• Natural Product Sciences
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• v.27 no.3
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• pp.141-150
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• 2021

This short review on the chemistry, pharmacological properties and patents of obovatol and obovatal from Magnolia obovata is the first publication. Pharmacological properties are focused on anti-cancer, anti-inflammatory, anti-platelet and neuroprotective activities. Obovatol and obovatal were first isolated from the leaves of M. obovata. Also reported in the bark and fruits of M. obovata, obovatol and obovatal are neolignans i.e., biphenolic compounds bearing a C-O coupling. Other classes of compounds isolated and identified from M. obovata include sesquiterpene-neolignans, dineolignans, trineolignan, lignans, dilignans, phenylpropanoids, phenylethanoid glycosides, flavonoids, phenolic acids, alkaloids, sesquiterpenes, ketone and sterols. The anti-cancer properties of obovatol and obovatal involve apoptosis, inhibition of the growth, migration and invasion of cancer cell lines. However, obovatol displays cytotoxicity against cancer cells but not obovatal. Similarly, anti-inflammatory, anti-platelet, neuroprotective, anxiolytic and other pharmacological activities were only observed in obovatol. The disparity in pharmacological properties of obovatol and obovatal may be attributed to the -CHO group present in obovatal but absent in obovatol. From 2007 to 2013, eight patents were published on obovatol with one mentioning obovatal. They were all published at the U.S. Patent and Trademark Office by scientists of the Korea Research Institute of Bioscience and Biotechnology (KRIBB) as inventors and assignee, respectively. Some future research and prospects are suggested.

• Journal of Acupuncture Research
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• v.25 no.2
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• pp.75-89
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• 2008

목적 : 후박(厚朴)(Magnolia obovata)에서 추출한 낮은 농도의 obovatol 약침액의 RAW264.7 세포에서 LPS로 유발된 염증, $TNF-{\alpha}$로 유발된 human colon carcinoma SW620 및 HCT116 세포의 세포증식에 대한 영향과 그 기전을 살펴보고자 하였다. 방법 : RAW264.7 세포에서 LPS로 염증을 유발하고 낮은 농도의 obovatol 약침액을 처리한 후 cell viability, NO 생성량, iNOS와 COX-2의 발현, $NF-{\kappa}B$활성, 전사능력을 관찰하기 위해 WST-1 assay, NO determination assay, western blot analysis, EMSA, luciferase activity assay를 시행하였고, HCT116, SW620 세포에 $TNF-{\alpha}$로 증식을 유도하고 낮은 농도의 obovatol 약침액을 처리한 후 cell growth, apoptosis 및 apoptosis와 연관된 $NF-{\kappa}B$의 활성 변화를 관찰하기 위해 WST-1, Cell morphogy test, DAPI staining and TUNEL assay, EMSA, luciferase activity assay를 시행하였다. 결과 : 1. RAW264.7 세포에서 낮은 농도의 obovatol 약침액 처리는 $NF-{\kappa}B$의 활성 및 전사능력을 낮추고 iNOS와 COX-2의 발현과 NO 생성을 감소시켜 LPS로 유발된 염증을 억제하였다. 2. HCT116, SW620 세포에서 낮은 농도의 obovatol 약침액 처리는 $NF-{\kappa}B$의 활성을 낮추어 세포자멸사를 촉진함으로써 $TNF-{\alpha}$로 유발된 암세포의 성장을 억제하였다. 결론 : 이상의 결과는 낮은 농도의 obovatol 약침액이 항염 및 인간 전립선암세포주인 SW620, HCT116에 대한 증식억제 효과가 있음을 입증한 것이며, 향후 이를 바탕으로 한 생체 연구에서의 긍정적인 결과는 obovatol 약침액이 만성염증성 질환 및 대장암의 예방과 치료에 대한 효과적인 치료제 개발에 초석이 될 것으로 기대된다.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.15-29
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• 2007

목적 : 후박(厚朴)(Magnolia Obovata)에서 추출한 낮은 농도의 Obovatol 약침액의 RAW264.7 세포에서 LPS로 유발된 염증，$TNF-{\alpha}$로 유발된 human Prostate carcinoma PC-3 및 LNCap 세포의 세포증식에 대한 영향과 그 기전을 살펴보고자 하였다. 방법 : RAW264.7 세포에서 LPS로 염증을 유발하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell viability, NO 생성량，iNOS와 COX-2의 발현, $NF-{\kappa}B$활성，전사능력을 관찰하기 위해 MTT assay, NO determination assay, western blot analysis, EMSA, luciferase activity assay를 시행하였고，LNCap, PC-3 세포에 $TNF-{\alpha}$로 증식을 유도하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell growth, apoptosis 및 apoptosis와 연관된 $NF-{\kappa}B$의 활성 변화를 관찰하기 위해 WST-1, Cell morphogy test, DAPI staining and TUNEL assay, EMSA, luciferase activity assay를 시행하였다. 결과 : 1. RAW264.7 세포에서 낮은 농도의 Obovatol 약침액 처리는 $NF-{\kappa}B$의 활성 및 전사능력을 낮추고 iNOS와 COX-2의 발현과 NO 생성을 감소시켜 LPS로 유발된 염증을 억제하였다. 2. LNCap, PC-3 세포에서 낮은 농도의 Obovatol 약침액 처리는 $NF-{\kappa}B$의 활성을 낮추어 세포자별사를 촉진함으로써 $TNF-{\alpha}$로 유발된 암세포의 성장을 억제하였다. 결론 : 이상의 결과는 낮은 농도의 Obovatol 약침액이 항염 및 인간 전립선암세포주인 PC-3, LNCap에 대한 증식억제 효과가 있음을 입증한 것이며，향후 이를 바탕으로한 생체 연구에서의 긍정적인 결과는 Obovatol 약침액이 만성염증성 질환 및 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 초석이 될 것으로 기대된다.

• Korean Journal of Pharmacognosy
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• v.37 no.4 s.147
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• pp.278-282
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• 2006

In this study, we analyzed and quantified the contents of magnolol (1), honokiol (2), and obovatol (3) in the leaves of Magnolia species by HPLC. HPLC methods were developed and validated by ICH guide lines comparing the linearity, intraday precision, inter-day precision. The optimal conditions were as follows; wavelength: 288 nm, column: Zorbax Eclipse XDBC18 $(2.1\times150\;mm,\;5{\mu}m)$, mobile phase: Acetonitril - 0.1 % $H_3PO_4$ (45:55, v/v) buffer, flow rate: 0.5 ml/min. The contents of magnolol, honokiol and obovatol were 1.08%, 2.37%, and 0.57% in the leaves of M. officinalis, 0.50%, 0.03%, and 1.54% in the leaves of M. biloba, 0.37%, 0.03%, and 0.76% in the leaves of M. obovata. The contents of effective ingredients in the leaves of M. officinalis and M biloba were higher than that of M. obovata. Especially, the content of obovatol in the leaves of M. biloba was remarkably high. This result showed that the shapes of leaves have a certain relationship with the content of obovatol.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.325-328
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• 2002

In the course of our work on anti-platelet constituents from plants, five phenolic compounds, magnolol, honokiol, obovatol, methyl caffeate, and syringin, were isolated from the methanol extracts of the barks and fruits of Magnolia obovata. The compounds were identified based on the spectroscopic data. Methyl caffeate was isolated for the first time from the genus Magnolia and it showed 3∼4-folds higher potency than ASA. The activities of obovatol and honokiol were comparable to ASA. Magnolol and syringin showed only very mild inhibitory effects to all the stimulators.

• Bulletin of the Korean Chemical Society
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• v.28 no.9
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• pp.1601-1604
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• 2007

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.187-194
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• 2011

Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

• Journal of Food Hygiene and Safety
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• v.26 no.3
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• pp.187-191
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• 2011

Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell(VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of atherosclerosis. The aim of this study was to assess the effect of YP 12, a newly synthesized obovatol derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The anti-proliferative effects of YP 12 on rat aortic VSMCs were examined by direct cell counting and by using $[^3H]$ thymidine incorporation assays. It was found that YP 12 potently inhibited the growth of VSMCs. The pre-incubation of YP 12 (1-4 ${\mu}M$) significantly inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. In accordance with these findings, YP 12 revealed blocking of the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Whereas, YP 12 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. These results also show that YP 12 may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.

• YAKHAK HOEJI
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• v.55 no.2
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• pp.116-120
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• 2011

Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development and progression of proliferative cardiovascular diseases, including hypertension and atherosclerosis. To find antiproliferative agent (A)-8 had inhibitory effect on VSMCs proliferation. Therefore, we examined the antiproliferative effect of A-8, a newly synthesized obovatol derivative. To investigate the antiproliferative effect of A-8, we examined cell counting and [$^3H$]-thymidine incorporation assays. The pre-incubation of A-8 (1~4 ${\mu}M$) significantly inhibited proliferation and DNA synthesis of 5% fetal bovine serum (FBS)-stimulated rat aortic VSMCs in concentration-dependent manner. Whereas, A-8 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. In addition, A-8 significantly inhibited 5% FBS-induced cell cycle progression in rat aortic VSMCs. These results show that A-8 may be developed as a potential antiproliferative agent for treatment of angioplasty restenosis and atherosclerosis. Furthermore, A-8 should be examined for further clinical application either as a single agent or in combination with other angioplasty restenosis or atherosclerosis agents.

• Natural Product Sciences
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• v.14 no.3
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• pp.196-201
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• 2008

Five neolignans (1 - 4, 8), two sesquiterpene-lignans (5 - 6), and two phenylpropanoids (7, 9) were isolated from the stem bark of Magnolia obovata Thunberg (Magnoliaceae) by repeated column chromatography. The structures of isolated compounds were identified as 4-methoxyhonokiol (1), obovatol (2), magnolol (3), honokiol (4), eudeshonokiol B (5), eudesobovatol B (6), coumaric acid (7), magnaldehyde B (8), and ${\rho}-coumaric$ acid (9) on the basis of spectroscopic analysis including 2D-NMR and MS data. Compounds 1 - 9 were evaluated for their anti-complement activities against the classical pathway of the complement system. Of them, compound 8 showed significant anti-complement activity on the classical pathway with $IC_{50}$ value of 102.7 ${\mu}M$, whereas compounds 1 - 7 and 9 were inactive. This result indicated that an aldehyde group in the neolignan is important for the anti-complement activity against the classical pathway.