress response, including neuropeptide Y, cortisol, nitric oxide, stress-activated protein kinase JNK, and forkhead-box transcription factor DAF-16; and the biosynthesis of ATP, which changes the energy source

Originally, the category of adaptogens was invented not for the purpose of enriching the herb sellers' vocabulary, but as a novel term to describe the next generations of medicines. The future medicines will no longer be anti-this, anti-that, but something-protectants: hepatoprotectants, radioprotectants, neuroprotectants etc. They will not only protect the existing state of the body, but will strengthen it as required by our duties at the moment.

ISOLATION OF BERGAMOTTIN AND RARE LUCIDAFURANOCOUMARIN A FROM PEUCEDANUM ALSATICUM FRUITS USING HIGH PERFORMANCE COUNTER CURRENT CHROMATOGRAPHY

© Koziot E.1, Marcourt L.2, Wolfender J.L.2, Skalicka-Wozniak K.1

1 Department of Pharmacognosy with Medicinal Plant Unit of Medical University of Lublin, Lublin, Poland;

2 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland

Peucedanum alsaticum L. is a perennial plant belonging to the Apiaceae family, known for secondary metabolites as chromones and furanocoumarins [1]. Previous studies have shown the presence of divaricatol, notoptol, ledebouriellol, alsaticol and alsaticocoumarin [2]. Traditional application of P. alsaticum includes expectorant, diaphoretic, diuretic, stomachic, sedative, and antimicrobial effects [3].

The aim of this study was to develop an efficient strategy for pure compound isolation and led to the identification of two major constituents from dichloromethane extract of the fruits of P. alsaticum. For this High Performance Counter Current Chromatography was applied. The solvent system composed of heptane/ethyl acetate/methanol/water (3:1:3:1) was successfully used in the reverse phase mode - first in

Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy]

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analytical, then in preparative scale. Sixty one-minute fractions were collected and analyzed by mean of HPLC. After injection of 500 mg of the oily extract 2,63 mg of lucidafuranocoumarin A and 8,82 mg of bergamottin was obtained in a single run in less than 50 minutes. The structure of compounds was determined by NMR and MS (UHPLC-TOF-MS) analyses.

Acknowledgements: The work was financed from grant No 4/POLTUR-1/2016

References:

1. Skalicka-Wozniak K, tos R, Gtowniak K, Malm A. 2008. Acta Chromatogr. 20(1):119-133.

2. Skalicka-Wozniak K, Mroczek T, Garrard I, Gtowniak K. 2012. J. Sep. Sci. 35(7): 790-797.

3. Skalicka-Wozniak K, tos R, Gtowniak K, Malm A. 2010. Chem. Biodivers. 7(11): 2748-2754.

EFFECTS OF LITSEA JAPONICA FRUIT EXTRACT AND ITS CONSTITUENTS ON HEPATITIS E VIRUS REPLICATION

© Gayong Park, Yoon-Jae Song

Department of Life Science, Gachon University, Seongnam-Si, Gyeonggi-Do, Republic of Korea

Hepatitis E virus (HEV) is the major etiological agent of acute viral hepatitis and a member of the genus Hepevirus of the family Hepeviridae [1]. To identify a novel antiviral candidate for the HEV-caused hepatitis E, crude ethanol extract of medicinal plants were screened for the potential inhibitory activity on HEV replication using a genotype 3 HEV-luciferase replicon [2]. Seventy percent ethanol extract of Litsea japonica fruit (LJE) reduced HEV replication by 67.2% without exhibiting any significant adverse effects on the viability of human hepatocarcinoma Huh-7.5 cell line. To determine the solvent fraction that inhibits HEV replication, activity-

guided fractionation of LJE was further performed. Among the solvent fractions tested, the ethyl acetate (EtOAc) fraction of LJE reduced HEV replication by 71% in vitro. Thus, the EtOAc fraction of LJE is a good source of novel drug candidates for treatment of the HEV-caused hepatitis E.

References:

1. Nan Y, Zhang YJ. 2016. Front Microbiol. 7:1419.

2. Pudupakam RS, Kenney SP, Cordoba L, Huang YW, Dryman BA, Leroith T, Pierson FW, Meng XJ. 2011. J Virol. 85:10031-10040.

ACUTE AND SUB-CHRONIC (28 DAYS) REPEATED ORAL TOXICITY TEST OF DRIED EXTRACT OF SAMBILOTO HERBS (ANDROGRAPHIS PANICULATA NEES.) AND MAHOGANY SEEDS (SWIETENIA MAHAGONI JACQ.) COMBINATION

© Sukardiman, Ricko Hartanto, Lusiana Arifianti, Herra Studiawan, Rakhmawati

Departmen of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia

The present study was carried out to evaluate the safety of dried extract of sambiloto herbs (Andrographis paniculata Nees.) and mahogany seeds (Swietenia mahagoni Jacq.) combination.

Sambiloto herbs (Andrographis paniculata Nees.) and mahogany seeds (Swietenia mahagoni Jacq.) was extracted by ethanol 96 %. Extraction results was continued to dried using avicell and cab-o-sil. Dried extract was continued to acute toxicity by using a fixed dose method and sub-chronic toxicity was performed according to the OECD guideline. In an acute toxicity study, a single dose of 1000, 2000, 4000, 8000 and 16000 mg/kg bw of its dried extract combination was administered p.o (orally) to healthy female mice following a sighting study. The animals were observed for mortality and clinical signs for 24 hour and then daily for 14 days. In the sub-chronic toxicity study, the extract was administered orally at doses of 250, 500 and

1000 mg/kg bw /day to healthy Wistar rats. The animals were given by dried extract of combination and once daily for 28 days, the administrations were stopped on the 28th day, while for the satellite group still observed until 14 days during the post observation period for assessment of reversibility, persistence or delayed occurrence of toxicity. At the end of the observation, all animals were autopsied and observed in parameters such as blood biochemical parameters, hematology and relative vital organ weight.

In the acute toxicity test, oral administration of 1000, 2000, 4000, 8.000 and 16.000 mg/kg bw produced neither mortality or changes in behavior or any other physiological activities and indicated that LD50 of dried extract combination was greater than 16.000 mg/kg bw in Wistar Rats. In sub-chronic 28-days repeated dose oral toxicity study, its combination dried exctract of 250 mg/ kg bw, 500 mg/kg bw 1000 mg/kg bw in male and female

Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] vol. 15/2017/suppLement 1

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