Project's information

Project's title Anti-inflammatory effects of natural compounds isolated from several selected Vietnam medicinal plants
Project’s code QTSK01.01/21.22
Research hosting institution Institute of Natural Products Chemistry
Coordinating unit, co-chair Centre of Experimental Medicine, Institute of Experimental Pharmacology and Toxicology, Slovakia Academy of Science (SAS)
Project leader’s name Pham Ngoc Khanh and Katarina Bauerova
Project duration 01/03/2021 - 30/09/2023
Project’s budget 200 million VND
Classify Excellent
Goal and objectives of the project

The objectives of this project is to research and discover some Vietnamese natural compounds possessing anti-inflammatory effects and initially study the mechanism of their anti-inflammatory effects.

Main results

- Screened for anti-inflammatory effects of 5 Vietnamese plant species. Among them, four plant species including Rhubarb (Rheum officinale Baill.), Ophiopogon fruticulosus), Pinus krempfii and Dysoxylum tpongense are continued to be studied for chemical compositions and bioactivity.
-  Isolated and determined the structures of 02 compounds including: tetratricontan-1-ol (Os.01) và 2,6,10 – bisabolatriene (Os.02) from the root of Ophiopogon fruticulosus. Sterols like β-sitosterol or stigmasterol were found abundant in the n-hexane fraction.
 - Isolated and determined the structures of 04 compounds including: rhapontigenin (RO1), chrysophanol (RO2), emodin (RO3) and trans-Piceatannol (RO4 ) from the root of Rhubarb (Rheum officinale Baill.). Among them, the stilbene rhapontigenin (1) and the anthranoid emodin (3) demonstrate anti-inflammatory effects through inhibition of NO production, with IC50 values ranging from 5.7 to 32 µg/mL. However, rhapontigenin is cytotoxic at high concentrations, so emodin is a better candidate for further study. All four compounds from rhubarb met the Lipinski criteria for good bioavailability.
- Screening bioactivity of 10 compounds including: a new triterpenoid: 3-O-acetate aglinin C (DT1), 5 triterpenoid: aglinin C (DT2), cabraleadiol (DT3), 24-epi-cabraleadiol (DT4), cabraleahydroxylactone (DT5), cabraleahydroxylactone-3-acetate (DT6), one furanoid diterpene: spathulenol (DT7), three sterol b-sitosterol (DT8), stiryst-22-en-3β-ol (DT9) and stiryst-4-en-3- one (DT10) from the stem and leaves of Dysoxylum tpongense. Among the compounds isolated from the leaves and stems of D. tpongense collected in Hoa Binh province, Vietnam, stiryst-4-en-3-one (10), which has a structure similar to cholesterol, has the effect LXR agonist with an EC50 value of 7.09 ± 0.97 (M). The triterpenoid compounds 3-O- acetate aglinin C (DT1), aglinin C (DT2) and 24-epi-cabraleadiol (DT4) showed inhibitory effects on the activation of the inflammatory factor NFB by TNF- caused on HepG2 cells with IC50 values of 12.45, 13.95 and 23.32 M, respectively. These compounds also inhibit iNOS enzyme expression. The LXR – NF-kB –iNOS factors have a close relationship and plays an important role in inflammation and atherosclerosis. Thus, the findings suggest that compounds from D. tpongense may be potential LXR agonists and are therefore worthy of further investigation.
-  Screening bioactivity of 04 flavonoid compounds including: tectochrysin (PK1), galangin (PK2), strobopinin (PK3) and cryptostrobin (PK4) from the root of Pinus krempfii. In vitro and in silico, two flavonoid compounds PK1 and PK2 inhibit AChE and BChE have been discovered as potential molecular targets in the treatment of neurological disorders, therefore, this study has contributed new results to drug discovery and development. Substances have neuroprotective effects and especially treat Alzheimer's disease.
- Supported the training of 01 bachelor of Vietnam Agricultural Academy.

Novelty and actuality and scientific meaningfulness of the results
- The triterpenoid compounds 3-O- acetate aglinin C (DT1), aglinin C (DT2) and 24-epi-cabraleadiol (DT4) showed inhibitory effects on the activation of the inflammatory factor NFB by TNF- caused on HepG2 cells.
- Tectochrysin (PK1) and galangin (PK2) isolated from the root of Pinus krempfii that inhibit AChE and BChE have been discovered as potential molecular targets in the treatment of neurological disorders
Products of the project
- Publications:
1. Pham N. K., Bui H. T., Tran T. H., Hoang T. N. A., Vu T. H., Do D. T., Kim Y. H., Song S. B., To D. C., Nguyen M. C. - Dammarane triterpenes and phytosterols from Dysoxylum tpongense Pierre and their anti-inflammatory activity against liver X receptors and NF-κB activation. Steroids, 175 (2021) 108902. https://doi.org/10.1016/j.steroids.2021.108902.
2. Cuong N. M., Khanh P. N., Nhung L. T. H., Ha N. X., Huong T. T., Bauerova K., Kim Y. H., Tung D. D., Thuy T. T., Anh N. T. H. - Acetylcholinesterase inhibitory activities of some flavonoids from the root bark of Pinus krempfii Lecomte: in vitro and in silico study. Journal of biomolecular structure & dynamics,  (2023) 1-14. 10.1080/07391102.2023.2223664.
Recommendations

   During the implementation of this international cooperation project, we have built a cooperative relationship with our Slovak colleagues. The project has achieved many important new results and made many new contributions, especially the discovery of many active ingredients with anti-inflammatory activity from medicinal plants in Vietnam.
Suggestion:
- Continue to study the in vivo anti-inflammatory effects of potential extracts of Dysoxylum tpongense, Rheum officinale, Pinus krempfii, Ophiopogon fruticulosus and Nelumbo nucifera.
- Continue to expand research into phase II to find directions for developing drugs with discovered active ingredients.

Images of project
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