Project's information
Project's title | Neuroprotective effects on Alzheimer's disease (AD) of some seaweed species in Vietnam |
Project’s code | VAST04.10/22-23 |
Research hosting institution | Institute of Biotechnology |
Project leader’s name | Prof. Dr. Dang Diem Hong |
Project duration | 01/01/2022 - 31/12/2023 |
Project’s budget | 600 million VND |
Classify | Grade A |
Goal and objectives of the project | Objectives: Elucidate the molecular mechanism underlying the neuroprotective effect of extracts/clean substances obtained from Vietnamese seaweed in order to exploit potential seaweed species as food to protect human health. |
Main results | *Academic research results: 1. 11 species belonging to 8 seaweed genera, of which 5 genera have large yields including Sargassum, Caulerpa, Kappaphycus, Ulva and Gracilaria have been obtained. 69 total extracts from 11 species belonging to 8 seaweed genera of Ulva, Kappaphycus, Sargassum, Eucheuma, Gracilariopsis, Caulerpa, Gracilaria and Padina extracted in different solvents and extraction conditions; 5 fucoxanthin from 5 different seaweed genera; 8 substances; 75% and 96% ethanol extract with ultrasound of seaweed Ulva spp. and Sargassum spp. have been identified. 2. From 69 total extracts, 6 substances were screened 23 extracts and fucoxanthine having antioxidant activity (by DPPH test) with the IC50 value of 23 extracts /substances screened ranged from 0.63 - 5.0 mg/mL. + From 23 extracts/substances at tested concentrations of 50 and 100 μg/mL, 11 extracts/substances was non toxic and had protective activity against cytoxicity induced by Aβ25-35 on C6 neural cell line (Addition of extracts SmE96S, SoE96S, SoE75S, UE75S, SoEA, SoMW, KsE96, KsE75, GsE96, EdE75, and fucosterol at concentrations of 50 μg/mL or 100 μg/mL increased survival rate of C6 cell higher than 6.19; 6.90; 38.66; 4.20; 26.83; 37.97; 4.46; 4.41; 45.54; 4.08 and 5.06% compared to the model group (DMSO + Aβ25-35), respectively). + In a total of 23 extracts/substances tested, 7 extracts/substances exhibit AChE inhibitory activity with IC50 value < 0.2 mg/mL, including extracts SmE96S, SmE96S, SoE96S, SoEA, SoMW, UE75S, GsE96 and fucosterol, reaching IC50 values of 0.073; 0.157; 0.180; 0.159; 0.161; 0.182 and 0.103 mg/mL, respectively. + From 7 extracts/fucosterol combined with seaweed sources, large quantities can be easily harvested for the research: 96% and 75% ethanol extracts combined with ultrasound of 2 genera Sargassum (Sargassum spp.) and Ulva were extracted in large quantities for tested experimental animal model in vivo. + From 5 fucoxanthin samples extracted from Sargassum oligocystum, Kappaphycus alvarezii, Caulerpa racemose, Ulva reticulata and Gracilaria bailina with 3 tests including for screening of oxidative activity, cytotoxicity and AChE inhibitory activity and protective activity against cytotoxicity induced by Aß25-35 on the C6 neuronal cell line in the AD model. 3. Fucoxanthin isolated from S. oligocystum exhibits a neuroprotective effect by protecting against H2O2 or Aß25-35 - induced neurotoxicity in C6 cell lines; fucoxanthin achieved this effect by regulating the activity and gene expression of antioxidant enzymes (such as CAT and GPx) and the ER pathway (such as caspase-3 and Bax), as well as promoting the expression of genes involved in PI3K/Akt signaling (GSK-3β), autophagy (p62 and ATG5), and the biosynthesis of acetylcholine (VAChT and ChAT). + Ethanol extract of Sargassum spp. has a lower protective effect than fucoxanthin on nerve cells, specifically expression of genes related to the antioxidant process, AChE enzyme, and oxidation reduction process through the PI3K/Akt/ pathway, ER stress pathway, apoptosis, autophagy were only 5%-15% higher than induction by galatamine + Aβ25-35. 4. The ultrasound- assisted 96% ethanol extract isolated from Sargassum spp., Ulva extract of Ulva spp. and fucoxanthin isolated from Sargassum oligocystum reached mass of 453g, 510g, and 160 g, respectively for in vivo experimental animal models. + Ethanol extract at a concentration of 10,000 mg/kg body weight and fucoxanthin at a concentration of 5,000 mg/kg body weight (maximum absorbable dose) did not produce acute toxicity in white mice. + Rats administered ethanol extract and fucoxanthin at both doses of 100 mg/kg body weight and 300 mg/kg body weight per day for 30 consecutive days did not cause sub-chronic toxicity in white rats: no effect on the whole body of the rat; no effect in the eating behaviour and body development of rat; no affect to the hematopoietic function of rat; no affect kidney and liver function of rat, and no affect in the histological structure of liver, kidney, spleen of experimental rat. + Ethanol extract and fucoxanthin (200 mg/kg body weight of rats) were able to improve cognitive dysfunction caused by scopolamine similar to donepezil at dose of 5 mg/kg body weight of rats (with a tendency to increased time spent exploring novel objects compared to scopolamine-induced memory impairment rat treated with physiological saline). * About papers published: 02 articles on SCI-E (Q1) journals, 01 article on VAST2 journal, 01 proceeding published at National Biotechnology Science Conference 2022, Tay Nguyen University, November 4th 2022, 01 presentaion at International Conference ISS2023 (24th International Seaweed Symposium 19-24, February 2023, Hobart, Tasmania, Australia), 01 poster at 5th Recontries de Quy Nhon - International Biology Conference 2022. August 17 - 19, 2022, ICISE, Quy Nhon, Vietnam. |
Novelty and actuality and scientific meaningfulness of the results | - For the first time, initially studying the molecular mechanism of fucoxanthin action isolated from S. oligocystum and ethanol extract isolated from seaweed Sargassum spp. of Vietnam were investigated. They exhibits a antioxidant activities, AChE inhibition activities and neuroprotective effect by protecting against H2O2 or Aß25-35 -induced neurotoxicity in C6 cell lines; fucoxanthin achieved this effect by regulating the activity and gene expression of antioxidant enzymes (such as CAT and GPx) and the ER pathway (such as caspase-3 and Bax), as well as promoting the expression of genes involved in PI3K/Akt signaling (GSK-3β), autophagy (p62 and ATG5), and the biosynthesis of acetylcholine (VAChT and ChAT). |
Products of the project | * Scientific papers in referred journal (list): - 02 articles on international journal: + Dang Diem Hong, Le Thi Thom, Nguyen Cam Ha, Ngo Thi Hoai Thu, Hoang Thi Minh Hien, Luu Thi Tam, Nguyen Manh Dat, Tran Mai Duc, Nguyen Van Tru, Nguyen Thi Minh Hang and Ranga Rao Ambati (2023). Isolation of Fucoxanthin from Sargassum oligocystum Montagne, 1845 Seaweed in Vietnam and Its Neuroprotective Activity, Biomedicines, 2023, 11, 2310. (IF: 4,7; Q1; Citiscore: 3,7) + Hoang Thi Minh Hien, Le Thi Thom, Nguyen Cam Ha, Luu Thi Tam, Ngo Thi Hoai Thu, Tru Van Nguyen, Vu Thi Loan, Nguyen Trong Dan and Dang Diem Hong (2022). Characterization and Optimization of Culture Conditions for Aurantiochytrium sp. SC145 Isolated from Sand Cay (Son Ca) Island, Vietnam, and Antioxidative and Neuroprotective Activities of Its Polyunsaturated Fatty Acid Mixture. Marine Drugs 20, 780 (IF: 5,4; Q1; Citiscore: 9,6) - 01 articles on VAST2 journal: + Luu Thi Tam, Hoang Thi Minh Hien, Le Thi Thom, Nguyen Cam Ha, Ngo Thi Hoai Thu, Nguyen Van Tru, Tran Mai Duc, Nguyen Thi Minh Hang, Dang Diem Hong (2022). Screening of neuroprotective substances relevant to alzheimer’s disease from seaweed species collected in Ninh Thuan and Khanh Hoa provinces. Vietnam Academia Journal of Biology 44(4): 33-45. - 01 proceeding at National Biotechnology Science Conference 2022: + Luu Thi Tam, Hoang Thi Minh Hien, Ngo Thi Hoai Thu, Le Thi Thom, Nguyen Cam Ha, Tran Mai Duc, Nguyen Manh Dat, Nguyen Thanh Vinh, Trinh Thi Hien, Trinh Dinh Kha, Nguyen Van Tru, Dang Diem Hong (2022). Neuroprotective effect against alhzeimer’s disease of extracts isolated from two seaweeds species Kappaphycus alvarezii and Ulva reticulata collected in Nha Trang, Khanh Hoa, Vietnam in vitro. Proceedings of Vietnam National Conference on Biotechnology 2022. pages 331 - 337. ISBN: 978-604-357-052-6. + 02 presentation and poster at international conferences: - ISS2023 (24th International Seaweed Symposium 19-24, February 2023, Hobart, Tasmania, Australia). “Screening of compounds/extracts with neuroprotective activity from Vietnam seaweeds” and Chairperson of a section on “Bioactives” of the conference from 15.15 to 16.45 Thursday 23 rd February 2023 in Harbour View 1. 01 Abstract posted. - 5th Recontries de Quy Nhon - International Biology Conference 2022. August 17 - 19, 2022, ICISE, Quy Nhon, Vietnam. Title of Poster: Le Thi Thom, Nguyen Cam Ha, Luu Thi Tam, Ngo Thi Hoai Thu, Hoang Thi Minh Hien, Tran Mai Duc, Nguyen Van Tru, Nguyen Thi Minh Hang, Dang Diem Hong (2022). Screening of substances with neuroprotective activity from seaweeds collected from Ninh Thuan and Khanh Hoa provinces. - Specific products (describe detail: technical characteristic, place): + Product 1 - List of potential Vietnamese seaweed species that have neuroprotective effects on Alzheimer's disease (AD): 11 seaweed species of 5 genera have high reserves and neuroprotective activities. + Product 2: Seaweed extract residue: 02 ethanol and fucoxanthin extract residues have data evaluating neuroprotective effects on in vitro, in vivo models, acute and sub-chronic toxicity and biopharmaceutical effects. +Product 3 - Substances: 08/01 substances and 8 sets of spectra to determine structure. In which, fucoxanthin reaches 93.7% purity and 14.9 mg. + Product 4: Model of screening compounds isolated from seaweed that have neuroprotective effects on Alzheimer's disease (AD) All products are kept at the Algae Technology Department, Institute of Biotechnology, Vietnam Academy of Science and Technology. * Other product (if applicable) + Training 02 student of Thuyloi University, Successfully defended in January 2023: Nguyen Manh Dat and Nguyen Thanh Vinh, Department of Biotectnology, Faculty of Chemistry and Environment. + Training 01 first year postgradute student Nguyen Manh Dat, Department of Life , University of Science and Technology of Hanoi (admission decision dated Augus 25th, 2023. |
Recommendations | Proposing Vietnam Academy of Science and Technology and the Institute of Biotechnology to continue researching the process of creating functional foods containing fucoxanthin and ethanol extract isolated from seaweed to support the treatment of Alzeimer's disease. |
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