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DOI: 10.1055/s-0036-1597068
Neuroprotective activity of compounds of Clematis mandshurica against glutamate-induced cell death in HT22 cells
Publikationsverlauf
Publikationsdatum:
14. Dezember 2016 (online)
Clematis mandshurica (C. mandshurica) is a traditional crude drug for treatment of urethritis, carbuncles and carcinoma [1 – 3]. We revealed that C. mandshurica have neuroprotective activity against glutamate-induced cell death in HT22 cells. We isolated and identified 24 compounds from C. mandshurica extract. The neuroprotective effect of 1 – 24 compounds was evaluated against glutamate-induced cell death in hippocampal HT22 cell line As a result, methyl 5-(4-methylcyclohexa-1,4-dienyl)hexanoate showed higher neuroprotective effect (relative protection of 28.74 ± 4.32% at 100µM) than that of other compounds. Methyl 5-(4-methylcyclohexa-1,4-dienyl)hexanoate also reduced ROS levels (84.28 ± 7.5% of 100µM) and intracellular Ca2+ accumulation (102.58 ± 5.04% at 100µM). Methyl 5-(4-methylcyclohexa-1,4-dienyl)hexanoate significantly recovered the mitochondrial membrane potential to 92.98 ± 2.13% of control at 100µM. Methyl 5-(4-methylcyclohexa-1,4-dienyl)hexanoate also significantly recovered glutamate-induced depletion of GSH (86.60 ± 1.99 at 100µM), GR (87.85 ± 2.46% at 100µM) and GPx (90.01 ± 5.13% at 100µM). These results suggest that Methyl 5-(4-methylcyclohexa-1,4-dienyl)hexanoate exerted neuroprotective effect by antioxidant effect. Neuroprotective effect of methyl 5-(4-methylcyclohexa-1,4-dienyl)hexanoate may be associated with anti-oxidantive effect.
No. |
Compound |
1 |
(2S,3S,4R,5S)-2-(3,4-dihydroxy-3,4-dihydro-2 H-pyran-2-yloxy)-6-(hydroxymethyl)tetrahydro-2 H-pyran-3,4,5-triol |
2 |
6-((2S,3S,4R,5S)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2 H-pyran-2-yloxy)-5,6-dihydro-2 H-pyran-2,4,5-triol |
3 |
methyl nonanoate |
4 |
methyl ester heptanoic acid |
5 |
(E)-methyl dodec-9-enoate |
6 |
linolenic acid |
7 |
linoleic acid |
8 |
5-[(β-D-glucopyranosyloxy)methyl]-, (5S)- 2(5 H)-furanone |
9 |
hexahydro-3a,7a-dimethyl-, (3aR,7aS)-rel-4(1 H)-isobenzofuranone |
10 |
3a,7,7-trimethylhexahydro-2 H-furo[2,3-c]pyran-2-one |
11 |
γ,4-dimethyl-1,4-cyclohexadiene-1-butanoic acid |
12 |
methyl 5-(4-methylcyclohexa-1,4-dienyl)hexanoate |
13 |
Stigmasterol |
14 |
stigmasterol glucoside |
15 |
β-sitosterol |
16 |
pyrocincholic acid methyl ester |
17 |
Hederagenin |
18 |
(3S,3'S,4R,4'R,5S,5'S,6S,6'S)-6,6'-(2-(hydroxymethyl)-3-(3-methylbut-2-enyl)-1,4-phenylene)bis(oxy)bis(2(hydroxymethyl)tetrahy -dro-2 H-pyran-3,4,5-triol) |
19 |
ferulic acid |
20 |
2-ethynyl-1,4-dimethoxybenzene |
21 |
6-ethoxy-3-oxochroman-8-carbaldehyde |
22 |
2,4-dihydroxy-6-(hydroxymethyl) benzaldehyde |
23 |
2-[(8-acetyl-6-methoxy-4-methyl-2-oxo-2 H-1-benzopyran-7-yl)oxy]-acetic acid |
24 |
2,3-dihydro-5-methyl-7-benzofurancarboxaldehyde |
Acknowledgements: This research was supported by Kangwon National University.
Keywords: Clematis mandshurica, neuroprotective effect, oxidative stress, isolation of compounds.
References:
[1] The Korea Food and Drug Administration. The Korean herbal pharmacopoeia: notification; 2014: 2014 – 2074.
[2] Jung YB, Roh KJ, Jung JA, Jung K, Yoo H, Cho YB, Kwak WJ, Kim DK, Kim KH, Han CK. Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study. Am J Chin Med 2001; 29: 485 – 491.
[3] Lee SW, Chung WT, Choi SM, Kim KT, Yoo KS, Yoo YH. Clematis mandshurica protected to apoptosis of rat chondrocytes. J Ethnopharmacol 2005; 101: 294 – 298.