Project's information

Project's title Developing an excellent research group of class I about structural research of new compounds with anti-inflammatory effects from selective medicinal plants
Project’s code NCXS 01.02/22-24
Research hosting institution Institute of Marine Biochemistry (IMBC)
Project leader’s name Assoc.Prof. Phan Van Kiem
Project duration 01/01/2022 - 31/12/2024
Project’s budget 5,900 million VND
Classify Grade A
Goal and objectives of the project

- To build and develop a strong research group with following research obejectives
+ Inverstigation of chemical structure from natural sources: isolation, structural elucidation of chemical components from 16 selected plants, discovery of new chemical structure.
+ Investigation on absolute configuration of natural compounds by advanced methods using special computational approaches. 
+ Evaluation of anti-inflammatory activities of isolated compound by inhibition of NO production, inhibiting expression of iNOS and p-NF-κB protein, inhibition of cytokines secreation such as IL-6, TNF-α, COX-2, PGE-2
+ Molecular docking studies targeting on anti-inflamatory protein including iNOS, TNF-α, and COX-2

Main results

-    Scientific results:
The 16 selected plants, including Abelmoschus sagittifolius, Aglaia elaeagnoidea, Ailanthus triphysa, Allium ramosum, Aphanamixis polystachya, Cryptolepis buchananii, Dracaena cambodiana, D. elliptica, D. fragrans, Kadsura induta, Piper mutabile, P. sarmentosum, Schisandra cauliflora, Syzygium attopeuense, S. bullockii, and  S. cerasiforme were collected and archived their voucher specimens.
From 16 selected plants, 210 different compounds were isolated and identified by moder spectrosopic methods such as HR-ESI-MS, 1D- and 2D-NMR, Circular dichroism spectroscopy and theoretical calculation of the spectral data. Among 210 obtained compounds, there were 67 new compounds. 
Absolute configuration of 24 new compounds were determined by comprehensive analysis of ECD spectra in combination with theoretical calculation of ECD (TD-DFT calculation) and NMR (GIAO calculation) using authorized program Gaussian16 and Spartan18.
NO inhibitory activity of the isolated compound were evaluated. Additionally, four selected compounds (AP23-AP25, AT1) were further evaluated on their inhibitory effects on the expresion of iNOS, p-NF-κB proteins and the secreation of inflammatory cytokines including IL-6, TNF-α, COX2, and PGE2.
Several dibenzocyclooctadiene lignans were performed molecular docking study on iNOS, TNF-α, and COX2 protein which indicated that these compounds showed good binding affinity towards active site of  iNOS and TNF-α but exhibited poor interaction with active site of COX2 protein
-    Applied results:
Two compounds AS1 and AS8 not only showed potent NO inhibitory activity but also high contents in the rhizome of Abelmoschus sagittifolius (15.37×10-3 % (0.1537 mg/g) and 9.59×10-3 % (0.0959 mg/g) in dried materials, respectively). They could be useful for further applied investigations such as starndard substances and quality control.
Chemical structures of isolated compounds and their results in anti-inflammatory activities could be useful for further applied investigations. 

Novelty and actuality and scientific meaningfulness of the results

-    Isolation and strutural determination of 67 new compounds
-    Determination of 3 novel compounds (AP23-AP25) possessing new carbon skeleton.
-    Determination absolute configurations of 24 new compounds using experimental circular dichroism (CD) spectroscopy, NMR  analysis and in combination with TDDFT, GIAO theoretical calculation of the spectral data (ECD and NMR) using Spartan18 and Gaussian16 softwares.

Products of the project

- Scientific papers in referred journals (list):
a) SCIE papers
1.    B. H. Tai, N. A. Bang, P. H. Yen, D. T. H. Yen, N. T. Cuc, D. T. Dung, P. T. T. Huong, D. T. Trang, N. X. Nhiem, N. T. Cuong, P. V. Kiem. Undescribed sesquiterpene-diterpene heterodimers from the fruits of Aphanamixis polystachya selectively modulate inflammatory markers in RAW 264.7 cells, Phytochemistry, 2024, 220, 113997 (Q1, IF = 3.8).
2.    N. A. Bang, D. T. H. Yen, D. T. T. Hang, P. H. Yen, N. H. Hoang, D. T. Trang, D. T. Dung, N. T. Cuc, N. T. Cuong, N. X. Nhiem, B. H. Tai, P. V. Kiem. New diterpene lactone derivatives from Aphanamixis polystachya leaves inhibit nitric oxide production in RAW 264.7 cells, RSC Adv., 2024, 14, 20536-20542 (Q1, IF = 3.9).
3.    B. H. Tai, P. H. Yen, N. H. Hoang, P. T. Thanh Huong, N. V. Dung, B. V. Thanh, N. T. Cuong, N. A. Bang, N. X. Nhiem, P. V. Kiem. New dibenzocyclooctadiene lignans from Kadsura induta with their anti-inflammatory activity, RSC Adv., 2022, 12, 25433-25439 (Q1, IF = 4.036).
4.    B. H. Tai, B. H. Ninh, P. H. Yen, D. T. Dung, N. H. Hoang, N. X. Nhiem, N. Van Tuyen, L. T. Anh, P. Van Kiem. New nitric oxide production inhibitors from Syzygium bullockii, J. Nat. Med., 2023, 77, 964-971 (Q1, IF = 3.192).
5.    N. A. Bang, N. D. Duy, B. H. Tai, N. T. K. Thuy, P. H. Yen, D. T. Dung, N. H. Hoang, N. X. Nhiem, N. K. Ban, P. V. Kiem. Cryptobuchanosides A-G: seven previously undescribed triterpene glycosides from Cryptolepis buchananii R.Br. ex Roem. and Schult. with nitric oxide production inhibition activity, J. Nat. Med., 2024, 78, 741-752 (Q1, IF = 3.3).
6.    P. V. Kiem, N. X. Nhiem, N. H. Hoang, N. A. Bang, P. H. Yen, D. T. Trang, D. T. Dung, N. T. Cuc, P. T. T. Huong, B. H. Tai. Undescribed (2-7′)-neolignans and polyoxygenated cyclohexene glycosides from the aerial parts of Piper mutabile C. DC. and their inhibitory effects on nitric oxide production, Fitoterapia, 2024, 175, 105903 (Q2, IF = 3.4).
7.    D. T. H. Yen, B. H. Tai, P. H. Yen, N. X. Nhiem, N. T. Cuong, N. V. Dung, P. T. T. Huong, P. V. Cuong, P. V. Kiem. Furostane Saponins from the Seeds of Allium ramosum and Their Lipid Accumulation Inhibitory Activity, Chem. Biodiversity, 2022, 19, e202200590 (Q2, IF = 2.408).
8.    P. H. Yen, N. H. Hoang, N. X. Nhiem, P. T. Thanh Huong, D. T. Dung, N. T. Cuc, N. T. Cuong, B. V. Thanh, B. H. Tai, P. V. Kiem. Dimethylbutyrylated Dibenzocyclooctadiene Lignans from the Fruits of Schisandra cauliflora Inhibit NO Production in LPS-Activated RAW264.7 Cells, Chem. Biodiversity, 2023, 20, e202300372 (Q2, IF = 2.745).
9.    B. H. Ninh, D. T. Dung, B. H. Tai, P. H. Yen, N. X. Nhiem, T. T. T. Hien, D. T. Trang, N. V. Tuyen, L. T. Anh, N. T. Hoai, P. V. Kiem. New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production, Chem. Biodiversity, 2023, 20, e202201048 (Q2, IF = 2.745).
10.    P. V. Kiem, B. H. Ninh, B. H. Tai, N. X. Nhiem, P. H. Yen, N. H. Hoang, D. T. Trang, D. T. Dung, N. V. Tuyen, L. T. Anh. Undescribed Phenolic Glycosides from Syzygium attopeuense and Their Inhibition of Nitric Oxide Production, Chem. Biodiversity, 2023, 20, e202301037 (Q2, IF = 2.9).
11.    N. D. Duy, N. A. Bang, P. H. Yen, D. T. Trang, B. T. N. Trang, N. T. K. Thuy, N. T. Cuc, N. X. Nhiem, P. V. Kiem, N. K. Ban, B. H. Tai. Four New Pentacyclic Triterpene Glycosides Isolated from the Fruits of Cryptolepis buchananii R.Br. ex Roem. & Schult and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells, Chem. Biodiversity, 2023, 20, e202301683 (Q2, IF = 2.9).
12.    P. H. Yen, B. H. Tai, N. H. Hoang, D. T. Dung, N. X. Nhiem, D. T. H. Yen, P. T. T. Huong, N. V. Dung, D. T. T. Hang, N. T. Ha, D. T. Trang, V. K. Thu, P. V. Kiem. Four New Steroidal Saponins from the Roots of Dracaena cambodiana with NO Production Inhibition Activity in LPS Activated RAW 264.7 Cells, Chem. Biodiversity, 2024, 21, e202301963 (Q2, IF = 2.9).
13.    N. H. Hoang, P. H. Yen, D. T. Trang, D. T. Dung, N. T. Cuc, N. A. Bang, B. T. N. Trang, N. X. Nhiem, B. H. Tai, P. V. Kiem. Four Steroidal Saponins from the Trunks of Dracaena cambodiana with Inhibition of NO Production in LPS Activated RAW264.7 Cells, Chem. Biodiversity, 2024, 21, e202301764 (Q2, IF = 2.9).
14.    N. A. Bang, D. T. T. Hang, D. T. H. Yen, N. H. Hoang, D. T. Dung, N. T. Cuong, P. H. Yen, N. X. Nhiem, B. H. Tai, P. V. Kiem. Four Unidentified Compounds Isolated from the Stem Barks of Aphanamixis polystachya and Their NO Production Inhibition in LPS Activated RAW 264.7 Cells, Chem. Biodiversity, 2024, 21, e202401118 (Q2, IF = 2.9).
15.    N. H. Hoang, D. T. Trang, N. A. Bang, P. H. Yen, D. T. Dung, N. X. Nhiem, L. T. Huyen, P. T. T. Huong, D. T. H. Yen, B. H. Tai, P. V. Kiem. Three New Sesquiterpenes from the Leaves of Aglaia elaeagnoidea with NO Inhibitory Activity, Chem. Biodiversity, https://doi.org/10.1002/cbdv.202402159 (Q2, IF = 2.3).
16.    N. D. Duy, D. T. Dung, D. T. Trang, N. A. Bang, P. H. Yen, N. X. Nhiem, N. T. Cuc, P. T. T. Huong, N. V. Dung, N. H. Hoang, D. T. H. Yen, N. T. K. Thuy, N. T. Cuong, B. H. Tai, P. V. Kiem. Four New Tirucallane Triterpenoids from the Leaves of Ailanthus Triphysa with Anti-Inflammatory Activities, Chem. Biodiversity, https://doi.org/10.1002/cbdv.202402584 (Q2, IF = 2.3).
b) SCOPUS papers
1.    B. H. Ninh, D. T. Dung, N. V. Tuyen, B. H. Tai, P. V. Kiem. Chemical constituents of Syzygium cerasiforme leaves and their nitric oxide inhibitory activity in LPS-activated RAW264.7 cells, Vietnam J. Chem., 2024, 62, 55-60.
- Patents (list):
[1] Patent name: Hợp chất dime sesquitecpen-ditecpen có tác dụng kháng viêm và phương pháp phân lập hợp chất này từ loài Aphanamixis polystachya, Application number 1-2024-02063, submitted on March 21, 2024.
- Technological products (Products are deposited at the Institute of Marine Biochemistry):
[1]. 16 voucher speciments of selected plants.
[2]. Reports on the chemical investigation of 16 selected plants
[3]. Reports on the evaluation of anti-inflammatory activities (in vitro, in silico) of selected compounds by inhibition of NO production; inhibiting expresion of iNOS and pNF-κB; inhibition of IL-6, TNF-α, COX2, and PGE-2 secreations
- Other products (if applicable): Graduate education
[1]. Dr. Bui Hai Ninh, Recived a PhD degree from the Graduate University of Science and Technology.
[2]. PhD candidate Ngo Anh Bang, 3rd year course from the Graduate University of Science and Technology.
[3].  PhD student Nguyen Duc Duy, 2nd year course from the Graduate University of Science and Technology.

Research area

All results recommend for deverlopment of two compounds AS1 and AS8 as standard refferes and qualiti control of processed products containing Abelmoschus sagittifolius.

Recommendations

The project was well completed all of the missions. Several objects were done beter than in the poposal. 
-Investigations on natural product chemistry should receive more attention and funding to find new compound, new lead compound for new drug discovery and deverlopment.
- Determination of absolute configurations by experimental and calculation of ECD and NMR spectra should be more encouraged which are requirments for high quality publications.

Images of project
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